Category Archives: pathology

“Wrong Tissue in Block” makalesine dair:

“Wrong Tissue in Block” makalesine dair:
Spesmenlerin karışma olasılığı olan yerlerden birisi makroskopide Ali yerine Veli’nin örneklenmesi.
Bu makalede anlatılan yöntemde bunu engellemek için spesmen istek kağıdının ve spesmen kutusunun barkod okuyucu ile okunması ve uyumsuzluk durumunda sistemin hata mesajı vermesi kurgulanmış. https://academic.oup.com/ajcp/article-abstract/156/4/700/6262319?redirectedFrom=fulltext
Benzer bir kurguyu biz de sudan alma sırasında blok ve lam karşılaştırması için düşünmüştük. O dönemki sistemde bunun yapılamayacağı ifade edilince önce google sheet ile daha sonra basit javascript ile spesmen no ve blok uyumunu ayrı ayrı denetleyebilen küçük sayfalar tasarlamıştık.
Rutin yoğun işler sırasında dalgınlıklar, disleksik okumalar oldukça sıklaşıyor. Bu durumları engellemek için aynı grup örneğe ardısıra numara vermemek, masada “tek örnek, tek kağıt, tek kaset” kuralına uymak ve sesli bir şekilde isim ve numarayı okuyup, eğer varsa bir yazıcıya teyit ettirmek geleneksel yöntemler. Belki bu geleneksel yöntemler ile kıyaslansaydı bu makalede önerilen informatik çözümün işe yarayıp yaramayacağı daha net anlaşılabilirdi.
Zorunlu okutma olmaması, hata yapanın anında uyarılması gibi “bias” oluşturan nedenlerle kurgu olarak eksikliklere girmeyeceğim.
Bu gibi işleyişle ilgili müdahaleci çalışmalarda klasik “Hawthorne” etkisinin düşünülmeyişi en büyük eksikliklerden vesselâm …

Ek rapor ya da düzeltilmiş rapor yazan patologları sevin. Onlar hastalarının düzgün tedavi alması için kendi hatalarını kabul eden, şikayeti, istihzayı ve küçük görülmeyi göze alan güzel insanlardır: Quality assurance in dermatopathology: A review of report amendments https://pubmed.ncbi.nlm.nih.gov/32740937/

Ek rapor ya da düzeltilmiş rapor yazan patologları sevin. Onlar hastalarının düzgün tedavi alması için kendi hatalarını kabul eden, şikayeti, istihzayı ve küçük görülmeyi göze alan güzel insanlardır: Quality assurance in dermatopathology: A review of report amendments – PubMed

https://pubmed.ncbi.nlm.nih.gov/32740937/

Our review points to several quality improvement areas that can be targeted to potentially avoid diagnostic errors in dermatopathology, including standardizing certain anatomic sites to prevent misidentification and seeking out clinicopathologic correlation in challenging melanocytic cases.

Source: Quality assurance in dermatopathology: A review of report amendments – PubMed

The PBPS is now accepting applications for this year’s PBPS Abstract Award. This award will go to a pathology trainee with an abstract (poster/platform) in pancreatobiliary pathology presented at the 2021 annual USCAP meeting. Submitted abstracts will be evaluated for originality, scientific merit and presentation, and the winner will receive a $500 prize. At least one author should be a PBPS member. Trainees are strongly encouraged to apply.

The PBPS is now accepting applications for this year’s PBPS Abstract Award. This award will go to a pathology trainee with an abstract (poster/platform) in pancreatobiliary pathology presented at the 2021 annual USCAP meeting. Submitted abstracts will be evaluated for originality, scientific merit and presentation, and the winner will receive a $500 prize. At least one author should be a PBPS member. Trainees are strongly encouraged to apply.

The deadline for submission of Award applications is January 30th, 2021.

Please email your completed abstract in Word format along with the information below to the education committee chair Dr. Michelle Reid (michelle.reid emory.edu).

Name:
Training Institution:
Position:
PGY Year:
Date/Time of Presentation:
Abstract Name:
Poster Number (if applicable):
Email:

Comments: 

Recent Articles on Pancreatobiliary #Pathology – 2020-11-17

These are the recent articles on Pancreatobiliary Pathology:

To see all journal watch articles please visit: http://pbpath.org/journal-watch-upcoming-issue/

New Pancreas Articles


  • Application of low dose pancreas perfusion CT combined with enhancement scanning in diagnosis of pancreatic neuroendocrine tumors

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Nov;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33191144

PURPOSE: To explore the diagnostic value of pancreatic perfusion CT combined with contrast-enhanced CT in one-time scanning (PCECT) in pancreatic neuroendocrine tumors (PNETs) and to evaluate the difference of perfusion parameters between different grades of PNETs.
MATERIALS AND METHODS: From October 2016 to December 2018, forty consecutive patients with histopathological-proven PNETs were identified retrospectively that received PCECT for the preoperative PNETs evaluation. Two board certified radiologists who were blinded to the clinical data evaluated the images independently. The image characters of PNETs vs. tumor-free pancreatic parenchymal and different grades of PNETs were analyzed.
RESULTS: One-time PCECT scanning had a detection rate of 89.1% for PNETs, which was higher than the detection accuracy of the perfusion CT only (83.6%). The perfusion parameters of PNETs including blood volume (BV), blood flow (BF), mean slope of increase (MSI), and capillary surface permeability (PS) were significantly increased than those of tumor-free pancreatic parenchyma (p < 0.05, respectively). For differential comparison between grade I (G1) and grade II (G2) tumors, the parameters of BF and impulse residue function (IRF) of tumor tissue were significantly higher in the G2 tumors (p < 0.05, for both). In this study, the total radiation dose of the whole PCECT scan was 16.241 ± 2.289 mSv.
CONCLUSION: The one-time PCECT scan may improve the detection of PNETs according to morphological features and perfusion parameters with a relative small radiation dose. The perfusion parameters of BF and IRF may be used to help distinguish G1 and G2 tumors in the preoperative evaluation.

doi: https://doi.org/10.1016/j.pan.2020.10.046



  • Paratesticular tumors. A clinicopathological study from a single tertiary hospital in North India

Annals of diagnostic pathology 2020 Nov;50():151658

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33189965

OBJECTIVE: Paratesticular tumors (PTT) are rare and form a heterogenous group, ranging from benign to malignant high grade sarcomas. This study was undertaken to describe the clinicopathological spectrum of PTTs received over a 20-year period.
METHODS: All primary and secondary PTTs diagnosed from 2000 to 2019 in the pathology department of a tertiary care hospital in North India were retrospectively reviewed. Gross, histopathological features and immunohistochemistry (IHC) findings were correlated with clinical details.
RESULTS: A total of 169 intra-scrotal tumors were diagnosed during the study period, out of which there were 30 PTTs (in 27 patients) comprising 17.75%. Age range was 4 to 85 years (median 58 years). Benign PTTs were the commonest (n = 21, 70%), followed by metastasis to the paratesticular region (n = 6, 20%) and then primary malignant PTTs (n = 3, 10%). The commonest benign PTT was lipoma (n = 16, 76.19%), followed by adenomatoid tumor (n = 3, 14.28%) with one case each (4.76%) of cellular angiofibroma and hemangioma. Among primary malignant PTT, there were two cases of rhabdomyosarcoma, and one case of biphasic malignant mesothelioma. Metastatic tumors included four cases of prostatic adenocarcinoma, and one case each of pancreatic signet ring cell carcinoma and clear cell renal cell carcinoma.
CONCLUSION: PTTs show a wide clinicopathological spectrum. Benign PTTs are commoner than malignant PTTs. Meticulous grossing and histopathological examination supplemented by IHC is essential for an accurate diagnosis of this heterogenous class of tumors, which influences the role of adjuvant therapy and patient prognosis.

doi: https://doi.org/10.1016/j.anndiagpath.2020.151658



  • The overlap between irritable bowel syndrome and organic gastrointestinal diseases

The lancet. Gastroenterology & hepatology 2020 Nov;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33189181

Irritable bowel syndrome (IBS) is a common functional bowel disorder characterised by symptoms of recurrent abdominal pain associated with a change in bowel habit. This condition is one of the most frequent reasons to seek a gastroenterology consultation in primary and secondary care. The diagnosis of IBS is made by identifying characteristic symptoms, as defined by the Rome criteria, and excluding organic gastrointestinal diseases that might otherwise explain these symptoms. Organic conditions that can be mistaken for IBS include coeliac disease, inflammatory bowel disease (IBD), colorectal cancer, and, in those with diarrhoea-predominant symptoms, chronic gastrointestinal infections, microscopic colitis, and primary bile acid diarrhoea. The concept of small intestinal bacterial overgrowth being associated with IBS is shrouded with controversy and uncertainty, mainly because of invalid tests due to poor sensitivity and specificity, potentially leading to incorrect assumptions. There is insufficient evidence to link IBS-type symptoms with exocrine pancreatic insufficiency or with symptomatic uncomplicated diverticular disease, since both are hampered by conflicting data. Finally, there is growing appreciation that IBS can present in patients with known but stable organic gastrointestinal diseases, such as quiescent IBD or coeliac disease. Recognising functional gut symptoms in these individuals is paramount so that potentially harmful escalations in immunosuppressive therapy can be avoided and attention can be focused on addressing disorders of gut-brain interaction. This Review endeavours to aid clinicians who practise adult gastroenterology in recognising the potential overlap between IBS and organic gastrointestinal diseases and highlights areas in need of further research and clarity.

doi: https://doi.org/10.1016/S2468-1253(20)30212-0



  • Recent epidemiology of patients with gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NEN) in Japan: a population-based study

BMC cancer 2020 Nov;20(1):1104

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33189127

BACKGROUND: The worldwide prevalence and incidence of neuroendocrine neoplasms (NEN) have been increasing recently, although few studies have analyzed data on the current situation of NENs in Japan. Here, the Japan Neuroendocrine Tumor Society (JNETS) planned to investigate the recent incidence and distribution of these tumors using data from the national cancer registry started in 2016. This study examined the incidence and distribution of primary sites as well as rate of advanced disease from this population-based registry.
METHODS: A retrospective, population-based study using data from the national cancer registry in Japan (NCR) was conducted to evaluate patients with gastro-entero-pancreatic NEN (GEP-NEN) in 2016. Associated population data were used to determine annual age-adjusted incidences.
RESULTS: A total of 6735 individuals were diagnosed with GEP-NEN in Japan in 2016. Annual onset incidence was 0.70/100,000 for pancreatic NEN and 2.84/100,000 for gastrointestinal NEN. NEN in the ileum accounted for only 1% of total GEP-NENs in Japan. Most NENs in the esophagus or lungs were neuroendocrine carcinomas (NECs), while the majority of those in the duodenum, ileum, appendix and rectum were grade 1 neuroendocrine tumors (NETs). Median age at initial diagnosis was in between 60 to 65. Tumors in the duodenum, appendix and rectum were mostly limited to local, while those in the esophagus, stomach and colon tended to show distant metastasis. In Japan, initial treatment for GEP-NENs was resection even if the tumor was NEC.
CONCLUSIONS: This is the first report of a national registry-based incidence and distribution of GEP-NEN in Japan. These data will serve as an important first step to determining the exact etiology and trends for this pathology in Japan.

doi: https://doi.org/10.1186/s12885-020-07581-y



  • Defining the Comprehensive Genomic Landscapes of Pancreatic Ductal Adenocarcinoma Using Real World Endoscopic Aspiration Samples

Clinical cancer research : an official journal of the American Association for Cancer Research 2020 Nov;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33188144

PURPOSE: Most patients with pancreatic ductal adenocarcinoma (PDAC) present with surgically unresectable cancer. As a result, endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the most common biospecimen source available for diagnosis in treatment-naïve patients. Unfortunately, these limited samples are often not considered adequate for genomic analysis, precluding the opportunity for enrollment on precision medicine trials.
EXPERIMENTAL DESIGN: Applying an EpCAM-enrichment strategy, we show the feasibility of using real-world EUS-FNAs for in depth, molecular-barcoded, whole-exome sequencing (WES) and somatic copy number alteration (SCNA) analysis in 23 PDAC patients.
RESULTS: Potentially actionable mutations were identified in >20% of patients. Further, an increased mutational burden and higher aneuploidy in WES data were associated with an adverse prognosis. To identify predictive biomarkers for first line chemotherapy, we developed an SCNA based complexity score (CS) that was associated with response to platinum-based regimens in this cohort.
CONCLUSIONS: Collectively, these results emphasize the feasibility of real-world cytology samples for in depth genomic characterization of PDAC and show the prognostic potential of SCNA for PDAC diagnosis.

doi: https://doi.org/10.1158/1078-0432.CCR-20-2667



  • An autopsy case of severe acute pancreatitis induced by administration of pazopanib following nivolumab

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Nov;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33184007

Drug-induced pancreatitis is often mild to moderate in severity, but severe and even fatal cases can occur. Here, we report a 74-year-old woman undergoing chemotherapy for recurrent renal cell carcinoma, who presented with abdominal pain after administration of pazopanib following nivolumab and was diagnosed with severe acute pancreatitis. Administration of methylprednisolone and conservative treatment were initiated, but clinical findings and laboratory tests rapidly worsened. When she died, an autopsy was performed. The autopsy findings suggested the possibility of pancreatitis as immune-related adverse events. To the best of our knowledge, no fatal cases of acute pancreatitis due to nivolumab or pazopanib have been reported. We considered that the effects of nivolumab were sustained in the pancreas, and pazopanib administration might have worsened the toxicity.

doi: https://doi.org/10.1016/j.pan.2020.11.002


New GallBladder Articles

Today there is no new Gallbladder Article.

New BileDuct Articles

Today there is no new Bile Duct Article.

New Ampulla Articles


  • Recent epidemiology of patients with gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NEN) in Japan: a population-based study

BMC cancer 2020 Nov;20(1):1104

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33189127

BACKGROUND: The worldwide prevalence and incidence of neuroendocrine neoplasms (NEN) have been increasing recently, although few studies have analyzed data on the current situation of NENs in Japan. Here, the Japan Neuroendocrine Tumor Society (JNETS) planned to investigate the recent incidence and distribution of these tumors using data from the national cancer registry started in 2016. This study examined the incidence and distribution of primary sites as well as rate of advanced disease from this population-based registry.
METHODS: A retrospective, population-based study using data from the national cancer registry in Japan (NCR) was conducted to evaluate patients with gastro-entero-pancreatic NEN (GEP-NEN) in 2016. Associated population data were used to determine annual age-adjusted incidences.
RESULTS: A total of 6735 individuals were diagnosed with GEP-NEN in Japan in 2016. Annual onset incidence was 0.70/100,000 for pancreatic NEN and 2.84/100,000 for gastrointestinal NEN. NEN in the ileum accounted for only 1% of total GEP-NENs in Japan. Most NENs in the esophagus or lungs were neuroendocrine carcinomas (NECs), while the majority of those in the duodenum, ileum, appendix and rectum were grade 1 neuroendocrine tumors (NETs). Median age at initial diagnosis was in between 60 to 65. Tumors in the duodenum, appendix and rectum were mostly limited to local, while those in the esophagus, stomach and colon tended to show distant metastasis. In Japan, initial treatment for GEP-NENs was resection even if the tumor was NEC.
CONCLUSIONS: This is the first report of a national registry-based incidence and distribution of GEP-NEN in Japan. These data will serve as an important first step to determining the exact etiology and trends for this pathology in Japan.

doi: https://doi.org/10.1186/s12885-020-07581-y


To see all journal watch articles please visit: http://pbpath.org/journal-watch-upcoming-issue/

Recent Articles on Pancreatobiliary #Pathology – 2020-11-14

These are the recent articles on Pancreatobiliary Pathology:

To see all journal watch articles please visit: http://pbpath.org/journal-watch-upcoming-issue/

New Pancreas Articles


  • Reassessment of the Optimal Number of Examined Lymph Nodes in Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma

Annals of surgery 2020 Nov;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33177357

OBJECTIVE: To reappraise the optimal number of examined lymph nodes (ELN) in pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC).
SUMMARY BACKGROUND DATA: The well-established threshold of 15 ELN in PD for PDAC is optimized for detecting one positive node (PLN) per the previous 7 edition of the AJCC staging manual. In the framework of the 8 edition, where at least four PLN are needed for an N2 diagnosis, this threshold may be inadequate for accurate staging.
METHODS: Patients who underwent upfront PD at two academic institutions between 2000 and 2016 were analyzed. The optimal ELN threshold was defined as the cut-point associated with a 95% probability of identifying at least 4 PLN in N2 patients. The results were validated addressing the N-status distribution and stage migration.
RESULTS: Overall, 1218 patients were included. The median number of ELN was 26 (IQR 17-37). ELN was independently associated with N2-status (OR 1.27, p < 0.001). The estimated optimal threshold of ELN was 28. This cut-point enabled improved detection of N2 patients and stage III disease (58% versus 37%, p = 0.001). The median survival was 28.6 months. There was an improved survival in N0/N1 patients when ELN exceeded 28, suggesting a stage migration effect (47 versus 29 months, adjusted HR 0.649, p < 0.001). In N2 patients, this threshold was not associated with survival on multivariable analysis.
CONCLUSION: Examining at least 28 LN in PD for PDAC ensures optimal staging through improved detection of N2/stage III disease. This may have relevant implications for benchmarking processes and quality implementation.

doi: https://doi.org/10.1097/SLA.0000000000004552



  • Alterations in Ki67 Labeling Following Treatment of Poorly Differentiated Neuroendocrine Carcinomas: A Potential Diagnostic Pitfall

The American journal of surgical pathology 2020 Nov;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33177340

Assessment of the Ki67 index is critical for grading well-differentiated neuroendocrine tumors (WD-NETs), which can show a broad range of labeling that defines the WHO grade (G1-G3). Poorly differentiated neuroendocrine carcinomas (PD-NECs) have a relatively high Ki67 index, >20% in all cases and commonly exceeding 50%. After anecdotally observing PD-NECs with an unexpectedly low and heterogeneous Ki67 index following chemotherapy in 5 cases, we identified 15 additional cases of treated high-grade neuroendocrine neoplasms (HG-NENs). The study cohort comprised 20 cases; 11 PD-NECs, 8 mixed adenoneuroendocrine carcinomas, and 1 WD-NET, G3 from various anatomic sites (gastrointestinal tract, pancreas, larynx, lung, and breast). The Ki67 index was evaluated on pretreatment (when available) and posttreatment samples. Topographic heterogeneity in the Ki67 index was expressed using a semi-quantitative score of 0 (no heterogeneity) to 5 (>80% difference between maximal Ki67 and minimal Ki67 indices). Relative to the pretreatment group (n=9, mean Ki67 of 86.3%, range 80% to 100%), the neoplasms in the posttreatment group (n=20, mean Ki67 of 47.7%, range 1% to 90%) showed a significantly lower Ki67 index (18/20 cases). Of the 18 cases with a relatively low Ki67 index, 15 showed heterogeneous labeling (mean heterogeneity score of 2.3, range 1 to 5) and in 3 cases it was a homogeneously low. This phenomenon was observed in all subtypes of HG-NENs. In 6 cases, the alterations in Ki67 index following treatment were sufficient to place these HG-NENs in the WHO G1 or G2 grade, erroneously suggesting a diagnosis of WD-NET, and in 9 cases there was sufficient heterogeneity in the Ki67 index to suggest that a limited biopsy may sample an area of low Ki67, even though hotspot regions with a Ki67 index of >20% persisted. In 7 cases, the alterations in the Ki67 index were accompanied by morphologic features resembling a WD-NET. These observations suggest that there is a potential for misinterpretation of previously treated PD-NECs as WD-NETs, or for assigning a lower grade in G3 WD-NETs. While the prognostic significance of treatment-associated alterations in Ki67 index is unknown, awareness of this phenomenon is important to avoid this diagnostic pitfall when evaluating treated NENs.

doi: https://doi.org/10.1097/PAS.0000000000001602



  • Efficacy of EUS-guided FNB using a Franseen needle for tissue acquisition and microsatellite instability evaluation in unresectable pancreatic lesions

BMC cancer 2020 Nov;20(1):1094

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33176750

BACKGROUND: The efficacy of immune checkpoint blockade in the treatment of microsatellite instability (MSI)-high tumors was recently reported. Therefore, the acquisition of histological specimens is desired in cases of unresectable solid pancreatic lesions (UR SPLs). This study investigated the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needle for UR SPL tissue acquisition and MSI evaluation.
METHODS: A total of 195 SPL patients who underwent EUS-guided fine-needle aspiration (EUS-FNA) or EUS-FNB (EUS-FNAB) between January 2017 and March 2020 were enrolled in this study. Among them, 89 SPL patients (FNB: 28, FNA: 61) underwent EUS-FNAB using a 22-G needle (UR SPLs: 58, FNB: 22, FNA: 36) (UR SPLs after starting MSI evaluation: 23, FNB: 9, FNA: 14).
RESULTS: The puncture number was significantly lower with FNB than with FNA (median (range): 3 (2-5) vs 4 (1-8), P <  0.01, UR SPLs: 3 (2-5) vs 4 (1-8), P = 0.036). Histological specimen acquisition was more commonly achieved with FNB than with FNA (92.9% (26/28) vs 68.9% (42/61), P = 0.015, UR SPLs: 100% (22/22) vs 72.2% (26/36), P <  0.01). The histological specimen required for MSI evaluation was acquired more often with FNB than with FNA (88.9% (8/9) vs 35.7% (5/14), P = 0.03).
CONCLUSIONS: EUS-FNB using a Franseen needle is efficient for histological specimen acquisition and sampling the required amount of specimen for MSI evaluation in UR SPL patients.

doi: https://doi.org/10.1186/s12885-020-07588-5


New GallBladder Articles

Today there is no new Gallbladder Article.

New BileDuct Articles

Today there is no new Bile Duct Article.

New Ampulla Articles

Today there is no new Ampulla Article.

To see all journal watch articles please visit: http://pbpath.org/journal-watch-upcoming-issue/

Recent Articles on Pancreatobiliary #Pathology – 2020-11-04

These are the recent articles on Pancreatobiliary Pathology:

To see all journal watch articles please visit: http://pbpath.org/journal-watch-upcoming-issue/

New Pancreas Articles


  • Neurons Release Serine to Support mRNA Translation in Pancreatic Cancer

Cell 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33142117

Pancreatic ductal adenocarcinoma (PDAC) tumors have a nutrient-poor, desmoplastic, and highly innervated tumor microenvironment. Although neurons can release stimulatory factors to accelerate PDAC tumorigenesis, the metabolic contribution of peripheral axons has not been explored. We found that peripheral axons release serine (Ser) to support the growth of exogenous Ser (exSer)-dependent PDAC cells during Ser/Gly (glycine) deprivation. Ser deprivation resulted in ribosomal stalling on two of the six Ser codons, TCC and TCT, and allowed the selective translation and secretion of nerve growth factor (NGF) by PDAC cells to promote tumor innervation. Consistent with this, exSer-dependent PDAC tumors grew slower and displayed enhanced innervation in mice on a Ser/Gly-free diet. Blockade of compensatory neuronal innervation using LOXO-101, a Trk-NGF inhibitor, further decreased PDAC tumor growth. Our data indicate that axonal-cancer metabolic crosstalk is a critical adaptation to support PDAC growth in nutrient poor environments.

doi: https://doi.org/10.1016/j.cell.2020.10.016



  • Does Major Pancreatic Surgery Have Utility in Nonagenarians with Pancreas Cancer?

Annals of surgical oncology 2020 Nov;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33141373

OBJECTIVE: This study aims to define the role of surgery and assess different therapies for nonagenarians with localized, nonmetastatic pancreatic adenocarcinoma (PDAC).
METHODS: The National Cancer Database (NCDB) was queried for patients ≥ 90 years of age with nonmetastatic, localized PDAC from 2004-2016. Postoperative mortality was assessed at 30 and 90 days in patients receiving pancreatoduodenectomy or total pancreatectomy. Overall survival (OS) was compared between three treatment groups: surgery alone, chemotherapy alone, and chemoradiation (chemoRT) alone.
RESULTS: Of 380,524 patients with PDAC, 98 patients ≥ 90 years of age underwent curative-intent resection; 55% were female and 75% had a Charlson-Deyo comorbidity score of 0. A total of 17% received postoperative chemotherapy, 51.1% had poorly differentiated tumors with a median tumor size of 3 cm, 55.1% had positive lymph nodes, and 19.4% had positive resection margins. Postoperative median length of stay was 11 days. Postoperative 30- and 90-day mortality was 10.0% and 18.9%, respectively. Median OS for the surgery alone group was 11.6 months compared with 20.4 months in those receiving adjuvant therapy (p = 0.01). Among nonoperative PDAC patients, median OS in patients receiving chemotherapy only (n = 207) was 7.2 months, while chemoRT only (n = 100) was similar to surgery only (11 versus 11.6 months, p = 0.97).
CONCLUSIONS: Even in well-selected nonagenarians, pancreatoduodenectomy or total pancreatectomy carries a high mortality rate. While adjuvant therapy after resection provides the best survival, it is seldom achieved, and chemoRT alone affords identical survival statistics as surgery alone. These data suggest it is reasonable to consider chemoRT as initial therapy, then reassess candidacy for resection if performance status allows.

doi: https://doi.org/10.1245/s10434-020-09279-8



  • Risk of digestive cancers in a cohort of 69 460 five-year survivors of childhood cancer in Europe: the PanCareSurFup study

Gut 2020 Nov;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33139271

BACKGROUND: Survivors of childhood cancer are at risk of subsequent primary neoplasms (SPNs), but the risk of developing specific digestive SPNs beyond age 40 years remains uncertain. We investigated risks of specific digestive SPNs within the largest available cohort worldwide.
METHODS: The PanCareSurFup cohort includes 69 460 five-year survivors of childhood cancer from 12 countries in Europe. Risks of digestive SPNs were quantified using standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence.
RESULTS: 427 digestive SPNs (214 colorectal, 62 liver, 48 stomach, 44 pancreas, 59 other) were diagnosed in 413 survivors. Wilms tumour (WT) and Hodgkin lymphoma (HL) survivors were at greatest risk (SIR 12.1; 95% CI 9.6 to 15.1; SIR 7.3; 95% CI 5.9 to 9.0, respectively). The cumulative incidence increased the most steeply with increasing age for WT survivors, reaching 7.4% by age 55% and 9.6% by age 60 years (1.0% expected based on general population rates). Regarding colorectal SPNs, WT and HL survivors were at greatest risk; both seven times that expected. By age 55 years, 2.3% of both WT (95% CI 1.4 to 3.9) and HL (95% CI 1.6 to 3.2) survivors had developed a colorectal SPN-comparable to the risk among members of the general population with at least two first-degree relatives affected.
CONCLUSIONS: Colonoscopy surveillance before age 55 is recommended in many European countries for individuals with a family history of colorectal cancer, but not for WT and HL survivors despite a comparable risk profile. Clinically, serious consideration should be given to the implementation of colonoscopy surveillance while further evaluation of its benefits, harms and cost-effectiveness in WT and HL survivors is undertaken.

doi: https://doi.org/10.1136/gutjnl-2020-322237



  • Role of ultrasound shear wave elastography in preoperative prediction of pancreatic fistula after pancreaticoduodenectomy

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33139201

BACKGROUND: Majority of predictors of postoperative pancreatic fistula (POPF) use intraoperative variables. We aimed to study the role of preoperative ultrasound shear wave elastography (USWE) to predict POPF.
METHODS: The consecutive patients who underwent pancreaticoduodenectomy (PD) between January 2019 to March 2020 were prospectively enrolled. All patients underwent USWE assessment at the pancreatic neck level. Intraoperative variables including pancreatic texture, pancreatic duct diameter, blood loss and histological grading of fibrosis were also recorded. Associations between USWE and intraoperative variables and histological grading with the development of POPF were analyzed.
RESULTS: Of the 62 patients assessed, 50 patients (mean age: 53 ± 14 years; 31 males) were included. POPF and clinically relevant POPF (CRPOPF) were observed in 22 (44%) and 7 (14%) patients respectively. Soft pancreas was an independent predictor of CRPOPF (p = 0.04). The mean USWE valve was significantly lower in patients with CRPOPF as compared to no CRPOPF (9.7 Kpa vs. 12.8Kpa, p = 0.016). At receiver operating characteristic curve analysis, USWE value of 12.65Kpa yielded sensitivity and specificity of 100% and 47%, respectively, for prediction of CRPOPF. USWE showed significant correlation with intraoperative pancreatic texture (Spearman's rank correlation coefficient (ρ) = 0.565, p = 0.001).
CONCLUSION: USWE helps in preoperative prediction of CRPOPF. This may further help to customize management strategy in high risk patients.

doi: https://doi.org/10.1016/j.pan.2020.10.047


New GallBladder Articles

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Recent Articles on Pancreatobiliary #Pathology – 2020-10-29

These are the recent articles on Pancreatobiliary Pathology:

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New Pancreas Articles


  • Age is in the eye of the beholder: Distinguishing molecular signatures in early-onset pancreatic adenocarcinomas

Clinical cancer research : an official journal of the American Association for Cancer Research 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33109735

Pancreatic adenocarcinoma (PDAC) is more prevalent in older patients, but early-onset cases (<55 years) may be a distinct genetic subpopulation. Differential expression of CDKN2A and transcription factor FOXC2 were found in early-onset cases. This finding opens the door to investigating additional features that distinguish PDAC tumors in this age group.

doi: https://doi.org/10.1158/1078-0432.CCR-20-3683



  • Pilot study examining the impact of a specialist multidisciplinary team clinic for patients with chronic pancreatitis

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33109470

OBJECTIVE: -To assess the efficacy of a pilot Chronic Pancreatitis (CP) Multidisciplinary (MDT) clinic.
METHODS: – 60 patients referred to a pilot MDT CP clinic were analysed. Anthropometric data, nutrition status, malabsorption evidence, glycaemic control, opiate use, bone mineral density (BMD) assessment and quality of life (QoL) were examined.
RESULTS: -The average age was 51.27 (±12.75). The commonest aetiology was alcohol (55%). Ninety one point five percent had evidence of ongoing pancreatic exocrine insufficiency, with 88.1% requiring initiation or up-titration of pancreatic enzyme replacement (PERT). Up to half of the patients exhibited micronutrient deficiency. Twenty eight percent were diagnosed with type IIIc diabetes. There was an average daily reduction of 6 mg of morphine usage per patient with a concurrent decline in median pain scores from 83.3 to 63.3, which was non-significant. The median QoL score was 33.3 compared to a score of 75 from the reference population. QoL scores increased from 31.0 to 37.3 at follow up appointments. Seventy two point five percent of patients had undiagnosed low BMD.
CONCLUSION: The data suggest that CP patients have significant nutritional deficiencies as well as undiagnosed diabetes, poor pain and glycaemic control which negatively impacts QoL. Assessment in a multi-disciplinary clinic ensures appropriate management.

doi: https://doi.org/10.1016/j.pan.2020.10.041


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Recent Articles on Pancreatobiliary #Pathology – 2020-10-22

These are the recent articles on Pancreatobiliary Pathology:

To see all journal watch articles please visit: http://pbpath.org/journal-watch-upcoming-issue/

New Pancreas Articles


  • Implications of Perineural Invasion on Disease Recurrence and Survival After Pancreatectomy for Pancreatic Head Ductal Adenocarcinoma

Annals of surgery 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33086324

OBJECTIVE: To describe PNI and to evaluate its impact on disease-free (DFS) and overall survival (OS) in patients with resected pancreatic ductal adenocarcinoma (PDAC).
SUMMARY OF BACKGROUND DATA: Although PNI is a prognostic factor for survival in many GI cancers, there is limited knowledge regarding its impact on tumor recurrence, especially in “early stage disease” (PDAC ≤20 mm, R0/N0 PDAC).
METHODS: This multicenter retrospective study included patients undergoing PDAC resection between 2009 and 2014. The association of PNI with DFS and OS was analyzed using Cox proportional-hazards models.
RESULTS: PNI was found in 87% of 778 patients included in the study, with lower rates in PDAC ≤20 mm (78.7%) and in R0/N0 tumors (70.6%). PNI rate did not differ between patients who underwent neoadjuvant therapy and upfront surgery (88% vs 84%, P = 0.08). Although not significant at multivariate analysis (P = 0.07), patients with PNI had worse DFS at univariate analysis (median DFS: 20 vs 15 months, P < 0.01). PNI was the only independent predictor of DFS in R0/N0 tumors (hazard ratio [HR]: 2.2) and in PDAC ≤20 mm (HR: 1.8). PNI was an independent predictor of OS in the entire cohort (27 vs 50 months, P = 0.01), together with G3 tumors, pN1 status, carbohydrate antigen (CA) 19.9 >37 and pain.
CONCLUSIONS: PNI represents a major determinant of tumor recurrence and patients' survival in pancreatic cancer. The role of PNI is particularly relevant in early stages, supporting the hypothesis that invasion of nerves by cancer cells has a driving role in pancreatic cancer progression.

doi: https://doi.org/10.1097/SLA.0000000000004464



  • Biliary Stricture after Necrotizing Pancreatitis: An Underappreciated Challenge

Annals of surgery 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33086318

OBJECTIVE: Biliary stricture in necrotizing pancreatitis (NP) has not been systematically categorized; therefore, we sought to define the incidence and natural history of biliary stricture caused by NP.
SUMMARY/BACKGROUND DATA: Benign biliary stricture occurs secondary to bile duct injury, anastomotic narrowing, or chronic inflammation and fibrosis. The profound loco-regional inflammatory response of NP creates challenging biliary strictures.
METHODS: NP patients treated between 2005-2019 were reviewed. Biliary stricture was identified on cholangiography as narrowing of the extrahepatic biliary tree to < 75% of the diameter of the unaffected duct. Biliary stricture risk factors and outcomes were evaluated.
RESULTS: Among 743 NP patients, 64 died, 13 were lost to follow up; therefore, a total of 666 patients were included in the final cohort. Biliary stricture developed in 108 (16%) patients. Mean follow up was 3.5 ± 3.3 years. Median time from NP onset to biliary stricture diagnosis was 4.2 months (IQR, 1.8-10.9). Presentation was commonly clinical or biochemical jaundice, n = 30 (28%) each. Risk factors for stricture development were splanchnic vein thrombosis and pancreatic head parenchymal necrosis. Median time to stricture resolution was 6.0 months after onset (2.8-9.8). A mean of 3.3 ± 2.3 procedures were performed. Surgical intervention was required in 22 (20%) patients. Endoscopic treatment failed in 17% (17/99) of patients and was not associated with stricture length. Operative treatment of biliary stricture was more likely in patients with infected necrosis or NP disease duration ≥6 months.
CONCLUSION: Biliary stricture occurs frequently after necrotizing pancreatitis and is associated with splanchnic vein thrombosis and pancreatic head necrosis. Surgical correction was performed in 20%.

doi: https://doi.org/10.1097/SLA.0000000000004470



  • Prospective Phase II Trials Validate the Effect of Neoadjuvant Chemotherapy on Pattern of Recurrence in Pancreatic Adenocarcinoma

Annals of surgery 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33086310

OBJECTIVE: The objective of this study was to characterize the patterns of first recurrence after curative-intent resection for pancreatic adenocarcinoma (PDAC).
SUMMARY BACKGROUND DATA: We evaluated the first site of recurrence after neoadjuvant treatment as locoregional (LR) or distant metastasis (DM). To validate our findings, we evaluated the pattern from two phase II clinical trials evaluating neoadjuvant chemotherapy (NAC) in PDAC.
METHODS: We identified site of first recurrence from a retrospective cohort of patients from 2011-2017 treated with neoadjuvant chemotherapy followed by chemoradiation and then an operation or an operation first followed by adjuvant therapy, as well as two separate prospective cohorts of patients derived from two phase II clinical trials evaluating patients treated with neoadjuvant chemotherapy in borderline-resectable and locally advanced PDAC RESULTS:: In the retrospective cohorts, 160 out of 285 patients (56.1%) recurred after a median disease-free survival (mDFS) of 17.2 months. The pattern of recurrence was DM in 81.9% of patients, versus LR in 11.1%. This pattern was consistent in patients treated with upfront resection and adjuvant chemotherapy (DM 83.0%, LR 16.9%) regardless of margin-involvement (DM 80.1%, LR 19.4%). The use of NAC did not alter pattern of recurrence; 81.7% had DM and 18.3% had LR. This pattern also remained consistent regardless of margin-involvement (DM 94.1%, LR 5.9%). In the Phase II borderline-resectable trial (NCI# 01591733) cohort of 32 patients, the mDFS was 34.2 months. Pattern of recurrence remained predominantly DM (88.9%) versus LR (11.1%). In the Phase II locally-advanced trial (NCI# 01821729) cohort of 34 patients, the mDFS was 30.7 months. Although there was a higher rate of local recurrence in this cohort, pattern of first recurrence remained predominantly DM (66.6%) versus LR (33.3%) and remained consistent independent of margin-status.
CONCLUSIONS: The pattern of recurrence in PDAC is predominantly DM rather than LR, and is consistent regardless of the use of NAC and margin involvement.

doi: https://doi.org/10.1097/SLA.0000000000004585



  • Modified Appleby Procedure, Distal Splenopancreatectomy with Celiac Axis Resection

Annals of surgical oncology 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33084990

BACKGROUND: Modified Appleby procedure could be indicated in stage III locally advanced body pancreatic ductal adenocarcinoma (PDAC) involving the celiac axis after neoadjuvant treatment.
PATIENTS AND METHODS: We report the case of a 38-year-old woman presenting a tumor arising from the body of the pancreas, involving the celiac trunk with the common hepatic artery and having contact with the anterior surface of the superior mesenteric artery. A fine-needle aspirate biopsy confirmed the diagnosis of PADC. Eight cycles of FOLFIRINOX followed by chemoradiotherapy (50.4 Gy) were conducted. After 6 months, the CA19-9 levels were normalized, and the tumor remained stable without local growth or distant metastasis. To reduce the risk of ischemia-related complications and develop the pancreaticoduodenal arcades, a preoperative embolization of the common hepatic artery was performed. Then, surgical resection was considered 4 weeks after embolization.
RESULTS: The patient underwent a modified Appleby procedure including distal splenopancreatectomy with en bloc celiac axis resection combined with lateral portal vein resection. Venous reconstruction was carried out using peritoneal patch.1 Pathologic evaluation revealed a 2.5-cm PDAC with negative resection margins. Postoperative course was marked by acute ischemic cholecystitis requiring reoperation at postoperative day 3. The treatment was completed with four cycles of FOLFIRINOX, and she was free of disease 6 months after surgery.
CONCLUSIONS: Nowadays, modified Appleby procedure is more frequently performed due to improvements in responses to chemotherapy and radiotherapy which have led to better local control and more aggressive approaches in highly selected patients.

doi: https://doi.org/10.1245/s10434-020-09212-z



  • Improved assessment of response status in patients with pancreatic cancer treated with neoadjuvant therapy using somatic mutations and liquid biopsy analysis

Clinical cancer research : an official journal of the American Association for Cancer Research 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33082211

PURPOSE: To evaluate somatic mutations, circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in the PDAC patients with pathological complete response (pCR) to neoadjuvant therapy (NAT) and find their associations with outcome.
DESIGN: Thirty-six PDAC patients with pCR were identified from 2009 to 2017. Macro-dissection was performed on resected specimens to isolate DNA from 332 regions of interest including fibrosis, normal duct, normal parenchyma, and undefined ductal cells (UDCs). Cell-free DNA (cfDNA) and CTCs were also extracted. Next-generation sequencing (NGS) was used to detect mutations of KRAS, CDKN2A, SMAD4, TP53, GNAS, and BRAF Results: KRAS mutation was detected in UDCs and fibrosis while SMAD4, TP53 and GNAS were only seen in UDCs. Patients with TP53 mutation showed relatively worse overall survival (OS) (HR=3.596, 95%=0.855-15.130, P=0.081). Five patients available for CTCs data were all positive for CTCs and seven of 16 pCR patients were detected with ctDNA at surgery. We proposed a new concept of regression assessment combining genomic analysis of resected specimens and liquid biopsy data for PDAC, namely molecular complete response (mCR). Three of six mCR patients recurred as compared with six in fifteen non-mCR patients. Seven of 15 non-mCR patients died during follow-up while there was only one in six mCR patients.
CONCLUSIONS: This study firstly reports that somatic mutations, CTCs and ctDNA existed even in PDAC patients with pCR to NAT, which could possibly predict early recurrence and reduced survival. The current regression evaluation system of PDAC needs to be re-assessed at a molecular level.

doi: https://doi.org/10.1158/1078-0432.CCR-20-1746



  • Endoscopic ultrasound acquired portal venous circulating tumor cells predict progression free survival and overall survival in patients with pancreaticobiliary cancers

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33082106

BACKGROUND AND AIMS: Despite recent advances, patients with pancreaticobiliary cancers have a poor prognosis. We previously demonstrated the efficacy of endoscopic ultrasound (EUS) guided acquisition of portal vein (PV) blood for enumeration of circulating tumor cells (CTCs). The aim of this study was to assess PV-CTCs as potential biomarkers for the assessment of progression-free (PFS) and overall survival (OS) in patients with pancreaticobiliary cancers.
METHODS: 17 patients with biopsy-proven pancreaticobiliary malignancy were enrolled. CTCs were enumerated from both peripheral and PV blood. All patients were followed until death. PFS and OS were evaluated with the log-rank test and summarized with the use of Kaplan-Meier methods. Unadjusted and adjusted Cox-proportional hazards models were fitted to study the relationship between PV-CTCs and PFS and OS.
RESULTS: After 3.5 years of follow-up, all patients had expired. PV-CTCs were detected in all patients (median PV-CTCs 62.0/7.5 mL (interquartile range [IQR] 17-132). The mean PFS in patients with PV-CTCs <185/7.5 mL was significantly longer than patients with PV-CTCs ≥185/7.5 mL (43.3 weeks vs. 12.8 weeks, log-rank p = 0.002). The mean OS in patients with PV-CTCs <185/7.5 mL was significantly longer than patients with PV-CTCs ≥185/7.5 mL (75.8 weeks vs. 29.5 weeks, log-rank p = 0.021). In an adjusted Cox-proportional hazards model, PV-CTCs were significant predictors of both PFS and OS (HR 1.004, p = 0.037; HR 1.004, p = 0.044 respectively).
CONCLUSION: In this pilot and feasibility study, EUS-acquired PV-CTCs predicted PFS and OS. Our findings suggest that PV-CTCs can help provide important prognostic data for both providers and patients.

doi: https://doi.org/10.1016/j.pan.2020.10.039


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New BileDuct Articles


  • Biliary Stricture after Necrotizing Pancreatitis: An Underappreciated Challenge

Annals of surgery 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33086318

OBJECTIVE: Biliary stricture in necrotizing pancreatitis (NP) has not been systematically categorized; therefore, we sought to define the incidence and natural history of biliary stricture caused by NP.
SUMMARY/BACKGROUND DATA: Benign biliary stricture occurs secondary to bile duct injury, anastomotic narrowing, or chronic inflammation and fibrosis. The profound loco-regional inflammatory response of NP creates challenging biliary strictures.
METHODS: NP patients treated between 2005-2019 were reviewed. Biliary stricture was identified on cholangiography as narrowing of the extrahepatic biliary tree to < 75% of the diameter of the unaffected duct. Biliary stricture risk factors and outcomes were evaluated.
RESULTS: Among 743 NP patients, 64 died, 13 were lost to follow up; therefore, a total of 666 patients were included in the final cohort. Biliary stricture developed in 108 (16%) patients. Mean follow up was 3.5 ± 3.3 years. Median time from NP onset to biliary stricture diagnosis was 4.2 months (IQR, 1.8-10.9). Presentation was commonly clinical or biochemical jaundice, n = 30 (28%) each. Risk factors for stricture development were splanchnic vein thrombosis and pancreatic head parenchymal necrosis. Median time to stricture resolution was 6.0 months after onset (2.8-9.8). A mean of 3.3 ± 2.3 procedures were performed. Surgical intervention was required in 22 (20%) patients. Endoscopic treatment failed in 17% (17/99) of patients and was not associated with stricture length. Operative treatment of biliary stricture was more likely in patients with infected necrosis or NP disease duration ≥6 months.
CONCLUSION: Biliary stricture occurs frequently after necrotizing pancreatitis and is associated with splanchnic vein thrombosis and pancreatic head necrosis. Surgical correction was performed in 20%.

doi: https://doi.org/10.1097/SLA.0000000000004470



  • Subtotal (segment II-VIII) hepatectomy for bilateral diffuse hepatolithiasis with compensatory caudate lobe hypertrophy: a report of two cases

BMC gastroenterology 2020 Oct;20(1):350

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33081716

BACKGROUND: Hepatolithiasis often leads to atrophy-hypertrophy complex due to bile duct obstruction, inflammation or infection in the affected liver segments and compensatory response in the normal segments. In severe bilateral diffuse cases, main liver can all be atrophic, leaving the caudate lobe to be extremely hypertrophic. Subtotal (segment II-VIII) hepatectomy can be an option in selected patients under such circumstances. Since rare cases have been reported, our study aims to highlight the preoperative evaluation and key points of this procedure.
CASE PRESENTATION: Two patients with primary and secondary bilateral diffuse hepatolithiasis, respectively, were enrolled in this case series. The atrophy of the left and right liver with an exceeding hypertrophy of the caudate lobe were observed. Since the liver anatomy had completely been changed, contrast computed tomography, magnetic resonance imaging combined with 3D liver reconstruction were employed for comprehensive evaluation and pre-operational planning. The patients underwent standard subtotal (segment II-VIII) hepatectomy. During operation, the hepatoduodenal ligament around porta hepatis was dissected firstly to expose the hepatic artery, portal vein, bile duct and their branches successively. And then the vessels and bile duct to caudate lobe were preserved safely through cutting off the left and right hepatic artery, portal vein and bile duct at a safe point distal to the origin of the branches to caudate lobe. Operation time was 300 min and 360 min, respectively. Blood loss was 200 ml and 300 ml. No evidence of liver dysfunction, hepatolithiasis relapse or cholangitis was observed during the follow-up of 12 and 26 months.
CONCLUSIONS: Subtotal (segment II-VIII) hepatectomy may be one of several treatments possible in selected patients with compensatory caudate lobe hypertrophy caused by bilateral diffuse hepatolithiasis.

doi: https://doi.org/10.1186/s12876-020-01503-9


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Recent Articles on Pancreatobiliary #Pathology – 2020-10-21

These are the recent articles on Pancreatobiliary Pathology:

To see all journal watch articles please visit: http://pbpath.org/journal-watch-upcoming-issue/

New Pancreas Articles


  • Epithelial Nr5a2 heterozygosity cooperates with mutant Kras in the development of pancreatic cystic lesions

The Journal of pathology 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33079429

Cystic neoplasms of the pancreas are an increasingly important public health problem. The majority of these lesions are benign but some progress to invasive pancreatic ductal adenocarcinoma (PDAC). There is a dearth of mouse models of these conditions. The orphan nuclear receptor NR5A2 regulates development, differentiation, and inflammation. Germline Nr5a2 heterozygosity sensitizes mice to the oncogenic effects of mutant Kras in the pancreas. Here, we show that – unlike constitutive Nr5a2+/- mice – conditional Nr5a2 heterozygosity in pancreatic epithelial cells, combined with mutant Kras, (KPN+/- ) leads to a dramatic replacement of the pancreatic parenchyma with cystic structures and an accelerated development of high grade PanINs and PDAC. Timed histopathological analyses indicated that in KPN+/- mice PanINs precede the formation of cystic lesions and the latter precede PDAC. A single episode of acute caerulein pancreatitis is sufficient to accelerate the development of cystic lesions in KPN+/- mice. Epithelial cells of cystic lesions of KPN+/- mice express MUC1, MUC5AC, and MUC6 but lack expression of MUC2, CDX2 and acinar markers, indicative of a pancreato-biliary/gastric phenotype. In accordance with this, in human samples we found a non-significantly decreased expression of NR5A2 in mucinous tumours, compared with conventional PDAC. These results highlight that the effects of loss of one Nr5a2 allele are time- and cell context-dependent. KPN+/- mice represent a new model to study the formation of cystic pancreatic lesions and their relationship with PanINs and classical PDAC. Our findings suggest that pancreatitis could also contribute to acceleration of cystic tumour progression in patients. This article is protected by copyright. All rights reserved.

doi: https://doi.org/10.1002/path.5570



  • Novel Technique for Single-Layer Pancreatojejunostomy is Not Inferior to Modified Blumgart Anastomosis in Robotic Pancreatoduodenectomy: Results of a Randomized Controlled Trial

Annals of surgical oncology 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33079303

BACKGROUND: A novel technique of single-layer continuous suturing (SCS) for pancreaticojejunostomy (PJ) during robotic pancreaticoduodenectomy (RPD), a technically straightforward procedure, has been shown to produce promising results in a previous study. The present RCT aims to show that SCS during RPD does not increase the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) when compared with modified Blumgart anastomosis (MBA).
PATIENTS AND METHODS: Between January 2019 and September 2019, consecutive patients (ASA score ≤ 2) who underwent RPD were enrolled and randomized to the SCS or the MBA group. The primary endpoint was the rate of CR-POPF. A noninferiority margin of 10% was chosen.
RESULTS: Of the 186 patients, 4 were excluded because PJ was not performed. The remaining 182 patients were randomized to the SCS group (n = 89) or MBA group (n = 93). CR-POPF rate was not inferior in the SCS group [SCS: 6.7%, MBA: 11.8%; 95% confidence interval (- 0.76, - 0.06), P = 0.0002]. PJ duration was significantly lower in the SCS group (P < 0.01). No significant differences were found between the two groups in operative time, estimated blood loss, postoperative hospital stay, or rates of conversion to laparotomy, morbidity, reoperation, or mortality. On subgroup analysis of patients with a soft pancreas and small main pancreatic duct, SCS significantly reduced the duration of PJ.
CONCLUSIONS: This study showed that SCS was not inferior to MBA in terms of the CR-POPF rate during RPD. Registration number: ChiCTR1800020086 ( www.Chictr.org.cn ).

doi: https://doi.org/10.1245/s10434-020-09204-z



  • Surveillance of high-risk individuals for pancreatic cancer with EUS and MRI: A meta-analysis

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33077384

BACKGROUND/OBJECTIVES: Consensus guidelines recommend surveillance of high-risk individuals (HRIs) for pancreatic cancer (PC) using endoscopic ultrasonography (EUS) and/or magnetic resonance imaging (MRI). This study aims to assess the yield of PC surveillance programs of HRIs and compare the detection of high-grade dysplasia or T1N0M0 adenocarcinoma by EUS and MRI.
METHODS: The MEDLINE and Embase (Ovid) databases were searched for prospective studies published up to April 11, 2019 using EUS and/or MRI to screen HRIs for PC. Baseline detection of focal pancreatic abnormalities, cystic lesions, solid lesions, high-grade dysplasia or T1N0M0 adenocarcinoma, and all pancreatic adenocarcinoma were recorded. Weighted pooled proportions of outcomes detected were compared between EUS and MRI using random effects modeling.
RESULTS: A total of 1097 studies were reviewed and 24 were included, representing 2112 HRIs who underwent imaging. The weighted pooled proportion of focal pancreatic abnormalities detected by baseline EUS (0.34, 95% CI 0.30-0.37) was significantly higher (p = 0.006) than by MRI (0.31, 95% CI 0.28-0.33). There were no significant differences between EUS and MRI in detection of other outcomes. The overall weighted pooled proportion of patients with high-grade dysplasia or T1N0M0 adenocarcinoma detected at baseline (regardless of imaging modality) was 0.0090 (95% CI 0.0022-0.016), corresponding to a number-needed-to-screen (NNS) of 111 patients to detect one high-grade dysplasia or T1N0M0 adenocarcinoma.
CONCLUSIONS: Surveillance programs are successful in detecting high-risk precursor lesions. No differences between EUS and MRI were noted in the detection of high-grade dysplasia or T1N0M0 adenocarcinoma, supporting the use of either imaging modality.

doi: https://doi.org/10.1016/j.pan.2020.10.025



  • Fatty acid ethyl ester (FAEE) associated acute pancreatitis: An ex-vivo study using human pancreatic acini

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33077383

BACKGROUND & AIM: Fatty acid ethyl esters (FAEEs), are produced by non-oxidative alcohol metabolism and can cause acinar cell damage and subsequent acute pancreatitis in rodent models. Even though experimental studies have elucidated the FAEE mediated early intra-acinar events, these mechanisms have not been well studied in humans. In the present study, we evaluate the early intra-acinar events and inflammatory response in human pancreatic acinar tissues and cells in an ex-vivo model.
METHODS: Experiments were conducted using normal human pancreatic tissues exposed to FAEE. Subcellular fractionation was performed on tissue homogenates and trypsin and cathepsin B activities were estimated in these fractions. Acinar cell injury was evaluated by histology and immunohistochemistry. Cytokine release from exposed acinar cells was evaluated by performing Immuno-fluorescence. Serum was collected from patients with AP within the first 72 h of symptom onset for cytokine estimation using FACS.
RESULTS: We observed significant trypsin activation and acinar cell injury in FAEE treated tissue. Cathepsin B was redistributed from lysosomal to zymogen compartment at 30 min of FAEE exposure. IHC results indicated the presence of apoptosis in pancreatic tissue at 1 & 2hrs of FAEE exposure. We also observed a time dependent increase in secretion of cytokines IL-6, IL-8, TNF-α from FAEE treated acinar tissue. There was also a significant elevation in plasma cytokines in patents with alcohol associated AP within 72 h of symptom onset.
CONCLUSION: Our data suggest that alcohol metabolites can cause acute acinar cell damage and subsequent cytokine release which could eventually culminant in SIRS.

doi: https://doi.org/10.1016/j.pan.2020.10.027



  • What should we trust to define, predict and assess pancreatic fistula after pancreatectomy?

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33077382

OBJECTIVE: The ISGPF postoperative pancreatic fistula (POPF) definition using amylase drain concentration is widely used. However, the interest of lipase drain concentration, daily drain output and absolute enzyme daily production (concentration x daily drain volume) have been poorly investigated.
MATERIAL AND METHODS: These predictive on postoperative day (POD) 1, 3, 5 and 7 were analyzed in a development cohort, and subsequently tested in an independent validation cohort.
RESULTS: Of the 227 patients of the development cohort, 17% developed a biochemical fistula and 34% a POPF (Grade B/C). Strong correlation was found between amylase/lipase drain concentration at all postoperative days (ρ = 0.90; p = 0.001). Amylase and lipase were both significantly higher in patients with a POPF (p < 0.001) presenting an equivalent under the ROC curve area (0.85 vs 0.84; p = 0.466). Combining POD1 and POD3 threefold enzyme cut-off value increased significantly POPF prediction sensibility (97.4% vs 77.8%) and NPV (97.1% vs 86.3%). These results were also confirmed in the validation cohort of 554 patients. Finally, absolute enzyme daily production and daily drain output were significantly higher in patients with a POPF (p < 0.001) but did not add clinical value when compared to drain enzyme concentration.
CONCLUSION: Lipase is as effective as amylase drain concentration to define POPF. Absolute enzyme daily production or daily drain output do not help to better predict clinically significant POPF occurrence and severity. Lipase and amylase should mainly be used for their negative predictive value to predict the absence of clinically significant POPF and could allow early drain removal and hospital discharge.

doi: https://doi.org/10.1016/j.pan.2020.10.036



  • Novel techniques for management of portal system hemorrhage in acute pancreatitis

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33077381

Current management of infected pancreatic necrosis is focused on a minimally invasive step-up approach. The step-up approach consists of initial percutaneous or endoscopic drainage of infected pancreatic necrosis, followed, if necessary, by minimally invasive surgical or endoscopic debridement. While there is reduced morbidity and mortality, vascular complications can be life-threatening. Reported vascular complications have been limited to arterial bleeding. Venous bleeding has not been previously reported. We present two cases of portal venous bleeding in patients who underwent treatment for infected pancreatic necrosis with a step-up approach. We discuss the clinical presentation, diagnosis, and initial management. Moreover, we present two different techniques that can be used to successfully manage venous bleeding in patients who have percutaneous drains in place as part of a step-up approach. These techniques involve tamponading the cavity or drain tract with topical hemostatics and direct embolization of the bleeding vein. These experiences can serve as a guide for managing portal venous bleeding in patients with infected pancreatic necrosis.

doi: https://doi.org/10.1016/j.pan.2020.09.022



  • Is Hospital Occupancy Rate Associated with Postoperative Outcomes Among Patients Undergoing Hepatopancreatic Surgery?

Annals of surgery 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33074907

OBJECTIVE: To define the association between hospital occupancy rate and postoperative outcomes among patients undergoing hepatopancreatic (HP) resection.
SUMMARY BACKGROUND DATA: Previous studies have sought to identify hospital-level characteristics associated with optimal surgical outcomes and decreased expenditures. The present study utilized a novel hospital quality metric coined “occupancy rate” based on publicly available data to assess differences in postoperative outcomes among Medicare beneficiaries undergoing HP procedures.
METHODS: Medicare beneficiaries who underwent an elective HP surgery between 2013 and 2017 were identified. Occupancy rate was calculated and hospitals were categorized into quartiles. Multivariable logistic regression was utilized to assess the association between occupancy rate and clinical outcomes.
RESULTS: Among 33,866 patients, the majority underwent a pancreatic resection (58.5%; n = 19,827), were male (88.4%; n = 7,488), or white (88.4%; n = 29,950); median age was 72 years [interquartile range (IQR): 68-77] and median Charleston Comorbidity Index was 3 (IQR 2-8). Hospitals were categorized into quartiles based on hospital occupancy rate (cutoffs: 48.1%, 59.4%, 68.2%). Most patients underwent an HP operation at a hospital with an above average occupancy rate (n = 20,865, 61.6%), whereas only a small subset of patients had an HP procedure at a low occupancy rate hospital (n = 1,218, 3.6%). On multivariable analysis, low hospital occupancy rate was associated with increased odds of a complication [(OR) 1.35, 95% confidence interval (CI) 1.18-1.55) and 30-day mortality (OR 1.58, 95% CI 1.27-1.97). Even among only high-volume HP hospitals, patients operated on at hospitals that had a low occupancy rate were at markedly higher risk of complications (OR 1.42, 95% CI 1.03-1.97), as well as 30 day morality (OR 2.20, 95% CI 1.27-3.83).
CONCLUSIONS: Among Medicare beneficiaries undergoing an elective HP resection, more than 1 in 4 hospitals performing HP surgeries utilized less than half of their beds on average. There was a monotonic relationship between hospital occupancy rate and the odds of experiencing a complication, as well as 30-day mortality, independent of other hospital level characteristics including procedural volume.

doi: https://doi.org/10.1097/SLA.0000000000004418



  • Are Volume Pledge Standards Worth the Travel Burden for Major Abdominal Cancer Operations?

Annals of surgery 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33074899

OBJECTIVE: The study objective is to determine the association between travel distance and surgical volume on outcomes after esophageal, pancreatic, and rectal cancer resections.
SUMMARY OF BACKGROUND DATA: “Take the Volume Pledge” aims to centralize esophagectomies, pancreatectomies, and proctectomies to hospitals meeting minimum volume standards. The impact of travel, and possible care fragmentation, on potential benefits of centralized surgery is not well understood.
METHODS: Using the National Cancer Database (2004-2016), patients who underwent esophageal, pancreatic, or rectal resections at far HVH meeting volume standards versus local intermediate (IVH) and low-volume (LVH) hospitals were identified. Perioperative outcomes and 5-year OS were compared.
RESULTS: Of 49,454 patients, 17,544 (34.5%) underwent surgery at far HVH, 11,739 (23.7%) at local IVH, and 20,171 (40.8%) at local LVH. The median (interquartile range) travel distances were 77.1 (51.1-125.4), 13.2 (5.8-27.3), and 7.8 (3.1-15.5) miles to HVH, IVH, and LVH, respectively. By multivariable analysis, LVH was associated with increased 30-day mortality for all resections compared to HVH, but IVH was associated with mortality only for proctectomies [odds ratio 1.90, 95% confidence interval (CI) 1.31-2.75]. Compared to HVH, both IVH (hazard ratio 1.25, 95% CI 1.19-1.31) and LVH (hazard ratio 1.35, 95% CI 1.29-1.42) were associated with decreased 5-year OS.
CONCLUSIONS: Compared to far HVH, 30-day mortality was higher for all resections at LVH, but only for proctectomies at IVH. Five-year OS was consistently worse at local LVH and IVH. Improving long-term outcomes at IVH may provide opportunities for greater access to quality cancer care.

doi: https://doi.org/10.1097/SLA.0000000000004361



  • A Critical Assessment of Postneoadjuvant Therapy Pancreatic Cancer Regression Grading Schemes With a Proposal for a Novel Approach

The American journal of surgical pathology 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33074853

Currently, there is no consensus on the optimal tumor response score (TRS) system to assess regression in pancreatic cancers resected after neoadjuvant therapy. We developed a novel TRS (Royal North Shore [RNS] system) based on estimating the percentage of tumor bed occupied by viable cancer and categorized into 3 tiers: grade 1 (≤10%), grade 2 (11% to 75%), and grade 3 (>75%). We assessed 147 resected carcinomas with this and other TRS systems (College of American Pathologists [CAP], MD Anderson Cancer Center [MDACC], and Evans). The 3-tiered RNS system predicted median survival after surgery for grades 1, 2, and 3 of 54, 23, and 9 months, respectively (P<0.05). The CAP, MDACC, and Evans systems also predicted survival (P<0.05) but less consistently. The median survival for MDACC and CAP grade 0 (complete regression) was less than MDACC grade 1 and CAP grades 1 and 2. There was no difference in survival between CAP grades 2 and 3 (P=0.960), Evans grades 1 and 2a (P=0.395), and Evans grades 2a and 2b (P=0.587). Interobserver concordance was weak for CAP (κ=0.431), moderate for MDACC (κ=0.691), minimal for Evans (κ=0.307), and moderate to strong for RNS (κ=0.632 to 0.84). Of age, sex, size, stage, grade, perineural and vascular invasion, extrapancreatic extension, margin status, and RNS score, only RNS score, vascular invasion, and extrapancreatic extension predicted survival in univariate analysis. Only extrapancreatic extension (P=0.034) and RNS score (P<0.0001) remained significant in multivariate analysis. We conclude that the RNS system is a reproducible and powerful predictor of survival after resection for pancreatic cancers treated with neoadjuvant therapy and should be investigated in larger cohorts.

doi: https://doi.org/10.1097/PAS.0000000000001601



  • CRS/HIPEC with Major Organ Resection in Peritoneal Mesothelioma Does not Impact Major Complications or Overall Survival: A Retrospective Cohort Study of the US HIPEC Collaborative

Annals of surgical oncology 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33073341

INTRODUCTION: CRS/HIPEC is thought to confer a survival advantage for patients with malignant peritoneal mesothelioma (MPM). However, the impact of nonperitoneal organ resection is not clearly defined. We evaluated the impact of major organ resection (MOR) on postoperative outcomes and overall survival (OS).
PATIENTS AND METHODS: The US HIPEC collaborative database (2000-2017) was reviewed for MPM patients who underwent CRS/HIPEC. MOR was defined as total or partial resection of diaphragm, stomach, spleen, pancreas, small bowel, colon, rectum, kidney, ureter, bladder, and/or uterus. MOR was categorized as 0, 1, or 2+ organs.
RESULTS: A total of 174 patients were identified. Median PCI was 16 (3-39). The distribution of patients with MOR-0, MOR-1, and MOR-2+ was 94, 45, and 35 patients, respectively. MOR-1 and MOR-2+ groups had a higher frequency of any complication compared with MOR-0 (57.8%, 74.3%, and 48.9%, respectively, p = 0.035), but Clavien ¾ complications were similar. Median length of stay was slightly higher in the MOR-1 and MOR-2+ groups (10 and 11 days) compared with the MOR-0 cohort (9 days, p = 0.005). Incomplete cytoreduction, ASA class 4, and male gender were associated with increased mortality on unadjusted analysis; however, their impact on OS was attenuated on multivariable analysis. MOR was not associated with OS based on these data (MOR-1: HR 1.67, 95% CI 0.59-4.74; MOR-2+ : HR 0.77, 95% CI 0.22-2.69).
CONCLUSIONS: MOR was not associated with an increase in major complications or worse OS in patients undergoing CRS/HIPEC for MPM and should be considered, if necessary, to achieve complete cytoreduction for MPM patients.

doi: https://doi.org/10.1245/s10434-020-09232-9



  • Nationwide compliance with a multidisciplinary guideline on pancreatic cancer during 6-year follow-up

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33069583

BACKGROUND: Compliance with national guidelines on pancreatic cancer management could improve patient outcomes. Early compliance with the Dutch guideline was poor. The aim was to assess compliance with this guideline during six years after publication.
MATERIALS AND METHODS: Nationwide guideline compliance was investigated for three subsequent time periods (2012-2013 vs. 2014-2015 vs. 2016-2017) in patients with pancreatic cancer using five quality indicators in the Netherlands Cancer Registry: 1) discussion in multidisciplinary team meeting (MDT), 2) maximum 3-week interval from final MDT to start of treatment, 3) preoperative biliary drainage when bilirubin >250 μmol/L, 4) use of adjuvant chemotherapy, and 5) chemotherapy for inoperable disease (non-metastatic and metastatic).
RESULTS: In total, 14 491 patients were included of whom 2290 (15.8%) underwent resection and 4561 (31.5%) received chemotherapy. Most quality indicators did not change over time: overall, 88.8% of patients treated with curative intent were discussed in a MDT, 42.7% were treated with curative intent within the 3-week interval, 62.7% with a resectable head tumor and bilirubin >250 μmol/L underwent preoperative biliary drainage, 57.2% received chemotherapy after resection, and 36.6% with metastatic disease received chemotherapy. Only use of chemotherapy for non-metastatic, non-resected disease improved over time (23.4% vs. 25.6% vs. 29.7%).
CONCLUSION: Nationwide compliance to five quality indicators for the guideline on pancreatic cancer management showed little to no improvement during six years after publication. Besides critical review of the current quality indicators, these outcomes may suggest that a nationwide implementation program is required to increase compliance to guideline recommendations.

doi: https://doi.org/10.1016/j.pan.2020.10.032



  • Hyalinized stroma is a characteristic feature of pancreatic intraductal oncocytic papillary neoplasm: An immunohistochemical study

Annals of diagnostic pathology 2020 Oct;49():151639

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33069084

Hyalinized stroma (HS) is a dense, eosinophilic, and amorphous extracellular material in the stroma. HS is observed in several tumors; however, it has not been comprehensively studied in pancreatic intraductal papillary mucinous neoplasm (IPMN) or intraductal oncocytic papillary neoplasm (IOPN). Here, we aimed to evaluate the immunohistochemical and microscopic characteristics of HS in IPMN and IOPN. The prevalence of HS was determined in 168 cases of IPMN, including intestinal type (IPMN-I), gastric type (IPMN-G), and pancreatobiliary type (IPMN-PB), as well as in 11 cases of IOPN. Immunohistochemical staining for laminin and collagen (types I, II, III, IV, and V), as well as Congo red staining were performed in IPMN and IOPN cases containing HS. The prevalence of HS among the IPMN and IOPN specimens was 1.2% (2/168 cases) and 45.5% (5/11 cases), respectively. The prevalence rates of HS in each IPMN subtype were as follows: 2.2% (2/91 cases) in IPMN-G, and 0% in IPMN-PB and IPMN-I. All seven HS cases were positive for collagen I, III, IV, and V but were negative for Congo red staining. Most cases showed negative, focal, or weak expression of laminin and type II collagen. These findings indicate that HS is associated with IOPN and is primarily composed of collagen fibers.

doi: https://doi.org/10.1016/j.anndiagpath.2020.151639



  • Neoadjuvant S-1 With Concurrent Radiotherapy Followed by Surgery for Borderline Resectable Pancreatic Cancer: A Phase II Open-Label Multicenter Prospective Trial (JASPAC05)

Annals of surgery 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33065644

OBJECTIVE: This study assessed whether neoadjuvant chemoradiotherapy (CRT) with S-1 increases the R0 resection rate in borderline resectable pancreatic cancer (BRPC).
SUMMARY BACKGROUND DATA: Although a multidisciplinary approach that includes neoadjuvant treatment has been shown to be a better strategy for BRPC than upfront resection, a standard treatment for BRPC has not been established.
METHODS: A multicenter, single-arm, phase II study was performed. Patients who fulfilled the criteria for BRPC received S-1 (40 mg/m bid) and concurrent radiotherapy (50.4 Gy in 28 fractions) before surgery. The primary endpoint was the R0 resection rate. At least 40 patients were required, with a one-sided α = 0.05 and β = 0.05 and expected and threshold values for the primary endpoint of 30% and 10%, respectively.
RESULTS: Fifty-two patients were eligible, and 41 were confirmed to have definitive BRPC by a central review. CRT was completed in 50 (96%) patients and was well tolerated. The rate of grade ¾ toxicity with CRT was 43%. The R0 resection rate was 52% among the 52 eligible patients and 63% among the 41 patients who were centrally confirmed to have BRPC. Postoperative grade III/IV adverse events according to the Clavien-Dindo classification were observed in 7.5%. Among the 41 centrally confirmed BRPC patients, the 2-year overall survival rate and median overall survival duration were 58% and 30.8 months, respectively.
CONCLUSIONS: S-1 and concurrent radiotherapy appear to be feasible and effective at increasing the R0 resection rate and improving survival in patients with BRPC.
TRIAL REGISTRATION: UMIN000009172.

doi: https://doi.org/10.1097/SLA.0000000000004535



  • Targeting KRAS(G12C): From Inhibitory Mechanism to Modulation of Antitumor Effects in Patients

Cell 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33065029

KRAS mutations are among the most common genetic alterations in lung, colorectal, and pancreatic cancers. Direct inhibition of KRAS oncoproteins has been a long-standing pursuit in precision oncology, one established shortly after the discovery of RAS mutations in human cancer cells nearly 40 years ago. Recent advances in medicinal chemistry have established inhibitors targeting KRAS(G12C), a mutation found in ∼13% of lung adenocarcinomas and, at a lower frequency, in other cancers. Preclinical studies describing their discovery and mechanism of action, coupled with emerging clinical data from patients treated with these drugs, have sparked a renewed enthusiasm in the study of KRAS and its therapeutic potential. Here, we discuss how these advances are reshaping the fundamental aspects of KRAS oncoprotein biology and the strides being made toward improving patient outcomes in the clinic.

doi: https://doi.org/10.1016/j.cell.2020.09.044



  • Mural Intracholecystic Neoplasms Arising in Adenomyomatous Nodules of the Gallbladder: An Analysis of 19 Examples of a Clinicopathologically Distinct Entity

The American journal of surgical pathology 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33060404

Intracholecystic neoplasms (ICNs) (pyloric gland adenomas and intracholecystic papillary neoplasms, collectively also called intracholecystic papillary/tubular neoplasms) form multifocal, extensive proliferations on the gallbladder mucosa and have a high propensity for invasion (>50%). In this study, 19 examples of a poorly characterized phenomenon, mural papillary mucinous lesions that arise in adenomyomatous nodules and form localized ICNs, were analyzed. Two of these were identified in 1750 consecutive cholecystectomies reviewed specifically for this purpose, placing its incidence at 0.1%. Median age was 68 years. Unlike other gallbladder lesions, these were slightly more common in men (female/male=0.8), and 55% had documented cholelithiasis. All were characterized by a compact multilocular, demarcated, cystic lesion with papillary proliferations and mucinous epithelial lining. The lesions' architecture, distribution, location, and typical size were suggestive of evolution from an underlying adenomyomatous nodule. All had gastric/endocervical-like mucinous epithelium, but 5 also had a focal intestinal-like epithelium. Cytologic atypia was graded as 1 to 3 and defined as 1A: mucinous, without cytoarchitectural atypia (n=3), 1B: mild (n=7), 2: moderate (n=2), and 3: severe atypia (n=7, 3 of which also had invasive carcinoma, 16%). Background gallbladder mucosal involvement was absent in all but 2 cases, both of which had multifocal papillary mucosal nodules. In conclusion, these cases highlight a distinct clinicopathologic entity, that is, mural ICNs arising in adenomyomatous nodules, which, by essentially sparing the “main” mucosa, not displaying “field-effect/defect” phenomenon, and only rarely (16%) showing carcinomatous transformation, are analogous to pancreatic branch duct intraductal papillary mucinous neoplasms.

doi: https://doi.org/10.1097/PAS.0000000000001603



  • The use of immunohistochemistry for IgG4 in the diagnosis of autoimmune pancreatitis: A systematic review and meta-analysis

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33060017

BACKGROUND: The diagnosis of autoimmune pancreatitis (AIP) remains challenging, especially when serum IgG4 is normal or imaging features are indeterminate. We performed a systematic review and meta-analysis to evaluate the performance of IgG4 immunostaining of pancreatic, biliary, and ampullary tissues as a diagnostic aid for AIP.
METHODS: A comprehensive literature search of the PubMed, EMBASE, and Ovid MEDLINE databases was conducted until February 2020. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. A random-effects model was used to summarize the diagnostic odds ratio and other measures of accuracy.
RESULTS: The meta-analysis included 20 studies comprising 346 patients with AIP and 590 patients with other pancreatobiliary diseases, including 371 pancreatobiliary malignancies. The summary estimates for tissue IgG4 in discriminating AIP and controls were as follows: diagnostic odds ratio 38.86 (95% confidence interval (CI), 18.70-80.75); sensitivity 0.64 (95% CI, 0.59-0.69); specificity 0.93 (95% CI, 0.91-0.95). The area under the curve was 0.939 for tissue IgG4 in discriminating AIP and controls. Subgroup analysis revealed no significant difference in diagnostic accuracy according to control groups (pancreatobiliary cancer versus other chronic pancreatitis) and sampling site (pancreas versus bile duct/ampulla).
CONCLUSIONS: Current data demonstrate that IgG4 immunostaining of pancreatic, biliary, and ampullary tissue has a high specificity but moderate sensitivity for diagnosing AIP. IgG4 immunostaining may be useful in supporting a diagnosis of AIP when AIP is clinically suspected, but a combination of imaging and serology does not provide a conclusive diagnosis.

doi: https://doi.org/10.1016/j.pan.2020.10.028



  • Worldwide Burden of, Risk Factors for, and Trends in Pancreatic Cancer

Gastroenterology 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33058868

BACKGROUND & AIMS: We evaluated global and regional burdens of, risk factors for, and epidemiologic trends in pancreatic cancer among groups of different sexes and ages.
METHODS: We used data from the GLOBOCAN database to estimate pancreatic cancer incidence and mortality in 184 countries. We examined the association between lifestyle and metabolic risk factors, extracted from the World Health Organization Global Health Observatory database, and pancreatic cancer incidence and mortality by univariable and multivariable linear regression. We retrieved country-specific on age-standardized rates (ASRs) of incidence and mortalities from cancer registries from 48 countries through 2017 for trend analysis by joinpoint regression analysis.
RESULTS: The highest incidence and mortality of pancreatic cancer were in regions with very high (ASRs, 7.7 and 4.9) and high HDIs (ASRs, 6.9 and 4.6) in 2018. Countries with higher incidence and mortality were more likely to have higher prevalence of smoking, alcohol drinking, physical inactivity, obesity, hypertension, and high cholesterol. From 2008 to 2017, 2007 to 2016, or 2003 to 2012, depending on the availability of the data, there were increases in incidence among men and women in 14 (average annual percent changes [AAPCs], 8.85 to 0.41) and 17 (AAPCs, 6.04 to 0.87) countries, respectively. For mortality, the increase was observed in eight (AAPCs, 4.20 to 0.55) countries among men and 14 (AAPCs, 5.83 to 0.78) countries among women. While the incidence increased in 18 countries (AAPCs, 7.83 to 0.91) among individuals 50 years or older, an increasing trend in pancreatic cancer was also identified among individuals younger than 50 years and 40 years in eight (AAPCs, 8.75 to 2.82) and four (AAPCs, 11.07 to 8.31) countries, respectively.
CONCLUSIONS: In an analysis of data from 48 countries, we found increasing incidence and mortality trends in pancreatic cancer, especially among women and populations 50 years or older, but also among younger individuals. More preventive efforts are recommended for these populations.

doi: https://doi.org/10.1053/j.gastro.2020.10.007



  • Race/Ethnicity and County-Level Social Vulnerability Impact Hospice Utilization Among Patients Undergoing Cancer Surgery

Annals of surgical oncology 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33057860

BACKGROUND: Integration of palliative care services into the surgical treatment plan is important for holistic patient care. We sought to examine the association between patient race/ethnicity and county-level vulnerability relative to patterns of hospice utilization.
PATIENTS AND METHODS: Medicare Standard Analytic Files were used to identify patients undergoing lung, esophageal, pancreatic, colon, or rectal cancer surgery between 2013 and 2017. Data were merged with the Centers for Disease Control and Prevention's social vulnerability index (SVI). Logistic regression was utilized to identify factors associated with overall hospice utilization among deceased individuals.
RESULTS: A total of 54,256 Medicare beneficiaries underwent lung (n = 16,645, 30.7%), esophageal (n = 1427, 2.6%), pancreatic (n = 6183, 11.4%), colon (n = 26,827, 49.4%), or rectal (n = 3174, 5.9%) cancer resection. Median patient age was 76 years (IQR 71-82 years), and 28,887 patients (53.2%) were male; the majority of individuals were White (91.1%, n = 49,443), while a smaller subset was Black or Latino (racial/ethnic minority: n = 4813, 8.9%). Overall, 35,416 (65.3%) patients utilized hospice services prior to death. Median SVI was 52.8 [interquartile range (IQR) 30.3-71.2]. White patients were more likely to utilize hospice care compared with minority patients (OR 1.24, 95% CI 1.17-1.31, p < 0.001). Unlike White patients, there was reduced odds of hospice utilization (OR 0.97, 95% CI 0.96-0.99) and early hospice initiation (OR 0.94, 95% CI 0.91-0.97) as SVI increased among minority patients.
CONCLUSIONS: Patients residing in counties with high social vulnerability were less likely to be enrolled in hospice care at the time of death, as well as be less likely to initiate hospice care early. The effects of increasing social vulnerability on hospice utilization were more profound among minority patients.

doi: https://doi.org/10.1245/s10434-020-09227-6



  • An Aggressive Approach to Locally Confined Pancreatic Cancer: Defining Surgical and Oncologic Outcomes Unique to Pancreatectomy with Celiac Axis Resection (DP-CAR)

Annals of surgical oncology 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33051739

BACKGROUND: Modern chemotherapeutics have led to improved systemic disease control for patients with locally advanced pancreatic cancer (LAPC). Surgical strategies such as distal pancreatectomy with celiac axis resection (DP-CAR) are increasingly entertained. Herein we review procedure-specific outcomes and assess biologic rationale for DP-CAR.
METHODS: A prospectively maintained single-institution database of all pancreatectomies was queried for patients undergoing DP-CAR. We excluded all patients for whom complete data were not available and those who were not treated with contemporary multi-agent therapy. Data were supplemented with dedicated chart review and outreach for long-term oncologic outcomes.
RESULTS: Fifty-four patients underwent DP-CAR between 2008 and 2018. The median age was 62.7 years. Ninety-eight percent received induction chemotherapy. Arterial reconstruction was performed in 17% and concomitant visceral resection in 30%. The R0 resection rate was 87%. Postoperative complications were common (43%) with chyle leak being the most frequent (17%). Length of stay was 8 days, readmission occurred in one-third, and 90-day mortality was 2%. Disease recurrence occurred in 74% during a median follow up of 17.4 months. Median recurrence-free (RFS) and overall survival (OS) were 9 and 25 months, respectively.
CONCLUSIONS: Following modern induction paradigms, DP-CAR can be performed with low mortality, manageable morbidity, and excellent rates of margin-negative resection in high-volume settings. The profile of complications of DP-CAR is distinct from pancreaticoduodenectomy and simple distal pancreatectomy. OS and RFS are similar to those undergoing resection of borderline resectable and resectable disease. Improved systemic disease control will likely lead to increasing utilization of aggressive surgical approaches to LAPC.

doi: https://doi.org/10.1245/s10434-020-09201-2



  • Subtype-discordant pancreatic ductal adenocarcinoma tumors show intermediate clinical and molecular characteristics

Clinical cancer research : an official journal of the American Association for Cancer Research 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33051307

Background RNA-sequencing-based subtyping of pancreatic ductal adenocarcinoma (PDAC) has been reported by multiple research groups, each using different methodologies and patient cohorts. 'Classical' and 'basal-like' PDAC subtypes are associated with survival differences, with basal-like tumors associated with worse prognosis. We amalgamated various PDAC subtyping tools to evaluate the potential of such tools to be reliable in clinical practice. Methods Sequencing data for 574 PDAC tumors was obtained from prospective trials and retrospective public databases. Six published PDAC subtyping strategies (Moffitt regression tools, clustering-based Moffitt, Collisson, Bailey, and Karasinska subtypes) were employed on each sample, and results were tested for subtype call consistency and association with survival. Results Basal-like and classical subtype calls were concordant in 88% of patient samples, and survival outcomes were significantly different (p<0.05) between prognostic subtypes. 12% of tumors had subtype-discordant calls across the different methods, showing intermediate survival in univariate and multivariate survival analyses. Transcriptional profiles compatible with that of a hybrid subtype signature were observed for subtype-discordant tumors, in which classical and basal-like genes were concomitantly expressed. Subtype-discordant tumors showed intermediate molecular characteristics, including subtyping gene expression (p<0.0001) and mutant KRAS allelic imbalance (p<0.001). Conclusions Nearly one in six patients with PDAC have tumors that fail to reliably fall into the classical or basal-like PDAC subtype categories, based on two regression tools aimed towards clinical practice. Rather, these patient tumors show intermediate prognostic and molecular traits. We propose close consideration of the non-binary nature of PDAC subtypes for future incorporation of subtyping into clinical practice.

doi: https://doi.org/10.1158/1078-0432.CCR-20-2831



  • Expression of the EWSR1-FLI1 fusion oncogene in pancreas cells drives pancreatic atrophy and lipomatosis

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33051146

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) harbors mutant KRAS as the most common driver mutation. Studies on mouse models have uncovered the tumorigenic characteristics of the Kras oncogene driving pancreatic carcinogenesis. Similarly, Ewing sarcoma predominantly depends on the occurrence of the EWSR1-FLI1 fusion oncogene. The expression of EWSR1-FLI1 affects pro-tumorigenic pathways and induces cell transformation. In this study, we investigated whether mutant Kras could be exchanged by another potent oncogene, such as EWSR1-FLI1, to initiate pancreatic cancer development.
METHODS: We generated two conditional mouse models expressing mutant KrasG12D (KC) or the EWSR1-FLI1 oncogene (E/F) in pancreas cells. Pancreatic tissue was collected from the mice at 4-6 weeks and 11-13 weeks of age as well as from survival cohorts to determine the development of spontaneous acinar-to-ductal metaplasia (ADM) and neoplastic lesions. Immunohistochemistry and immunofluorescence staining were performed to characterize and quantify changes in tissue morphology.
RESULTS: The expression of the EWSR1-FLI1 fusion protein in pancreas cells was confirmed by positive FLI1 immunohistochemistry staining. Notably, the EWSR1-FLI1 expression in pancreas cells resulted in a strong depletion of the acinar cell mass and an extensive lipomatosis. Although the E/F mice exhibited spontaneous ADM formation and a shorter overall survival rate compared to KC mice, no development of neoplastic lesion was observed in aging E/F mice.
CONCLUSIONS: The expression of the EWSR1-FLI1 oncogene leads to a strong pancreatic atrophy and lipomatosis. ADM formation indicates that pancreatic acinar cells are susceptible for EWSR1-FLI1-mediated oncogenic transformation to a limited extent. However, the EWSR1-FLI1 oncogene is insufficient to induce pancreatic cancer development.

doi: https://doi.org/10.1016/j.pan.2020.10.033



  • FOLFIRINOX as second-line chemotherapy for advanced pancreatic cancer: A subset analysis of data from a nationwide multicenter observational study in Japan

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Oct;20(7):1519-1525

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32972834

BACKGROUND: Data on FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer are limited. In the JASPAC06 study-a nationwide, multicenter, observational study-FOLFIRINOX for patients with unresectable or recurrent pancreatic cancer as any line of treatment showed favorable efficacy and safety in Japanese clinical practice.
METHODS: We performed exploratory analyses of patients with unresectable or recurrent pancreatic cancer who received FOLFIRINOX as the second-line chemotherapy in Japanese clinical settings.
RESULTS: Of the 399 evaluable patients, 44 were eligible for inclusion in the analysis. The patients' characteristics were as follows: median age, 62 years; men, 26 (59%); Eastern Cooperative Oncology Group-Performance status 0/1, 30 (68%)/14 (32%); disease status, recurrent/local/metastatic: 4 (9%)/8 (18%)/32 (73%). The initial dose was reduced in 28 (64%) patients. The median time to treatment failure and number of cycles were 4.5 (range, 0.2-19.1) months and 6 cycles (range, 1-13 or more), respectively. The major grade ¾ adverse events were neutropenia in 29 (66%), leucopenia in 17 (39%), anorexia in 7 (16%), febrile neutropenia in 5 (11%), and anemia in 5 (11%) patients. The median overall survival, progression-free survival, and 1-year survival rates were 10.3 (95% confidence interval [CI], 7.2-13.3), 4.1 (95% CI, 2.6-5.5) months, and 30%, respectively.
CONCLUSION: Our findings suggest that FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer was effective in patients with a good performance status. It displayed toxicity similar to that observed with its use as a first-line treatment.

doi: https://doi.org/10.1016/j.pan.2020.07.006



  • The quality of pain management in pancreatic cancer: A prospective multi-center study

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Oct;20(7):1511-1518

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32952041

BACKGROUND/OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is frequently associated with severe pain. Given the almost inevitably fatal nature of the disease, pain control is crucial. However, data on quality of pain management in PDAC is scarce.
METHODS: This is a multi-center, prospective study to evaluate the quality of pain management in PDAC. Insufficient pain treatment (undertreatment) was prevalent if there was an incongruence between the patients level of pain and the potency of analgesic drug therapy. Determinants of pain and undertreatment were identified using multivariable logistic regression.
RESULTS: 139 patients with histologically confirmed PDAC were analyzed. The prevalence of pain was 63%, with approximately one third of the patients grading their pain as moderate to severe. Palliative stage (OR: 3.37, 95%CI: 1.23-9.21, p = 0.018) and localization of the primary tumor in the body or tail (OR: 2.57, 95%CI: 1.05-6.31, p = 0.039) were independent determinants of pain. Of those reporting pain, 60% were undertreated and in 89% pain interfered with activities and emotions. Age ≥ 70 years (OR: 3.20, 95%CI: 1.09-9.41, p = 0.035) was an independent predictor of undertreatment. Patients with longer-known PDAC ( ≥ 30 days) showed improved pain management compared to new cases (OR: 0.19, 95%CI: 0.05-0.81, p = 0.025). Treatment by gastroenterologists (OR: 0.22, 95%CI: 0.05-0.89, p = 0.034) was associated with less undertreatment.
CONCLUSIONS: The results show a high proportion of PDAC patients with pain, pain interference and undertreatment, whose characteristics could help to identify patients at risk in the future. Several changes in the management of cancer-related pain are necessary to overcome barriers to optimal treatment.

doi: https://doi.org/10.1016/j.pan.2020.08.017



  • Computerized tomography scan in pre-diagnostic pancreatic ductal adenocarcinoma: Stages of progression and potential benefits of early intervention: A retrospective study

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Oct;20(7):1495-1501

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32950386

BACKGROUND: The frequency, nature and timeline of changes on thin-slice (≤3 mm) multi-detector computerized tomography (CT) scans in the pre-diagnostic phase of pancreatic ductal adenocarcinoma (PDAC) are unknown. It is unclear if identifying imaging changes in this phase will improve PDAC survival beyond lead time.
METHODS: From a cohort of 128 subjects (Cohort A) with CT scans done 3-36 months before diagnosis of PDAC we developed a CTgram defining CT Stages (CTS) I through IV in the radiological progression of pre-diagnostic PDAC. We constructed Cohort B of PDAC resected at CTS I and II and compared survival in CTS I and II in Cohort A (n = 22 each; control natural history cohort) vs Cohort B (n = 33 and 72, respectively; early interception cohort).
RESULTS: CTs were abnormal in 16% and 85% at 24-36 and 3-6 months respectively, before PDAC diagnosis. The PDAC CTgram stages, findings and median lead times (months) to clinical diagnosis were: CTS I: Abrupt duct cut-off/duct dilatation (-12.8); CTS II: Low density mass confined to pancreas (-9.5), CTS III: Peri-pancreatic infiltration (-5.8), CTS IV: Distant metastases (only at diagnosis). PDAC survival was better in cohort B than in cohort A despite inclusion of lead time in Cohort A: CTS I (36 vs 17.2 months, p = 0.03), CTS II (35.2 vs 15.3 months, p = 0.04).
CONCLUSION: Starting 12-18 months before PDAC diagnosis, progressive and increasingly frequent changes occur on CT scans. Resection of PDAC at the time of pre-diagnostic CT changes is likely to provide survival benefit beyond lead time.

doi: https://doi.org/10.1016/j.pan.2020.07.410



  • Clinical outcomes of acute pancreatitis in elderly patients: An experience of single tertiary center

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Oct;20(7):1296-1301

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32900631

BACKGROUND: Although well understanding the course of diseases in geriatric population is of paramount importance in order to provide the optimal treatment, there is only a few studies with controversial results that have been conducted about the course and outcomes of acute pancreatitis (AP) in elderly. We aimed to compare clinical outcomes of AP disease in geriatric age group and to evaluate the risk factors affecting outcomes.
METHODS: A total of 336 patients diagnosed with AP, hospitalized and followed-up in our hospital between July/2013-February/2019 were included in this study. Patients aged 65 years and over were assessed as elderly population. Patients' demographic data, comorbidities, duration of hospitalization, local systemic complications, and mortality rates were documented.
RESULTS: 196(58.3%) of the patients were female with a mean age of 54.1 ± 17.9 years. The number of patients was 114(33.9%) in the elderly group and 222(66.1%) in the non-elderly group. Although there was no significant difference between both groups in terms of abscess, pseudocyst and necrosis, pancreatic necrosis and systemic complications were higher in the elderly group (p < 0.05). The durations of oral intake and hospitalization were longer, the mortality rate and severity of AP according to the Ranson and Atlanta criteria were significantly higher in the geriatric population (p < 0.05). In addition, age and severity of AP were found to be independent predictive factors of developing complications.
CONCLUSIONS: Early recognition of AP is important in the geriatric population. Clinical and laboratory investigations, and early diagnosis in severe patients will be largely helpful in providing close follow-up and the optimal treatment.

doi: https://doi.org/10.1016/j.pan.2020.06.006



  • Pancreatic neuroendocrine carcinoma G3 may be heterogeneous and could be classified into two distinct groups

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Oct;20(7):1421-1427

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32891532

BACKGROUND/OBJECTIVES: Pancreatic neuroendocrine carcinoma (PanNEC)-G3 often presents along with genetic abnormalities such as KRAS, RB1, and TP53 mutations. However, the association between these genetic findings and response to chemotherapy and prognosis has not been clarified. This study aimed to clarify the clinicopathological features of PanNEC-G3.
METHODS: We performed a subgroup analysis of the Japanese PanNEN-G3 study (multicenter, retrospective study), which revealed that Rb loss and KRAS mutation were predictors of the response to platinum-based regimen in PanNEN-G3. We re-classified WHO grades of PanNENs using the 2017 WHO classification and then analyzed the clinicopathological features and prognostic factors in 49 patients with PanNEC-G3.
RESULTS: The rates of Rb loss and KRAS mutation in PanNEC-G3 were 54.5% and 48.7%, respectively. Patients with Rb loss and/or KRAS mutation showed a higher response rate to first-line platinum-based regimen than those without Rb loss or KRAS mutation (object response rate 70.0% vs 33.3%, odds ratio 9.22; 95% CI 1.26-67.3, P = 0.029), but tended to have shorter overall survival rates than those without Rb loss or KRAS mutation (median 239 vs 473 days, hazard ratio 2.11; 95% CI 0.92-4.86, P = 0.077).
CONCLUSIONS: Patients with PanNEC-G3 have varied clinical outcomes for platinum-based regimen. When grouped based on Rb loss and KRAS mutation, there seemed to be two groups with distinct prognoses and responses to the platinum-based regimen. PanNEC-G3 could, therefore, be classified into two distinct groups based on immunohistochemical and genetic findings.

doi: https://doi.org/10.1016/j.pan.2020.07.400



  • Serum fibrinogen as a diagnostic and prognostic biomarker for pancreatic ductal adenocarcinoma

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Oct;20(7):1465-1471

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32873483

BACKGROUND/OBJECTIVES: Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is important as PDAC can lead to mortality; however, no specific biomarker has been identified for its early diagnosis. We previously identified fibrinogen α chain as a promising biomarker for differentiating between patients with and without PDAC using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Here, we aimed to validate the clinical usefulness of serum fibrinogen as a biomarker for PDAC.
METHODS: From 2009 to 2011, blood samples of 67 PDAC patients and 43 healthy adults (controls) were prospectively collected. Serum fibrinogen levels and their clinical significances were evaluated.
RESULTS: Mean fibrinogen levels were significantly higher in the PDAC group than in the control group (3.08 ± 0.565 vs. 2.54 ± 0.249 log10 ng/mL, P < 0.001). In the receiver operating characteristic analysis, overall sensitivity, and specificity of serum fibrinogen levels for differentiating PDAC patients from control patients were 67.4% and 83.6%, respectively, with a 427-ng/mL cutoff value. Serum fibrinogen levels were significantly higher in PDAC patients with distant metastasis than in those without distant metastasis (3.38 ± 0.581 vs. 2.93 ± 0.499 log10 ng/mL, P = 0.002). Median overall survival was significantly longer in PDAC patients with low fibrinogen levels (<1000 ng/mL) than in those with high fibrinogen levels (≥1000 ng/mL) [489 days (95% confidence interval, 248.1-729.9) vs. 172 days (58.4-285.6) (P = 0.008)]. Although serum fibrinogen levels were poorly correlated with carbohydrate antigen 19-9 levels, these two biomarkers together predicted survival better.
CONCLUSIONS: Serum fibrinogen levels may be a useful biomarker for diagnosing and predicting PDAC prognosis.

doi: https://doi.org/10.1016/j.pan.2020.06.010


New GallBladder Articles


  • Mural Intracholecystic Neoplasms Arising in Adenomyomatous Nodules of the Gallbladder: An Analysis of 19 Examples of a Clinicopathologically Distinct Entity

The American journal of surgical pathology 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33060404

Intracholecystic neoplasms (ICNs) (pyloric gland adenomas and intracholecystic papillary neoplasms, collectively also called intracholecystic papillary/tubular neoplasms) form multifocal, extensive proliferations on the gallbladder mucosa and have a high propensity for invasion (>50%). In this study, 19 examples of a poorly characterized phenomenon, mural papillary mucinous lesions that arise in adenomyomatous nodules and form localized ICNs, were analyzed. Two of these were identified in 1750 consecutive cholecystectomies reviewed specifically for this purpose, placing its incidence at 0.1%. Median age was 68 years. Unlike other gallbladder lesions, these were slightly more common in men (female/male=0.8), and 55% had documented cholelithiasis. All were characterized by a compact multilocular, demarcated, cystic lesion with papillary proliferations and mucinous epithelial lining. The lesions' architecture, distribution, location, and typical size were suggestive of evolution from an underlying adenomyomatous nodule. All had gastric/endocervical-like mucinous epithelium, but 5 also had a focal intestinal-like epithelium. Cytologic atypia was graded as 1 to 3 and defined as 1A: mucinous, without cytoarchitectural atypia (n=3), 1B: mild (n=7), 2: moderate (n=2), and 3: severe atypia (n=7, 3 of which also had invasive carcinoma, 16%). Background gallbladder mucosal involvement was absent in all but 2 cases, both of which had multifocal papillary mucosal nodules. In conclusion, these cases highlight a distinct clinicopathologic entity, that is, mural ICNs arising in adenomyomatous nodules, which, by essentially sparing the “main” mucosa, not displaying “field-effect/defect” phenomenon, and only rarely (16%) showing carcinomatous transformation, are analogous to pancreatic branch duct intraductal papillary mucinous neoplasms.

doi: https://doi.org/10.1097/PAS.0000000000001603


New BileDuct Articles


  • Mantle cell lymphoma with EBV-positive Hodgkin and Reed-Sternberg-like cells in a patient after autologous PBSCT: Phenotypically distinct but genetically related tumors

Pathology international 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33079423

The case of 70-year-old man with mantle cell lymphoma (MCL) carrying t(11;14) translocation that relapsed as nodal lymphoma combining MCL and classic Hodgkin lymphoma (cHL) 9 years after autologous peripheral blood stem cell transplant (auto-PBSCT) is reported. Lymph nodes contained two separate areas of MCL and cHL-like components. Hodgkin and Reed-Sternberg (HRS)-like cells were accompanied by a prominent histiocyte background. HRS-like cells were CD5- , CD15+ , CD20- , CD30+ , PAX5+ , Bob.1- , Oct2- and EBER+ . The MCL component expressed cyclin D1 and SOX11, whereas cyclin D1 and SOX11 expressions were reduced and lost, respectively, in HRS-like cells. Polymerase chain reaction results showed a single clonal rearrangement of the IGH gene in MCL and cHL-like components. CCND1 break apart fluorescence in situ hybridization showed split signals in both MCL and HRS-like cells, suggesting that MCL and cHL-like components were clonally related. Acquisition of p53 expression and Epstein-Barr virus (EBV)-positivity was seen in HRS-like cells. The patient died of disease progression with elevated hepatobiliary enzymes. The autopsy showed both MCL and cHL-like components around the bile ducts, splenic white pulp and bone marrow. The two components were phenotypically distinct, but genetically related, suggesting that transformation of MCL to HRS-like cells during the course of MCL in association with EBV infection.

doi: https://doi.org/10.1111/pin.13038



  • The use of immunohistochemistry for IgG4 in the diagnosis of autoimmune pancreatitis: A systematic review and meta-analysis

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33060017

BACKGROUND: The diagnosis of autoimmune pancreatitis (AIP) remains challenging, especially when serum IgG4 is normal or imaging features are indeterminate. We performed a systematic review and meta-analysis to evaluate the performance of IgG4 immunostaining of pancreatic, biliary, and ampullary tissues as a diagnostic aid for AIP.
METHODS: A comprehensive literature search of the PubMed, EMBASE, and Ovid MEDLINE databases was conducted until February 2020. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. A random-effects model was used to summarize the diagnostic odds ratio and other measures of accuracy.
RESULTS: The meta-analysis included 20 studies comprising 346 patients with AIP and 590 patients with other pancreatobiliary diseases, including 371 pancreatobiliary malignancies. The summary estimates for tissue IgG4 in discriminating AIP and controls were as follows: diagnostic odds ratio 38.86 (95% confidence interval (CI), 18.70-80.75); sensitivity 0.64 (95% CI, 0.59-0.69); specificity 0.93 (95% CI, 0.91-0.95). The area under the curve was 0.939 for tissue IgG4 in discriminating AIP and controls. Subgroup analysis revealed no significant difference in diagnostic accuracy according to control groups (pancreatobiliary cancer versus other chronic pancreatitis) and sampling site (pancreas versus bile duct/ampulla).
CONCLUSIONS: Current data demonstrate that IgG4 immunostaining of pancreatic, biliary, and ampullary tissue has a high specificity but moderate sensitivity for diagnosing AIP. IgG4 immunostaining may be useful in supporting a diagnosis of AIP when AIP is clinically suspected, but a combination of imaging and serology does not provide a conclusive diagnosis.

doi: https://doi.org/10.1016/j.pan.2020.10.028


New Ampulla Articles


  • Patterns of Mycobacterium avium-intracellulare complex infection in duodenal endoscopic biopsies in HIV/AIDS patients

Annals of diagnostic pathology 2020 Oct;49():151638

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33069083

Mycobacterium avium-intracellulare complex (MAIC) is a nontuberculous opportunistic infection in immunocompromised patients. Involvement of the gastrointestinal tract (GIT) is usually part of a disseminated disease in AIDS patients with a low CD4 count, however with standard antiretroviral therapy (ART), a localized presentation is more likely. It can affect any part of the GIT, mostly the duodenum and typically as patches. Incomplete or refractory ART for HIV-strains, therapy-related side effects, noncompliant or incomplete treatment to previous MAIC infections, superimposed complications and comorbid opportunistic infections may result in atypical clinical, endoscopic and histopathologic manifestations. We performed a retrospective review study retrieving cases of MAIC in duodenal endoscopic biopsy. We found five cases of MAIC in HIV/AIDS patients. They were males with an average age of 40-years. They showed different histopathologic features, variable patterns of MAIC-histiocytic infiltrates, and varying intensity of intracellular acid-fast positive bacilli. Enterocytes vacuolization and transepithelial elimination were also observed. Three cases were associated with cytomegalovirus and cryptococcal infections. A case was complicated by lymphangiectasia-associated protein-losing enteropathy. Initially, three cases were morphologically missed. Ziehl-Neelsen stain helped reach the correct diagnosis. Pathologists have an important role in patients' management by guiding clinicians to the correct diagnosis. Pathologists should be aware of these different histopathologic manifestations, their potential pitfalls, look for certain helpful clues complemented with multiple levels and special stains. In particular, AFB stains are mandatory in all mucosal biopsy specimens from HIV/AIDS patients regardless of their appearances.

doi: https://doi.org/10.1016/j.anndiagpath.2020.151638



  • The use of immunohistochemistry for IgG4 in the diagnosis of autoimmune pancreatitis: A systematic review and meta-analysis

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=33060017

BACKGROUND: The diagnosis of autoimmune pancreatitis (AIP) remains challenging, especially when serum IgG4 is normal or imaging features are indeterminate. We performed a systematic review and meta-analysis to evaluate the performance of IgG4 immunostaining of pancreatic, biliary, and ampullary tissues as a diagnostic aid for AIP.
METHODS: A comprehensive literature search of the PubMed, EMBASE, and Ovid MEDLINE databases was conducted until February 2020. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. A random-effects model was used to summarize the diagnostic odds ratio and other measures of accuracy.
RESULTS: The meta-analysis included 20 studies comprising 346 patients with AIP and 590 patients with other pancreatobiliary diseases, including 371 pancreatobiliary malignancies. The summary estimates for tissue IgG4 in discriminating AIP and controls were as follows: diagnostic odds ratio 38.86 (95% confidence interval (CI), 18.70-80.75); sensitivity 0.64 (95% CI, 0.59-0.69); specificity 0.93 (95% CI, 0.91-0.95). The area under the curve was 0.939 for tissue IgG4 in discriminating AIP and controls. Subgroup analysis revealed no significant difference in diagnostic accuracy according to control groups (pancreatobiliary cancer versus other chronic pancreatitis) and sampling site (pancreas versus bile duct/ampulla).
CONCLUSIONS: Current data demonstrate that IgG4 immunostaining of pancreatic, biliary, and ampullary tissue has a high specificity but moderate sensitivity for diagnosing AIP. IgG4 immunostaining may be useful in supporting a diagnosis of AIP when AIP is clinically suspected, but a combination of imaging and serology does not provide a conclusive diagnosis.

doi: https://doi.org/10.1016/j.pan.2020.10.028


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