Ampullary Neuroendocrine Tumors: Insight into a Rare Histology.

BACKGROUND: Ampullary neuroendocrine tumors (NETs) make up < 1% of all gastroenteropancreatic NETs, and information is limited to case series. This study compares patients with ampullary, duodenal, and pancreatic head NETs. METHODS: The National Cancer Database (2004-2016) was queried for patients with ampullary, duodenal, and pancreatic head NETs. Survival was evaluated using Kaplan-Meier analysis and Cox regression. RESULTS: Overall, 872, 9692, and 6561 patients were identified with ampullary, duodenal, and pancreatic head NETs, respectively. Patients with ampullary NETs had more grade 3 tumors (n = 149, 17%) than patients with duodenal (n = 197, 2%) or pancreatic head (n = 740, 11%) NETs. Patients with ampullary NETs had more positive lymph nodes (n = 297, 34%) than patients with duodenal (n = 950, 10%) or pancreatic head (n = 1513, 23%) NETs. On multivariable analysis for patients with ampullary NETs, age (hazard ratio [HR] 1.03, p < 0.0001), Charlson-Deyo score of 2 (HR 2.3, p = 0.001) or ≥3 (HR 2.9, p = 0.013), grade 2 (HR 1.9, p = 0.007) or grade 3 tumors (HR 4.0, p < 0.0001), and metastatic disease (HR 2.0, p = 0.001) were associated with decreased survival. At 5 years, the overall survival (OS) for patients with ampullary, duodenal, and pancreatic head NETs was 59%, 71%, and 50%, respectively (p < 0.0001), whereas the 5-year OS for patients with ampullary, duodenal, and pancreatic head NETs who underwent surgery was 62%, 78%, and 76%, respectively (p < 0.0001). CONCLUSIONS: Ampullary NETs were more likely to present with high-grade tumors and lymph node metastases. Based on the clinicopathologic and survival data, ampullary NETs have a unique underlying biology compared with duodenal and pancreatic head NETs.

Association between adipokines and critical illness outcomes.

BACKGROUND: Adipose tissue is an endocrine organ that plays a critical role in immunity and metabolism by virtue of a large number of hormones and cytokines, collectively termed adipokines. Dysregulation of adipokines has been linked to the pathogenesis of multiple diseases, but some questions have arisen concerning the value of adipokines in critical illness setting. The objective of this review was to evaluate the associations between blood adipokines and critical illness outcomes. METHODS: PubMed, CINAHL, Scopus, and the Cochrane Library databases were searched from inception through July 2016 without language restriction. Studies reporting the associations of adipokines, leptin, adiponectin, resistin, and/or visfatin with critical illness outcomes mortality, organ dysfunction, and/or inflammation were included. RESULTS: A total of 38 articles were selected according to the inclusion/exclusion criteria of the study. Significant alterations of circulating adipokines have been reported in critically ill patients, some of which were indicative of patient outcomes. The associations of leptin and adiponectin with critical illness outcomes were not conclusive in that blood levels of both adipokines did not always correlate with the illness severity scores or risks of organ failure and mortality. By contrast, studies consistently reported striking increase of blood resistin and visfatin, independently of the critical illness etiology. More interestingly, increased levels of these adipokines were systematically associated with severe inflammation, and high incidence of organ failure and mortality. CONCLUSIONS: There is strong evidence to indicate that increased levels of blood resistin and visfatin are associated with poor outcomes of critically ill patients, including higher inflammation, and greater risk of organ dysfunction and mortality. LEVEL OF EVIDENCE: Systematic review, level III.

Digital communications and social media use in surgery: how to maximize communication in the digital age.

Communication among patients, colleagues, and staff in healthcare has changed dramatically in the last decade. Digital technology and social media sites have allowed instantaneous access to information. The potential for information technology to improve access to healthcare, enhance the quality, and lower the cost is significant. Text messaging, tweeting, chatting, and blogging are rapidly replacing e-mail as the preferred means of communication in healthcare. This review will highlight how digital technology is changing the way surgeons communicate with colleagues and patients as well as provide some guidance as to how to avoid some of the pitfalls and problems that this form of communication can bring.

Open repair of large abdominal wall hernias with and without components separation; an analysis from the ACS-NSQIP database.

BACKGROUND: Components separation technique emerged several years ago as a novel procedure to improve durability of repair for ventral abdominal hernias. Almost twenty-five years since its initial description, little comprehensive risk adjusted data exists on the morbidity of this procedure. This study is the largest analysis to date of short-term outcomes for these cases. METHODS: The ACS-NSQIP database identified open ventral or incisional hernia repairs with components separation from 2005 to 2012. A data set of cohorts without this technique, matched for preoperative risk factors and operative characteristics, was developed for comparison. A comprehensive risk-adjusted analysis of outcomes and morbidity was performed. RESULTS: A total of 68,439 patients underwent open ventral hernia repair during the study period (2245 with components separation performed (3.3%) and 66,194 without). In comparison with risk-adjusted controls, use of components separation increased operative duration (additional 83 min), length of stay (6.4 days vs. 3.8 days, p < 0.001), return to the OR rate (5.9% vs. 3.6%, p < 0.001), and 30-day morbidity (10.1% vs. 7.6%, p < 0.001) with no increase in mortality (0.0% in each group). CONCLUSIONS: Components separation technique for large incisional hernias significantly increases length of stay and postoperative morbidity. Novel strategies to improve short-term outcomes are needed with continued use of this technique.

Tube cholecystostomy before cholecystectomy for the treatment of acute cholecystitis.

BACKGROUND AND OBJECTIVES: Percutaneous cholecystostomy is currently indicated for patients with cholecystitis who might be poor candidates for operative cholecystectomy. We performed a study to evaluate the long-term outcome of patients undergoing emergent tube cholecystostomy. METHODS: This study was a retrospective chart review of patients who underwent tube cholecystostomy from July 1, 2005, to July 1, 2012. RESULTS: During the study period, 82 patients underwent 125 cholecystostomy tube placements. Four patients (5%) died during the year after tube placement. The mean hospital length of stay for survivors was 8.8 days (range, 1-59 days). Twenty-eight patients (34%) required at least 1 additional percutaneous procedure (range, 1-6) for gallbladder drainage. Twenty-nine patients (34%) ultimately underwent cholecystectomy. Surgery was performed a mean of 7 weeks after cholecystostomy tube placement. Laparoscopic cholecystectomy was attempted in 25 operative patients but required conversion to an open approach in 8 cases (32%). In another 4 cases, planned open cholecystectomy was performed. Major postoperative complications were limited to 2 patients with postoperative common bile duct obstruction requiring endoscopic retrograde cholangiopancreatography, 1 patient requiring a return to the operating room for hemoperitoneum, and 2 patients with bile leak from the cystic duct stump. CONCLUSIONS: In high-risk patients receiving cholecystostomy tubes for acute cholecystitis, only about one third will undergo surgical cholecystectomy. Laparoscopic cholecystectomy performed in this circumstance has a higher rate of conversion to open surgery and higher hepatobiliary morbidity rate.

Race/Ethnicity is predictive of lymph node status in patients with early gastric cancer.

BACKGROUND: Race/ethnicity has long been suspected to affect survival in patients with gastric adenocarcinoma. However, the clinicohistopathological impact of race or ethnicity on early gastric cancer (EGC) is not known. METHODS: From 2000 to 2013, 286 patients underwent gastrectomy and 104 patients had pathological confirmation of EGC. A retrospective analysis of pathological and clinical prognostic indicators was performed. RESULTS: The study population consisted of 38 (37%) Asian Americans and 66 (63%) non-Asian Americans. Of these, 2 (5.3%) Asian Americans and 19 (28.8%) non-Asian Americans had pathological confirmation of lymph node metastasis (LNM) (p = 0.004). Univariate analysis comparing the clinicohistopathological characteristics in each group did not reveal significant difference regarding histotype, tumor size, grade, location, morphology, or lymphovascular invasion, except for the LNM rate and mean body mass index (23.2 versus 26.6, p < 0.001). Multivariate analysis showed that non-Asian race/ethnicity (odds ratio (OR), 9.09; 95% confidence interval (CI), 1.12-71.43; p = 0.038), younger age (OR, 1.11; 95% CI, 1.01-1.12; p = 0.046), and lymphovascular invasion (OR, 13.9; 95% CI, 2.40-79.99; p = 0.003) were significant predictors for LNM. CONCLUSIONS: This study demonstrated that Asian American race in EGC is associated with a significantly decreased rate of LNM in comparison to non-Asian Americans, despite similar histopathological characteristics of each group.

Palliative treatment and the role of surgical resection in gastric cancer.

Adenocarcinoma of the stomach is often diagnosed in the late stages of the disease. Surgical resection of all gross and microscopic disease is essential for curative treatment. Complete resection is often not achievable when patients present with advanced stage IV cancer. In the absence of symptoms, chemotherapy without resection has been the standard of care in most major centers. With improvements in response to chemotherapy and less invasive surgical approaches, patients with metastatic gastric cancer have had better survival outcomes than in the past. The challenge today when treating these patients is in defining who will benefit from more aggressive interventions. Reviewing the literature for guidance is difficult because the goals of treatment are often not clearly defined. Finding the proper balance of aggressiveness needed to extend survival while preserving and maximizing quality of life is a decision that clinicians have to make with increasing frequency. This review will attempt to provide a framework to aid in determining what role, if any, gastrectomy has in the management of patients with stage IV gastric cancer.

Early results of trans-oral endoscopic plication and revision of the gastric pouch and stoma following Roux-en-Y gastric bypass surgery.

OBJECTIVE: A new technique for endoscopic plication and revision of the gastric pouch (EPRGP) for patients who underwent gastric bypass (RGB) surgery was evaluated in patients with severe GERD, dumping syndrome, failure of weight loss, or all of these. PATIENTS AND METHODS: Patients underwent EPRGP over a 12-month period. The StomaphyX device (Endogastric Solutions, Redmond, WA) was utilized over a standard flexible gastroscope. Patients were kept on a liquid diet for 1 week. RESULTS: The study included 64 patients with a mean age of 48 years who underwent 67 procedures. EPRGP was performed an average of 5 years after RGB. The mean preoperative BMI was 39.5 kg/m². The primary indications for the procedure were inadequate weight loss, dumping syndrome (42), and GERD (15). The mean follow-up period was 5.8 months (range, 3 to 12). The average operative time was 50 minutes, with a significant reduction with increased operator experience. There were only 2 (3%) intraoperative complications during the early period (equipment failure), which did not result in any morbidity. All symptoms from dumping syndrome or reflux improved, with no further operative-related complications. The mean weight loss was 7.3 kg. CONCLUSIONS: This study demonstrates the technical feasibility, safety, and efficacy of EPRGP.

Phenotypic subpopulations of metastatic colon cancer stem cells: genomic analysis.

BACKGROUND: Human cancer is characterized by high heterogeneity in gene expression, varieties of differentiation phenotypes and tumor-host interrelations. Growing evidence suggests that tumor-initiating, or cancer stem cells (CSCs), may also represent a heterogeneous population. The present study was undertaken to isolate and characterize the different phenotypic subpopulations of metastatic colon cancer and to develop a working colon CSC model for obtaining highly tumorigenic and clonogenic cells in sufficient numbers. MATERIALS AND METHODS: Different phenotypic cell subpopulations were isolated based on differential levels and patterns of expression of several stemness markers, including CD133, CD44, CD166 and CD49b. Stemness properties of isolated cells were tested by analysis of their ability to form floating colonospheres in vitro, to induce tumors in NOD/SCID mice after transplantation at relatively low cell numbers, and to produce progenitors of different phenotypes. RESULTS: The metastatic colon cancer HCT116 cell line, which expressed a majority of known CSC markers, closely resembling the patterns of expression in exfoliated peritoneal cells from several metastatic colon cancer patients, was selected as a reference material. Genome-wide microarray analysis (Affymetrix; DAVID) of CD133(high) CSC-enriched versus CSC-depleted cell populations revealed 4,351 differentially expressed genes with an overrepresentation of those responsible for apoptosis resistance, regulation of cell cycle, proliferation, stemness and developmental pathways. Simultaneous analysis of 84 stem cell- and metastasis-related genes with corresponding PCR arrays identified genes differentially expressed in several colon CSC phenotypic populations versus bulk tumor cells, and in relation to each other. It was found that colonospheres induced by tumorigenic cells with the highest expression of CD133 and those which were induced by CD133/CD44-negative cells possessed profoundly different stem cell-related gene expression profiles. CONCLUSION: The proposed approaches allow for reliable isolation and propagation of highly tumorigenic and clonogenic cells of different phenotypes. Genomic analysis of several candidate CSC phenotypic populations may contribute to the identification of novel targets for colon cancer stem cell-targeted drug development and treatment.

Clinical significance of telomerase activity in peritoneal disseminated cells: gastrointestinal cancers.

Early detection and accurate staging of gastrointestinal (GI) cancers are difficult. The aim of this study was to evaluate whether telomerase activity (TA) in exfoliated/disseminated epithelial cells could be used as a reliable marker for GI cancers. TA was evaluated with the real-time RTQ-TRAP in immunomagnetically sorted peritoneal epithelial cells from 60 patients undergoing surgical treatment. Thirty-two patients were clinically diagnosed with a variety of GI cancers: 1 had premalignant disease, 2 had history of GI cancers, and 25 patients were clinically negative for cancer. Here we report that all types and all cases of gastrointestinal cancers were telomerase positive, thereby demonstrating 100% sensitivity for cancer. Eighteen of 25 nonmalignant cases had undetectable levels of TA, 2 had low, and 5 of 25 expressed high TA levels. Because normal epithelial cells usually have low TA and a lesser tendency to exfoliate compared with cancer cells, it is of great importance to have close follow-up for these patients to exclude possible malignant disease. We conclude that RTQ-TRAP assessment of TA in immunomagnetically sorted peritoneal epithelial cells has 100% sensitivity and 100% negative predictive value for GI cancers, and therefore, can be considered as a valuable tool and useful addition to current standard diagnostic methods. Clinical significance of unusually high telomerase activity in some clinically negative for cancer cases requires further study.

Measuring outcomes in randomized prospective trials in palliative care.

Palliative care aims to improve the quality of life of patients and their families and reduce suffering from life-threatening illness. In assessing palliative care efficacy, researchers must consider a broad range of potential outcomes, including those experienced by the patient's family/caregivers, clinicians, and the health care system. The purpose of this article is to summarize the discussions and recommendations of an Outcomes Working Group convened to advance the palliative care research agenda, particularly in the context of randomized controlled trials. These recommendations address the conceptualization of palliative care outcomes, sources of outcomes data, application of outcome measures in clinical trials, and the methodological challenges to outcome measurement in palliative care populations. As other fields have developed and refined methodological approaches that address their particular research needs, palliative care researchers must do the same to answer important clinical questions in rigorous and credible ways.

Evolution of preoperative and postoperative therapies in the management of localized gastroesophageal cancers.

Recent changes in the epidemiology of gastroesophageal cancers in the United States and many parts of Europe require reassessment of traditional surgical and adjuvant treatment approaches to these tumors. Careful preoperative staging and classification aid in the selection of appropriate treatments. While molecular genetic methods to distinguish esophageal from gastric tumor origins are awaited, a practical system that classifies adenocarcinomas of the esophagogastric junction into one of three types is contributing to the understanding of these tumors as well as determining the best surgical approach. Treatments that have significantly improved outcomes over those achieved with surgery alone include neoadjuvant chemotherapy with epirubicin, cisplatin, and 5-fluorouracil (ECF), or postoperative chemoradiotherapy using 5-fluorouracil, leucovorin, and 45 Gy radiation. This paper reviews studies of preoperative and postoperative chemotherapy and radiotherapy in patients with gastroesophageal cancers, as well as studies of the optimal extent of lymph node dissection.

RAB32 hypermethylation and microsatellite instability in gastric and endometrial adenocarcinomas.

The recently described gene, RAB32, is a ras proto-oncogene family member that encodes an A-kinase-anchoring protein. RAB32 has been found to be frequently hypermethylated in microsatellite instability-high (MSI-H) colon cancers. We sought to determine the prevalence of RAB32 hypermethylation in gastric and endometrial adenocarcinomas, the 2 other major tumor types in which MSI-H is common. Moreover, we delineated the association of RAB32 hypermethylation with microsatellite instability (MSI) and hMLH1 hypermethylation. MSI status and hypermethylation of the RAB32 and hMLH1 genes were studied in paired primary normal and tumor tissues from 48 patients with gastric cancer. An additional 80 endometrial cancer patients were studied for RAB32 methylation and MSI status. Thirteen (27%) of 48 gastric cancers demonstrated evidence of RAB32 hypermethylation. MSI status was determined in 46 of the tumors, with 7 (100%) of 7 MSI-H tumors, 1 (33%) of 3 MSI-low (MSI-L) tumors and 4 (11%) of 36 microsatellite-stable (MSS) tumors found to harbor RAB32 hypermethylation. RAB32 methylation was significantly associated with intestinal type histology and concomitant hMLH1 hypermethylation in gastric cancer. In contrast, RAB32 methylation occurred in only 1 of 80 endometrial cancers, including 20 MSI-H, 8 MSI-L and 52 MSS tumors. Hypermethylation of hMLH1 was noted in 16 (20%) of 80 endometrial tumors. We conclude that although RAB32 methylation is rare in endometrial cancers, it is strongly associated with hMLH1 hypermethylation and MSI in gastric adenocarcinomas. Given its similar involvement in colon cancer, RAB32 inactivation may represent a component of the oncogenic pathway of microsatellite-unstable gastrointestinal adenocarcinomas.

Clinical outcomes with laparoscopic stage M1, unresected gastric adenocarcinoma.

OBJECTIVE: For patients with laparoscopic stage M1 gastric adenocarcinoma, no resection of the primary tumor, and systemic chemotherapy, this study investigated the incidence of subsequent palliative intervention and survival. SUMMARY BACKGROUND DATA: Laparoscopy was performed for patients with computed tomography scan stage M0 disease and no significant obstruction or bleeding. METHODS: A prospectively maintained database for 1993 to 2002 was used to identify 165 patients (median age, 63 years) with laparoscopic M1 disease in the peritoneum (P1, adjacent to stomach, 9%; P2, few distant sites, 35%; or P3, disseminated, 30%) or liver (10%) or both (16%). Functional performance status (FPS, Eastern Cooperative Oncology Group) was 0 to 1 (84%) or 2 (16%). RESULTS: Subsequent intervention was performed on 50% of patients, at median interval of 4 months (range, 1-35 months) after laparoscopy. Intervention was performed on the stomach for obstruction (33%), bleeding (8%), or perforation (1%) or on a distant site for a metastasis-related complication (20%). More than one intervention (maximum, 4) was performed in 21%. Laparotomy was necessary in 12%; the remainder had endoscopic or radiologic procedures or radiation therapy only. There was one intervention-related death. Median survival was 10 months, with 1-year survival of 39%. On multivariate analysis, better FPS (0-1; odds ratio, 4; P=0.001) and limited peritoneal metastasis (P1 or P2; 2; P=0.01) were independently associated with improved survival. CONCLUSIONS: The incidence of subsequent intervention was 50%, but few patients had laparotomy. Intervention-related mortality was minimal. The burden of metastatic disease and functional performance status were important prognostic factors.

Selection of patients with gastric adenocarcinoma for laparoscopic staging.

BACKGROUND: To refine selection criteria for laparoscopic staging of gastric adenocarcinoma, preoperatively available clinical and radiologic factors that may predict the risk of M1 disease were investigated. METHODS: During 1993-2002, laparoscopy was performed if patients had minimal symptoms and there was no definite M1 disease at computed tomography (CT) scanning. High-quality, spiral, CT scans were reviewed in detail for 65 recent patients. RESULTS: Laparoscopy was conducted for 657 patients and M1 was detected in 31%. M1 was significantly more prevalent with tumor location at the gastroesophageal junction (GEJ; M1 in 42%) or whole stomach (66%), poor differentiation (36%) or age < or = 70 years (34%). On spiral CT scan, lymphadenopathy > or = 1 cm (49%) or T3/T4 tumors (63%) were associated with significantly higher prevalence of M1. On multivariate analyses, only tumor location (GEJ or whole stomach) and lymphadenopathy were independently significant and M1 was not detected in any patient with neither risk factor. CONCLUSIONS: With spiral CT staging, laparoscopy may be avoided if the primary tumor is not at the GEJ or whole stomach and there is no lymphadenopathy.

Gastric cancer: standards for the 21st century.

Although the incidence of gastric cancer has been decreasing in the United States, it remains a leading cause of cancer death in the world, only lung cancer causes more deaths worldwide. The combination of relatively low prevalence, lack of pathognomonic symptoms, and lack of defined risk factors are associated with a delay in diagnosis leading to a dismal prognosis. For localized disease, surgery remains a cornerstone of treatment but much controversy remains regarding optimal peri-operative therapy. For advanced disease, several new agents and new combination chemotherapies have offered encouraging results. This paper seeks to review the major topics surrounding gastric cancer and cover the results of recently reported and ongoing trials.

Validation of a nomogram for predicting disease-specific survival after an R0 resection for gastric carcinoma.

BACKGROUND: A statistical model for predicting disease-specific survival in patients with gastric carcinoma, based on a single U.S. institution experience, was tested for validity in a sample of patients treated at different institutions. METHODS: The authors analysed 459 patients from the Dutch Gastric Cancer trial that compared limited (D1) with extended (D2) lymph node dissection. The discrimination ability of the nomogram with respect to 5 and 9-year disease-specific survival probabilities was superior to that of the American Joint Committee on Cancer (AJCC) staging system. RESULTS: There was considerable heterogeneity of risk within many of the AJCC stages. Calibration plots suggested that predicted probabilities from the nomogram corresponded closely to actual disease-specific survival. The gastric carcinoma nomogram performed well when applied to patients treated in a large number of institutions. CONCLUSIONS: The nomogram provided predictions that discriminated better than the AJCC staging system, regardless of the extent of lymph node dissection. Patient counseling and adjuvant therapy decision-making should benefit from use of the nomogram.

Should gastric cancer surgery be performed in community hospitals?

Once the most common solid tumor malignancy in the United States, stomach cancer now ranks about 14th in incidence, with approximately 22,000 cases of adenocarcinoma of the stomach diagnosed annually. Gastrectomy for cancer is thus an infrequent operation, and indeed, the number of surgical residents completing 5-year training programs with an adequate number of gastrectomies is steadily shrinking. As time passes and experience with gastric surgery continues to diminish, questions concerning who and where gastric cancer surgery should be performed become increasingly relevant. For patients in major metropolitan areas, locating a high-volume hospital or surgeon is usually not an issue, but for a large portion of the country this may represent a major burden. Moreover, adding this additional volume of patients to an already overburdened system of a busy hospital may not be practical. A significant number of Americans continue to receive their care in low-volume hospitals. The majority of Americans receive their medical care locally and would much prefer a solution that would improve the medical care in their own back yard without altering their support system.