Metachronous Gastrointestinal Stromal Tumors of Different Histologies: An Unusual Case.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors accounting for only a small fraction of all primary malignant tumors of the gastrointestinal tract. Histologically, GISTs are classified as epithelioid, spindle type, or mixed. We present a case of a 66-year-old male incidentally noted to have a pedunculated gastric mass along the lesser curvature of the stomach during a laparoscopic Nissen fundoplication and hiatal hernia repair. A wedge resection was performed and the pathology demonstrated a 3.7 cm GIST of epithelioid type. Four years after the initial surgery, a jejunal mass was identified via CT enterography as part of a workup for ongoing iron deficiency anemia. A laparoscopic small bowel resection was performed, and the pathology revealed a new primary 3.2 cm GIST of the spindle cell subtype. Three years after surgery, surveillance imaging is negative for any recurrence. This appears to be the first report of the occurrence of metachronous primary GISTs of different histologic subtypes, separated by location.

Hybrid Approach for Treatment of a Symptomatic Giant Splenic Artery Aneurysm.

A 56-year-old female presented with a symptomatic giant fusiform mid-splenic artery aneurysm (7.3 x 6.4 cm). The patient underwent hybrid management of the aneurysm with endovascular embolization of the aneurysm and inflow splenic artery followed by laparoscopic splenectomy with control and division of the outflow vessels. The patient had an uneventful post-operative course. This case demonstrates the safety and efficacy of an innovative, hybrid management of a giant splenic artery aneurysm with endovascular embolization and laparoscopic splenectomy that spares the pancreatic tail.

Gallbladder cancer presenting as hemobilia on capsule endoscopy.

Gallbladder adenocarcinoma is a rare gastrointestinal malignancy and is associated with a poor prognosis. These malignancies are most often discovered incidentally in [Formula: see text]1% of all cholecystectomy procedures. We report an 80-year-old male patient with iron deficiency anemia, who underwent an unremarkable endoscopy and colonoscopy, and was subsequently found to have hemobilia discovered on capsule endoscopy. Magnetic resonance cholangiopancreatography revealed a space-occupying process involving the posterior wall of the gallbladder. The patient underwent an unremarkable laparoscopic cholecystectomy with final pathology revealing a well-differentiated, 8 cm intracystic papillary neoplasm with high-grade dysplasia involving the majority of the gallbladder, with focally invasive adenocarcinoma invading the muscular layer of the gallbladder wall. Postoperative staging work-up revealed no evidence of metastatic disease. Patient then underwent a radical resection of segments 4B/5 of the gallbladder fossa and lymph node resection of the porta hepatis. Final pathology revealed Stage I adenocarcinoma of the gallbladder (T1bNxM0).

Are we ready for bundled payments for major bowel surgery?

BACKGROUND: The Centers for Medicare & Medicaid Services (CMS) recently announced a new voluntary episode payment model for major bowel surgery. The purpose of this study was to examine the financial impact of bundled payments for major bowel surgery. METHODS: An institutional database was retrospectively queried for all patients who underwent major bowel surgery between July 2016 and June 2018. Procedures were categorized using MS-DRG coding: MS-DRG 329 (with MCC, major complications and comorbidity), MS-DRG 330 (with CC, complications and comorbidity), and MS-DRG 331 (without CC/MCC). RESULTS: A total of 745 patients underwent 798 procedures, with mean age 62.1 years and BMI 29.2 kg/m2. The median LOS was 4.0 days, with 12.5% of patients being discharged to a post-acute care facility for an average of 38.5 days. The mean hospital cost was $18,525. The mean payment to a post-acute care facility was $423 per day. The 90-day readmission rate was 8.6% at an average cost of $12,859 per readmission. Patients with major complications and comorbidity (MS-DRG 329) had higher CMS Hierarchical Condition Categories scores, longer LOS, higher costs, more required home health services or post-acute care facilities, and had higher 90-day readmissions. In a fee-for-service model, hospital reimbursements resulted in a negative margin of - 8.2% for MS-DRG 329, - 2.6% for MS-DRG 330, but a positive margin of 2.8% for MS-DRG 331. In a bundled payment model, the hospital would incur a loss of - 13.1%, - 11.1%, and - 1.9% for MS-DRG 329, 330, and 331, respectively. CONCLUSIONS: Patients undergoing major bowel surgery are often a heterogeneous population with varied pre-existing comorbid conditions who require a high level of complex care and utilize greater hospital resources. Further study is needed to identify areas of cost containment without compromising the overall quality of care.

Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults.

OBJECTIVE: The colonic microbiota ferment dietary fibres, producing short chain fatty acids. Recent evidence suggests that the short chain fatty acid propionate may play an important role in appetite regulation. We hypothesised that colonic delivery of propionate would increase peptide YY (PYY) and glucagon like peptide-1 (GLP-1) secretion in humans, and reduce energy intake and weight gain in overweight adults. DESIGN: To investigate whether propionate promotes PYY and GLP-1 secretion, a primary cultured human colonic cell model was developed. To deliver propionate specifically to the colon, we developed a novel inulin-propionate ester. An acute randomised, controlled cross-over study was used to assess the effects of this inulin-propionate ester on energy intake and plasma PYY and GLP-1 concentrations. The long-term effects of inulin-propionate ester on weight gain were subsequently assessed in a randomised, controlled 24-week study involving 60 overweight adults. RESULTS: Propionate significantly stimulated the release of PYY and GLP-1 from human colonic cells. Acute ingestion of 10 g inulin-propionate ester significantly increased postprandial plasma PYY and GLP-1 and reduced energy intake. Over 24 weeks, 10 g/day inulin-propionate ester supplementation significantly reduced weight gain, intra-abdominal adipose tissue distribution, intrahepatocellular lipid content and prevented the deterioration in insulin sensitivity observed in the inulin-control group. CONCLUSIONS: These data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans. TRIAL REGISTRATION NUMBER: NCT00750438.

Prostate cancer: Important steps and considerations in the design of therapeutic vaccines.

Vaccine-based immunotherapy can increase the overall survival of patients with advanced prostate cancer. However, the efficacy of vaccine-elicited anticancer immune responses is heavily influenced by the physical, nutritional, and psychological status of the patient. Given their importance, these parameters should be carefully considered for the design of future clinical trials testing this immunotherapeutic paradigm in prostate cancer patients.

Fermentable carbohydrate alters hypothalamic neuronal activity and protects against the obesogenic environment.

Obesity has become a major global health problem. Recently, attention has focused on the benefits of fermentable carbohydrates on modulating metabolism. Here, we take a system approach to investigate the physiological effects of supplementation with oligofructose-enriched inulin (In). We hypothesize that supplementation with this fermentable carbohydrate will not only lead to changes in body weight and composition, but also to modulation in neuronal activation in the hypothalamus. Male C57BL/6 mice were maintained on a normal chow diet (control) or a high fat (HF) diet supplemented with either oligofructose-enriched In or corn starch (Cs) for 9 weeks. Compared to HF+Cs diet, In supplementation led to significant reduction in average daily weight gain (mean ± s.e.m.: 0.19 ± 0.01 g vs. 0.26 ± 0.02 g, P < 0.01), total body adiposity (24.9 ± 1.2% vs. 30.7 ± 1.4%, P < 0.01), and lowered liver fat content (11.7 ± 1.7% vs. 23.8 ± 3.4%, P < 0.01). Significant changes were also observed in fecal bacterial distribution, with increases in both Bifidobacteria and Lactobacillius and a significant increase in short chain fatty acids (SCFA). Using manganese-enhanced MRI (MEMRI), we observed a significant increase in neuronal activation within the arcuate nucleus (ARC) of animals that received In supplementation compared to those fed HF+Cs diet. In conclusion, we have demonstrated for the first time, in the same animal, a wide range of beneficial metabolic effects following supplementation of a HF diet with oligofructose-enriched In, as well as significant changes in hypothalamic neuronal activity.

Effect of Lactobacillus acidophilus NCDC 13 supplementation on the progression of obesity in diet-induced obese mice.

There is an increased interest in investigating the relationship between the gut microbiota and energy homeostasis. Probiotics are health beneficial microbes mainly categorised under the genus Lactobacillus and Bifidobacterium, which when administered in adequate amounts confer health benefits to the host, and have been implicated in various physiological functions. The potential role of probiotics in energy homeostasis is a current and an emerging area of research. In the present study, Lactobacillus acidophilus NCDC 13 was used to evaluate its anti-obesity potential in diet-induced obese (C57BL/6) mice. The probiotic bacterial culture was administered in Indian yogurt preparation called 'dahi', prepared using native starter cultures, and compared with control dahi containing only dahi starter cultures. The dietary intervention was followed for 8 weeks, and whole-body fat composition, and liver and muscle adiposity were measured using MRI. Changes in gut microbiota were assessed by fluorescent in situ hybridisation in faeces and caecal contents. The feeding of the probiotic brought no changes in body-weight gain, food and dahi intake when compared with the control dahi-fed animals. No significant changes in body fat composition, liver and muscle adiposity were also observed. At the end of the dietary intervention, a significant increase (P < 0·05) in the number of total Bifidobacterium was observed in both faeces and caecal contents of mice as a result of probiotic dahi administration. Thus, L. acidophilus NCDC 13 supplementation could be beneficial in shifting the gut microbiota balance positively. However, its anti-obesity potential could not be established in the present study and warrants further exploration.

The surgeon's role in cancer prevention. The model in colorectal carcinoma.

Cancer Prevention is an emerging field, capturing the old traditional concept of anticipating the development of a major disease and preventing its full impact by early detection, treatment, or aborting the tumorigenic process by a "molecular vaccine" and alleviating the full impact of the disease. Surgeons are important clinician scientists who can carry this discipline forward and develop its full potential in the clinics and in the community. Advances in molecular biology, genetics, and other technologies have permitted seminal understanding of the carcinogenic pathways and identification of targets and intermediate end points in neoplasia. In this review, we will see that we have the means of preventing significant numbers of colorectal carcinomas (CRC).

An MVA vaccine overcomes tolerance to human p53 in mice and humans.

BACKGROUND: The cellular regulatory protein p53 is overexpressed by almost 50% of all malignancies making it an attractive target for a vaccine approach to cancer. A number of immunotherapy approaches targeting p53 have been evaluated successfully in murine models, but translation of these preclinical findings to the clinic has been unsuccessful. Prior studies in our laboratory employing murine models demonstrated that a modified vaccinia virus Ankara (MVA) vaccine expressing murine p53 could stimulate p53 specific immunity. Systemic administration of the MVA vaccine was able to effect the rejection of established tumors. To better understand the immunologic mechanisms that underlie the vaccine function of human p53, we utilized a murine model in which the murine germ line copy of p53 was replaced with a modified human one. These mice, referred to as Hupki, were evaluated as a tolerant model to explore the capacity of MVA expressing human p53 to overcome tolerance and reject human p53-expressing tumors. RESULTS: MVAp53 immunization of Hupki mice resulted in the generation of p53-specific CD8(+) T cells and the rejection of a highly aggressive murine mammary carcinoma cell line 4T1(H-2d) transfected with human p53 (4T1p53). An immunologic correlate of tumor protection was evaluated utilizing an overlapping peptide library spanning the full length of human p53. This reagent was also used in combination with MVAp53 to stimulate p53-specific CD8(+) T cell responses in cancer patients. CONCLUSION: These studies demonstrate the potential of MVAp53 to overcome tolerance to p53 for cancer immunotherapy.

Metaplastic breast cancer: clinical features and outcomes.

Metaplastic carcinoma of the breast, a neoplasm with both epithelial and mesenchymal elements, represents less than 1 per cent of all breast cancer. We reviewed the records of all patients diagnosed with localized metaplastic breast cancer from 1991 to 2003 at our institution. We identified 21 patients. Mean primary tumor size was 4.62 cm. Eight patients (38%) had axillary node involvement at presentation. All the tumors were high grade. Only two (10%) of the tumors were hormone receptor positive. Seventeen (81%) of the patients received adjuvant chemotherapy, and 12 (57%) of the patients received radiation. Ten (29%) patients suffered a local recurrence. With a mean follow-up of 46 months, the 5-year disease-free and overall survival was 42 per cent (95% CI: 20% to 65%) and 71 per cent (95% CI: 46% to 96%), respectively. Stage-specific overall survival was 100 per cent, 83 per cent, and 53 per cent for stages I, II, and III, respectively. By multivariate analysis, there was no impact on recurrence or survival with regard to size, age, menopausal status, nodal status, histologic subtype, adjuvant therapy, or extent of surgery. Metaplastic breast cancer is a unique neoplasm that tends to present at an advanced stage and has a propensity for local recurrence. When stratified by stage, however, survival appears similar to that of adenocarcinoma of the breast, and these tumors should be treated as such.

Detection of breast cancer on screening mammography allows patients to be treated with less-toxic therapy.

OBJECTIVE: Therapy for breast cancer is accompanied by acute and chronic toxicity. Little research has been conducted to determine the impact of the mode of breast cancer detection on the likelihood of receiving different types of treatment. The objective of this study was to determine whether detection of breast cancer on screening mammography is associated with less-toxic therapy. MATERIALS AND METHODS: The study group for this retrospective cohort study consisted of 992 women with invasive breast cancer detected on screening mammography (n = 460) or at physical examination (n = 532) at a single institution between 1990 and 2001. To address the generalizability of study findings, we compared the characteristics of study participants with those diagnosed with breast cancer in a population-based mammography registry. RESULTS: The patients whose breast cancer was detected on screening mammography more frequently had lymph nodes free of metastases (84% vs 58%, p < 0.0001), had smaller tumors (1.5 vs 2.9 cm, p < 0.0001), were more likely to be treated with breast conservation (56% vs 32%, p < 0.0001), and were less likely to be treated with chemotherapy (28% vs 56%, p < 0.0001). In a multivariate analysis with adjustments for age and functional status, patients whose cancer was detected at physical examination were more than twice as likely to undergo mastectomy (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.9-3.3) and nearly three times as likely to be treated with chemotherapy (OR, 2.9; 95% CI, 2.1-3.9). For younger women (40-49 years old), the likelihood of receiving chemotherapy was more than doubled if the cancer was detected at physical examination rather than on screening mammograms (OR, 2.3; 95% CI, 1.3-4.0). For older women (>/= 70 years old), patients whose cancer was detected at physical examination were five times more likely to undergo mastectomy (OR, 5.8; 95% CI, 3.2-10.5) and four times more likely to receive chemotherapy (OR, 4.6; 95% CI, 1.6-13) than the group whose tumors were detected on screening mammography. CONCLUSION: Breast cancers detected on screening mammography are smaller, are less likely to metastasize to lymph nodes, and are more likely to be treated with breast conservation and without chemotherapy. These findings provide an additional rationale for performing screening mammography, especially for women at age extremes for whom the survival benefit of screening mammography is debated.

Allobaculum stercoricanis gen. nov., sp. nov., isolated from canine feces.

Morphological, biochemical, and molecular genetic studies were performed on an unknown anaerobic, catalase-negative, non-spore-forming, rod-shaped bacterium isolated from dog feces. The unknown bacterium was tentatively identified as a Eubacterium species, based on cellular morphological and biochemical tests. 16S rRNA gene sequencing studies, however, revealed that it was phylogenetically distant from Eubacterium limosum, the type species of the genus Eubacterium. Phylogenetically, the unknown species forms a hitherto unknown sub-line proximal to the base of a cluster of organisms (designated rRNA cluster XVI), which includes Clostridium innocuum, Streptococcus pleomorphus, and some Eubacterium species. Based on both phenotypic and phylogenetic criteria, it is proposed that the unknown bacterium be classified as a new genus and species, Allobaculum stercoricanis. Using a specific rRNA-targeted probe designed to identify Allobaculum stercoricanis, in situ hybridisation showed this novel species represents a significant organism in canine feces comprising between 0.1% and 3.7% of total cells stained with DAPI (21 dog fecal samples). The type strain of Allobaculum stercoricanis is DSM 13633(T)=CCUG 45212(T).

Equipotent Generation of Protective Antitumor Immunity by Various Methods of Dendritic Cell Loading With Whole Cell Tumor Antigens.

Multiple clinically applicable methods have been used to induce dendritic cells (DCs) to express whole cell tumor antigens, including pulsing DCs with tumor lysate, and mixing DCs with apoptotic or live tumor cells. Herein we demonstrate, using two different tumor systems, that these methods are equipotent inducers of systemic antitumor immunity. Furthermore, tumor lysate pulsed DC vaccines generate more potent antitumor immunity than immunization with irradiated tumor cells plus the classic adjuvant, Corynebacterium parvum.