Fecal and Tissue Microbiota Are Associated with Tumor T-Cell Infiltration and Mesenteric Lymph Node Involvement in Colorectal Cancer.

Colorectal cancer (CRC) is associated with alterations of the fecal and tissue-associated microbiome. Preclinical models support a pathogenic role of the microbiome in CRC, including in promoting metastasis and modulating antitumor immune responses. To investigate whether the microbiome is associated with lymph node metastasis and T cell infiltration in human CRC, we performed 16S rRNA gene sequencing of feces, tumor core, tumor surface, and healthy adjacent tissue collected from 34 CRC patients undergoing surgery (28 fecal samples and 39 tissue samples). Tissue microbiome profiles-including increased Fusobacterium-were significantly associated with mesenteric lymph node (MLN) involvement. Fecal microbes were also associated with MLN involvement and accurately classified CRC patients into those with or without MLN involvement. Tumor T cell infiltration was assessed by immunohistochemical staining of CD3 and CD8 in tumor tissue sections. Tumor core microbiota, including members of the Blautia and Faecalibacterium genera, were significantly associated with tumor T cell infiltration. Abundance of specific fecal microbes including a member of the Roseburia genus predicted high vs. low total and cytotoxic T cell infiltration in random forests classifiers. These findings support a link between the microbiome and antitumor immune responses that may influence prognosis of locally advanced CRC.

Anal Sphincteroplasty in the Minimally Invasive Era: Assessment of National Trends and Complications.

Fecal incontinence is a debilitating and underreported condition. Despite introduction of novel therapies in recent years, anal sphincteroplasty (AS) remains the surgical choice for certain patients. Previous reports have primarily focused on single-surgeon or single-center experience with AS. The purpose of this study was to assess patient characteristics and perioperative outcomes of AS using a national cohort. Patients (n = 586) who underwent AS as a primary procedure between 2009 and 2015 were identified by the CPT code as recorded in the study and were evaluated and examined for association with 30-day complications. The number of sphincteroplasties performed decreased seven-fold between 2009 and 2015. Wound infection, wound dehiscence, and urinary tract infection were the most common complications, occurring in 30 (5.1%), 12 (2.1%), and 6 (1%) patients, respectively. Preoperative steroid use and surgeon specialty were associated with wound complications on multivariate analysis. We present the first national study of patients undergoing AS and identify factors that predispose to wound complications. In addition, we demonstrate that the number of anal sphincteroplasties performed in the United States is decreasing dramatically, likely because of novel therapy for fecal incontinence. We hope that this study will assist in patient counseling and call attention to preserving surgical training as utilization of AS rapidly declines.

Re-exploration of vertical rectus abdominis myocutaneous flap for vaginal reconstruction: Case report and review of the literature.

The vertical rectus abdominis myocutaneous (VRAM) flap is a versatile and well-established reconstructive technique for many defects created as a result of colorectal and gynecologic extirpation. However, major re-operation in the pelvis following a VRAM flap reconstruction several months later is uncommon, and the safety and integrity of the VRAM flap in this setting has not been described. This case examines VRAM flap preservation during repeat exploratory laparotomy, and a unique view of the VRAM flap during interval exploration. We demonstrate an intact flap after lysis of adhesions with an audible Doppler signal, and maintenance of flap integrity in the postoperative period. This further substantiates its use as a durable rotational flap for perineal tissue defects.

Complications of Diverting Ileostomy after Low Anterior Resection for Rectal Carcinoma.

There have been few studies directly comparing the postoperative complications in patients with a diverting ileostomy to patients who were not diverted after low anterior resection (LAR) for rectal carcinoma. This study is a retrospective chart review of all rectal carcinoma patients (99) who underwent a LAR from January 2009 to December 2014 at Loma Linda University Medical Center and Veterans Affairs Loma Linda Healthcare System. A majority of patients were diverted (58% vs 42%). The diverted patients were more likely to have a low tumor location (P < 0.01), preoperative chemoradiation (P < 0.01), and more intraoperative blood loss (P < 0.01). Our study shows a statistically significant higher overall complication rate among patients receiving a diverting ileostomy in the six months after LAR (61% vs 38%, P = 0.02). The difference is due to a higher rate of readmission (27% vs 14%) and acute kidney injury (14% vs 5%) in patients with a diverting ileostomy. It also shows that there is a higher rate of unplanned reoperation (11% vs 6%) due to anastomotic leak (17% vs 5%) in nondiverted patients. Further studies are needed to refine the specific indications to maximize the benefit of diverting ileostomy after LAR for rectal carcinoma.

Impact of splenectomy on thrombocytopenia, chemotherapy, and survival in patients with unresectable pancreatic cancer.

BACKGROUND: Patients with unresectable pancreatic cancer (PDAC) or endocrine tumors (PET) often develop splenic vein thrombosis, hypersplenism, and thrombocytopenia which limits the administration of chemotherapy. METHODS: From 2001 to 2009, 15 patients with recurrent or unresectable PDAC or PET underwent splenectomy for hypersplenism and thrombocytopenia. The clinical variables of this group of patients were analyzed. The overall survival of patients with PDAC was compared to historical controls. RESULTS: Of the 15 total patients, 13 (87%) had PDAC and 2 (13%) had PET. All tumors were either locally advanced (n = 6, 40%) or metastatic (n = 9, 60%). The platelet counts significantly increased after splenectomy (p < 0.01). All patients were able to resume chemotherapy within a median of 11.5 days (range 6-27). The patients with PDAC had a median survival of 20 months (range 4-67) from the time of diagnosis and 10.6 months (range 0.6-39.8) from the time of splenectomy. CONCLUSIONS: Splenectomy for patients with unresectable PDAC or PET who developed hypersplenism and thrombocytopenia that limited the administration of chemotherapy, significantly increased platelet counts, and led to resumption of treatment in all patients. Patients with PDAC had better disease-specific survival as compared to historical controls.

Improved survival following pancreaticoduodenectomy to treat adenocarcinoma of the pancreas: the influence of operative blood loss.

HYPOTHESIS: Although the safety of pancreaticoduodenectomy has notably improved over the past several decades, the reported survival of patients with pancreatic cancer remains poor. We hypothesized that, in recent years, the survival of patients with pancreatic adenocarcinoma following pancreaticoduodenectomy has substantially improved. DESIGN: Retrospective case series. SETTING: Major academic medical and pancreatic surgery center. PATIENTS: A total of 182 consecutive patients underwent pancreaticoduodenectomy for various diagnoses between 1987 and 2005. Patients from 1987-1995 were compared with patients from 1996-2005. INTERVENTIONS: Pancreaticoduodenectomy for patients with a diagnosis of pancreatic adenocarcinoma. MAIN OUTCOME MEASURES: Survival after pancreaticoduodenectomy and patient outcomes. RESULTS: During the time period analyzed, 182 patients underwent pancreaticoduodenectomy to treat ductal adenocarcinoma. There were no operative deaths, and 86.3% of patients had an R0 resection. The 5-year survival rate for the entire group was 27.4%. However, survival improved from 15.8% to 35.5% during the study period. Both groups had equivalent demographic and pathological characteristics, and the only predictors of poor survival in multivariate analysis were operative blood loss of more than 400 mL (hazard ratio, 2.17), poorly differentiated tumors (3.03), lymph node metastases (1.92), perineural invasion (2.66), and undergoing an operation before 1996 (1.42). CONCLUSIONS: The survival rate for patients undergoing pancreaticoduodenectomy to treat pancreatic cancer has substantially improved. This finding is partially owing to improved operative technique and limited operative blood loss.

Resection of pancreatic neuroendocrine tumors: results of 70 cases.

HYPOTHESIS: Neuroendocrine tumors of the pancreas can be managed surgically with excellent outcomes. DESIGN: Retrospective case series. SETTING: Academic medical center. PATIENTS: Seventy consecutive patients who underwent resection for pancreatic neuroendocrine tumors between January 1, 1990, and December 31, 2005. INTERVENTIONS: Pancreaticoduodenectomy, distal pancreatectomy, or enucleation. MAIN OUTCOME MEASURES: Postoperative morbidity, mortality, and long-term survival. RESULTS: Of the 70 patients, 50 (71.4%) had nonfunctional tumors. Thirty-seven patients (52.9%) had neuroendocrine carcinomas and 13 (18.6%) had benign islet cell neoplasms. Twenty patients had functional tumors. Of these 20 patients, 16 had insulinomas, 2 had glucagonomas, and 2 had gastrinomas. Twenty-seven patients underwent pancreaticoduodenectomy, 32 had distal pancreatectomy, and 11 underwent enucleation. Patients undergoing enucleation as compared with those not undergoing enucleation were younger (mean age, 39 vs 51 years, respectively; P = .009) and had smaller tumors (mean tumor size, 2 vs 5 cm, respectively; P<.001). Postoperative complications occurred in 13 patients (48.1%) after pancreaticoduodenectomy, in 4 patients (12.5%) after distal pancreatectomy, and in 0 patients after enucleation. There were no perioperative mortalities. With a median follow-up of 50 months, the 5-year actuarial survival for the patients with malignant neuroendocrine carcinomas (n = 37) was 77%, and all of the patients with functional tumors are alive. The presence of lymphovascular invasion closely approached significance when survival was evaluated (P = .06). Lymph node status, perineural invasion, and liver metastasis did not impact survival. CONCLUSIONS: This single-institutional case series demonstrates that pancreatic neuroendocrine tumors can be safely resected without mortality and with minimal morbidity. The presence of lymphovascular invasion can be used to classify neuroendocrine tumors as malignant, and this appears to predict survival. Patients with malignant tumors can expect long-term survival even in the setting of metastatic disease.

The clinical significance of MAGEA3 expression in pancreatic cancer.

The MAGEA gene family that encodes cancer testis antigens is differentially expressed in many cancers. Though MAGEA3 expression has been detected in gastrointestinal malignancies, its role in pancreatic ductal adenocarcinoma (PDAC) has not been well established. We assessed 57 patients who underwent intent-to-cure surgery for PDAC. Total RNA from paraffin-embedded pancreatic tumors was extracted and assessed for MAGEA3 gene expression by an optimized probe-based quantitative real-time RT-PCR (qRT) assay. MAGEA3 gene expression was detected by qRT in 25 (44%) patients. For the entire cohort, detection of MAGEA3 expression was associated with significantly decreased overall survival (median, 16 vs 33 months; log-rank, p = 0.032). When clinicopathologic factors, including age, gender, stage, tumor extent, lymph node metastasis, tumor grade, perineural invasion and lymphovascular invasion were assessed by univariate analysis, MAGEA3 gene expression and tumor grade were significant prognostic factors for poor survival (HR 2.1, 95% CI: 1.0-4.4, p = 0.041; and HR 3.7, 95% CI: 1.8-7.6, p = 0.0004, respectively). Immunohistochemistry (IHC) was performed and confirmed MAGEA3 protein in PDAC specimens. In conclusion, MAGEA3 is differentially expressed in patients with PDAC; its expression correlates with significantly worse survival. Molecular assessment for MAGEA3 should be considered to improve prognostic evaluation and to identify eligible patients for potential immune-based therapy.

Management of pancreatic fistulas after pancreaticoduodenectomy: results in 437 consecutive patients.

HYPOTHESIS: Pancreatic fistula (PF), a common and potentially lethal complication of pancreaticoduodenectomy, can be managed nonoperatively in most cases. DESIGN: Retrospective case series. SETTING: Major academic medical and pancreatic surgery center. PATIENTS: A total of 437 consecutive patients who underwent pancreaticoduodenectomy for various diagnoses between January 1, 1988, and August 31, 2004. INTERVENTIONS: Conservative management of PF with an intraoperatively placed closed-suction drain near the pancreaticojejunostomy anastomosis, computed tomography-guided percutaneous drainage, and surgery. MAIN OUTCOME MEASURES: Incidence of PF after pancreaticoduodenectomy and patient outcomes. RESULTS: Fifty-five patients (12.6%) developed a PF, which was most common after resections for ampullary tumors (21.1%) and cystic neoplasms (31.3%), and uncommon after resection for pancreatic cancer (6.5%). The mean number of complications (excluding PF) was greater in the PF group (PF, 1.24; no PF, 0.54; P<.001), but these did not prolong hospital stay (PF, 15.2 days; no PF, 13.7 days; P = .20). Biliary fistula, sepsis, reoperation, and late biliary stricture were more common in patients with PF (P<.05), but mortality rate and long-term survival in patients with either pancreatic or ampullary cancer were unaffected by the presence of PF (P>.40). Fifty-two patients (94.5%) had successful conservative management of their PF with prolonged tube drainage; 4 also required CT-guided percutaneous drainage. Three patients (5.5%) underwent reoperation and 1 died. CONCLUSIONS: Pancreatic fistula is a common problem after pancreaticoduodenectomy. It is associated with increased morbidity, but it does not affect the mortality rate. More than 90% of PF cases can be managed nonoperatively without significantly prolonging hospital stay.

Laparoscopic gastrojejunostomy for gastric outlet obstruction in pancreatic cancer.

Up to 20 per cent of patients with pancreatic cancer develop gastric outlet obstruction. Traditionally, these patients have been managed with an open gastrojejunostomy. Laparoscopic gastrojejunostomy may now be a preferable approach. We conducted a retrospective review of nine patients who underwent laparoscopic gastrojejunostomy in 2001-2004. All nine patients had unresectable pancreatic cancer. There were six men and three women. Median age was 66 years (range 36-87). Two patients had prior laparotomies for attempted resection. Four patients had previously placed duodenal stents that failed. Four others had undergone unsuccessful attempts of duodenal stenting. Median operating time was 116 minutes (range 75-300). There were no intraoperative complications or conversions to open procedure. Median time to postoperative oral intake was 4 days (range 3-6), and median postoperative length of stay was 7 days (range 5-18). Eight of our nine patients were palliated successfully using this technique. There were no complications or deaths related to the operation. All patients were discharged from the hospital. Six patients have since died, with a median postoperative survival of 2.5 months (range 1.5-8). Laparoscopic gastrojejunostomy provides safe and effective palliation of gastric outlet obstruction in patients with unresectable pancreatic cancer. This approach allows for rapid palliation in a group of patients with a very limited survival.

Peptide YY exhibits a mitogenic effect on pancreatic cells while improving acute pancreatitis in vitro.

BACKGROUND: Peptide YY (PYY), a gastrointestinal regulatory peptide, improves survival and histologic parameters in animal models of acute pancreatitis. Its effects on pancreatic cell growth and acute pancreatitis in pancreatic acinar and ductal cells are unknown. We hypothesized that PYY would affect cell growth and attenuate acute pancreatitis in pancreatic acinar and ductal cells in vitro. METHODS: Rat pancreatic acinar and ductal cells were cultured in the presence of 1) cerulein, a synthetic cholecystokinin analog that induces pancreatitis, 2) PYY, or 3) a combination group pretreated with PYY prior to addition of cerulein. Cell survival was measured at 48 h using MTT assay. Amylase secretion, as marker for pancreatitis, was measured at 48 h using an amylase activity assay. Statistical significance was calculated using analysis of variance and the Student's t test. RESULTS: Peptide yy significantly increased cell growth and decreased amylase secretion compared with control and cerulein groups. Pretreatment with PYY significantly protected against the pancreatitis effects of cerulein. CONCLUSIONS: We have shown for the first time that PYY has a mitogenic effect on pancreatic acinar and ductal cells in vitro. In addition, it directly protects against cerulein-induced pancreatitis. Its potential therapeutic benefit in acute pancreatitis would therefore be twofold: amelioration of the inflammatory process, and augmenting growth of normal pancreas to replace necrotic or apoptotic cell loss.