Recent Articles on Pancreatobiliary #Pathology – 2020-09-19

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


  • Intestinal Metaplasia Around The Gastroesophageal Junction Is Frequently Associated With Antral Reactive Gastropathy: Implications For Carcinoma At The Gastroesophageal Junction

Human pathology 2020 Sep;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32941964

Increasing evidence suggests that bile reflux (BR) plays a major role in mucosal injury leading to adenocarcinoma of the proximal stomach and distal esophagus. However, gastric BR is difficult to diagnose and investigate. Reactive gastropathy (RG), in the absence of non-steroidal anti-inflammatory drugs (NSAIDs) and other known causes likely represents bile-mediated injury to gastric mucosa. The goal of this study is to explore the association between antral RG and gastroesophageal junction (GEJ) mucosal inflammation and intestinal metaplasia. The pathology database was searched for patients who had gastric biopsies with a diagnosis of antral RG and concurrent gastric cardia/GEJ/distal esophagus biopsies from 2013-2015. Age and sex matched patients with normal gastric antral biopsies served as controls. Biopsies from the GEJ region were evaluated for histological changes, including inflammation, antral and pancreatic metaplasia, RG, type of gastric glands, proton-pump inhibitor (PPI) changes and intestinal metaplasia. Detailed clinical history and medication use (including PPIs and NSAIDs) were recorded. Intestinal metaplasia in the GEJ region was more frequent in patients with antral RG compared to controls [33.0% vs. 5.2%, 95% CI (18.3%-37.3%)]. In addition, inflammation, other mucosal changes around the GEJ (RG & foveolar hyperplasia), antral IM and PPI associated mucosal changes were also more frequently seen in patients with antral RG. Our results show that antral RG is associated with mucosal injury and intestinal metaplasia around GEJ suggesting a role for bile reflux. Further studies are needed to study duodenogastric-esophageal bile reflux and its role in development of proximal gastric and distal esophageal adenocarcinoma.

doi: https://doi.org/10.1016/j.humpath.2020.08.007



  • Fate of Patients With Intraductal Papillary Mucinous Neoplasms of Pancreas After Resection According to the Pathology and Margin Status: Continuously Increasing Risk of Recurrence Even After Curative Resection Suggesting Necessity of Lifetime Surveillance

Annals of surgery 2020 Sep;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32941274

OBJECTIVE: This study evaluated the associated factors and prognosis according to pathology and margin after surgical resection of intraductal papillary mucinous neoplasms (IPMN).
BACKGROUND: There is limited information on recurrence patterns according to pathology and margin in IPMN.
METHODS: Total 577 patients who underwent operation for IPMN at a tertiary center were included. Factors associated with recurrence, survival and recurrence outcomes according to pathology and margin were analyzed.
RESULTS: Among 548 patients analyzed, 353 had low-grade dysplasia (LGD); 78, high-grade dysplasia (HGD); and 117, invasive IPMN. Total 50 patients developed recurrences, with four resection margins, eight remnant pancreas, 11 locoregional, and 35 distant recurrences. Invasive IPMN showed worse 5-year cumulative recurrence risk (LGD vs HGD vs invasive: 0.7% vs 4.3% vs 37.6%, p < 0.001) and 5-year survival rate (89.0% vs 84.0% vs 48.4%, p < 0.001). Recurrence risk increased after 5 years, even in LGD and HGD. Malignant margin (HGD and invasive) had worse 5-year cumulative recurrence rate (R0 vs LGD vs malignant: 8.3% vs 5.9% vs 50.6%, p < 0.001) and 5-year survival rate (80.7% vs 83.0% vs 30.8%, p < 0.001). CA19-9 > 37 (p = 0.003), invasive IPMN (p < 0.001), and malignant margin (p = 0.036) were associated with recurrence.
CONCLUSIONS: Invasive IPMN developed more recurrences and had worse survival than LGD or HGD, indicating the need for more efficient postoperative treatment strategies. Patients with LGD and HGD also need regular follow-up for recurrence after 5 years. Malignant margins need additional resection to achieve negative or at least LGD margin.

doi: https://doi.org/10.1097/SLA.0000000000004478



  • Curative Surgery and Ki-67 Value Rather than Tumor Differentiation Predict the Survival of Patients with High-grade Neuroendocrine Neoplasms

Annals of surgery 2020 Sep;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32941267

OBJECTIVE: To elucidate the role of surgery in patients with high-grade neuroendocrine neoplasms (hg-NENs) and Ki-67 > 20%.
BACKGROUND: Although surgery is the first treatment choice in patients with low-grade NENs, whether it increases the survival of patients with hg-NENs is debatable.
METHODS: Between 2005 and 2018, 63 patients pathologically diagnosed with hg-NENs treated at our institution were retrospectively analyzed. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were analyzed, and OS was compared between each treatment group.
RESULTS: The median observation time was 21.2 months, and the median Ki-67 value was 52%. Patients with hg-NENs were classified into low Ki-67 (Ki-67 < 52%) and high Ki-67 (Ki-67 ≥ 52%) groups. Multivariate analysis for OS identified surgery (P = 0.013) and low Ki-67 value (P = 0.007) as independent risk factors, while morphological differentiation defined by the WHO 2017 criteria showed no association with OS. Patients with low Ki-67 value subjected to R0/1, R2, and chemotherapy had a median survival time (MST) of 83.8, 16.6, and 28.1 months, respectively. The MST for R0/1 group was significantly longer than that for chemotherapy group (P = 0.001). However, no difference in survival was reported between patients from R0/1 and chemotherapy groups with high Ki-67. Ki-67 value could determine RFS (P = 0.006) in patients that underwent R0/1 surgery for pancreatic hg-NENs.
CONCLUSION: R0/1 surgery predicted prognoses in the low Ki-67 group. The indication of surgery for patients with hg-NENs did not depend on tumor differentiation.

doi: https://doi.org/10.1097/SLA.0000000000004495



  • The European evidence-based guidelines on pancreatic cystic neoplasms (PCN) in clinical practice: The development of relative and absolute indications for surgery during prospective IPMN surveillance

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

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32938553

INTRODUCTION: The European evidence-based guidelines on PCN recommend surveillance for IPMN patients who are fit for surgery but who have no indication for immediate surgery. Our aim was to demonstrate the feasibility of the new guidelines in clinical practice.
METHODS: This is a prospective cohort study of patients included in the IPMN register in Tampere University Hospital, Finland. IPMN was diagnosed from January 1, 2013 to December 31, 2018. Patients were analyzed for surveillance and indications for surgery according to the European guidelines on PCN.
RESULTS: Out of 128 patients in register 23 was decided to operate upfront and 105 patients were included in the surveillance programme. Invasive carcinoma was found in 4/23 of operated patients. Median follow-up time was 26 months (6-69). Median size of the cyst at the beginning and end of the surveillance was 16 mm (4-58 mm). During surveillance 0/105 (0.0%) patients had or developed an absolute indication for surgery. Relative indication for surgery was present in 8/105 (7.6%) patients in the beginning surveillance and 9/105 (8.6%) patients developed at least one relative indication for surgery during surveillance. From the surveillance cohort 2/105 patients were operated. Surveillance was abandoned in 15/105 (14.1%) patients all due to poor general condition or other medical conditions.
CONCLUSIONS: In clinical practice, surveillance of IPMN according to the European guidelines on PCN is feasible. Among our patients 16% were detected to have relative indications for surgery during the median 26 (range 3-135) months of surveillance. Nearly 15% became surgically unfit during surveillance period.

doi: https://doi.org/10.1016/j.pan.2020.09.003



  • Early laboratory biomarkers for severity in acute pancreatitis; A systematic review and meta-analysis

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

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32938552

BACKGROUND/OBJECTIVES: Acute pancreatitis is complicated by local and systemic complications in 20-30% of the patients. Accurate prediction of severity may be important for clinical decision making. Our aim is to identify and compare the accuracy of laboratory biomarkers that predict severity and complications in adult patients.
METHODS: Medline, EMBASE, Web of Science and Cochrane Library (1993 to August 2020) were searched for studies with an unselected population of patients with acute pancreatitis, that contains accuracy data for ≥1 laboratory biomarker(s) and/or APACHE-II score for the prediction of a patient outcomes of interest during the first 48 h of admission. The primary outcome is moderate severe or severe acute pancreatitis (MSAP/SAP). Secondary outcomes are severe acute pancreatitis, pancreatic necrosis and organ failure. Risk of bias was assed using QUADAS-2. Biomarkers extracted from ≥3 unique sources, were analyzed using hierarchical summary receiver operating characteristic (HSROC) and bivariate model analysis.
RESULTS: In total, 181 studies were included in the qualitative analysis reporting on 29 biomarkers. For the primary outcome at admission, summary sensitivities and specificities were, respectively, 87% (95% CI 69-95%) and 88% (95% CI 80-93%) for IL-6 at a threshold of >50 pg/ml, 72% (95% CI 64-79%) and 76% (95% CI 67-84%) for an APACHE-II score of ≥8, and 53% (95% CI 35-71%) and 82% (95% CI 74-88%) for CRP >150 mg/l. HSROC curve analysis confirmed these results.
CONCLUSION: This study indicates superiority of IL-6 for the early prediction of MSAP/SAP and may be used for to guide clinical decision making.

doi: https://doi.org/10.1016/j.pan.2020.09.007



  • Protruded duodenal tumor arising from Santorini's duct of the pancreas: a rare case of intraductal papillary mucinous neoplasm mimicking a duodenal polypoid tumor

BMC gastroenterology 2020 Sep;20(1):303

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32938427

BACKGROUND: We experienced a rare case of intraductal papillary mucinous neoplasm arising from Santorini's duct (SD) forming a tumor protruding into the duodenum .
CASE PRESENTATION: A 71-year-old woman was incidentally diagnosed with a 3 cm type Isp polypoid tumor in the second portion of the duodenum at another hospital. Enhanced CT and endoscopic ultrasound revealed that the origin of this protruding tumor was arising from SD and that the tumor mimicked a pedunculated duodenal tumor. Our preoperative diagnosis was a malignant pancreatic tumor arising from SD with invasion into the duodenum. She underwent a subtotal stomach-preserving pancreaticoduodenectomy, and the resected specimen showed a 25 mm tumor protruding into the duodenum with a villous surface. The pathological findings revealed that the tumor was intraductal papillary mucinous adenoma (IPMA) arising from SD.
CONCLUSIONS: To the best of our knowledge, this is the first case of IPMA protruding into the duodenal lumen from SD, although most of the tumors arising from SD have been reported to be malignant.

doi: https://doi.org/10.1186/s12876-020-01449-y



  • Intraductal papillary mucinous neoplasm complicated with intraductal bleeding in a young woman mimicked a cystic solid pseudo-papillary tumor: a case report

BMC gastroenterology 2020 Sep;20(1):304

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32938404

BACKGROUND: There are only 6 cases of intraductal papillary mucinous neoplasm (IPMN) complicated with intraductal hemorrhage have been reported in English literatures. All these 6 cases of IPMN occurred in the old people. The present rare case of IPMN complicated with intraductal hemorrhage occurred in a young woman, and mimicked a cystic solid pseudo-papillary neoplasm (SPN) on preoperative imaging findings.
CASE PRESENTATION: A 29-year-old young woman complained of a sustained mild right upper quadrant abdominal pain. CT and MRI showed a lobulated, partly ill-defined cystic lesion located in the pancreatic head. Spotted calcification within cystic wall was seen on CT. The lesion was demonstrated as predominantly homogeneous hyperattenuation on CT and homogeneous high signal without decreased signal on fat suppression sequence on T1WI. After contrast administration, the cystic wall and septa of lesion was showed gradually mild to moderate degree of enhancement over time both on CT and MRI. No communication between lesion and the main duct was found on MRCP and the main pancreatic duct and common bile duct were not dilated. Considering patient's age, gender and manifestations of lesion on CT and MRI (calcification, bleeding and gradually enhanced pattern), the present case mimicked as a cystic SPN. The lesion was pathologically confirmed a branch type IPMN after surgical resection.
CONCLUSION: We propose that IPMN may need to be taken into account in the differential diagnosis when pancreatic cystic lesions occur in young women with bleeding, calcification, progressive enhancement of cystic wall and no communication with the main pancreatic duct.

doi: https://doi.org/10.1186/s12876-020-01436-3



  • The Effect of Pancreatoduodenectomy Plus Intraperitoneal Hyperthermic Perfusion on Resectable Pancreatic Head Cancer: Cohort Study

Annals of surgical oncology 2020 Sep;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32935266

BACKGROUND: Intraperitoneal hyperthermic perfusion (IPHP) has achieved positive results in treating various abdominal cancers but infrequently reported in resectable pancreatic head cancer. This study was designed to explore the safety and efficacy of pancreaticoduodenectomy plus intraperitoneal hyperthermic perfusion (PD + IPHP) in patients with pancreatic cancer.
METHODS: Data of pancreatic cancer patients undergoing pancreaticoduodenectomy were retrospectively analyzed, including PD + IPHP (n = 28) and PD group (n = 29). IPHP was performed during surgery, on postoperative day (POD) 2, and POD 4 with normal saline as the perfusion solution. Complications and overall survival of these patients were observed and recorded.
RESULTS: There was no significant difference in the incidence of major postoperative complications between PD + IPHP group and PD group. The median overall survival (OS) time of the PD + IPHP group was 19.0 months, the 1-year survival rate was 82.35%, and the 2-year survival rate was 49.41%. The median OS time of the PD group was 13.0 months, the 1-year survival rate was 51.00%, and the 2-year survival rate was 27.33% (Log-rank, P = 0.030; Breslow, P = 0.039). Cox proportional risk model showed that IPHP was an independent factor to improve survival outcomes of these patients (hazard ratio = 0.363, 95% confidence interval: 0.14-0.94; P = 0.038).
CONCLUSIONS: Intraperitoneal hyperthermic perfusion significantly improves the survival outcomes of pancreatic head cancer patients undergoing PD and does not bring extra risks of complications.

doi: https://doi.org/10.1245/s10434-020-09095-0



  • Positivity for SATB2 distinguishes Islet1 positive rectal neuroendocrine tumours from pancreaticoduodenal neuroendocrine tumours

Journal of clinical pathology 2020 Sep;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32934105

AIMS: Determining the site of origin of a metastatic neuroendocrine tumour (NET) can be challenging and has important prognostic and therapeutic implications. An immunohistochemical (IHC) panel consisting of TTF1, CDX2, PAX8/PAX6 and Islet1 is often employed. However, there can be a significant IHC overlap among different primary sites. Herein, we sought to determine the utility of including Special AT-rich sequence binding protein-2 (SATB2) in the IHC panel that is used for determining the site of origin of a metastatic NET.
METHODS: Paraffin tissue microarrays consisting of 137 primary NETs (26 lung, 22 jejunoileal, 8 appendix, 5 stomach, 4 duodenum, 17 rectum and 55 pancreas) were stained for SATB2, in addition to the well-described lineage-associated markers, such as TTF1, CDX2, PAX6 and Islet1. Additionally, a tissue microarray consisting of 21 metastatic NETs (1 lung, 1 stomach, 8 jejunoileal and 11 pancreas) was stained for TTF1, CDX2, SATB2 and Islet1. The results were recorded as no staining, weak staining and moderate to strong staining.
RESULTS: All appendiceal NETs and majority (88%) of the rectal NETs were positive for SATB2. All primary foregut NETs (stomach, pancreas, duodenum and lung) were negative for SATB2, except for one pulmonary NET with weak staining. However, among the metastatic tumours, 5 of 11 pancreatic NETs, 1 stomach NET, 1 lung NET and 2 of 8 jejunoileal NETs showed weak staining. Receiver operating characteristic analysis incorporating sensitivity and specificity data of IHC panel, considering moderate to strong staining as truly positive cases, showed that inclusion of SATB2 to the previously described NET IHC panel outperformed the panel without SATB2, raising the specificity for pancreaticoduodenal NETs from 81.2% to 100%, with a positive predictive value (PPV) of 100% and negative predictive value (NPV) of 82.22% (p<0.0001); for appendiceal NETs the specificity changed from 99.1% to 98.5% and sensitivity increased from 11.8% to 80%, with a PPV and NPV of 66.67% and 99.26%, respectively (p<0.0001); and for rectal NETs the specificity increased from 97.6% to 99.3% and sensitivity raised from 7.1% to 66.7%, with a PPV and NPV of 80% and 98.53%, respectively (p<0.0001).
CONCLUSIONS: SATB2 stain is useful in differentiatingIslet1/PAX6 positive pancreatic and rectal NETs, as rectal NETs are typically moderately to strongly positive for SATB2 and pancreatic NETs are usually negative or weakly positive for SATB2. Moderate to strong staining for SATB2 is suggestive of an appendiceal or a rectal primary. SATB2 may complement the panel of CDX2, TTF1 and Islet1 in determining the site of origin of an NET in a metastatic setting.

doi: https://doi.org/10.1136/jclinpath-2020-206645



  • TSPO-targeted PET and Optical Probes for the Detection and Localization of Pre-Malignant and Malignant Pancreatic Lesions

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

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32933996

PURPOSE: Pancreatic cancer is among the most aggressive malignancies and is rarely discovered early. However, pancreatic 'incidentalomas', particularly cysts, are frequently identified in asymptomatic patients through anatomical imaging for unrelated causes. Accurate determination of the malignant potential of cystic lesions could lead to life-saving surgery or spare patients with indolent disease undue risk. Current risk assessment of pancreatic cysts requires invasive sampling, with attendant morbidity and sampling errors. Here, we sought to identify imaging biomarkers of high-risk pancreatic cancer precursor lesions.
EXPERIMENTAL DESIGN: Translocator protein (TSPO) expression, which is associated with cholesterol metabolism, was evaluated in pre-malignant and pancreatic cancer lesions from human and genetically engineered mouse (GEM) tissues. In vivo imaging was performed with [18F]V-1008, a TSPO-targeted positron emission tomography (PET) agent, in two GEM models. For image-guided surgery (IGS), V-1520, a TSPO ligand for near-infrared optical imaging based upon the V-1008 pharmacophore, was developed and evaluated.
RESULTS: TSPO was highly expressed in human and murine pancreatic cancer. Notably, TSPO expression was associated with high-grade, pre-malignant intraductal papillary mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasia (PanIN) lesions. In GEM models, [18F]V-1008 exhibited robust uptake in early pancreatic cancer, detectable by PET. Furthermore, V-1520 localized to pre-malignant pancreatic lesions and advanced tumors enabling real-time IGS.
CONCLUSIONS: We anticipate that combined TSPO PET/IGS represents a translational approach for precision pancreatic cancer care through discrimination of high-risk indeterminate lesions and actionable surgery.

doi: https://doi.org/10.1158/1078-0432.CCR-20-1214



  • Clinical and genomic characterisation of mismatch repair deficient pancreatic adenocarcinoma

Gut 2020 Sep;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32933947

OBJECTIVE: To describe the clinical, pathological and genomic characteristics of pancreatic cancer with DNA mismatch repair deficiency (MMRD) and proficiency (MMRP).
DESIGN: We identified patients with MMRD and MMRP pancreatic cancer in a clinical cohort (N=1213, 519 with genetic testing, 53 with immunohistochemistry (IHC)) and a genomic cohort (N=288 with whole-genome sequencing (WGS)).
RESULTS: 12 out of 1213 (1.0%) in the clinical cohort were MMRD by IHC or WGS. Of the 14 patients with Lynch syndrome, 3 (21.4%) had an MMRP pancreatic cancer by IHC, and 4 (28.6%) were excluded because tissue was unavailable for testing. MMRD cancers had longer overall survival after surgery (weighted HR after coarsened exact matching 0.11, 95% CI 0.02 to 0.78, p=0.001). One patient with an unresectable MMRD cancer has an ongoing partial response 3 years after starting treatment with PD-L1/CTLA-4 inhibition. This tumour showed none of the classical histopathological features of MMRD. 9 out of 288 (3.1%) tumours with WGS were MMRD. Despite markedly higher tumour mutational burden and neoantigen loads, MMRD cancers were significantly less likely to have mutations in usual pancreatic cancer driver genes like KRAS and SMAD4, but more likely to have mutations in genes that drive cancers with microsatellite instability like ACV2RA and JAK1. MMRD tumours were significantly more likely to have a basal-like transcriptional programme and elevated transcriptional markers of immunogenicity.
CONCLUSIONS: MMRD pancreatic cancers have distinct clinical, pathological and genomic profiles. Patients with MMRD pancreatic cancer should be considered for basket trials targeting enhanced immunogenicity or the unique genomic drivers in these malignancies.

doi: https://doi.org/10.1136/gutjnl-2020-320730



  • Pancreaticoduodenectomy: Outcomes of a complex surgical procedure from a developing country

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

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32928685

BACKGROUND: Pancreaticoduodenectomy (PD) plays an integral part in the management of pancreatic, periampullary and duodenal cancers, along with a few other pathologies of this region. Despite advances in surgery PD continues to have significant morbidity and noteworthy mortality. The aim of this study is to provide an in-depth report on the patient characteristics, indications and the outcomes of PD) in a tertiary cancer hospital in Pakistan.
MATERIALS AND METHODS: The study population included patients who underwent PD between January 1, 2014 and march 31, 2019, at Shaukat Khanum Memorial Cancer Hospital and Research Center (SKMCH&RC) in Pakistan. The data was retrospectively analyzed from the Hospital Information System (HIS), which is a prospectively maintained patient electronic database of SKMCH&RC. Patient characteristics, procedural details and post-operative outcomes according to internationally accepted definitions were reported.
RESULTS: A total of 161 patients underwent PD at our hospital in the study period at a median age of 53 years, ranging from 19 to 78 years. 62% of the patients were males while 37% were females. Jaundice was the most common presenting symptom (64.6%), followed by abdominal pain (26.7%). PD with pancreaticogastrostomy was performed in 110 patients (68.3%), while pancreaticojejunostomy was performed in the rest of the cohort. Surgical site infection (SSI) was observed in 64 patients (40%). The incidence of Pancreatic Fistula grade C based on the International Study Group on Pancreatic Fistula (ISGPF) definition was 7.45% (n = 12). The 30 days mortality rate was 3.1%. Median survival of the cohort was 21 ±1.13 months and disease-free survival was 16±2.62 months.
CONCLUSION: PD can be performed with acceptable morbidity and mortality in a resource constrained country, as long as it is undertaken in a high-volume center. This is in keeping with data published from other well-reputed international centers.

doi: https://doi.org/10.1016/j.pan.2020.08.013


New GallBladder Articles


  • Innervation of the proximal human biliary tree

Virchows Archiv : an international journal of pathology 2020 Sep;477(3):385-392

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=31993770

The autonomic nervous system plays a role in a variety of liver regenerative and metabolic functions, including modulating bile secretion and cholangiocyte and hepatobiliary progenitors of the canals of Hering. However, the nature and location of nerves which link to the proximal biliary tree have remained uncertain. We investigate the anatomic relationship of nerves to the proximal biliary tree including the putative stem/progenitor cell niche of the canal of Hering. Using double immunostaining (fluorescence, histochemistry) to highlight markers of cholangiocytes (biliary-type keratins), nerves (S100, neurofilament protein, PGP9.5, tyrosine hydroxylase), and stellate cells (CRBP-1), we examined sections from normal adult livers from autopsy or surgical resections. There is extensive contact between nerves and interlobular bile ducts, bile ductules, and canals of Hering (CoH). In multiple serial sections from 4 normal livers, biliary-nerve contacts were seen in all of these structures and were more common in the interlobular bile ducts (78/137; 57%) than in the ductules and CoH (95/294; 33%) (p < 0.001). Contacts appear to consist of nerves in juxtaposition to the biliary basement membrane, though crossing through basement membrane to interface directly with cholangiocytes is also present. These nerves are positive for tyrosine hydroxylase and are, thus, predominately adrenergic. Electron microscopy confirms nerves closely approximating ductules. Nerve fiber-hepatic stellate cell juxtaposition is observed but without stellate cell approximation to cholangiocytes. We present novel findings of biliary innervation, perhaps mediated in part, by direct cholangiocyte-nerve interactions. The implications of these findings are protean for studies of neuromodulation of biliary physiology and hepatic stem/progenitor cells.

doi: https://doi.org/10.1007/s00428-020-02761-4


New BileDuct Articles


  • Intraductal papillary mucinous neoplasm complicated with intraductal bleeding in a young woman mimicked a cystic solid pseudo-papillary tumor: a case report

BMC gastroenterology 2020 Sep;20(1):304

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32938404

BACKGROUND: There are only 6 cases of intraductal papillary mucinous neoplasm (IPMN) complicated with intraductal hemorrhage have been reported in English literatures. All these 6 cases of IPMN occurred in the old people. The present rare case of IPMN complicated with intraductal hemorrhage occurred in a young woman, and mimicked a cystic solid pseudo-papillary neoplasm (SPN) on preoperative imaging findings.
CASE PRESENTATION: A 29-year-old young woman complained of a sustained mild right upper quadrant abdominal pain. CT and MRI showed a lobulated, partly ill-defined cystic lesion located in the pancreatic head. Spotted calcification within cystic wall was seen on CT. The lesion was demonstrated as predominantly homogeneous hyperattenuation on CT and homogeneous high signal without decreased signal on fat suppression sequence on T1WI. After contrast administration, the cystic wall and septa of lesion was showed gradually mild to moderate degree of enhancement over time both on CT and MRI. No communication between lesion and the main duct was found on MRCP and the main pancreatic duct and common bile duct were not dilated. Considering patient's age, gender and manifestations of lesion on CT and MRI (calcification, bleeding and gradually enhanced pattern), the present case mimicked as a cystic SPN. The lesion was pathologically confirmed a branch type IPMN after surgical resection.
CONCLUSION: We propose that IPMN may need to be taken into account in the differential diagnosis when pancreatic cystic lesions occur in young women with bleeding, calcification, progressive enhancement of cystic wall and no communication with the main pancreatic duct.

doi: https://doi.org/10.1186/s12876-020-01436-3



  • Gastric submucosal abscess caused by Edwardsiella tarda infection: a case report

BMC gastroenterology 2020 Sep;20(1):299

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32928124

BACKGROUND: Edwardsiella tarda is a motile, facultatively anaerobic gram-negative bacillus that is isolated from a wide spectrum of animals in aquatic environments but rarely causes infection in humans. Here, we describe the case of a gastric submucosal abscess caused by E. tarda infection.
CASE PRESENTATION: The patient was a 74-year-old man with a history of hypertension and chronic alcohol consumption who was admitted to our hospital for abdominal pain, appetite loss and vomiting. Contrast-enhanced computed tomography (CT) revealed choledocholithiasis in the common bile duct, a gastric wall abscess and an intra-abdominal abscess. Endoscopic ultrasound (EUS)-guided drainage with antibiotics successfully cured the patient.
CONCLUSION: The combination of CT, endoscopy and EUS-guided drainage with antibiotic therapy might be effective for diagnosis and treatment of a gastric submucosal abscess caused by E. tarda infection.

doi: https://doi.org/10.1186/s12876-020-01446-1


New Ampulla Articles


  • Protruded duodenal tumor arising from Santorini's duct of the pancreas: a rare case of intraductal papillary mucinous neoplasm mimicking a duodenal polypoid tumor

BMC gastroenterology 2020 Sep;20(1):303

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32938427

BACKGROUND: We experienced a rare case of intraductal papillary mucinous neoplasm arising from Santorini's duct (SD) forming a tumor protruding into the duodenum .
CASE PRESENTATION: A 71-year-old woman was incidentally diagnosed with a 3 cm type Isp polypoid tumor in the second portion of the duodenum at another hospital. Enhanced CT and endoscopic ultrasound revealed that the origin of this protruding tumor was arising from SD and that the tumor mimicked a pedunculated duodenal tumor. Our preoperative diagnosis was a malignant pancreatic tumor arising from SD with invasion into the duodenum. She underwent a subtotal stomach-preserving pancreaticoduodenectomy, and the resected specimen showed a 25 mm tumor protruding into the duodenum with a villous surface. The pathological findings revealed that the tumor was intraductal papillary mucinous adenoma (IPMA) arising from SD.
CONCLUSIONS: To the best of our knowledge, this is the first case of IPMA protruding into the duodenal lumen from SD, although most of the tumors arising from SD have been reported to be malignant.

doi: https://doi.org/10.1186/s12876-020-01449-y



  • Positivity for SATB2 distinguishes Islet1 positive rectal neuroendocrine tumours from pancreaticoduodenal neuroendocrine tumours

Journal of clinical pathology 2020 Sep;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32934105

AIMS: Determining the site of origin of a metastatic neuroendocrine tumour (NET) can be challenging and has important prognostic and therapeutic implications. An immunohistochemical (IHC) panel consisting of TTF1, CDX2, PAX8/PAX6 and Islet1 is often employed. However, there can be a significant IHC overlap among different primary sites. Herein, we sought to determine the utility of including Special AT-rich sequence binding protein-2 (SATB2) in the IHC panel that is used for determining the site of origin of a metastatic NET.
METHODS: Paraffin tissue microarrays consisting of 137 primary NETs (26 lung, 22 jejunoileal, 8 appendix, 5 stomach, 4 duodenum, 17 rectum and 55 pancreas) were stained for SATB2, in addition to the well-described lineage-associated markers, such as TTF1, CDX2, PAX6 and Islet1. Additionally, a tissue microarray consisting of 21 metastatic NETs (1 lung, 1 stomach, 8 jejunoileal and 11 pancreas) was stained for TTF1, CDX2, SATB2 and Islet1. The results were recorded as no staining, weak staining and moderate to strong staining.
RESULTS: All appendiceal NETs and majority (88%) of the rectal NETs were positive for SATB2. All primary foregut NETs (stomach, pancreas, duodenum and lung) were negative for SATB2, except for one pulmonary NET with weak staining. However, among the metastatic tumours, 5 of 11 pancreatic NETs, 1 stomach NET, 1 lung NET and 2 of 8 jejunoileal NETs showed weak staining. Receiver operating characteristic analysis incorporating sensitivity and specificity data of IHC panel, considering moderate to strong staining as truly positive cases, showed that inclusion of SATB2 to the previously described NET IHC panel outperformed the panel without SATB2, raising the specificity for pancreaticoduodenal NETs from 81.2% to 100%, with a positive predictive value (PPV) of 100% and negative predictive value (NPV) of 82.22% (p<0.0001); for appendiceal NETs the specificity changed from 99.1% to 98.5% and sensitivity increased from 11.8% to 80%, with a PPV and NPV of 66.67% and 99.26%, respectively (p<0.0001); and for rectal NETs the specificity increased from 97.6% to 99.3% and sensitivity raised from 7.1% to 66.7%, with a PPV and NPV of 80% and 98.53%, respectively (p<0.0001).
CONCLUSIONS: SATB2 stain is useful in differentiatingIslet1/PAX6 positive pancreatic and rectal NETs, as rectal NETs are typically moderately to strongly positive for SATB2 and pancreatic NETs are usually negative or weakly positive for SATB2. Moderate to strong staining for SATB2 is suggestive of an appendiceal or a rectal primary. SATB2 may complement the panel of CDX2, TTF1 and Islet1 in determining the site of origin of an NET in a metastatic setting.

doi: https://doi.org/10.1136/jclinpath-2020-206645


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