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


New GallBladder Articles

Today there is no new Gallbladder Article.

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


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/