Factors influencing patterns of recurrence following pancreaticoduodenectomy for patients with distal bile duct cancer and ampulla of Vater cancer.

PurposeTo compare survival outcomes between bile duct segmental resection (BDR) and pancreatoduodenectomy (PD) for the treatment of middle and distal bile duct cancer.MethodsFrom 1997 to 2013, a total of 96 patients who underwent curative intent surgery for middle and distal bile duct cancer were identified. The patients were divided into 2 groups based on the type of operation; 20 patients were included in the BDR group and 76 patients were in the PD group. We retrospectively reviewed the clinical outcomes.ResultsThe number of lymph nodes (LNs) was significantly greater in patients within the PD group compared to the BDR group. The total number of LNs was 6.5 ± 8.2 vs. 11.2 ± 8.2 (P = 0.017) and the number of metastatic LNs was 0.4 ± 0.9 vs. 1.0 ± 1.5 (P = 0.021), respectively. After a median follow-up period of 24 months (range, 4–169 months), the recurrence-free survival of the PD group was superior to that of the BDR group (P = 0.035). In the patients with LN metastases, the patients undergoing PD had significantly better survival than the BDR group (P < 0.001).ConclusionSurgeons should be cautious in deciding to perform BDR for middle and distal common bile duct cancer. PD is recommended if LN metastases are suspected.

Background and objectives: There have been many reports of pancreaticoduodenectomy performed for the surgical treatment of periampullary cancer. However, any differences in the perioperative courses of different types of periampullary tumour are unclear. In this study, we evaluated the differences in morbidity among the three main types of periampullary tumour. Methods: Prospectively collected data from patients who underwent pancreaticoduodenectomy for periampullary tumour between 2004 to 2018 were reviewed. The patients were divided into three groups: those with pancreatic head cancer, ampulla of Vater (AOV) cancer, or distal common bile duct (CBD) cancer. Results: Among the 645 patients who underwent pancreaticoduodenectomy, 298 (46.2%) were diagnosed with pancreatic head cancer, 172 (26.7%) with AOV cancer, and 175 (27.1%) with distal CBD cancer. The group with distal CBD cancer had the highest mean age (68.45 ± 9.2 years; p = 0.002) and the highest total bilirubin level (8.72 ± 0.6) mg/dl among the three groups. The group with pancreatic head cancer had the highest rate of firm pancreatic texture (71.7%) and the greatest duct diameter (4.64 ± 0.2 mm) among the three groups. Pancreatic fistula and pulmonary complications were more frequent in the groups with AOV cancer and distal CBD cancer. Post-operative haemorrhage occurred at a higher rate in the group with distal CBD cancer (12%). The hospital stay was longer in the group with distal CBD cancer (27.30 ± 1.3 days). Conclusion: Among the three main types of periampullary tumour, the group with distal CBD cancer had the highest complication rate and the longest hospital stay.

Histone modification is associated with tumorigenesis and cancer progression. Recent studies have revealed the prognostic value of histone modification; however, its prognostic role in distal bile duct cancer remains unclear. We analyzed the expression of H3K9me3, H4K20me3, and H3K36me3 and its correlation with survival outcomes in resected samples from 88 patients with distal bile duct cancer. Low expression rates of H3K9me3, H4K20me3, and H3K36me3 were significantly associated with poor overall survival (p=0.003, 0.008, and 0.047, respectively) and event-free survival (p=0.03 for H3K9m3). Additionally, low-expression of H3K9me3 was an independent poor prognostic indicator (p<0.001; HR=7.85; 95% CI=2.693-22.883). H3K9me3 was an independent poor prognostic factor in distal common bile duct cancer. Our results suggest that histone markers are potential prognostic markers and provide better management for patients at risk for an aggressive course of disease.

To evaluate differences in the R1 rates of ampullary (AC), pancreatic (PC), and distal bile duct (DBD) cancers in pancreatoduodenectomies (PD) using standardised pathology assessment. Data of PD (2010-2011) analysed in accordance with the Royal College of Pathologists (UK) protocol, were retrieved. Clinicopathologic features, including frequency, topography, and mode of margin involvement in AC (n = 87), PC (n = 18), and DBD (n = 5) cancers were evaluated. The R1 rate was 7%, 67%, and 20% in the AC, PC, and DBD cancers (p < 0.001). Within the PC cohort, R1 rate was heterogeneous (chemo-naïve, 77%; post-neoadjuvant, 40%). Commonest involved margins were as follows: posterior in overall PD (35%), AC (43%), overall PC (33%), and post-neoadjuvant PC (100%); superior mesenteric artery margin in chemo-naïve PC (38%) and common bile duct margin in DBD (100%) cancers. In AC, majority (66%) of R1 were signet ring cell type. Indirect margin involvement due to tumour within lymph node, perineural sheath or lymphovascular space was observed in 26% cases, and altered R1 rate in AC, PC, and DBD cohorts by 1%, 12%, and 0%, respectively. Although not statistically significant, patients with R1 had lower disease-free survival than those with R0 (mean, 25.4months versus 44.4months). Tumour origin impacts R1 data in PD necessitating its accurate classification by pathologists. Indirect involvement, histology, and neoadjuvant therapy influence the R1 rate, albeit in a minority of cases. Generating cogent R1 data based on standardised pathology reporting is the foremost need of the hour.

Objective: Immunohistochemical fatty acid synthase expression is a prognostic marker in several cancers and is related to cancer aggressiveness. Here, we analyzed fatty acid synthase expression as an indicator of adjuvant chemotherapy for distal bile duct and ampullary cancer cases. Methods: Forty-three cases of distal bile duct cancer and thirty-seven ampullary cancer cases resected between 2000 and 2017 were examined. We investigated immunohistochemical fatty acid synthase expression in resected specimens and the involvement of lymph nodes. We compared these findings with patient prognosis using medical history of postoperative adjuvant chemotherapy. Patient survival was expressed by the Kaplan-Meyer method and analyzed by a log-rank test. Results: There were twenty-two fatty acid synthase-positive cases for distal bile duct cancer and seventeen for ampullary cancer. For distal bile duct cancer cases, the relapse-free survival and overall survival of fatty acid synthase-positive cases were shorter than those for fatty acid synthase-negative cases (p=0.0094 and p=0.0327, respectively). For ampullary cancer cases, the relapse-free survival and overall survival of fatty acid synthase-positive cases were also shorter than those for fatty acid synthase-negative cases (p=0.0225 and p=0.0103, respectively). Adjuvant chemotherapy occurred in twelve of the twenty-two fatty acid-positive distal bile duct cancer cases and in eight of the seventeen fatty acid-positive ampullary cancer cases. Relapse-free survival and overall survival of cases with adjuvant chemotherapy did not differ from those without adjuvant chemotherapy in both distal bile duct cancer and ampullary cancer. Conclusion: Although fatty acid synthase expression was a prognostic factor in bile duct cancer and ampullary cancer, it was not an indicating marker for adjuvant chemotherapy.

Postoperative Morbidity and Long-term Survival After Pancreaticoduodenectomy With Superior Mesenterico−Portal Vein Resection

Clinical/prognostic significance of Syndecan-1 expression in invasive breast carcinoma with distant metastasis and its correlation with tumor immunity

High-grade precursor lesions can be used as surrogate markers to identify the epicenter of periampullary carcinomas

Comparison of relapse and long-term survival between pylorus-preserving and whipple pancreaticoduodenectomy in periampullary cancer

Assessment of the origin of adenocarcinoma in pancreatoduodenectomy specimens (pancreatic, ampullary or biliary) and resection margin status is not performed in a consistent manner in different centres. The aim of this review was to identify the impact of such variations on patient outcome. A systematic literature search for articles on pancreatic, ampullary, distal bile duct and periampullary cancer was performed, with special attention to data on resection margin status, pathological examination and outcome. The frequent reclassification of tumour origin following slide review, and the wide variation in published incidence of pancreatic (33-89 per cent), ampullary (5-42 per cent) and distal bile duct (5-38 per cent) cancers indicate that the histopathological distinction between the three cancer groups is less accurate than generally believed. Recent studies have shown that the wide range of rates of microscopic margin involvement (R1) in pancreatoduodenectomy specimens (18-85, 0-27 and 0-72 per cent respectively for pancreatic, ampullary and distal bile duct cancers) is mainly caused by differences in pathological assessment rather than surgical practice and patient selection. As a consequence of the existing inconsistency in reporting of these data items, the clinical significance of microscopic margin involvement in each of the three cancer groups remains unclear. Inaccurate and inconsistent distinction between pancreatic, ampullary and distal bile duct cancer, combined with inaccuracies in resection margin assessment, results in obfuscation of key clinicopathological data. Specimen dissection technique plays a key role in the quality of the assessment of both tumour origin and margin status. Unless the pathological examination is meticulous and standardized, comparison of results between centres and observations in multicentre trials will remain of limited value.

Aims: The only curative treatment for patients with invasive pancreatic duct cancer (IPDC) and distal bile duct cancer (DBDC) of the pancreas head is pancreaticoduodenectomy (PD). However, the clinicopathological difference between IPDC and DBDC after PD has not been thoroughly discussed. In this study, we retrospectively analyzed the clinical and pathological difference between IPDC and DBDC in patients who underwent PD. Methods: Sixty-six patients who underwent curative PD were enrolled (IPDC, n = 35; DBDC, n = 31). Preoperative, intraoperative, and postoperative parameters and pathological factors (stages, lymph node metastasis, lymphatic invasion, vascular invasion, and perineural invasion) were compared. Results: Jaundice was frequently detected and preoperative biliary drainage was frequently performed in patients with DBDC (60.5% and 90.3%, respectively). Additionally, the preoperative serum total bilirubin concentration and C-reactive protein/albumin ratio were higher in patients with DBDC than IPDC. As a result, the occurrence of postoperative pancreatic fistula occurred more frequently in patients with DBDC. In contrast, lymph node metastasis, lymphatic invasion, and vascular invasion were detected more frequently in patients with IPDC. The overall 5-year survival rate of the 35 patients with IPDC (13.4%) was much worse than that of the 31 patients with DBDC (52.3%, p less than 0.001). Conclusion: The oncological characteristics of IPDC are much different from those of DBDC. More effective treatment should be started in patients with IPDC as soon as possible.

Objective: To compare and analyze the clinical efficacy of pancreaticoduodenectomy for distal bile duct cancer and pancreatic head cancer. Methods: Clinical data of 1 005 patients who underwent pancreaticoduodenectomy and postoperative pathological examination confirmed the diagnosis of distal bile duct cancer and pancreatic head cancer at the Pancreas Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to December 2020 were analyzed retrospectively. There were 112 cases in the distal bile duct cancer group, 71 males and 41 females,with age (M(IQR)) of 65(15) years(range: 40 to 87 years); 893 cases in the pancreatic head cancer group, 534 males and 359 females,with age of 64(13)years(range: 16 to 91 years). The differences between clinicopathological characteristics and postoperative overall survival of the two groups were analyzed by χ2 test, Fisher's exact probability method, rank sum test or log-rank test, respectively. The difference in postoperative overall survival between the two groups was compared using Kaplan-Meier method after propensity score matching (1∶1). Results: Compared with the pancreatic head cancer group,the distal bile duct cancer group had shorter operative time (240.0(134.0) minutes vs. 261.0(97.0) minutes, Z=2.712, P=0.007),less proportion of combined venous resection (4.5% (5/112) vs. 19.4% (173/893), χ²=15.177,P<0.01),smaller tumor diameter (2.0(1.0) cm vs. 3.0(1.5) cm,Z=10.567,P<0.01),higher well/moderate differentiation ratio (51.4% (56/112) vs. 38.0% (337/893), χ²=7.328, P=0.007),fewer positive lymph nodes (0(1) vs. 1(3), Z=5.824, P<0.01),and higher R0 resection rate (77.7% (87/112) vs. 38.3%(342/893), χ²=64.399, P<0.01),but with a higher incidence of overall postoperative complications (50.0% (56/112) vs. 36.3% (324/892), χ²=7.913,P=0.005),postoperative pancreatic fistula (28.6% (32/112) vs. 13.9% (124/893), χ²=16.318,P<0.01),and postoperative abdominal infection (21.4% (24/112) vs. 8.6% (77/892), χ²=18.001,P<0.01). After propensity score matching, there was no statistical difference in postoperative overall survival time between patients in the distal bile duct cancer group and the pancreatic head cancer group (50.6 months vs. 35.1 months,Z=1.640,P=0.201),and multifactorial analysis showed that tumor site was not an independent risk factor affecting the prognosis of patients in both groups after matching (HR=0.73,95%CI:0.43 to 1.23,P=0.238). Conclusions: Patients with distal bile duct cancer are more likely to benefit from early diagnosis and surgical treatment than patients with pancreatic head cancer,but with a relative higher postoperative complication rates. The different tumor origin site is not an independent risk factor for prognosis of patients with distal bile duct cancer and pancreatic head cancer after propensity score matching.

To assess efficacy or long-term result of metastasectomy for recurrent or metastatic biliary tract carcinoma (BTC), we conducted a retrospective review of the outcomes of metastasectomy for recurrent or metastatic BTCs, comprising intrahepatic cholangiocellular carcinoma (IHCCC), proximal and distal common bile duct cancer (pCBDC and dCBDC), gallbladder cancer (GBC), and ampulla of Vater cancer (AoVC). The clinicopathological features and outcomes of BTC patients who underwent surgical resection for the primary and metastatic disease at the Gachon University Gil Medical Centre from 2003 to 2013 were reviewed retrospectively. We found 19 eligible patients. Primary sites were GBC (seven patients, 37%), IHCCC (five patients, 26%), dCBDC (three patients, 16%), pCBDC (two patients, 11%), and AoVC (two patients, 11%). Eight patients (42%) had synchronous metastasis whereas 11 (58%) had metachronous metastasis. The most common metastatic site was liver (nine patients, 47%), lymph node (nine patients, 47%), and peritoneum (three patients, 16%). Nine patients (47%) achieved R0 resection, whereas four (21%) and six (32%) patients had R1 and R2 resection, respectively. With a median follow-up period of 26.7 months, the estimated median overall survival (OS) was 18.2 months (95% confidence interval, 13.6-22.9 months). Lower Eastern Cooperative Oncology Group performance status (P = 0.023), metachronous metastasis (P = 0.04), absence of lymph node metastasis (P = 0.009), lower numbers of metastatic organs (P < 0.001), normal postoperative CA19-9 level (P = 0.034), and time from diagnosis to metastasectomy more than 1 year (P = 0.019) were identified as prognostic factors for a longer OS after metastasectomy. For recurrent or metastatic BTCs, metastasectomy can be a viable option for selected patients.

PurposeThis study addressed the feasibility and effect of surgical treatment of metachronous periampullary carcinoma after resection of the primary extrahepatic bile duct cancer. The performance of this secondary curative surgery is not well-documented.MethodsWe reviewed, retrospectively, the medical records of 10 patients who underwent pancreaticoduodenectomy (PD) for secondary periampullary cancer following extrahepatic bileduct cancer resection from 1995 to 2011.ResultsThe mean age of the 10 patients at the second operation was 61 years (range, 45-70 years). The primary cancers were 7 hilar cholangiocarcinomas, 2 middle common bile duct cancers, and one cystic duct cancer. The secondary cancers were 8 distal common bile duct cancers and 2 carcinomas of the ampulla of Vater. The second operations were 6 Whipple procedures and 4 pylorus-preserving pancreaticoduodenectomies. The mean interval between primary treatment and metachronous periampullary cancer was 20.6 months (range, 3.4-36.6 months). The distal resection margin after primary resection was positive for high grade dysplasia in one patient. Metachronous tumor was confirmed by periampullary pathology in all cases. Four of the 10 patients had delayed gastric emptying (n = 2) or pancreatic fistula (n = 2) after reoperation. There were no perioperative deaths. Median survival after PD was 44.6 months (range, 8.5-120.5 months).ConclusionBased on the postoperative survival rate, PD may provide an acceptable protocol for resection in patients with metachronous periampullary cancer after resection of the extrahepatic bile duct cancer.

BackgroundAlthough Peutz-Jeghers syndrome (PJS) is known to be associated with pancreatic cancer (PC), estimates of this risk differ widely. This hampers counselling of patients and implementation of surveillance strategies. We...