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Background Use of laparoscopic pancreaticoduodenectomy (LPD) in place of open pancreaticoduodenectomy (OPD) remains controversial. Our aim was to evaluate the results of LPD versus OPD in non-pancreatic periampullary adenocarcinoma (NPPC), a less aggressive tumor. Methods Here, 488 NPPC patients who underwent LPD or OPD were analyzed in this study. The propensity score matching was used to balance the patients in two groups. Statistical analysis was conducted to investigate the differences between LPD and OPD in patients with NPPC. Results The LPD group had shorter operative time, less intraoperative bleeding, and less postoperative hospital stay than OPD group. The 30- and 90-day mortality rates were significantly lower in LPD than in OPD group. There was no statistical difference in long-term survival between the two groups. Conclusions For NPPC, LPD may be the preferred surgical treatment due to its advantages over OPD in terms of intraoperative blood loss and short-term mortality.

Background Approximately 30-40% of pancreatoduodenectomies for adenocarcinomas result in nonpancreatic periampullary adenocarcinoma as the final diagnosis. Depending on the origin, a distinction is made between four different carcinomas with histomorphological subtypes. Objective Carcinoma location and subtype are of prognostic and therapeutic relevance; however, the preoperative differentiation is often incorrect despite modern diagnostics. Material and methods Overview of the current literature on the classification and preoperative diagnostics of periampullary adenocarcinomas. Results A precise knowledge of the papillary anatomy is necessary for the correct classification of diagnostic findings. Current studies demonstrate diagnostically valuable information from the anamnesis, imaging and endoscopy. Conclusion In ca. 70-80% of cases a correct diagnosis of the type of periampullary adenocarcinoma is possible on the basis of interdisciplinary diagnostics. This potentially enables a correspondingly individualized treatment planning in the preoperative phase.

Background: Periampullary cancers constitute about 5% of gastrointestinal malignancies. They are comprised of tumors of diverse origins and are generally subdivided into pancreatic and non-pancreatic carcinomas. Immune checkpoint regulators, cytotoxic T-lymphocyte antigen 4 (CTLA-4), and the programmed cell death ligand-1 (PDL-1) have emerged as promising new targets for cancer therapeutics. Aim: This study aims to determine the possible role of immune checkpoint inhibitors PDL-1 and CTLA-4 in periampullary carcinoma of pancreatic and non-pancreatic adenocarcinoma subtypes, in an attempt to investigate the possible introduction of their related immunotherapy in the management of these tumors. Materials and Methods: Expression of immune inhibitory molecules was examined by immunohistochemistry in 40 cases including (20) pancreatic adenocarcinoma and (20) non-pancreatic adenocarcinoma. The association between markers and clinicopathological parameters was evaluated. Results: Statistically significant differences in the immunoexpression of both CTLA-4 and PDL-1 in the two studied groups were noticed with higher expression in non-pancreatic adenocarcinoma in relation to pancreatic adenocarcinoma (P=0.004, P=0.008) respectively. PDL-1 expression was positive in 15% and 55% of pancreatic and non-pancreatic adenocarcinoma cases, respectively with a significant correlation with lymph nodes metastasis in non-pancreatic adenocarcinoma cases. CTLA-4 was positive in 20% of pancreatic carcinoma with a significant correlation with lymph node metastasis, perineural invasion and T stage. In non-pancreatic periampullary adenocarcinoma, CTLA-4 was positive in 65% of cases with a significant association with lymph nodes metastasis and T stage. Conclusions: Immunotherapy using anti-PDL-1 and CTLA-4 are proposed as a novel promising management tool in non-pancreatic periampullary adenocarcinoma not in pancreatic adenocarcinomas.

Backgrounds/aims Diabetes mellitus (DM) is a known risk factor for morbidity, length of hospital stay, or mortality after surgery, however, its impact on postoperative course and long-term survival after pancreaticoduodenectomy (PD) is not clear. Methods This is a retrospective analysis of prospectively maintained database of 141 patients with periampullary and pancreatic head adenocarcinoma operated between January 2001 and March 2019. Clinico-pathological records and follow-up data were retrieved and analyzed. Cumulative hazard was computed for comparing the survival between DM and non-DM. Results DM was present in 31/141 (21.9%) patients, while 16/31 (51.6%). were new-onset DM (NODM). Tumor size, lymphovascular & perineural invasion, type of surgery, lymph node positivity and R0 resection rate were comparable between diabetic and non-diabetic. There was no significant difference in postoperative pancreatic fistula, delayed gastric emptying, infectious complication, hospital stay and mortality between DM and nondiabetics. Patients with DM had worse survival at 3 years (OS: HR, 3.11 [1.43-6.76] p=0.004, DFS: HR, 2.61 [1.23-5.53] p=0.01) and 5 years (OS: HR, 3.32 [1.46-7.53] p=0.004, DFS: HR, 2.87 [1.29-6.41] p=0.009). On multivariate analysis, DM (3 year OS: HR, 2.61 [1.14-5.98] p=0.022, DFS: HR, 2.19; p=0.058) (5 year OS: HR, 2.55; p=0.04, DFS: HR, 2.25; p=0.068) and pylorus resecting surgery were significantly associated with worse survival at 3 and 5 years. Conclusions Preoperative DM has no significant effect on postoperative course but has negative impact on 3-year and 5-year OS and DFS after PD for pancreatic and periampullary adenocarcinoma.

Because of the distinct and complex anatomy of the ampullary region, the exact origin of the periampullary tumors was often difficult to ascertain. In this study, we evaluated 78 patient samples, including 26 small intestinal adenocarcinomas, 35 pancreatic ductal adenocarcinomas, and 17 cholangiocarcinomas by immunohistochemical detection of cadherin-17 (CDH17), CDX2, CK20, and CK19 protein expression. The result showed that CDH17 and CDX2 expression was higher in small intestinal adenocarcinoma (73.1% and 65.4%) than in pancreatic (14.3% and 2.9%) and bile duct (41.2% and 23.5%) cancers, respectively. CK20 expression was low in 78 tumor tissues, but relatively high in small intestinal adenocarcinoma (42.3%). CK19 showed a strong positive expression in all 78 adenocarcinoma tissues. The CDH17-high/CDX2-high pattern was predominantly expressed in small intestinal cancer tissues (75%), whereas the CDH17-low/CDX2-low pattern was observed in pancreatic cancers (63.8%) and bile duct cancers (20.9%). The study concluded that CDH17-high/CDX2-high adenocarcinomas more likely originated from small intestine versus pancreas or bile duct, whereas CDH17-low/CDX2-low ones are more likely of pancreatic origin. The combined use of CDH17 and CDX2 could be helpful in providing support for the histologic origin of periampullary adenocarcinoma.

Periampullary adenocarcinomas are rare neoplasm that originates from the pancreatic head, the ampulla of vater, the distal bile duct or the duodenum. Surgical resection followed by adjuvant therapy is considered as the standard of care treatment for these carcinomas. Despite several advances in diagnostics and therapeutics, only 5% of these patients have an overall survival of five years or more. Currently, there is a dearth of viable therapeutic targets for this disease. The role of HER2 in cancer biology has been studied extensively in several tumour subtypes, and HER2 based targeted therapies have shown to have therapeutic benefits on different cancers. In this case report, we present a case of HER2 positive distal common bile duct carcinoma - a subtype of periampullary carcinoma with multiple relapses where multi-analyte testing with Encyclopedic Tumor Analysis (ETA) (Exacta®) identified amplification and over expression of HER2 gene which was used as a potential target to treat the patient with trastuzumab. Synchronous in vitro chemosensitivity profiling on Circulating Tumor Asscociated Cells (C-TACs) isolated from blood aided us to design the personalized chemotherapeutic regimen with cyclophosphamide and methotrexate. The combination of trastuzumab with cyclophosphamide and methotrexate yielded excellent treatment response with the patient remaining in complete response till the last follow-up. Our study suggests HER2 directed therapy as a potent pathway for treatment in the subset of HER-2 amplified distal common bile duct carcinomas.

Background Pancreatic cancer is a devastating disease with a dismal prognosis. Despite profound medical advances in systemic therapies for other types of aggressive tumours during recent years, a diagnosis of pancreatic cancer is still often synonymous with a fatal outcome. The term periampullary cancer includes pancreatic cancer and applies to the group of tumours found in proximity to the ampulla of Vater. Molecular events and immune response in the host during chemotherapy remain largely unexplored in this group of tumours. Therefore, the “Chemotherapy, Host Response and Molecular Dynamics in Periampullary Cancer (CHAMP)” study aims to monitor these processes to gain new insight into this perplexing disease. Methods The CHAMP study is a prospective, single-arm observational study. All patients diagnosed with pancreatic or other periampullary adenocarcinoma undergoing adjuvant or palliative chemotherapy treatment in the Department of Oncology, Skåne University Hospital, are invited to participate. Clinical and pathological data will be compiled at study entry. A single tissue microarray (TMA) block is constructed for each patient with a resected tumour and blood samples are drawn before, during and after chemotherapy in order to sample peripheral blood mononuclear cells (PBMC), cytokines and circulating tumour DNA (ctDNA). Next generation sequencing will be performed on tumour tissue and ctDNA to detect changes in the clonal landscape over space and time. Discussion Despite the recent emergence of some promising biomarkers for periampullary cancer, there has been a lack of success in clinical implementation. Cancer cells continuously adapt and become resistant to treatment during chemotherapy. To be able to keep pace with and hopefully overtake this rapid evolution we must, with the help of new diagnostic tools, be ready to adapt and alter treatment accordingly. It seems to us that the only way forward is to gain a better understanding of the dynamics of the disease during treatment. With insights gained from the CHAMP study we hope to find answers to key questions in this largely unexplored territory. Trial registration This study has been registered 30th October 2018 at clinicaltrials.gov as NCT03724994.

OBJECTIVE To determine the safety of pancreaticogastrostomy in pancreaticoduodenectomy in patients with periampullary and pancreatic head neoplasms in terms of surgical technique, pancreatic fistula rate, 30 days mortality and three years survival. STUDY DESIGN Cohort study. PLACE AND DURATION OF STUDY Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, from October 2014 to September 2017. METHODOLOGY Patients undergoing pancreaticoduodenectomy for pancreatic head and periampullary tumors were included. Patients having metastatic disease or involvement of celiac artery, hepatic artery or superior mesenteric artery on preoperative scans, complete encasement of portal vein and superior mesenteric vein (SMV) were excluded. Patients' characteristics including the demographics, surgical technique, postoperative pancreatic fistula, 30 days mortality and three years survival were recorded. Mean ± standard deviation was used for continuous variables while frequencies and percentages were used for categorical variables. Kaplan-Meier method was used to estimate survival as a function of time, and survival differences were analysed by either Log-Rank test or Tarone-Ware test. Statistical significance was defined as a two-tailed p-value 0.05. RESULTS One hundred and one patients underwent pancreaticoduodenectomy. Fifty-eight (57.4%) were males and 43 (42.4%) were females (n=43). Mean age was 51.5 ±14.17 years. The commonly found tumor was periampullary adenocarcinoma which was present in 49.5% (n=50) patients followed by pancreatic head adenocarcinoma which was present in 32.7% (n=33) patients and 17.8% (n=18) patients had other tumors. Most common pathological T-stage was T3 present in 47.5% (n=48) patients, followed by T2 found in 36.6% (n=37) patients and T1 stage was present in 15.8% (n=16) patients. 57.4% (n=58) patients had node positive disease. Pancreaticogastrostomy was done in 87.13% (n=88) patients, while pancreaticojejunostomy was done in 12.87% (n=13) patients. Recurrent disease was noticed in 11.9% (n=12) patients. Mean survival of pancreatic head adenocarcinoma was 787.04 ±81.89 days, which was comparatively less than periampullary adenocarcinoma, i.e. 983.10 ±52.27 days (p=0.08). Overall mean survival was 924 ±41.3 days. CONCLUSION Patients with periampullary tumors had a better outcome than pancreatic head tumors in this series. Pancreaticogastrostomy can be a safe alternative to pancreaticojejunostomy, especially in patients having non-dilated pancreatic duct and soft pancreas.

PURPOSE Periampullary adenocarcinomas encompass a heterogeneous group of tumors with dismal prognosis and limited treatment options. Emerging evidence shows that tumor morphology (ie, intestinal type [I-type] or pancreatobiliary type [PB-type]) is a more relevant prognostic factor than tumor origin. Knowledge is sparse, however, on whether key mutations differ according to morphology. MATERIALS AND METHODS Next-generation sequencing was applied to assess the mutational status of 70 genes in 102 tumors from a retrospective cohort of 175 patients with resected periampullary adenocarcinoma. Brahma-related gene 1 protein expression was examined by immunohistochemistry on tissue microarrays with primary tumors from the original cohort. RESULTS APC mutations were significantly more common in I-type than in PB-type tumors (27.5% v 0%; P < .001), as were ERBB3 mutations (20.8% v 4.8%; P = .016), whereas CDKN2A mutations were more common in PB-type than in I-type tumors (19.4% v 2.5%; P = .013). KRAS mutation was an independent factor of poor prognosis in I-type tumors (hazard ratio, 3.73; 95% CI, 1.10 to 12.67). In PB-type tumors, SMARCA4 mutation was an adverse prognostic factor in patients not receiving adjuvant chemotherapy, and there was a significant treatment interaction between expression of Brahma-related gene 1 protein, the protein encoded by SMARCA4, and adjuvant chemotherapy ( Pinteraction = .007). CONCLUSION To our knowledge, this is the first description of the mutational landscape in the full spectrum of periampullary adenocarcinoma that demonstrates that the distribution and prognostic and predictive significance of commonly mutated genes differ by morphology. The results emphasize that morphology is an important factor to consider in the search for novel biomarkers and targeted personalized treatment of these patients. In addition, the findings support the concept that molecular profiling of these tumors could be of clinical benefit.

BACKGROUND For periampullary adenocarcinoma, the histological subtype is a better prognostic predictor than the site of tumor origin. Intestinal-type periampullary adenocarcinoma (IPAC) is reported to have a better prognosis than the pan-creatobiliary-type periampullary adenocarcinoma (PPAC). However, the classification of histological subtypes is difficult to determine before surgery. Apparent diffusion coefficient (ADC) histogram analysis is a noninvasive, non-enhanced method with high reproducibility that could help differentiate the two subtypes. AIM To investigate whether volumetric ADC histogram analysis is helpful for distinguishing IPAC from PPAC. METHODS Between January 2015 and October 2018, 476 consecutive patients who were suspected of having a periampullary tumor and underwent magnetic resonance imaging (MRI) were reviewed in this retrospective study. Only patients who underwent MRI at 3.0 T with different diffusion-weighted images (b-values = 800 and 1000 s/mm2) and who were confirmed with a periampullary adenocarcinoma were further analyzed. Then, the mean, 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of ADC values and ADCmin, ADCmax, kurtosis, skewness, and entropy were obtained from the volumetric histogram analysis. Comparisons were made by an independent Student's t-test or Mann-Whitney U test. Multiple-class receiver operating characteristic curve analysis was performed to determine and compare the diagnostic value of each significant parameter. RESULTS In total, 40 patients with histopathologically confirmed IPAC (n = 17) or PPAC (n = 23) were enrolled. The mean, 5th, 25th, 50th, 75th, 90th, and 95th percentiles and ADCmax derived from ADC1000 were significantly lower in the PPAC group than in the IPAC group (P < 0.05). However, values derived from ADC800 showed no significant difference between the two groups. The 75th percentile of ADC1000 values achieved the highest area under the curve (AUC) for differentiating IPAC from PPAC (AUC = 0.781; sensitivity, 91%; specificity, 59%; cut-off value, 1.50 × 10-3 mm2/s). CONCLUSION Volumetric ADC histogram analysis at a b-value of 1000 s/mm2 might be helpful for differentiating the histological subtypes of periampullary adenocarcinoma before surgery.

Purposes To present preliminary perioperative and long-term outcomes in elderly patients compared with younger patients who underwent laparoscopic pancreaticoduodenectomy (LPD). Materials and methods A total of 199 patients who underwent LPD were included in this study. The primary data relating to these patients were collected and analyzed in our center from October 2010 to 2017. Results The intraoperative and postoperative information, including the rate and severity of short-term complications, pathologic outcomes, and other surgical outcomes, showed no significant differences between the 2 groups. Furthermore, the median overall survival for 2 malignant diseases of the young patients was not significantly better than the elderly. Conclusions Our data suggest that patient age showed little influence on postoperative morbidity, mortality, and long-term survival in pancreatic adenocarcinoma and periampullary adenocarcinoma following LPD, whereas studies with larger sample sizes and longer follow-up are necessary before definitive conclusions can be made.

Background/Aim There is no standard salvage chemotherapy for metastatic periampullary adenocarcinoma and duodenal adenocarcinoma and the prognosis of those who fail oxaliplatin, irinotecan, and 5FU is dismal. We examined nanoparticle albumin‐bound paclitaxel (nab‐paclitaxel) as salvage therapy for these two malignancies. Methods Patients who failed oxaliplatin, irinotecan, and 5FU and whose archival tumors stained immunohistochemical (IHC) tumor positive for CK7 or MUC1 received nab‐paclitaxel and gemcitabine therapy with or without cisplatin. Results Three patients, 2 with metastatic ampullary adenocarcinoma and 1 with duodenal adenocarcinoma with positive IHC staining for CK7 or MUC1 who failed 2 lines of chemotherapy with oxaliplatin, irinotecan, and 5FU received nab‐paclitaxel and gemcitabine with or without cisplatin. All achieved excellent tumor response on CT scans with marked falls in tumor markers CA19‐9 and CEA as well as ≥1 year of progression‐free survival. All 3 have continued to survive 2‐3 years since diagnosed with stage 4 metastatic adenocarcinoma. Conclusions Nab‐paclitaxel plus gemcitabine with or without cisplatin should be investigated as a standard‐of‐care chemotherapy regimen for patients with ampullary adenocarcinoma and duodenal adenocarcinoma.

Introduction: Malignant tumors are associated with a low incidence of postoperative pancreatic fistulas. The presence of peritumoral fibrosis is considered the protective factor for the development of postoperative pancreatic fistulas after pancreatic resections for pancreatic ductal adenocarcinomas. Methods: We analyzed a series of 109 consecutive patients with pancreatic resections for malignant pathology: pancreatic ductal adenocarcinomas and periampullary adenocarcinomas. The incidence of postoperative pancreatic fistulas has been reported in tumor histological type, in the presence of peritumoral fibrosis, and in the association between adenocarcinomas and areas of acute pancreatitis. The data obtained were processed with the statistical analysis program SPSS, and statistically significant p were considered at a value p = 0.002. The presence of peritumoral fibrous tissue was observed in 49.31% of cases without pancreatic fistulas, and in 54.54% of cases that developed this postoperative complication (p = 0.5). Also, the peritumoral fibrous tissue had a uniform distribution depending on the main diagnosis (56.14% in pancreatic ductal adenocarcinoma group vs. 37.04% in periampullary adenocarcinoma group, with a p = 0.08). In the group of patients who associated areas of acute pancreatitis on the resections, the incidence of postoperative pancreatic fistulas was 7.8 times higher (30% vs. 3.8%, p = 0.026). Conclusions: Peritumoral fibrous tissue was not a factor involved in the developing of postoperative pancreatic fistulas. The association of adenocarciomas with areas of acute pancreatitis has led to a significant increase in postoperative pancreatic fistulas, which is a significant and independent risk factor.

Periampullary carcinoma is a broad term used to define the group of carcinomas arising from the head of the pancreas, the distal common bile duct, and the duodenum. It is clinically important to differentiate ampullary from periampullary carcinoma as this can affect resectability and prognosis. Atypical left-sided chest pain is an atypical presentation of periampullary duodenal adenocarcinoma. A 58-year-old man presented with a two-month duration of worsening intermittent, atypical, migratory left-sided chest pain. Imaging studies were unremarkable; however, endoscopic evaluation demonstrated a duodenal mass. While most periampullary carcinomas are generally curable with pancreaticoduodenectomy, if left untreated, these tumors are uniformly fatal.

BACKGROUND: Pancreatic and periampullary adenocarcinomas account for some of the most aggressive malignancies, and the leading causes of cancer‐related mortalities. Partial pancreaticoduodenectomy (PD) with negative resection margins is the only potentially curative therapy. The high prevalence of lymph node metastases has led to the hypothesis that wider excision with the removal of more lymphatic tissue could result in an improvement of survival, and higher rates of negative resection margins. OBJECTIVES: To compare overall survival following standard (SLA) versus extended lymph lymphadenectomy (ELA) for pancreatic head and periampullary adenocarcinoma. We also compared secondary outcomes, such as morbidity, mortality, and tumour involvement of the resection margins between the two procedures. SEARCH METHODS: We searched CENTRAL, MEDLINE, PubMed, and Embase from 1973 to September 2020; we applied no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCT) comparing PD with SLA versus PD with ELA, including participants with pancreatic head and periampullary adenocarcinoma. DATA COLLECTION AND ANALYSIS: Two review authors independently screened references and extracted data from study reports. We calculated pooled risk ratios (RR) for most binary outcomes except for postoperative mortality, for which we estimated a Peto odds ratio (Peto OR), and mean differences (MD) for continuous outcomes. We used a fixed‐effect model in the absence of substantial heterogeneity (I² < 25%), and a random‐effects model in cases of substantial heterogeneity (I² > 25%). Two review authors independently assessed risk of bias, and we used GRADE to assess the quality of the evidence for important outcomes. MAIN RESULTS: We included seven studies with 843 participants (421 ELA and 422 SLA). All seven studies included Kaplan‐Meier curves for overall survival. There was little or no difference in survival between groups (log hazard ratio (log HR) 0.12, 95% confidence interval (CI) ‐3.06 to 3.31; P = 0.94; seven studies, 843 participants; very low‐quality evidence). There was little or no difference in postoperative mortality between the groups (Peto odds ratio (OR) 1.20, 95% CI 0.51 to 2.80; seven studies, 843 participants; low‐quality evidence). Operating time was probably longer for ELA (mean difference (MD) 50.13 minutes, 95% CI 19.19 to 81.06 minutes; five studies, 670 participants; moderate‐quality evidence). There was substantial heterogeneity between the studies (I² = 88%; P < 0.00001). There may have been more blood loss during ELA (MD 137.43 mL, 95% CI 11.55 to 263.30 mL; two studies, 463 participants; very low‐quality evidence). There was substantial heterogeneity between the studies (I² = 81%, P = 0.02). There may have been more lymph nodes retrieved during ELA (MD 11.09 nodes, 95% CI 7.16 to 15.02; five studies, 670 participants; moderate‐quality evidence). There was substantial heterogeneity between the studies (I² = 81%, P < 0.00001). There was little or no difference in the incidence of positive resection margins between groups (RR 0.81, 95% CI 0.58 to 1.13; six studies, 783 participants; very low‐quality evidence). AUTHORS' CONCLUSIONS: There is no evidence of an impact on survival with extended versus standard lymph node resection. However, the operating time may have been longer and blood loss greater in the extended resection group. In conclusion, current evidence neither supports nor refutes the effect of extended lymph lymphadenectomy in people with adenocarcinoma of the head of the pancreas.

Herein, we report on a patient with known Lynch Syndrome and periampullary adenocarcinoma that exhibited a pathological complete response to neoadjuvant nivolumab plus ipilimumab. Two MSH2 mutations, high microsatellite instability (MSI-high), high tumor mutational burden (TMB) and elevated PD-L1 expression were identified by next-generation sequencing (NGS) and immunohistochemistry (IHC). Following FOLFIRINOX (Fluorouracil/Leucovorin/Irinotecan/Oxaliplatin) administration and disease progression, nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) were administered every 3 weeks for 4 total cycles. The patient responded well with minimal adverse effects and significant improvement in epigastric pain, appetite and body weight. She then underwent resection consisting of pancreaticoduodenectomy, which demonstrated pathological complete response. Complete genomic profiling of periampullary carcinomas is crucial for optimal treatment selection as true ampullary masses and pancreatic ductal adenocarcinoma (PDAC) have different genetic profiles. This case provides an example of a patient who may have further benefited from first-line nivolumab plus ipilimumab to avoid the reduced efficacy and significant side effects associated with chemotherapy. KEY POINTS: A patient with known Lynch Syndrome and ampullary adenocarcinoma harboring two MSH2 mutations, high microsatellite instability (MSI-high), high tumor mutational burden (TMB) and elevated PD-L1 expression achieved pathological complete response with neoadjuvant nivolumab plus ipilimumab The combination of nivolumab plus ipilimumab may be a better first-line option for patients with ampullary adenocarcinomas harboring deficient mismatch repair (dMMR), MSI-high and high TMB Complete genomic profiling of periampullary adenocarcinomas is crucial for optimal treatment selection as true ampullary masses and pancreatic ductal adenocarcinoma (PDAC) have different genetic profiles The presence of either MSI-high or high TMB could be an appropriate predictive biomarker for response to nivolumab plus ipilimumab in the context of Lynch Syndrome IMPLICATIONS FOR PRACTICE: This case provides an example of a patient with MSI-high and dMMR ampullary adenocarcinoma who may have benefited from first-line checkpoint inhibitor therapy, specifically with nivolumab plus ipilimumab. Comprehensive genomic profiling is beneficial in periampullary adenocarcinomas as it can identify tumors with specific genetic characteristics, like MSI-high, dMMR or high TMB that respond well to immune checkpoint inhibitors. When these characteristics are present and the goal of treatment is to facilitate downstage and prolong progression free survival, nivolumab plus ipilimumab should be considered, but trials in periampullary adenocarcinomas are required to confirm usage.

Background Periampullary adenocarcinoma (PAAC) had a poor prognosis, and pancreaticoduodenectomy (PD) remains the only potentially curative treatment. The study aimed to identify the impact of different clinicopathological factors on long-term survival following PD for PAAC. Patients and methods This study is a retrospective cohort study for the patients who underwent PD for pathologically proven PAAC from January 2010 to January 2019. Statistical analysis was done using Cox regression multivariate analyses for independent risk factors for survival. Result There were 137 patients with PAAC who underwent PD, 79 patients (57.7%) underwent pylorus-preserving PD. Pancreatico-jejunostomy was done in 108 patients (78.8%). The primary analysis showed that risk factors for poor long-term survival include patients with co-morbidities like hypertension or ischemic heart disease, Carbohydrate Antigen 19-9 > 400U/ml, tumor size > 3 cm, poor tumor differentiation, positive lymph nodes invasion, lymphovascular invasion, and Perineural invasion. Multivariate analysis demonstrated that large tumor size > 3 cm (HR: 0.177, 95%CI: 0.084–0.374, P = 0.002), poorly differentiated tumor (HR: 0.059, 95%CI: 0.020–0.0174, P = 0.016), and perineural invasion in the pathological study (HR: 0.101, 95%CI: 0.046–0.224, P = 0.006) were independent risk factors for poor 5-years survival. The prognosis was better in ampullary adenocarcinoma (5-year survival was 42.1%) than pancreatic adenocarcinoma (5-year survival was 24.3%). The 1, 3, 5 and 7-year overall survival rates were 84.5%, 57.4%, 35.9% and 20.1% respectively. Conclusion It seems from the current study that Tumor size > 3 cm, poor tumor differentiation, and Perineural invasion were independent predictors of poor survival in patients with PAAC., Highlights • Periampullary adenocarcinoma (PAAC) is highly aggressive tumor. • It has late diagnosis with poor prognosis. • Pancreaticoduodenectomy (PD) is still the only curative treatment option. • PD surgery is associated with high morbidity and mortality. • It is important to determine which patients who can receive benefit from surgery.

Background Pancreatic Ductal Adenocarcinoma (PDAC) is a cancer of the exocrine pancreas and 5-year survival rates remain constant at 7%. Along with PDAC, Periampullary Adenocarcinoma (PAC) accounts for 0.5–2% of all gastrointestinal malignancies. Genomic observations were well concluded for PDAC and PACs in western countries but no reports are available from India till now. Methods Targeted Next Generation Sequencing were performed in 8 (5 PDAC and 3 PAC) tumour normal pairs, using a panel of 412 cancer related genes. Primary findings were replicated in 85 tumour samples (31 PDAC and 54 PAC) using the Sanger sequencing. Mutations were also validated by ASPCR, RFLP, and Ion Torrent sequencing. IHC along with molecular dynamics and docking studies were performed for the p.A138V mutant of TP53. Key polymorphisms at TP53 and its associated genes were genotyped by PCR-RFLP method and association with somatic mutations were evaluated. All survival analysis was done using the Kaplan-Meier survival method which revealed that the survival rates varied significantly depending on the somatic mutations the patients harboured. Results Among the total 114 detected somatic mutations, TP53 was the most frequently mutated (41%) gene, followed by KRAS, SMAD4, CTNNB1, and ERBB3. We identified a novel hotspot TP53 mutation (p.A138V, in 17% of all patients). Low frequency of KRAS mutation (33%) was detected in these samples compared to patients from Western counties. Molecular Dynamics (MD) simulation and DNA-protein docking analysis predicted p.A138V to have oncogenic characteristics. Patients with p.A138V mutation showed poorer overall survival (p = 0.01). So, our finding highlights elevated prevalence of the p53p.A138V somatic mutation in PDAC and pancreatobiliary PAC patients. Conclusion Detection of p.A138V somatic variant in TP53 might serve as a prognostic marker to classify patients. It might also have a role in determining treatment regimes. In addition, low frequency of KRAS hotspot mutation mostly in Indian PDAC patient cohort indicates presence of other early drivers in malignant transformation.

Pancreatic Ductal AdenoCarcinoma (PDAC) is one of the most lethal malignancies of all solid cancers. Precancerous lesions for PDAC include PanIN, IPMNs and MCNs. PDAC has a poor prognosis with a 5-year survival of approximately 6%. Whereas Periampulary AdenoCarcinoma (PAC) having four anatomic subtypes, pancreatic, Common Bile Duct (CBD), ampullary and duodenum shows relative better prognosis. The highest incidence of PDAC has been reported with black with respect to white population. Similarly, incidence rate of PAC also differs with different ethnic populations. Several lifestyle, environmental and occupational exposures including long-term diabetes, obesity, and smoking, have been linked to PDAC, however, for PAC the causal risk factors were poorly described. It is now clear that PDAC and PAC are a multi-stage process resulting from the accumulation of genomic alterations in the somatic DNA of normal cells as well as inherited mutations. Approximately 10% of PDAC have a familial inheritance. Germline mutations in CDKN2A, BRCA2, STK11, PALB2, PRSS1, etc., as well as certain syndromes have been well associated with predisposition to PDAC. KRAS, CDKN2A, TP53 and SMAD4 are the 4 “mountains” (high-frequency driver genes) which have been known to earliest somatic alterations for PDAC while relatively less frequent in PAC. Our understanding of the molecular carcinogenesis has improved in the last few years due to extensive research on PDAC which was not well explored in case of PAC. The genetic alterations that have been identified in PDAC and different subgroups of PAC are important implications for the development of genetic screening test, early diagnosis, and prognostic genetic markers. The present review will provide a brief overview of the incidence and prevalence of PDAC and PAC, mainly, increased risk in India, the several kinds of risk factors associated with the diseases as well as required genetic alterations for disease initiation and progression.

Periampullary malignancy is the term utilized for neoplasms emerging from the head of pancreas, ampulla of Vater, distal bile pipe and periampullary distinct of duodenum. Of these, the pancreatic adenocarcinoma conveys the most noticeably awful anticipation with greater part of mortalities.Studies have shown that pancreatic carcinoma has the most limited middle endurance of 17.1 months of all periampullary carcinomas. Herein, we present a case of a 63-year-old male patient without any history of trauma or important previous symptoms presented to the tertiary care hospital with compliance of sudden weight loss and abdominal pain over the preceding 3 months. On examination he was deeply jaundice. His laboratory and radiological examination revealed periampullary adenocarcinoma. This individual had successfully underwent Whipple procedure and followed by Chemotherapy. This case is being presented not only the cancer is rare but also to understand and improve better clinical insight on this rare disease

Background: Laparoscopic pancreaticoduodenectomy (LPD), a surgical option for nonpancreatic periampullary adenocarcinoma (NPPA), is a complex procedure that has become increasing popular. However, there is no consensus as to whether this technique should be performed routinely. Our aim was to evaluate the outcomes of LPD compared with open pancreaticoduodenectomy (OPD). Materials and Methods: From October 2010 to September 2015, 58 LPDs were performed to treat NPPA and were compared with 58 OPDs, which can theoretically be carried out by laparoscopic approach. Patients were also matched based on their demographic data and pathologic diagnosis. Demographic information, intraoperative and postoperative data, pathologic data, and follow-up evaluation data were collected at our center. Results: All patients had a median follow-up of 34 months (range, 8 to 60 mo). Overall median survival during the study between the groups was not different (P=0.760). No significant differences between the 2 groups were found in terms of patient demographics, short-term complications, pathologic outcomes, or tumor-node-metastasis stage. With regard to operative time, the LPD group was slightly longer than the OPD group (P

Purpose: The purpose of this study was to report toxicity and long-term survival outcomes of 2 prospective trials evaluating mitomycin C (MMC) with 5-fluorouracil–based adjuvant chemoradiation in resected periampullary adenocarcinoma. Methods and materials: From 1996 to 2002, 119 patients received an adjuvant 4-drug chemotherapy regimen of 5-fluorouracil, leucovorin, MMC, and dipyridamole with chemoradiation on 2 consecutive trials (trials A and B). Trial A patients received upfront chemoradiation (50 Gy split-course, 2.5 Gy/fraction) followed by 4 cycles of the 4-drug chemotherapy with bolus 5-fluorouracil. Trial B patients received 1 cycle of the 4-drug chemotherapy with continuous infusion 5-fluorouracil followed by continuous chemoradiation (45-54 Gy, 1.8 Gy/fraction) and 2 additional cycles of chemotherapy. Cox proportional hazards models were performed to identify prognostic factors for overall survival (OS). Results: Of the 62 trial A patients, 61% had pancreatic and 39% nonpancreatic periampullary carcinomas. Trial B (n = 57) consisted of 68% pancreatic and 32% nonpancreatic periampullary carcinomas. Resection margin and lymph node status were similar for both trials. Median follow-up was longer for trial A than trial B (197.5 vs 107.0 months), with median OS of 32.2 and 24.2 months, respectively. Rates of 3-, 5-, and 10-year OS were 48%, 31%, and 26% in trial A and 32%, 23%, and 9% in trial B. On multivariate analysis, lymph node–positive resection was the strongest prognostic factor for OS. A pancreatic primary and positive margin status were also associated with inferior survival (P

The preoperative imaging-to-surgery time interval (ISI) influences the risk of unexpected progression (UP) found at surgery for pancreatic adenocarcinoma. We aimed to assess whether ISI influences disease recurrence and/or survival. A single-institution, ethics board-approved retrospective analysis of all patients who underwent attempted resection of pancreatic (PDAC) or periampullary adenocarcinoma (AmpAC) between 1st January 2010 and 31st December 2015 was performed. All patients underwent preoperative abdominal computed tomography (CT). Exclusion criteria were borderline resectable disease and neoadjuvant chemo/radiotherapy. Patients were followed up until 30th June 2016. The population was divided into ISI ≥/