Endoscopic treatment for early duodenal papillary carcinoma: long-term outcomes.

BACKGROUND AND AIM: This study aims to determine whether endoscopic papillectomy (EP) is a safe and effective treatment for early duodenal papillary carcinoma with long-term follow-up. METHODS: From June 2012 to September 2022, 48 patients with early duodenal papilloma carcinoma who received endoscopic treatment were included. The histological types, percentage of complete resections, postoperative residuals, adverse events, and recurrences were evaluated. RESULTS: EP was successful in all patients; 46 were lumped, and two were fragmented, with a 95.8% intact removal rate (46/48). The preoperative biopsy pathological positive rate was 70.8% (34/48). The incidence of early postoperative adverse events (within 1 month after EP) were 16.7% (8/48), including four cases of acute pancreatitis, three cases of delayed bleeding, and one case of acute cholangitis. In addition, 4.2% (2/48) of the late adverse events were bile duct stenosis. After 6 months, the postoperative residual rate was 0%. The median time to recurrence was 17.5 months, and the postoperative recurrence rate was 16.7% (8/48) in patients treated with radiofrequency ablation. The median progression-free survival was 18.6 months (95% CI, 12.1-25.1), and the median overall survival was 121.5 months (95% CI, 105.6-120.9). CONCLUSIONS: EP is a safe and efficient alternative therapy for early duodenal papillary carcinoma. Endoscopic follow-up and treatment are essential because of the potential for recurrence.

Development and validation of a nomogram for primary duodenal carcinoma: a multicenter, population-based study.

Aim: This study aimed to develop a predictive model for patients with duodenal carcinoma. Methods: Duodenal carcinoma patients from the Surveillance, Epidemiology, and End Results database (2010-2015) and the First Affiliated Hospital of Nanchang University (2010-2021) were enrolled. A nomogram was constructed according to least absolute shrinkage and selection operator regression analysis, the Akaike information criterion approach and Cox regression analysis. Results: Five independent prognostic factors were significantly associated with the prognosis of the duodenal carcinoma patients. A nomogram was constructed with a C-index in the training and validation cohorts of 0.671 (95% CI: 0.578-0.716) and 0.662 (95% CI: 0.529-0.773), respectively. Conclusion: The established nomogram model provided visualization of the risk of each prognostic factor.

Ampullary carcinoma of the duodenum: current clinical issues and genomic overview.

Ampullary carcinomas of the duodenum are uncommon. Moreover, the diversity in the clinical outcomes of these patients makes it difficult to interpret previous studies and clinical trial results. The difficulty in proper staging of ampullary carcinomas, especially with regard to the T category of the tumor in the TNM system, reflects the anatomic complexity and non-uniform histopathologic subtypes. One major reason for this difficulty in interpretation is that the tumors may arise from any of the three epithelia (duodenal, biliary, or pancreatic) that converge at this location. Generally, ampullary carcinomas are classified into intestinal and pancreaticobiliary types based on morphology and immunohistochemical features. While many studies have described their specific characteristics and clinical impact, the prognostic value of these subtypes is controversial. In recent years, whole-exome sequencing analyses have advanced our understanding of the genomic overview of ampullary carcinoma. Gene mutations serve as prognostic and predictive biomarkers for this disease. Therefore, basic knowledge of the genomic profile of ampullary carcinomas is required for surgeons to understand how best to apply precision medicine as well as surgery and adjuvant therapies. This review provides an overview of the current basic and clinical issues of ampullary carcinoma.

Incidence and Mortality in Upper Gastrointestinal Cancer After Negative Endoscopy for Gastroesophageal Reflux Disease.

BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is associated with an increased risk of cancer of the upper gastrointestinal tract. This study aimed to assess whether and to what extent a negative upper endoscopy in patients with GERD is associated with decreased incidence and mortality in upper gastrointestinal cancer (ie, esophageal, gastric, or duodenal cancer). METHODS: We conducted a population-based cohort study of all patients with newly diagnosed GERD between July 1, 1979 and December 31, 2018 in Denmark, Finland, Norway, and Sweden. The exposure, negative upper endoscopy, was examined as a time-varying exposure, where participants contributed unexposed person-time from GERD diagnosis until screened and exposed person-time from the negative upper endoscopy. The incidence and mortality in upper gastrointestinal cancer were assessed using parametric flexible models, providing adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Among 1,062,740 patients with GERD (median age 58 years; 52% were women) followed for a mean of 7.0 person-years, 5324 (0.5%) developed upper gastrointestinal cancer and 4465 (0.4%) died from such cancer. Patients who had a negative upper endoscopy had a 55% decreased risk of upper gastrointestinal cancer compared with those who did not undergo endoscopy (HR, 0.45; 95% CI, 0.43-0.48), a decrease that was more pronounced during more recent years (HR, 0.34; 95% CI, 0.30-0.38 from 2008 onward), and was otherwise stable across sex and age groups. The corresponding reduction in upper gastrointestinal mortality among patients with upper endoscopy was 61% (adjusted HR, 0.39; 95% CI, 0.37-0.42). The risk reduction after a negative upper endoscopy in incidence and mortality lasted for 5 and at least 10 years, respectively. CONCLUSIONS: Negative upper endoscopy is associated with strong and long-lasting decreases in incidence and mortality in upper gastrointestinal cancer in patients with GERD.

Molecular profiling and identification of prognostic factors in Chinese patients with small bowel adenocarcinoma.

Small bowel adenocarcinoma (SBA) is a rare malignancy with a poor prognosis and limited treatment options. Despite prior studies, molecular characterization of this disease is not well defined, and little is known regarding Chinese SBA patients. In this study, we conducted multigene next-generation sequencing and 16S ribosomal RNA gene sequencing on samples from 76 Chinese patients with surgically resected primary SBA. Compared with colorectal cancer and Western SBA cohorts, a distinctive genomic profile was revealed in Chinese SBA cohorts. According to the levels of clinical actionability to targetable alterations stratified by OncoKB system, 75% of patients harbored targetable alterations, of which ERBB2, BRCA1/2, and C-KIT mutations were the most common targets of highest-level actionable alterations. In DNA mismatch repair-proficient (pMMR) patients, significant associations between high tumor mutational burden and specific genetic alterations were identified. Moreover, KRAS mutations/TP53 wild-type/nondisruptive mutations (KRASmut /TP53wt/non-dis ) were independently associated with an inferior recurrence-free survival (hazard ratio [HR] = 4.21, 95% confidence interval [CI] = 1.94-9.14, P < .001). The bacterial profile revealed Proteobacteia, Actinobacteria, Firmicutes, Bacteroidetes, Fusobacteria, and Cyanobacteria were the most common phyla in SBA. Furthermore, patients were clustered into three subgroups based on the relative abundance of bacterial phyla, and the distributions of the subgroups were significantly associated with the risk of recurrence stratified by TP53 and KRAS mutations. In conclusion, these findings provided a comprehensive molecular basis for understanding SBA, which will be of great significance in improving the treatment strategies and clinical management of this population.

Pancreas-Preserving Total Duodenectomy: A Systematic Review.

BACKGROUND: The management of the pancreas in patients with duodenal trauma or duodenal tumors remains a controversial issue. Pancreas-preserving total duodenectomy (PPTD) requires a meticulous surgical technique. The most common indication is familial duodenal adenomatous polyposis (FAP). The aims of this study are to carry out a systematic review of the literature on the indications for PPTD and to highlight the risks and benefits compared with other more aggressive procedures. SUMMARY: A systematic literature review was performed following PRISMA recommendations of studies published in PubMed, Embase, and Cochrane library until May 2019. Thirty articles describing 211 patients were chosen. The mean age was 48 years. The surgical indication in 75% of patients was FAP. The mean operating time was 329 min and mean intraoperative bleeding 412 mL. Postoperative morbidity rate was 49.7% (76% Clavien-Dindo 97.8%. Key Messages: PPTD is indicated for patients with benign and premalignant duodenal lesions without involvement of the pancreatic head. It is a feasible procedure offering an alternative to other more aggressive procedures in selected patients. Mortality is below 1.5%.

Clinical features, treatment, and prognosis of different histological types of primary small bowel adenocarcinoma: A propensity score matching analysis based on the SEER database.

PURPOSE: This aim of this study was to provide a comprehensive understanding of the clinical characteristics, treatment, and prognosis of patients with small bowel adenocarcinoma (SBA), mucinous small bowel adenocarcinoma (MSBA), and signet ring cell carcinoma of the small bowel (SRCSB). METHODS: Information on patients with SBA, MSBA, and SRCSB (2004-2015) was obtained from the Surveillance, Epidemiology and End Results (SEER) database. Cox proportional hazards models and Kaplan-Meier curves were used for the survival analyses. Propensity-score matching (PSM) was implemented to determine the differences among these tumors. RESULTS: In all, 3697 patients with SBA (n = 3196), MSBA (n = 325) and SRCSB (n = 176) were ultimately eligible for this study. Poor differentiation, local invasion, and lymph node metastasis were more likely to be observed in SRCSB than in SBA and MSBA. Surgery was the most common treatment modality in all groups. The prognosis of SBA was similar to that of MSBA, but better than that of SRCSB in both unmatched and matched cohorts. M stage, surgery, and chemotherapy were identified as independent predictors of survival in all patients. Surgery and chemotherapy could significantly improve outcomes in all groups before and after PSM. Radiotherapy was associated with a survival benefit in patients with SBA, but this trend was not maintained after PSM. Survival advantages of SBA and MSBA were remarkable in the stratified analysis of surgery after PSM. CONCLUSION: Patients with SRCSB had the worst prognosis among all histological types examined. However, surgery and chemotherapy could improve patients survival, regardless of histological type.

Tumor Microenvironmental Prognostic Risk in Primary Operable Small Intestinal Adenocarcinoma.

The tumor microenvironment (TME) has become an important area of investigation with respect to improving prognosis in malignancies. Here we evaluated TME prognostic risk in small intestinal adenocarcinomas based on histologic assessment of tumor budding at the peritumoral-invasive front (pTB) and stromal tumor-infiltrating lymphocytes (sTILs). pTB and sTILs were analyzed in 230 surgically resected small intestinal adenocarcinomas, as recommended by the International Tumor Budding Consensus Conference (ITBCC) and the International TILs Working Group (ITWG). On the basis of high levels of pTB count (≥10) and sTIL density (≥20%), we combined pTB and sTIL to produce a collective TME-based prognostic risk index: low-risk (pTBLow/sTILHigh; n=39, 17.0%), intermediate-risk (pTBLow/sTILLow or pTBHigh/sTILHigh; n=99, 43.0%), and high-risk groups (pTBHigh/sTILLow; n=92, 40.0%). TME risk index provided better prognostic stratification than the individual pTB and sTIL (14.9 vs. 6.7 vs. 10.3). Tumors with higher TME prognostic risk were associated with an infiltrative growth pattern and nonintestinal immunophenotype (both P=0.001), pancreatic invasion (P=0.010), lymphovascular (P<0.001) or perineural invasion (P=0.006), higher T-category (P<0.001), N-category (P=0.004), and stage grouping (P=0.002), and KRAS mutation (P=0.008). In multivariate analysis, higher TME prognostic risk index (P<0.001), distal tumor location and nonintestinal immunophenotype (both P=0.001), higher N-category (P<0.001), and microsatellite stable (P=0.015) were worse-independent prognosticators. TME prognostic risk index consistently stratified patient survival regardless of tumor location (P<0.001 in proximal; P=0.002 in distal), stages (P<0.001 in lower stages I to II; P=0.028 in stage III), and DNA mismatch repair gene status (P<0.001 in microsatellite stable; P=0.001 in microsatellite instability). TME risk index is a powerful prognostic predictor for risk stratification of patients with small intestinal adenocarcinoma.

Simple Versus Radical Resection for Duodenal Adenocarcinoma: A Propensity Score Matched Analysis of National Cancer Database.

BACKGROUND: Duodenal adenocarcinoma treatment consists of either simple or radical surgical resection. Existing evidence suggests similar survival outcomes between the two but is limited by small numbers and single-institution analysis. We aim to compare survival after partial versus radical resection for duodenal adenocarcinoma using the National Cancer Database (NCDB). METHODS: Using NCDB results from 2004 to 2014, we compared patients with duodenal adenocarcinoma undergoing partial resection (n = 1247) and radical resection (n = 1240) by age, sex, facility type, facility location, cancer stage, cancer grade, lymph node sampling, node status, tumor size, margin status, neoadjuvant therapy, and adjuvant therapy using chi-square analysis. Survival was compared using propensity matching. RESULTS: Patients undergoing partial resection had overall earlier cancer stage, more favorable tumor grade, and were less likely to undergo lymph node sampling and neoadjuvant therapy. When overall survival was compared between the 2 propensity-matched groups, the median survival was 46.7 months after partial resection and 43.2 months after radical resection (P = .329), and overall survival was similar between the 2 groups (P = .894). The use of adjuvant therapy demonstrated improved survival over either surgery alone (P < .0001, P = .0037). CONCLUSION: Partial resection did not demonstrate worse survival outcomes than radical resection for duodenal adenocarcinoma. The use of adjuvant therapy in addition to surgery demonstrated improved survival regardless of surgery type and played a larger role in survival than the type of surgery. Our findings provide evidence to support the continued use of both partial and radical surgical resections to treat duodenal malignancy.

Clinical outcomes of tumor bleeding in duodenal gastrointestinal stromal tumors: a 20-year single-center experience.

BACKGROUND: Duodenal gastrointestinal stromal tumors (GISTs) are rare, and reports on duodenal GIST bleeding are few. We analyzed the risk factors and clinical outcomes of hemorrhagic duodenal GISTs and compared them with those of gastric GISTs. METHODS: Primary duodenal GISTs surgically diagnosed between January 1998 and December 2017 were retrospectively reviewed. Furthermore, patients with duodenal GIST were compared with those with primary gastric GIST histopathologically diagnosed between January 1998 and May 2015 using previously published data. RESULTS: Of the 170 total patients with duodenal GISTs, 48 (28.2%) exhibited tumor bleeding. Endoscopic intervention, embolization, and non-interventional conservative treatment were performed for initial hemostasis in 17, 1, and 30 patients, respectively. The 5-year survival rate was 81.9% in the bleeding group and 89.4% in the non-bleeding group (P = 0.495). Multivariate analysis showed that p53 positivity was a significant risk factor for duodenal GIST bleeding (hazard ratio [HR] 2.781, P = 0.012), and age ≥ 60 years (HR 3.163, P = 0.027), a large maximum diameter (comparing four groups: < 2, 2-5, 5-10, and ≥ 10 cm), and mitotic count ≥ 5/high-power field (HPF) (HR 3.265, P = 0.032) were risk factors for overall survival. The incidence of bleeding was significantly higher in duodenal GISTs than in gastric GISTs (28.2% vs. 6.6%, P < 0.001), and the re-bleeding rate after endoscopic hemostasis was also higher in duodenal GISTs than in gastric GISTs (41.2% vs. 13.3%, P = 0.118). CONCLUSION: In patients with duodenal GIST with old age, large tumor diameter, and mitotic count ≥ 5/HPF, a treatment plan should be established in consideration of the poor prognosis, although tumor bleeding does not adversely affect the prognosis. Duodenal GISTs have a higher incidence of tumor bleeding and re-bleeding rate after endoscopic hemostasis than gastric GISTs.

The Role of Neoadjuvant Versus Adjuvant Therapy for Duodenal Adenocarcinoma: A National Cancer Database Propensity Score Matched Analysis.

INTRODUCTION: Adjuvant therapy is recommended in duodenal adenocarcinoma (DA), but the role of neoadjuvant therapy remains undefined. We compared the effect of neoadjuvant therapy to adjuvant therapy on overall survival, 30-day, and 90-day mortality following the resection of DA. METHODS: A retrospective review of the National Cancer Database was performed on patients with DA who received either adjuvant or neoadjuvant therapy in addition to surgical resection. Propensity score matching was done for patient, socioeconomic, and tumor characteristics. Overall survival, 30-day, and 90-day mortality were compared. RESULTS: A total of 112 patients were identified; 55 received adjuvant therapy; 57 received neoadjuvant therapy. There was no difference in 30-day (0% vs. 1.75%; P = 1.00), 90-day mortality (1.82% vs. 7.02%; P = .36), nor overall survival (1 yr: 86% vs. 76; 3 yr: 49% vs. 46%; 5 yr: 42% vs. 39%; P = .28). CONCLUSIONS: There was no difference in overall survival after propensity score matched analysis.

Duodenal, ampullary, and pancreatic neuroendocrine tumors: Oncologic outcomes are driven by tumor biology and tissue of origin.

BACKGROUND: Periampullary neuroendocrine tumors (NETs) arise from the duodenum, ampulla, and periampullary pancreas. Duodenal and ampullary NETs are rare and may have distinct biologic behavior from pancreatic NETs (P-NETs). We examined the outcomes of these entities. METHODS: An institutional database was queried for patients undergoing resection for pancreatic head, duodenal, or ampullary NETs from 2000 to 2018. Patients with MEN1 syndrome or follow up less than 12 months were excluded. RESULTS: Three hundred and ten patients were identified. Tumor locations were ampulla (n = 15), duodenum (n = 35) and pancreas (n = 260). Median follow-up and recurrence-free survival (RFS) were 60.9 (interquartile range [IQR]: 34.8-99.3) and 171.7 (IQR: 84.0-NR) months. Clinicopathologic data and survival outcomes were similar for duodenal and ampullary NETs (RFS: p = .347 and overall survival [OS]: p = .246) and were combined into an intestinal subtype (IS) group. There were no differences in OS or RFS when comparing IS-NET and P-NET. On multivariate analysis, tissue of origin was not associated with risk of recurrence. The current American Joint Committee on Cancer staging guidelines, which account for origin tissue, were predictive of outcomes for all subtypes. CONCLUSION: Tissue of origin does not appear to impact long-term outcomes when comparing IS-NETs and P-NETs. The AJCC staging system offers good discriminatory capacity in the context of the tissue type.

Comparative Analysis of Outcomes and Clinicopathological Characteristics of Duodenal Adenocarcinoma: A SEER Analysis.

Duodenal adenocarcinoma is an uncommon, malignant tumor usually accompanied by a poor prognosis. We identified 3150 duodenal adenocarcinoma cases from the SEER database (1988-2013) to analyze clinical characteristics and outcomes. The Kaplan-Meier method was used to evaluate cancer-specific survival (CSS). Cox regression analysis was used to explore the prognostic factors of CSS. Adverse prognostic factors include higher tumor grade, later stage, tumor size ≥ 2cm, positive regional lymph nodes, and not undergoing surgical resection. Our results suggest, surgery is the optimal treatment for duodenal cancer, and combined radiotherapy does not improve survival.

Survival outcomes after surgical management of sporadic or familial adenomatous polyposis associated duodenal cancer.

BACKGROUND: Duodenal cancer is the second most common cause of cancer death in familial adenomatous polyposis (FAP) patients. In this study, we compare oncologic outcomes between sporadic and FAP-associated duodenal cancer. METHODS: In this retrospective study, all patients who underwent surgeries between 2000 and 2014 for either sporadic or FAP duodenal cancer were identified. The patients were grouped based on diagnoses and perioperative and survival outcomes were compared. RESULTS: A total of 56 patients with duodenal cancer (43 sporadic, 13 FAP) who underwent surgery were identified. Pancreatoduodenectomy (PD) was the most common procedure performed. The overall median survival was 7.5 years (1 year: 92%; 5 years: 58.1%). FAP patients had earlier tumor, node, and metastasis stage, less margin involvement, less perineural, and angiolymphatic invasion but had a comparable survival to sporadic patients. The median survival for FAP duodenal cancer was 7.4 vs 9.6 years for sporadic (P = .97) with similar utilization of adjuvant chemotherapy. Although not statistically significant, PD had an improved median survival compared to segmental duodenal resection (SDR) (9.6 years for PD vs 3.6 years for SDR, P = .17). Non-periampullary location and presence of positive lymph nodes were significant predictors of mortality on multivariate analysis. CONCLUSIONS: FAP duodenal cancer has no survival advantage compared to sporadic duodenal cancer despite an improved stage of resection with extraampullary lesions having a worse survival.

Negative Lymph Node Count is an Independent Impact Factor for Predicting the Specific Survival of Primary Duodenal Neoplasms under Surgical Procedures.

BACKGROUND: The work aimed to assess the influence of negative lymph node numbers on specific survival of primary duodenal neoplasms under surgical procedures. METHODS: This study focused on the primary duodenal neoplasm patients that have been registered in the "surveillance, epidemiology, and end results" (SEER). First, the important factors were screened by the Kaplan-Meier (Log-rank) in R and the Cox's proportional hazards regression model. Subsequently, a nomogram was established based on key proportional hazards including the negative lymph node count. Finally, the analysis of the specific survival by Kaplan-Meier (Log-rank) and X-Tile was performed to identify the cutoff values of negative lymph node numbers. RESULTS: There were 463 selected patients. Five impact factors were screened including the negative lymph node count (between 10 and 32), age (< 73), differentiation of cancers (well or moderate), primary tumors' invasion to tissues' superficial parts, no distant metastasis. The C-index of the nomogram in this paper was 0.74. CONCLUSIONS: The negative lymph node count and the other four factors were used for predicting the specific survival of primary duodenal neoplasms under surgical treatment, and the highest 2-year cancer's specific survival occurred when the negative lymph node numbers were 10 - 32. Besides, the nomogram in this paper proved to be more useful in predicting the survival effects than the traditional American Joint Committee on Cancer classifica-tion methods.

Development and Validation of Prognostic Nomograms for Patients with Duodenal Neuroendocrine Neoplasms.

BACKGROUND This study was designed to predict prognosis of patients with primary duodenal neuroendocrine neoplasms (D-NENs) by developing nomograms. MATERIAL AND METHODS Patients diagnosed with D-NENs between 1988 and 2015 were queried from the SEER database and a total of 965 appropriate cases were randomly separated into the training and validation sets. Kaplan-Meier analysis was used to generated survival curves, and the difference among the groups was assessed by the log-rank test. Independent prognostic indicators were acquired by Cox regression analysis, and were used to develop predictive overall survival (OS) and cancer-specific survival (CSS) nomograms. Harrell's concordance index (C-index), area under the curve (AUC), calibration curves, and decision curve analysis (DCA) were used to assess the efficacy of nomograms. Tumor stage was regarded as a benchmark in predicting prognostic compared with the nomograms built in this study. RESULTS The C-index was 0.739 (0.690-0.788) and 0.859 (0.802-0.916) for OS and CSS nomograms, respectively. Calibration curves exhibited obvious consistency between the nomograms and the actual observations. In addition, C-index, AUC, and DCA were better than tumor stage in the evaluative performance of nomograms. CONCLUSIONS The nomograms were able to predict the 1-, 5-, and 10-year OS and CSS for D-NENs patients. The good performance of these nomograms suggest that they can be used for evaluating the prognosis of patients with D-NENs and can facilitate individualized treatment in clinical practice.

Clinicopathological Features, Treatment Strategy, and Prognosis of Primary Non-Hodgkin's Lymphoma of the Duodenum: A SEER Database Analysis.

Objective: Primary duodenum lymphoma (PDL) is extremely rare with limited data available in the literature. In this study, we sought to describe clinical features and identify factors affecting survival in patients with PDL using a large population cohort. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried from 1998 to 2015. Results: A total of 1060 cases of PDLs were identified. Clinicopathological features as well as survival data of PDLs were analyzed and compared with 10573 primary gastric lymphomas (PGLs) and 3239 primary small intestinal lymphomas (PSILs) from the SEER database. PDL patients were younger in age (60.96 ± 15.205), and the proportion of stage I (53.21%) was higher in Ann Arbor staging. The proportion of PDLs treated by surgery (8.68%) is the lowest among PDLs, PGLs, and PSILs. The DSS of PDLs were significantly better than those of PGLs and PSILs, respectively (10-year survival rate: 21.24% vs. 20.40%, P=0.027; 10-year survival rate: 21.24% vs. 16.79%, P=0.001). Age, gender, Ann Arbor staging, and histological type were regarded as independent prognostic factor for the DSS by multivariate analysis (all P < 0.05). Patients with <65 years, female, stage I, and FL were found to be significantly associated with good DSS. The treatment modality (surgery vs. conservative treatment) was not statistically related to DSS. The proportion of PDL patients who received surgical treatment gradually decreased from 15.60% in period 2 to 5.26% in period 4. Conclusions: The clinicopathologic features of duodenal lymphoma were significantly different from those of gastric lymphoma and small intestinal lymphoma. The prognosis of PDLs was significantly better than those of the other two groups, and there was no statistical survival benefit from surgery in PDLs.

Small Bowel Adenocarcinomas: Impact of Location on Survival.

BACKGROUND: Proximal (duodenal) small bowel adenocarcinomas have a worse prognosis than distal (jejuno-ileal) tumors, but differences in patient, tumor, and treatment factors between locations remain unclear. METHODS: Patients in the National Cancer Database with surgically resected pathologic stage I-IV small bowel adenocarcinomas between 2004 and 2015 were analyzed. Clinical stage IV patients were excluded. RESULTS: Proximal tumors (n = 3767) were more likely to be higher grade (OR 1.52, CI 1.22-1.85 for moderately; OR 1.83, CI 1.49-2.33 for poorly differentiated, P < 0.01 for both) and have positive lymph nodes (OR 2.04, CI 1.30-3.23, P < 0.01), while distal tumors (n = 3252) were likely to be larger (OR 1.31, CI 1.07-1.60 for size > 5 cm, P < 0.01). Proximal tumors were associated with worse overall survival (OS) and stage-specific survival compared with distal tumors (all P < 0.01). Cox regression analysis of the entire cohort showed worse survival with community versus academic cancer programs, higher comorbidity scores, pathologic stage IV, poorly differentiated histology, positive nodal or margin status, and proximal location, while female gender, larger tumor size, and chemotherapy predicted better survival. On separate Cox regression analyses of each location, neoadjuvant chemotherapy was associated with better OS in the proximal cohort (HR 0.70, CI 0.55-0.88, P < 0.01), while adjuvant chemotherapy was associated with better OS for both proximal (HR 0.49, CI 0.42-0.57, P < 0.01) and distal tumors (HR 0.68, CI 0.57-0.81, P < 0.01). CONCLUSIONS: Proximal small bowel adenocarcinomas are associated with worse overall and stage-specific survival. This may be due to tumor biologic differences as proximal tumors were more likely to have higher grade. Future studies should further investigate differences between proximal and distal tumors to guide targeted treatment algorithms.

Prognostic factors and benefits of adjuvant therapy for ampullary cancer following pancreatoduodenectomy: A systematic review and meta-analysis.

Ampullary cancer is a relatively rare gastrointestinal malignancy. The purpose of this study was to evaluate prognostic factors for survival and assess the benefits of adjuvant therapy following pancreaticoduodenectomy for this entity. Medline and EMBASE databases were searched to identify eligible studies from January 2000 to August 2019. Review Manager 5.3 statistical software was used for meta-analysis. 71 studies met the inclusion criteria and were included in the analysis for a total of 8280 patients. The median (range) 5-year overall survival and disease-free survival rates were 58% (32-82%) and 51% (28-73%) respectively. In meta-analysis, age >65 years at diagnosis, tumor size >20 mm, poor differentiation, pancreaticobiliary histotype, pT3-4 stage disease, presence of metastatic lymph node, number of metastatic nodes, perineural invasion, lymphovascular invasion, vascular invasion, pancreatic invasion, and positive surgical margins were independently associated with worse overall survival, whereas adjuvant therapy was associated with improved overall survival. In summary, in patients with ampullary cancer undergoing pancreaticoduodenectomy, tumor factors are the main predictors of worse survival and adjuvant treatment confers a survival benefit.

Prognostic relevance of programmed death-ligand 1 expression and microsatellite status in small bowel adenocarcinoma.

Background: Small bowel adenocarcinoma (SBA) is a dreadful disease. Patient prognosis is limited due to late presentation and ineffective chemotherapy. PD-1/PD-L1 checkpoint immunotherapy is regarded as a promising approach in several cancer entities. The association of PD-1/PD-L1 expression and its impact on patient prognosis with SBA is unclear. Material and methods: Seventy-five consecutive patients who underwent surgery for SBA were retrospectively analyzed and stained for PD-L1 expression in the tumour or the stroma. Analysis of mismatch repair genes was performed to determine microsatellite status. Kaplan-Meier estimate was used to analyze patient survival. Univariate and multivariable Cox regression-analyses were used to assess the impact of PD-L1 expression and microsatellite status on patient survival.Results: PD-L1 was weakly upregulated within the tumour or the stroma and associated with prolonged survival (p = .0071 and p = .0472, respectively). Fifty-one tumours (68%) revealed microsatellite stability (MSS) and 24 tumours (32%) were microsatellite instable (MSI) without correlating with patient survival (p = .611). Neither PD-L1 expression in the tumour nor in the stroma was identified as an independent risk factor influencing survival (p = .572 and p = .3055).Conclusion: Although PD-L1 expression is associated with prolonged survival, it was not identified as an independent prognostic marker. Microsatellite status did not influence long-term survival.