Search

Non-pancreatic periampullary tumors have long been neglected, leading to blurred adjuvant treatment strategies. Recent research, like the ISGACA group's study, is uncovering nuances in chemotherapy efficacy for these diverse cancers. Tailored approaches show promise, with artificial intelligence (AI) aiding in personalized treatment plans., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background/aims: : Palliative chemotherapy (PC) is not standardized for patients with advanced ampulla of Vater adenocarcinoma (AA). This multicenter, retrospective study evaluated first-line PC outcomes in patients with AA., Methods: : Patients diagnosed with AA between January 2010 and December 2020 who underwent PC were enrolled from 10 institutions. Overall survival (OS) and progression-free survival (PFS) according to the chemotherapy regimen were analyzed., Results: : Of 255 patients (mean age, 64.0±10.0 years; male, 57.6%), 14 (5.5%) had locally advanced AA and 241 (94.5%) had metastatic AA. Gemcitabine plus cisplatin (GP) was administered as first-line chemotherapy to 192 patients (75.3%), whereas capecitabine plus oxaliplatin (CAPOX) was administered to 39 patients (15.3%). The median OS of all patients was 19.8 months (95% confidence interval [CI], 17.3 to 22.3), and that of patients who received GP and CAPOX was 20.4 months (95% CI, 17.2 to 23.6) and 16.0 months (95% CI, 11.2 to 20.7), respectively. The median PFS of GP and CAPOX patients were 8.4 months (95% CI, 7.1 to 9.7) and 5.1 months (95% CI, 2.5 to 7.8), respectively. PC for AA demonstrated improved median outcomes in both OS and PFS compared to conventional bile duct cancers that included AA., Conclusions: : While previous studies have shown mixed prognostic outcomes when AA was analyzed together with other biliary tract cancers, our study unveils a distinct clinical prognosis specific to AA on a large scale with systemic anticancer therapy. These findings suggest that AA is a distinct type of tumor, different from other biliary tract cancers, and AA itself could be expected to have a favorable response to PC.

Periampullary carcinoma is a malignant gastrointestinal tumor originating from the head of the pancreas, distal bile duct, duodenum, or the ampulla of Vater. Currently, surgery remains the primary treatment option, yet the postoperative recurrence rate remains high. Chemotherapy is the main approach for controlling postoperative recurrence. Histologically, periampullary carcinoma is categorized into two types: intestinal (IN) and pancreaticobiliary (PB) subtype. Each subtype requires different therapeutic approaches, with the PB type primarily treated with gemcitabine and the IN type with 5-FU. Despite these options, patient outcomes are still unsatisfactory. In recent years, the feasibility of immunotherapy in tumor treatment has been increasingly evidenced, although research on its efficacy in periampullary carcinoma treatment is still limited. In this report, we present a case of a periampullary carcinoma patient who experienced recurrence and metastasis after undergoing radical pancreatoduodenectomy and receiving gemcitabine-based chemotherapy post-surgery. Through next-generation sequencing (NGS), we identified high expression levels of programmed cell death-ligand 1 (PD-L1) with a combined positive score (CPS) of 35, high tumor mutation burden (TMB-H), and high microsatellite instability (MSI-H) in this patient. Therefore, we implemented a combination therapy using Tislelizumab and chemotherapy. According to the latest follow-up, the tumors are effectively controlled. Our utilization of immunotherapy combined with chemotherapy holds significant implication for the treatment of periampullary carcinoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tang, Kong, Xu, Duan, Fu, Fang and Liang.)

Background: Despite differences in tumour behaviour and characteristics between duodenal adenocarcinoma (DAC), the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype of ampullary adenocarcinoma and distal cholangiocarcinoma (dCCA), the effect of adjuvant chemotherapy (ACT) on these cancers, as well as the optimal ACT regimen, has not been comprehensively assessed. This study aims to assess the influence of tailored ACT on DAC, dCCA, AmpIT, and AmpPB., Patients and Methods: Patients after pancreatoduodenectomy for non-pancreatic periampullary adenocarcinoma were identified and collected from 36 tertiary centres between 2010 - 2021. Per non-pancreatic periampullary tumour type, the effect of adjuvant chemotherapy and the main relevant regimens of adjuvant chemotherapy were compared. The primary outcome was overall survival (OS)., Results: The study included a total of 2866 patients with DAC (n = 330), AmpIT (n = 765), AmpPB (n = 819), and dCCA (n = 952). Among them, 1329 received ACT, and 1537 did not. ACT was associated with significant improvement in OS for AmpPB (P = 0.004) and dCCA (P < 0.001). Moreover, for patients with dCCA, capecitabine mono ACT provided the greatest OS benefit compared to gemcitabine (P = 0.004) and gemcitabine - cisplatin (P = 0.001). For patients with AmpPB, no superior ACT regime was found (P > 0.226). ACT was not associated with improved OS for DAC and AmpIT (P = 0.113 and P = 0.445, respectively)., Discussion: Patients with resected AmpPB and dCCA appear to benefit from ACT. While the optimal ACT for AmpPB remains undetermined, it appears that dCCA shows the most favourable response to capecitabine monotherapy. Tailored adjuvant treatments are essential for enhancing prognosis across all four non-pancreatic periampullary adenocarcinomas., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Adenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting., Methods: This investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy., Results: From January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78-5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56-11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49-4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47-5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3-4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%)., Conclusions: This study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use., (© 2024. The Author(s).)

Background: The role of adjuvant chemotherapy (AC) in patients with ampullary adenocarcinoma (AA) remains controversial. This study aimed to determine if AC could improve the prognosis of patients with resected AA., Study Design: This study enrolled patients diagnosed with AA at 9 tertiary teaching hospitals. Patients who did and did not receive AC were matched 1:1 using propensity score. The overall survival (OS) and recurrence-free survival (RFS) were compared between the 2 groups., Results: Of the 1,057 patients with AA, 883 underwent curative-intent pancreaticoduodenectomy, and 255 received AC. Because patients with advanced-stage AA received AC more frequently, the no AC group unexpectedly had a longer OS (not reached vs 78.6 months; p < 0.001) and RFS (not reached vs 18.7 months; p < 0.001) than did the AC group in the unmatched cohort. In the propensity score-matched cohort (n = 296), no difference between the 2 groups in terms of OS (95.9 vs 89.8 months, p = 0.303) and RFS (not reached vs 25.5 months; p = 0.069) was found. By subgroup analysis, patients with advanced stage (pT4 or pN1-2) showed longer OS in the AC group than in the no AC group (not reached vs 15.7 months, p = 0.007: 89.8 vs 24.2 months, p = 0.006, respectively). There was no difference in RFS according to AC in the propensity score-matched cohort., Conclusions: Given its favorable long-term outcomes, AC can be recommended for patients with resected AA, especially those in the advanced stage (pT4 or pN1-2)., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Although surgery is the primary treatment for ampullary cancer (AC), the benefit of adjuvant chemotherapy (CTx) has not yet been confirmed., Methods: AC patients who were administered 5-fluorouracil(FU)/leucovorin(LV)-based CTx after curative intent surgery between 2011 and 2019 were included. Prognosis was compared between the observation (OB) and CTx groups after propensity score matching (PSM) using perioperative variables to control differences in patient characteristics., Results: Before PSM, of 475 patients, those in the CTx group (n = 281) had worse 5-year overall survival (OS) (82.1% vs. 78.5%, p = 0.017) and worse 5-year recurrence-free survival (RFS) (54.9% vs. 75.7%, p < 0.001) than those in the OB group (n = 194). In addition, the CTx group had a higher rate of poor prognostic factors such as a high T stage (p < 0.001), node metastasis (p < 0.001), and poor differentiation (p < 0.001). After PSM, perioperative outcomes were comparable. In addition, there were no significant differences in OS (hazard ratio [HR], 1.085; 95% confidence interval [CI], 0.688-1.710; p = 0.726) or RFS (HR, 0.883; 95% CI, 0.613 1.272; p = 0.505) between the CTx (n = 123) and OB (n = 123) groups even after stratification by TNM stage. Intestinal subtype showed better 5-year OS (83.7% vs 33.2%, p = 0.015) and RFS (46.5% vs 24.9%, p = 0.035) rate compared with pancreatobiliary/mixed subtype., Conclusion: Patients who received adjuvant chemotherapy based on 5-FU/LV showed comparable oncologic outcomes to patients in the OB group even after stratification by tumor stage. The patients with intestinal subtype showed oncologic benefit for adjuvant 5-FU/LV CTx compared with pancreatobiliary or mixed subtypes., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: Biliary tract cancer (BTC) exhibits diverse molecular characteristics. However, reliable biomarkers that predict therapeutic responses are yet to be discovered. We aimed to identify the molecular features of treatment responses to chemotherapy and immunotherapy in BTCs., Approach and Results: We enrolled 121 advanced BTC patients (68 cholangiocarcinomas [33 intrahepatic, 35 extrahepatic], 41 gallbladder cancers, and 12 Ampulla of Vater cancers) whose specimens were analyzed by clinical sequencing platforms. All patients received first-line palliative chemotherapy; 48 patients underwent programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade therapy after failed chemotherapy. Molecular and histopathological characterization was performed using targeted sequencing and immunohistochemical staining to investigate treatment response-associated biomarkers. Genomic analysis revealed a broad spectrum of mutational profiles according to anatomical location. Favorable responses to chemotherapy were observed in the small-duct type compared with the large-duct type intrahepatic cholangiocarcinoma, with frequent mutations in BRCA1-associated protein-1/isocitrate dehydrogenase 1/2 and KRAS proto-oncogene, GTPase/SMAD family member 4 genes, respectively. The molecular features were further analyzed in BTCs, and transforming growth factor beta and DNA damage response pathway-altered tumors exhibited poor and favorable chemotherapy responses, respectively. In PD-1/PD-L1 blockade-treated patients, KRAS alteration and chromosomal instability tumors were associated with resistance to immunotherapy. The majority of patients (95.0%) with these resistance factors show no clinical benefit to PD-1/PD-L1 blockade and low tumor mutational burdens. Low tumor-infiltrating lymphocyte (TIL) density in tumors with these resistance factors indicated immune-suppressive tumor microenvironments, whereas high intratumoral TIL density was associated with a favorable immunotherapy response., Conclusions: This study proposes predictive molecular features of chemotherapy and immunotherapy responses in advanced BTCs using clinical sequencing platforms. Our result provides an intuitive framework to guide the treatment of advanced BTCs benefiting from therapeutic agents based on the tumors' molecular features., (© 2021 by the American Association for the Study of Liver Diseases.)

Background: Outcomes in ampullary cancer (AC) may differ by pathologic subtype. No guidelines exist for the administration of adjuvant therapy (AT). We sought to evaluate the effect of subtype and AT on survival., Methods: An institutional review of patients undergoing resection for AC from 2008-17 was performed. Recurrence-free (RFS) and overall survival (OS) were assessed by Kaplan-Meier and Cox proportional hazards modeling., Results: Of 53 patients, two-thirds (62%) were stage III. Histologic subtype was evenly split between intestinal and pancreatobiliary (43% and 40%). Half of patients received AT. RFS and OS were 25 (95% CI 16-32) and 41 (CI 22-60) months, respectively, without significant difference by subtype. Stage II/III disease was associated with worse OS (HR 3.7, P = 0.03), which was improved with receipt of AT (HR 0.44, P < 0.05)., Conclusion: Stage is the primary determinant of survival in AC, which may be improved with AT., Competing Interests: Declaration of competing interest None of the authors have any conflict of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: The usefulness of adjuvant chemotherapy in biliary tract cancer (BTC) is poorly reported. This study aimed to evaluate the effectiveness and safety of adjuvant gemcitabine plus S-1 (GS) chemotherapy after curative surgical resection for BTC., Methods: 225 BTC patients who underwent surgical resection between January 2006 and May 2019 were enrolled in this study. Twenty-seven patients received adjuvant chemotherapy with GS (GS group), whereas 67 patients underwent surgery alone (S group). Twenty-three matching pairs were derived through propensity score (PS) matching analysis. Patients received 12 cycles of adjuvant chemotherapy (70 mg/m2 oral S-1 for 7 consecutive days plus intravenous gemcitabine 1,000 mg/m2 on day 7). The primary end point was recurrence-free survival (RFS). The secondary end points were the 1-, 2-, and 3-year RFS and overall survival (OS) rates, tolerability, and frequency of grade 3/4 toxicity., Results: The completion rate was 81.5%; no treatment-related deaths were observed. Grade 3/4 adverse events were seen in 40.7% of the patients. RFS (3-year RFS rate: 59.3% vs. 39.1%, p = 0.049) and OS (3-year OS rate: 71.7% vs. 53.4%, p = 0.008) were significantly better in the GS group than in the S group among PS-matched pairs., Discussion/conclusion: GS chemotherapy after curative surgery was well tolerated, showed better clinical benefit in the adjuvant setting, and can effectively reduce BTC recurrence., (© 2021 S. Karger AG, Basel.)

Background: Whether patients who undergo resection of ampullary adenocarcinoma have a survival benefit from adjuvant chemotherapy is currently unknown. The aim of this study was to compare survival between patients with and without adjuvant chemotherapy after resection of ampullary adenocarcinoma in a propensity score-matched analysis., Methods: An international multicentre cohort study was conducted, including patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma between 2006 and 2017, in 13 centres in six countries. Propensity scores were used to match patients who received adjuvant chemotherapy with those who did not, in the entire cohort and in two subgroups (pancreatobiliary/mixed and intestinal subtypes). Survival was assessed using the Kaplan-Meier method and Cox regression analyses., Results: Overall, 1163 patients underwent pancreatoduodenectomy for ampullary adenocarcinoma. After excluding 187 patients, median survival in the remaining 976 patients was 67 (95 per cent c.i. 56 to 78) months. A total of 520 patients (53·3 per cent) received adjuvant chemotherapy. In a propensity score-matched cohort (194 patients in each group), survival was better among patients who received adjuvant chemotherapy than in those who did not (median survival not reached versus 60 months respectively; P = 0·051). A survival benefit was seen in patients with the pancreatobiliary/mixed subtype; median survival was not reached in patients receiving adjuvant chemotherapy and 32 months in the group without chemotherapy (P = 0·020). Patients with the intestinal subtype did not show any survival benefit from adjuvant chemotherapy., Conclusion: Patients with resected ampullary adenocarcinoma may benefit from gemcitabine-based adjuvant chemotherapy, but this effect may be reserved for those with the pancreatobiliary and/or mixed subtype., (© 2020 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Aim: To improve the outcomes in patients with resectable biliary cancer., Material and Methods: There were 263 procedures for cholangiocellular carcinoma (CCC) for the period 1998—2017. Adjuvant chemotherapy was performed in 102 (38.8%) patients. Extensiveliver resections (78.9%) prevailed for intrahepatic cholangiocellular carcinoma (n=128), 6 (4.7%) patients required vascular resection. Seventy-seven pancreatoduodenectomies were performed for common bile duct cancer, portal vein resection was done in 8 (10.4%) patients. In case of Klatskin tumor (n=58) liver resection combined with bile duct resection (n=52) prevailed. Portal vein resection was done in 16 (27.6%) patients., Results: Postoperative morbidity in patients with intrahepatic CCC was revealed in 68 (53.1%) cases, mortality — in 5 (3.9%) cases. Among patients with Klatskin tumor morbidity was revealed in 51 (87.9%) cases, mortality — in 6 (10.3%) cases. In patients with common bile duct cancer morbidity was revealed in 53 (68.8%) cases, mortality — in 4 (5.2%) cases. In whole cohort median overall survival was 30 months. R0-resection was associated with better long-term results (median 37 months) compared with R1—R2 resection (20 months; p=0.01). Lymph node involvement is associated with significantly worse prognosis (p=0.016), however 5-year survival is observed (25.6%). Adjuvant chemotherapy in R0-resection significantly improved long-term results: median was 46 months (vs. 30 in group without chemotherapy; p=0.02). In intrahepatic CCC patients multiple lesions or mechanical jaundice did not aggravate long-term results., Conclusion: R0-resection including lymphadenectomy, resection of adjacent organs and vessels is advisable for CCC. Isolated bile duct resection should be used as an exception. Adjuvant therapy improved long-term results. Multiple lymph node lesion or bile duct infiltration are not contraindications to surgery in intrahepatic CCC patients.

Purpose: Attempts have been made to revise the nodal stage due to simplicity of current N staging system in ampullary adenocarcinoma. However, because of the disease rarity, there have only been a few studies assessing the prognostic impact of lymph node (LN) parameters., Methods: We retrospectively analyzed 120 patients who underwent radical resection followed by adjuvant chemoradiotherapy for ampullary adenocarcinoma. The effect of LN parameters (number of total harvest LNs, number of metastatic LN (MLN), lymph node ratio (LNR), and log odds of positive LNs (LODDS)) on overall survival (OS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival were evaluated. Cutoff points of MLN, LNR and LODDs were determined using maximal χ 2 method., Results: Fifty-seven patients (48%) were staged as pN1 and their survival was not significantly decreased compared with pN0 patients. There was also no significant difference between patients with MLN 0 vs. 1. In univariate analyses, MLN (0-1 vs. ≥2), LNR (≤17% vs. >17%) and perineural invasion were common prognosticators for OS and LRFS. Distant metastasis-free survival was not influenced by LN status. In addition, multivariate analysis revealed that among the LN parameters, LNR was able to independently predict both OS and LRFS., Conclusions: LNR performs better than other LN related parameters for predicting survival. After radical resection followed by adjuvant treatment, survival of patients with one positive LN does not seem to differ from patients without LN metastasis., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Periampullary cancers are uncommon malignancies, often amenable to surgery. Several studies have suggested a role for adjuvant chemotherapy and chemoradiotherapy in improving survival of patients with periampullary cancers, with variable results. The aim of this meta-analysis was to determine the survival benefit of adjuvant therapy for periampullary cancers., Methods: A systematic review was undertaken of literature published between 1 January 2000 and 31 December 2015 to elicit and analyse the pooled overall survival associated with the use of either adjuvant chemotherapy or chemoradiotherapy versus observation in the treatment of surgically resected periampullary cancer. Included articles were also screened for information regarding stage, prognostic factors and toxicity-related events., Results: A total of 704 titles were screened, of which 93 full-text articles were retrieved. Fourteen full-text articles were included in the study, six of which were RCTs. A total of 1671 patients (904 in the control group and 767 who received adjuvant therapy) were included. The median 5-year overall survival rate was 37·5 per cent in the control group, compared with 40·0 per cent in the adjuvant group (hazard ratio 1·08, 95 per cent c.i. 0·91 to 1·28; P = 0·067). In 32·2 per cent of patients who had adjuvant therapy, one or more WHO grade 3 or 4 toxicity-related events were noted. Advanced T category was associated worse survival (regression coefficient -0·14, P = 0·040), whereas nodal status and grade of differentiation were not., Conclusion: This systematic review found no associated survival benefit for adjuvant chemotherapy or chemoradiotherapy in the treatment of periampullary cancer., (© 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: Capecitabine with oxaliplatin (CAPOX) has previously demonstrated clinical activity in patients with small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC). Herein, the authors conducted a phase 2 trial to evaluate the benefit of adding bevacizumab to CAPOX., Methods: In this phase 2, single-arm, single-center, open-label study, patients aged ≥18 years with untreated, advanced SBA or AAC were recruited. Patients received capecitabine at a dose of 750 mg/m 2 orally twice daily on days 1 to 14, oxaliplatin at a dose of 130 mg/m 2 intravenously on day 1, and bevacizumab at a dose of 7.5 mg/kg intravenously on day 1 of a 21-day cycle. The primary endpoint was progression-free survival (PFS) at 6 months. Secondary objectives included response rate, overall PFS, overall survival, and toxicity., Results: Between August 2011 and November 2014, a total of 30 patients were enrolled into the study (male/female ratio of 13/17; median age of 63 years [range, 33-78 years]; and 7 patients with an Eastern Cooperative Oncology Group performance status [ECOG PS] of 0, 20 patients with an ECOG PS of 1, and 3 patients with an ECOG PS of 2). Of the 30 patients, 23 (77%) had SBA (18 of duodenal origin and 5 of jejunal/ileal origin) and 7 patients (23%) had AAC (5 of pancreaticobiliary subtype, 1 of mixed subtype, and 1 of intestinal subtype). The most common grade 3 toxicities observed were fatigue and hypertension (7 patients each [23%]), neutropenia (6 patients [20%]), and diarrhea (3 patients [10%]) (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). The probability of PFS at 6 months was 68% (95% confidence interval [95% CI], 52% to 88%). The response rate was 48.3%, with 1 complete response and 13 partial responses; 10 patients achieved stable disease. At a median follow-up of 25.9 months, the median PFS was 8.7 months (95% CI, 4.9-10.5 months) and the median overall survival was 12.9 months (95% CI, 9.2-19.7 months)., Conclusions: The results of the current study indicate that CAPOX with bevacizumab is an active and well-tolerated regimen for patients with SBA and AAC. These findings support the need for further investigation into the clinical benefit of targeting angiogenesis in patients with SBA and AAC. Cancer 2017;123:1011-17. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

A 75-year-oldman presenting with obstructive jaundice was referredto our hospital. Basedon a diagnosis of carcinoma of the ampulla of Vater, we performed pancreatoduodenectomy. Postoperative histopathological examination revealed a welldifferentiated papillotubular adenocarcinoma, T3, N0, M0, Stage III . Six months after surgery, an isolatedliver metastasis in S6 was identifiedon CT scan andMRI; therefore, we administeredgemcitabine plus cisplatin chemotherapy. After 6 courses of this regimen, a clinical complete response(CR)was obtained. After 12 courses, the clinical CR continued; however, grade 3 lower-extremity peripheral neuropathy appeared. Therefore, gemcitabine monotherapy was administered as second line chemotherapy. However, multiple liver metastases appearedandthe patient passedaway owing to exacerbation of the disease 2 years after initiating chemotherapy. Although recurrent ampullary carcinoma is difficult to treat, our patient had a long-term survival. Here we report the details of our case and review the relevant literature.

Purpose: Combination chemotherapy with gemcitabine and cisplatin is a standard treatment for patients with advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of gemcitabine- and cisplatin-based concurrent chemoradiotherapy in patients with unresectable biliary tract cancer., Methods: Patients with pathologically proven, unresectable, non-metastatic biliary tract cancer were enrolled. Gemcitabine was administered intravenously at a dose of 1000 mg/m(2) on days 1, 8, and 15. Cisplatin was administered intravenously at a dose of 70 mg/m(2) on day 1. All the patients underwent concurrent radiotherapy with 45 Gy in 1.8-Gy daily fractions. After treatment completion, tumor response was evaluated by using computed tomography., Results: Eighteen patients were enrolled between June 2007 and October 2011. Their median age was 61 years (range, 38-72 years). Eight patients (44.5 %) were diagnosed with gallbladder cancer, six (33.3 %) with Klatskin's tumor, and four (22.2 %) with distal common bile duct cancer. After treatment completion, partial response was achieved in five patients (27.8 %) and stable disease in 13 patients (72.2 %). The overall response rate was 27.8 %, and the disease stabilization rate was 100 %. No grade 4 adverse events or treatment-related deaths occurred. The most common grade 3 adverse events were thrombocytopenia (33.3 %) and anemia (11.1 %). The median progression-free and overall survival times were 6.8 months (range, 4.5-19.8 months) and 9.6 months (5.4-30.4 months), respectively., Conclusions: This study shows that gemcitabine- and cisplatin-based concurrent chemoradiotherapy is feasible and tolerable in patients with unresectable and non-metastatic biliary tract cancer.

Background: An adequate management strategy for ampullary carcinoma (AC), a rare neoplasm, has yet to be determined. The aim of this study was to identify specific molecular markers allowing for the adequate management of AC., Methods: The clinicopathological data of 41 patients who underwent curative resection of AC were reviewed retrospectively. The expression of thymidylate synthase (TS) and Bcl-2 19-kDa interacting protein 3 (BNIP3), two sensitive markers for S-1 and gemcitabine, respectively, was evaluated immunohistochemically. The relationship between the expression levels of these markers and the clinicopathological data were then investigated., Results: The 5-year overall survival rate in the study population was 62%. In univariate and multivariate analyses, lymph node metastasis, neural invasion, lymphatic invasion, and the high-level BNIP3 expression were significant predictive factors for a poor postoperative prognosis. Neither TS nor BNIP3 expression were able to predict survival or the disease recurrence rate in patients who received postoperative adjuvant chemotherapy for AC., Conclusions: BNIP3 expression may serve as a prognostic marker for patients with AC, but neither TS nor BNIP3 contributes to the selection criteria for adjuvant chemotherapy for AC, at least with respect to current drug regimens., (© 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Here, we present a case of an 84-year-old woman who developed obstructive jaundice and was diagnosed with nonoperable adenocarcinoma originating from the ampulla of Vater, a lethal disease with a median overall survival of less than a year. Her tumor was examined by next-generation sequencing, which showed BRAF and NRAS mutations. To target these mutations, a MEK inhibitor was chosen for treatment. The patient has been treated with a MEK inhibitor for the last 12 months since diagnosis, with clinical and laboratory improvement and manageable side effects. PET-computed tomography imaging has shown stable disease or improvement in the primary and metastatic lesions. This is the first case report of an ampulla of a Vater cancer patient with NRAS and BRAF mutations, identified in next-generation sequencing, and treated successfully with a MEK inhibitor.

Background: Ampulla of Vater cancer (AoV Ca) is a rare tumor, and its adjuvant treatment has not been established. The purpose of this study was to find out prognostic factors including host immunity and role of adjuvant treatment in AoV Ca., Methods and Findings: We reviewed 227 AoV Ca patients with curative resection. Clinical characteristics, adjuvant treatment, disease-free survival (DFS) and overall survival (OS) were analyzed. Among all patients, 63.9, 36.1 and 33.9% had T1/T2, T3/T4 stage and lymph node-positive disease (LN+), respectively. OS of all patients was 90.9 months (95% CI: 52.9-129.0). OS was different according to neutrophil-to-lymphocyte ratio (HR 1.651, 95% CI: 1.11-2.47), platelet-to-lymphocyte ratio (HR 1.488, 95% CI: 1.00-2.21) and systemic inflammatory index (HR 1.669, 95% CI: 1.13-2.47). In multivariate analysis, adverse prognostic factors for OS included vascular invasion (HR 2.571, 95% CI: 1.20-5.53) and elevated CA 19-9 (HR 1.794, 95% CI: 1.07-3.05). A total of 104 patients (46.3%) received adjuvant treatment (25 out of 111of T1/T2 & LN (-), 79 out of 116 of T3/T4 or LN (+)). In T3/T4 or LN (+) stage, adjuvant CCRT with maintenance chemotherapy provided the longest OS (5-year OS rate: 47.0 vs. 41.4%)., Conclusions: Vascular invasion and elevated CA 19-9 were adverse prognostic factors in resected AoV Ca. In T3/T4 or LN (+) stage, adjuvant CCRT with maintenance chemotherapy provided the best survival outcome. Adjuvant treatment should be further defined in AoV Ca, especially with poor prognostic factors.

Objectives: Periampullary cancers (PACs) include the following 4 traditional anatomic subtypes: pancreatic, ampullary, biliary, or duodenal cancers. This review was performed to highlight recent advances in the genomic and molecular understanding of each PAC subtype and the advances in chemotherapeutic and molecular trials in these cancer subtypes., Results: Recent advances have highlighted differences in the genomic and molecular features within each PAC subtype. Ampullary cancers can now be further defined accurately into their intestinal and pancreatobiliary subtypes using histomolecular profiling. K-ras mutation, which occurs in most pancreatic cancers, is found to occur less frequently in ampullary (42%-52%), biliary (22%-23%), and duodenal cancers (32%-35%), suggesting crucial differences in targetable mutations in these cancer subtypes.Ampullary cancers of intestinal subtype and duodenal cancers seem to share similarities with colorectal cancer, given that they respond to similar chemotherapeutic regimens. This has potential implications for clinical trials and treatment selection, where PACs are often considered together., Conclusions: Future trials should be designed in view of our increased understanding of the different anatomic and histomolecularly profiled subtypes of PAC cancers, which respects their individual molecular characteristics, phenotype, and response to treatment.

The scientific literature on adenocarcinoma of the ampulla (papilla) of Vater suggests that it either represents a distinct entity or is more closely related to small bowel adenocarcinoma than to the biliary malignancies. The ambiguity surrounding this rare cancer has kindled research exploring its immunohistochemistry aspects and gene expression profiling. While the basis of management for resectable disease remains surgical intervention, the role of adjuvant chemotherapy is not clear. A recent large phase 3 clinical trial conducted in patients with resected ampulla of Vater adenocarcinoma favored adjuvant chemotherapy over observation alone. The standards of therapy for the advanced small bowel adenocarcinoma and biliary cancer are fluoropyrimidine derivatives and gemcitabine-based combinations, respectively. In addition, new biologic and targeted agents may enhance clinical results seen in this cancer type. Therefore, diligently designed clinical trials are necessary to establish its optimal treatment strategies. We describe herein a patient with ampulla of Vater adenocarcinoma who had an exceptional response to fluoropyrimidine-based chemotherapy. We further include a discussion reviewing the clinicopathologic aspects of this neoplasm as well as focus on currently available and future therapeutic options., (© The Author(s) 2014.)

Background: The need for adjuvant chemotherapy after resection of ampullary cancer (PapCa) remains undefined. Recent data suggest that a different epithelial origin of PapCa might be associated with different tumor biology. The aim of the present study was to assess the clinical value of morphologic and immunohistochemic subclassification of PapCa into intestinal-type (IT) and pancreaticobiliary-type (PT) to predict chemotherapy response and overall survival (OS)., Methods: Via a prospective database, 112 PapCa were identified, of which 95 could be included in the present study. Those were compared with 206 matching patients with periampullary pancreatic cancer (ie, pancreatic ductal adenocarcinoma, PDAC). IT and PT PapCa were classified morphologically, and tissue microarray was prepared with immunohistochemistry for CK7, CK20, MUC2, CDX2, ß-Catenin, and Villin. Multivariate survival analysis was performed., Results: OS of PT patients was less compared with IT patients (25 vs 98 months; P < .001), whereas it was comparable with patients with PDAC (25 vs 14 months; P = .123). PT patients receiving adjuvant gemcitabine chemotherapy featured improved OS (32 vs 13 months; P = .013), whereas gemcitabine tended to be associated with decreased OS in IT patients (35 vs 112 months; P = .193). Besides histopathologic classification, expression of CK7 and MUC2 were important prognostic variables. PT patients with CK7-positivity or MUC2-negativity were segregated into an even poorer prognostic group., Conclusion: PapCa is not a separate tumor entity. We demonstrate important differences between IT-PapCa and PT-PapCa not only in long-term survival but also in response to adjuvant gemcitabine. Tumor biology and clinical course of PT tumors resemble those of PDAC. PT tumors should therefore be treated like PDAC., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Treatment of periampullary cancer involves Whipple surgery, followed by adjuvant radiotherapy and chemotherapy. Postoperative radiotherapy is particularly useful in managing high-risk patients (tumors involving the pancreas, poorly differentiated histology, involved lymph nodes and positive margins). Here, we review our results of treatment of 84 patients treated by surgery and adjuvant radiotherapy and chemotherapy., Material and Methods: A retrospective analysis of 84 patients of periampullary cancers treated in our department between January 2007 and December 2012 was carried out. All patients underwent Whipples surgery followed by postoperative radiotherapy 45-50 Gy/25-28 number in those presenting with high-risk features. Radiotherapy was delivered using three-dimensional conformal technique with 6 MV photons using three field treatment plans. Chemotherapy was given for 6 cycles using gemcitabine and oxaliplatin regimen repeated 2 weekly., Results: Eighty four postoperative patients with high-risk features were available for the final analysis. There were 69 males and 15 female patients. There were 34.5% stage I, 57.1% stage II and 8.3% stage III patients. At end of adjuvant treatment with radiotherapy and chemotherapy 70% patients had a complete response, 7.5% had residual disease, 15% showed progressive disease, 5% were dead and 2.5% defaulted the treatment. The mean number of chemotherapy cycles received was 2.6. At 1 year follow-up the probability of disease free survival was 80% for node-negative patients versus 73% for node-positive disease (P = 0.27). Patients with stage up to IIA had a 1 year disease free survival of 83% versus 40% for patients with stage beyond IIA (P = 0.024)., Conclusions: Our results showed a trend favoring lymph node negative status with disease free survival. With computed tomography based planning, adequate delineation of draining nodes is possible, and radiation toxicity has significantly decreased. Adequate coverage of nodal basins during radiotherapy planning is important, and stage of the disease seems to be an important prognostic factor.

Background: Gemcitabine plus a platinum-based agent (eg, cisplatin or oxaliplatin) is the standard of care for advanced biliary cancers. We investigated the addition of cetuximab to chemotherapy in patients with advanced biliary cancers., Methods: In this non-comparative, open-label, randomised phase 2 trial, we recruited patients with locally advanced (non-resectable) or metastatic cholangiocarcinoma, gallbladder carcinoma, or ampullary carcinoma and a WHO performance status of 0 or 1 from 18 hospitals across France and Germany. Eligible patients were randomly assigned (1:1) centrally with a minimisation procedure to first-line treatment with gemcitabine (1000 mg/m(2)) and oxaliplatin (100 mg/m(2)) with or without cetuximab (500 mg/m(2)), repeated every 2 weeks until disease progression or unacceptable toxicity. Randomisation was stratified by centre, primary site of disease, disease stage, and previous treatment with curative intent or adjuvant therapy. Investigators who assessed treatment response were not masked to group assignment. The primary endpoint was the proportion of patients who were progression-free at 4 months, analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00552149., Findings: Between Oct 10, 2007, and Dec 18, 2009, 76 patients were assigned to chemotherapy plus cetuximab and 74 to chemotherapy alone. 48 (63%; 95% CI 52-74) patients assigned to chemotherapy plus cetuximab and 40 (54%; 43-65) assigned to chemotherapy alone were progression-free at 4 months. Median progression-free survival was 6·1 months (95% CI 5·1-7·6) in the chemotherapy plus cetuximab group and 5·5 months (3·7-6·6) in the chemotherapy alone group. Median overall survival was 11·0 months (9·1-13·7) in the chemotherapy plus cetuximab group and 12·4 months (8·6-16·0) in the chemotherapy alone group. The most common grade 3-4 adverse events were peripheral neuropathy (in 18 [24%] of 76 patients who received chemotherapy plus cetuximab vs ten [15%] of 68 who received chemotherapy alone), neutropenia (17 [22%] vs 11 [16%]), and increased aminotransferase concentrations (17 [22%] vs ten [15%]). 70 serious adverse events were reported in 39 (51%) of 76 patients who received chemotherapy plus cetuximab (34 events in 19 [25%] patients were treatment-related), whereas 41 serious adverse events were reported in 25 (35%) of 71 patients who received chemotherapy alone (20 events in 12 [17%] patients were treatment-related). One patient died of atypical pneumonia related to treatment in the chemotherapy alone group., Interpretation: The addition of cetuximab to gemcitabine and oxaliplatin did not seem to enhance the activity of chemotherapy in patients with advanced biliary cancer, although it was well tolerated. Gemcitabine and platinum-based combination should remain the standard treatment option., Funding: Institut National du Cancer, Merck Serono., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: Ampullary carcinoma is a rare tumor. There are neither sufficient available data related to management after resection of the neoplasm of the ampulla of Vater, nor any international recommendations. The aim of this study was to identify factors associated with recurrence and survival after curative resection., Methods: A retrospective follow-up study was conducted including patients with ampullary carcinoma who underwent resection with curative intent in 12 French surgical centers between January 1990 and November 2011., Results: In this study, 319 patients underwent surgical resection for an ampullary neoplasm. Disease recurred in 120 patients (37.6%), and the 5- and 10-year disease-free survival rates were 48.9% and 40.4%, respectively. In multivariable Cox regression, preoperative bilirubin, T stage, pancreaticobiliary histology subtype, and lymph node involvement were each significantly associated with the risk of recurrence., Conclusions: Ampullary carcinomas are a heterogeneous group that can be classified as intestinal and pancreaticobiliary subtypes. Our findings indicate that pancreaticobiliary differentiation, advanced stage, and lymph node involvement are predictors of both poor disease-free and poor overall survival. It is still unclear what adjuvant treatment after curative resection of ampullary carcinoma is optimal. It would be informative to evaluate adjuvant therapy according to histological subtype.

Objective: Ampullary adenocarcinoma is a rare disease entity and little information regarding these tumors is available. The aim of the present study was to clarify the treatment outcome of systemic chemotherapy in patients with advanced ampullary adenocarcinoma., Methods: This study consisted of a retrospective review of data obtained from patients diagnosed as having advanced ampullary adenocarcinoma who received non-surgical treatment at a single institution between 1997 and 2010., Results: We identified 26 patients (15 men, 11 women; median age, 62.0 years) who received treatment for advanced ampullary adenocarcinoma. Twelve patients had Stage IV disease and 14 had recurrences. The chemotherapy regimens consisted of 5-fluorouracil-based regimens (5-fluorouracil + cisplatin, n = 3; tegafur-uracil + doxorubicin, n = 5 and tegafur, gimeracil and oteracil potassium, n = 3) and gemcitabine-based regimens (gemcitabine, n = 10 and gemcitabine + cisplatin, n = 5). The overall response rate was 7.7%. The median progression-free survival period was 3.2 months (2.5 months in the 5-fluorouracil group vs. 3.5 months in the gemcitabine group), and the median overall survival time was 9.1 months (8.0 months in the 5-fluorouracil group vs. 12.3 months in the gemcitabine group). The median overall survival was significantly longer in stage IV disease than in recurrent disease. The histological phenotype was determined in 10 of the 26 patients. Eight patients had intestinal-type adenocarcinomas and remaining two patients had pancreatobiliary-type adenocarcinomas., Conclusions: The treatment outcome of patients with advanced ampullary adenocarcinoma was poor. Further development of novel treatments is necessary to improve the prognosis.

Background/aims: This retrospective study aimed to evaluate adjuvant chemotherapy using gemcitabine for resected distal bile duct and ampullary cancers., Methodology: Thirty-seven patients who had curative surgery for distal bile duct and ampullary cancers were classified into two groups: A, 19, surgery alone, and B, 18, surgery plus gemcitabine adjuvant chemotherapy between 2004 and 2010. Outcomes, including backgrounds, overall survival (OS), disease free survival (DFS), and adverse events are reported., Results: There were no differences in characteristics between patients of groups A and B for age, gender, location of tumor, UICC stage, UICC pT factor, UICC pN factor, curability, and operative procedures. For all stages, except stage II, there was no difference between groups A and B for OS and DFS. For stage II however, groups A and B showed significant differences in median survival times for OS and DFS. Grade 3 or 4 adverse events included 5.6% with leucopenia., Conclusions: Adjuvant chemotherapy using gemcitabine showed the potential of contributing to prolonged OS and DFS in stage II resected distal bile duct and ampullary cancers. However, a large cohort will be needed to confirm the overall efficacy in all stages of resected BTC's.

A 36-year-old female was hospitalized with symptoms suggesting intestinal occlusion. She was diagnosed with adenocarcinoma of the ampulla of Vater (pT4N0 stage) and underwent cephalic duodenopancreatectomy 8 months ago. Five cycles of postoperative chemotherapy were administrated using capecitabine and oxaliplatin (CAPOX or XELOX), the last one being completed 1 month ago. During the present hospitalization, because of normal computed tomography and ultrasound abdominal examination, rehydration and antibiotherapy were administrated. However, 4 days after hospital admission, the patient died. At autopsy and histological examination, we found a severe myocardial sclerosis with large scarring areas, severe steatohepatitis, chronic pancreatitis with large fibrotic areas, and acute enteritis. Alcohol consumption was denied. The patient died due to associated heart, liver and pancreatic failure. This multiorgan toxicity and death following CAPOX regimen had not yet been reported in the literature., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6472150549833105.

When a distal common bile duct neoplasm is at the stage of carcinoma in situ or high-grade dysplasia, it is difficult for the surgeon to decide whether to perform pancreaticoduodenectomy. Here we describe a patient with a progressive dysplastic lesion in the common bile duct, which developed from moderate-high to high-grade dysplasia in approximately 2 mo. The patient refused major surgery. Therefore, endoscopic-assisted photodynamic therapy was performed. The result at follow-up using a trans-T-tube choledochoscope showed that the lesion was completely necrotic. This report is the first to describe the successful treatment of high-grade dysplasia of the distal bile duct using photodynamic therapy via a choledochoscope.

Background: Whether carcinomas of the ampulla of Vater should be classified with biliary tract tumors and treated in a similar manner remains unknown. We sought to compare the outcomes of similarly staged periampullary adenocarcinomas (AAs) and analyze the chemotherapy responsiveness of AAs., Patients and Methods: A total of 905 patients with resected periampullary adenocarcinomas were identified from a prospective surgical registry from 1988 to 2010. A second cohort of 64 metastatic AA patients from 1992 to 2009 who received either front-line fluoropyrimidine-based or gemcitabine-based chemotherapy was also identified., Results: Overall survival (OS) for AAs was similar to survival with duodenal adenocarcinomas, but was significantly different from both extrahepatic biliary and pancreatic adenocarcinomas (P < 0.001 for each comparison). In multivariate analysis, AAs had a significantly improved OS in comparison with extrahepatic biliary adenocarcinomas (HR = 1.97, P = 0.006). Fluoropyrimidine-based as opposed to gemcitabine-based chemotherapy for metastatic AAs resulted in a significant improvement in time to progression (P = 0.001) but only a trend toward benefit for OS (P = 0.07) in multivariate analysis., Conclusions: Differences in the natural history of ampullary and extrahepatic biliary adenocarcinomas exist. Analyses of metastatic ampullary adenocarcinomas suggest that fluoropyrimidine-based chemotherapy may represent a more appropriate front-line chemotherapy approach.

Adenocarcinoma arising from the ampulla of Vater is a rare disease and has limited data regarding outcome of chemotherapy. The ampulla of Vater is a heterogeneous junctional structure located at the union of the common bile duct, the pancreatic duct, and the small intestine. Thus, ampullary adenocarcinoma is classified as either intestinal type or pancreatobiliary type. We investigated the efficacy of the XELOX (capecitabine plus oxaliplatin) chemotherapy in patients with recurrent or metastatic ampullary adenocarcinoma, and analyzed the histopathologic features and outcomes. From November 2009 to December 2011, 21 patients were treated with XELOX regimen. XELOX was administered in outpatient clinic every 3 weeks according to the following protocol: oral administration of capecitabine 750 mg/m² twice a day on days 1-14 and intravenous injection of oxaliplatin 130 mg/m² on day 1. With follow-up of median 16.6 months, median time to progression (TTP) was 7.6 months (95% confidence interval [CI], 6.7-8.5), and median overall survival was 19.7 months (95% CI, 14.8-23.6). Two patients (9%) achieved complete response and 6 patients (29%) showed partial response. In subgroup analysis with tissue specimens obtained from 17 patients, median TTP was longer among patients with the intestinal-type adenocarcinoma (n = 7), compared to those with the pancreatobiliary type (n = 10) (13.1 vs. 6.4 months, P = 0.038). The most common grade 3-4 adverse event was neutropenia (27%), and most events were mild. XELOX chemotherapy shows favorable efficacy with manageable toxicity for advanced intestinal-type ampullary adenocarcinoma.

Aims and Background: For advanced cancers of the bile duct, gallbladder and ampulla of Vater, there are only a few treatment options. We explored the efficacy of the combination of gemcitabine, 5-fluorouracil and cisplatin for advanced biliary cancers., Methods: From September 2003 to April 2010, 28 patients with recurrent or metastatic biliary tract cancer were enrolled. A treatment regimen consisting of gemcitabine (800 mg/m² at a fixed dose rate on days 1 and 8), 5-fluorouracil (1 g/m²/day continuous infusion for 4 days) and cisplatin (60 mg/m² on day 2) was repeated every 3 weeks., Results: One (3.6%) patient showed complete response, 8 (28.6%) partial response, 14 (50%) stable disease and 5 (17.9%) disease progression. Overall, the objective response rate was 32.1% (95% CI, 17.9-50.6%) and the disease control rate was 82.1% (95% CI, 64.4-92.1%). Median progression-free survival and overall survival were 7.6 months (95% CI, 5.5-9.7) and 11.2 months (95% CI, 6.8-15.5), respectively. G3/4 neutropenia was observed in 44 (24.3%) of 181 cycles and G3/4 thrombocytopenia in 48 (26.5%) of 181 cycles. There was no treatment-related mortality., Conclusions: The combined regimen of gemcitabine, 5-fluorouracil and cisplatin has comparable activity for patients with advanced cancer of the bile duct, gallbladder and ampulla of Vater. Toxicity was tolerable but substantial.

Context: Patients with periampullary adenocarcinomas undergo the same resectional surgery as that of patients with pancreatic ductal adenocarcinoma. Although adjuvant chemotherapy has been shown to have a survival benefit for pancreatic cancer, there have been no randomized trials for periampullary adenocarcinomas., Objective: To determine whether adjuvant chemotherapy (fluorouracil or gemcitabine) provides improved overall survival following resection., Design, Setting, and Patients: The European Study Group for Pancreatic Cancer (ESPAC)-3 periampullary trial, an open-label, phase 3, randomized controlled trial (July 2000-May 2008) in 100 centers in Europe, Australia, Japan, and Canada. Of the 428 patients included in the primary analysis, 297 had ampullary, 96 had bile duct, and 35 had other cancers., Interventions: One hundred forty-four patients were assigned to the observation group, 143 patients to receive 20 mg/m2 of folinic acid via intravenous bolus injection followed by 425 mg/m2 of fluorouracil via intravenous bolus injection administered 1 to 5 days every 28 days, and 141 patients to receive 1000 mg/m2 of intravenous infusion of gemcitabine once a week for 3 of every 4 weeks for 6 months., Main Outcome Measures: The primary outcome measure was overall survival with chemotherapy vs no chemotherapy; secondary measures were chemotherapy type, toxic effects, progression-free survival, and quality of life., Results: Eighty-eight patients (61%) in the observation group, 83 (58%) in the fluorouracil plus folinic acid group, and 73 (52%) in the gemcitabine group died. In the observation group, the median survival was 35.2 months (95%% CI, 27.2-43.0 months) and was 43.1 (95%, CI, 34.0-56.0) in the 2 chemotherapy groups (hazard ratio, 0.86; (95% CI, 0.66-1.11; χ2 = 1.33; P = .25). After adjusting for independent prognostic variables of age, bile duct cancer, poor tumor differentiation, and positive lymph nodes and after conducting multiple regression analysis, the hazard ratio for chemotherapy compared with observation was 0.75 (95% CI, 0.57-0.98; Wald χ2 = 4.53, P = .03)., Conclusions: Among patients with resected periampullary adenocarcinoma, adjuvant chemotherapy, compared with observation, was not associated with a significant survival benefit in the primary analysis; however, multivariable analysis adjusting for prognostic variables demonstrated a statistically significant survival benefit associated with adjuvant chemotherapy., Trial Registration: clinicaltrials.gov Identifier: NCT00058201.

This is the first ever reported case about a cutaneous relapse of small bowel adenocarcinoma. The ampulla of Vater is the area of the small bowel that presents more frequently malignant transformation, nevertheless ampullary adenocarcinomas are rare but aggressive diseases. However, distant metastases are infrequent. Cutaneous metastases constitute the 5.3% of skin tumours, and are usually found in the 12% of malignancies. Their management usually includes local treatment if they are unique and systemic treatment when they are multiple. Chemotherapy schemes used in ampullary adenocarcinoma are those used in cholangiocarcinomas, pancreas and tumours of the gallbladder; nevertheless, given the intestinal origin of these tumours combinations of capecitabine and oxaliplatin are commonly used.

A 70-year-old female patient underwent pylorus-preserving pancreaticoduodenectomy for carcinoma of the ampulla of Vater in March 2007. In April 2009, multiple lung metastases were detected by CT scanning. The patient was treated with S-1 (80mg/day, day 1-28, followed by 2-weeks withdrawal)from April 2009. The shrinkage of lung metastases was diagnosed as a complete response based on the Response Evaluation Criteria in Solid Tumors(RECIST). No severe toxicities were observed. S-1 is an effective and safe anti-cancer agent available for lung metastases of carcinoma of the ampulla of Vater.

Objectives: The authors present 3 cases of various pathologically confirmed malignancies (one gallbladder, one periampullary, and one liver). These patients underwent Psorinum therapy as the primary cancer treatment. Psorinum therapy is a homeopathic approach to treat patients with cancer., Subjects: According to the American Joint Committee on Cancer tumor, nodes, metastasis system, all 3 patients were diagnosed at Stage IV. Their Karnofsky performance status was between 20% and 50% and their Eastern Cooperative Oncology Group score status was between 3 and 4. In these cases, conventional cancer treatments could not be initiated due to the advanced stage of their disease, poor general health performance status, and their financial constraints., Interventions and Outcome: In these patients, Psorinum-6x was administered orally at a dose of 0.02 mL/kg body weight/day on an empty stomach for a complete course duration of 2 years, along with allopathic and homeopathic supportive treatment. According to the Response Evaluation Criteria in Solid Tumors criteria, complete tumor response occurred in 1 case and partial tumor response occurred in the other 2 cases. All 3 patients remained alive and maintained a stable quality of life for at least 2 years. The patients reported no adverse side-effects from Psorinum-6x., Conclusions: This report indicates the clinical efficacy of Psorinum therapy in treating those 3 patients. Thorough basic research and well-designed clinical trials should be conducted for further investigation of this homeopathic cancer treatment in order to integrate it into the mainstream of oncology treatments.