Randomized Trial of Perioperative Probiotics Among Patients Undergoing Major Abdominal Operation.

BACKGROUND: We investigated the utility and safety of short-course oral probiotics among patients undergoing major abdominal operations. Perioperative probiotics can decrease length of stay and lower rates of infectious complications. We assessed whether perioperative probiotics decrease major complications among patients undergoing high-risk gastrointestinal operations in a pragmatic randomized trial. STUDY DESIGN: This double-blind trial randomized 135 patients undergoing elective major gastrointestinal operations to perioperative oral probiotic VSL#3 taken just before operation and twice daily up to 15 total doses (n = 67) or placebo (n = 68). The primary outcomes measure was 30-day composite end point of death, unplanned readmission, or any infection. RESULTS: Primary end point occurred among 17 patients in the placebo group (25.0%) vs 22 patients in the probiotic group (32.8%; p = 0.315). Thirty-day mortality was 2 (2.9%) in the placebo group compared with 1 (1.5%) in the probiotic group (p = 1.000). The placebo group patients experienced lower 30-day readmission rate (3 of 68 [4.4%]) compared with the probiotic group (11 of 67 [16.4%]; p = 0.022). None of the placebo patients were readmitted for dehydration, but 5 of 11 probiotic group patients (45%; p = 0.049) were readmitted for dehydration as a consequence of diet intolerance and/or diarrhea. There was no difference in 30-day infection rate between the groups (15 or 68 [22%] in the placebo group vs 15 of 67 [22.4%] in the probiotic group; p = 0.963). CONCLUSIONS: Perioperative use of VSL#3 probiotic did not affect 30-day composite end point of mortality, readmission, and infection rate. A significantly higher readmission rate was observed among those exposed to probiotics. Additional studies remain warranted.

Introduction of Minimally Invasive Esophagectomy in a Community Teaching Hospital.

BACKGROUND AND OBJECTIVES: The safety of minimally invasive esophagectomy (MIE) outside of high-volume centers has not been studied. Therefore, we evaluated our experience with the introduction of MIE in the setting of a community teaching hospital. METHODS: A retrospective cohort of all elective esophagectomy patients treated in a community hospital from 2008 through 2015 was evaluated (n = 57; open = 31 vs MIE = 26). Clavien-Dindo complication grades were recorded prospectively. RESULTS: Mean age was 63 ± 11 years (range, 30-83), mean Charlson comorbidity index was 4.5 ± 1.7 and proportion of ASA score ≥3 was 87%. The groups did not differ in age, gender distribution, or comorbidity indices. There were 108 complications observed, including 2 deaths (3.5%, both coronary events). Postoperative complication rate was 77.1% and serious complication rate (grades 3 and 4) was 50.8% in the entire cohort. The rate of serious complications was similar (58% for open vs 42% for MIE group; 2-sided P = .089). MIE operations were longer (342 ± 109 vs 425 ± 74 minutes; P = .001). Length of stay trended toward not being significantly shorter among MIE cases (15 ± 13 vs 12 ± 12 days; P = .071). Logistic regression models including MIE status were not predictive of complications. CONCLUSIONS: Introduction of MIE esophagectomy in our community hospital was associated with prolonged operative time, but no detectable adverse outcomes. Length of stay was nonsignificantly shortened by the use of MIS esophagectomy.

Rare breast cancer: 246 invasive secretory carcinomas from the National Cancer Data Base.

BACKGROUND AND OBJECTIVES: Invasive secretory breast carcinoma (SBC) is a rare subtype of breast malignancy. METHODS: Cases of SBC and infiltrating ductal carcinoma (IDC) from the National Cancer Database (1998-2011) were queried. RESULTS: Patients with SBC (n = 246) and IDC were identified (n = 1,564,068). The group with SBC was younger (age 56.4 ± 16.0 vs. 60.4 ± 13.9 years, P < 0.001), had similar tumor size (19.9 ± 17.8 vs. 21.6 ± 25.5 mm, P = 0.297), more frequently African-Americans (24.1 vs. 14.8 vs. 13.7; P = 0.004), more well-differentiated (32 vs. 18%, P < 0.001) and less likely to be hormone receptor positive (ER: 64 vs. 76%, P = 0.001; PR: 43 vs. 65%, P < 0.001). No differences were found for incidence of node-positivity (32 vs. 34%, P = 0.520) and stage IV presentation (2.4 vs. 3.6%, P = 0.372). Breast conserving surgery (60 vs. 58%, P = 0.405) and hormonal therapy (67 vs. 71%, P = 0.489) rates were similar. Systemic chemotherapy was used less often for SBC (38 vs. 45%, P = 0.035). The overall survival of all patients with SBC was better than all patients with IDC (median not reached vs. 14.8 years, P = 0.025). CONCLUSION: SBC is an uncommon tumor that is often well-differentiated and seen in younger women. Contrary to prior reports, they are frequently hormone receptor-positive. Compared to IDC, overall survival is improved. J. Surg. Oncol. 2016;113:721-725. © 2016 Wiley Periodicals, Inc.

Esophagectomy Timing After Neoadjuvant Therapy for Distal Esophageal Adenocarcinoma.

BACKGROUND: The time elapsed between completion of neoadjuvant therapy and esophagectomy may influence response rate and possibly allow for avoidance of surgical intervention in selected cases ("wait and see" approach). However, a very long postradiation interval has been associated with worsened surgical outcomes in esophageal carcinoma. Therefore we analyzed outcomes of patients with invasive distal esophageal adenocarcinoma treated with neoadjuvant chemoradiation and esophagectomy based on the time elapsed between completion of neoadjuvant chemoradiation and resection. METHODS: Patients with invasive distal esophageal carcinoma diagnosed between 2003 and 2011 and treated by neoadjuvant chemoradiation followed by esophagectomy within 26 weeks were identified in the National Cancer Data Base (NCDB). Primary outcome measures were 30- and 90-day postsurgical mortality and overall survival. RESULTS: In all, 4,284 patients aged 60.3 ± 9.4 years were analyzed (mean ± standard deviation). The interval after radiation therapy until esophagectomy was 7.8 ± 3.4 weeks (median, 7.1 weeks). The postradiation interval was 8 weeks or more in 35% of patients. Thirty-day mortality was 2.9% (n = 127), and 90-day mortality was 7.8% (n = 336). A postradiation interval of 9 weeks or more was associated with increased perioperative mortality odds both at the 30-day (adjusted odds ratio [OR], 2.160; 95% confidence interval, 1.099-4.242; p = 0.025) and 90-day follow-up (adjusted OR, 1.912; 95% confidence interval, 1.290-2.835; p < 0.001). Similarly, a postradiation interval of 9 weeks or more was associated with an increased mortality risk (adjusted hazard ratio [HR], 1.194; 95% confidence interval, 1.032-1.380; p = 0.017). CONCLUSIONS: Perioperative mortality and overall survival are significantly associated with the time interval between neoadjuvant chemoradiation and esophagectomy. A "wait and see" approach after neoadjuvant therapy for esophageal adenocarcinoma may not be safe. Further studies based on more detailed data are needed.

Current use and surgical efficacy of laparoscopic colectomy in colon cancer.

BACKGROUND: The Clinical Outcomes in Surgical Therapy trial demonstrated that laparoscopic colectomy (LC) was equivalent to open colectomy (OC) for 30-day mortality, time to recurrence, and overall survival in colon cancer (CC) patients. Current use of LC for CC is not well known. STUDY DESIGN: Surgical data were reviewed for all patients randomized into a national phase III clinical trial for adjuvant therapy in stage III CC (North Central Cancer Treatment Group trial N0147). Colon resections were grouped as open (traditional laparotomy) or laparoscopic, including laparoscopic; laparoscopic assisted; hand assisted; and laparoscopic converted to OC. Statistical methods included nonparametric methods, categorical analysis, and logistic regression modeling. RESULTS: A total of 3,393 evaluable patients were accrued between 2004 and 2009; 53% were male, median age was 58 years, 86% were white, and 70% had a body mass index >25 kg/m(2). Two thousand one hundred thirteen (62%) underwent OC. One thousand two hundred eighty (38%) were initiated as laparoscopic procedures, 25% (n = 322) were laparoscopic, 32% (n = 410) were laparoscopic assisted, 26% (n = 339) were hand assisted, and 16% (n = 209) were LC converted to OC. Significant predictors of LC (vs OC) in multivariate models were T stage (T1 or T2 vs T3 or T4; p = 0.0286), and absence of perforation, bowel obstruction, or adherence to surrounding organs (p < 0.01 each). Increasing rates of LC were observed over time, with LC eclipsing OC in 2009 (p < 0.0001). Surgical efficacy, measured by lymph node retrieval, was similar, with the mean number of lymph nodes retrieved higher in the LC group (20.6 vs 19.5 nodes; p = 0.0006). CONCLUSIONS: This study demonstrated a steadily increasing use of LC for the surgical treatment of CC between 2004 and 2009, with LC preferred by study completion. Surgical efficacy was similar in stage III CC patients.

Survival among pancreaticoduodenectomy patients treated for pancreatic head cancer <1 or 2 cm.

BACKGROUND: Size of primary tumor has implications for staging, imaging, and treatment of pancreatic head carcinomas. Limited data suggest that small tumor size is associated with better survival. The objective of this population study is to analyze characteristics and survival of patients with resected pancreatic head ductal carcinomas sized <1 and 2 cm. METHODS: Analysis of resected invasive pancreatic head ductal carcinomas captured within SEER Program from 1998 to 2008. RESULTS: A total of 7,135 cases were analyzed with nodal metastases in 31, 55, and 67 % for subcentimeter, 1.1-2 cm, and >2 cm tumors, respectively. Median survival was longest for node-negative tumors (38, 26, 19 months for tumors measuring ≤ 1, 1.1-2, and >2 cm, respectively; p < 0.001) versus node-positive tumors (18, 19, 14 months, p < 0.001). In multivariate analysis, large tumor size was associated with higher risk of death (hazard ratio (HR) = 1.179 for tumors 1.1-2 cm, p = 0.152; HR = 1.665 for tumors >2 cm, p < 0.001). CONCLUSIONS: Small pancreatic cancers have a poor prognosis and surprisingly high rate of nodal involvement; therefore, they cannot be considered early cancers. Size-based screening is unlikely to save lives with current treatment options.

Impact of radiation therapy sequence on survival among patients with resected pancreatic head ductal carcinoma.

BACKGROUND: Neoadjuvant therapy for pancreatic cancer is increasingly studied, but no randomized data is available to address its clinical utility. The purpose of this study is to compare the impact of the sequencing of radiation therapy and surgery on overall survival (OS) of patients, who received both pancreaticoduodenectomy and radiation therapy. METHODS: Surveillance, Epidemiology, and End Results data on pancreatic head carcinoma patients diagnosed between 1991 and 2007 was used. OS of patients receiving neoadjuvant (nRT, n=111) versus adjuvant radiation therapy (aRT, n=1839) was the primary end point. Excluded were cases in which resection or radiation therapy were omitted. RESULTS: The groups were comparable with respect to age (63±9 vs. 62±10years, P=0.490) and gender distribution. Median OS was similar in the nRT and aRT groups (19 vs. 20 months, P=0.688). On multivariate analysis, nodal status (hazard ratio [HR] 1.35, P<0.001) and age (HR 1.01/year, P<0.001) were predictive of OS, but RT sequence was not. CONCLUSIONS: Survival of patients undergoing pancreaticoduodenectomy for pancreatic head carcinoma does not seem to be affected by sequence of perioperative radiation therapy. This finding would imply that prospective studies comparing nRT to aRT is warranted to examine potential clinical benefits of nRT and can be carried out without compromising patient outcome.

Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a pooled analysis of north central cancer treatment group phase III trials N9741 and N9841.

PURPOSE: Symptoms and complications of metastatic colorectal cancer (mCRC) differ by metastatic sites. There is a paucity of prospective survival data for patients with peritoneal carcinomatosis colorectal cancer (pcCRC). We characterized outcomes of patients with pcCRC enrolled onto two prospective randomized trials of chemotherapy and contrasted that with other manifestations of mCRC (non-pcCRC). METHODS: A total of 2,095 patients enrolled onto two prospective randomized trials were evaluated for overall survival (OS) and progression-free survival (PFS). A Cox proportional hazard model was used to assess the adjusted associations. RESULTS: The characteristics of the pcCRC group (n = 364) were similar to those of the non-pcCRC patients in median age (63 v 61 years, P = .23), sex (57% males v 61%, P = .23), and performance status (Eastern Cooperative Oncology Group performance status 0 or 1 94% v 96%, P = .06), but differed in frequency of liver (63% v 82%, P < .001) and lung metastases (27% v 34%, P = .01). Median OS (12.7 v 17.6 months, hazard ratio [HR] = 1.3; 95% CI, 1.2 to 1.5; P < .001) and PFS (5.8 v 7.2 months, HR = 1.2; 95% CI, 1.1 to 1.3; P = .001) were shorter for pcCRC versus non-pcCRC. The unfavorable prognostic influence of pcCRC remained after adjusting for age, PS, liver metastases, and other factors (OS: HR = 1.3, P < .001; PFS: HR = 1.1, P = .02). Infusional fluorouracil, leucovorin, and oxaliplatin was superior to irinotecan, leucovorin, and fluorouracil as a first-line treatment among pcCRC (HR for OS = 0.62, P = .005) and non-pcCRC patients (HR = 0.66, P < .001). CONCLUSION: pcCRC is associated with a significantly shorter OS and PFS as compared with other manifestations of mCRC. Future trials for mCRC should consider stratifying on the basis of pcCRC status.

Surgery for obesity: a review of the current state of the art and future directions.

The number of patients undergoing surgery for the treatment of obesity, and the proportion of the health care budget dedicated to this health problem, is growing exponentially. There are several competing surgical approaches for the management of morbid obesity. We review the literature relating to four of these: gastric bypass, biliopancreatic diversion, gastric banding, and gastric pacing. Our review finds that while enhancing the malabsorptive activity of these procedures may induce an incremental increase in excess body weight loss, the proportion of patients who fail to lose more than 50% of their excess body weight is similar no matter how radical is the surgery performed. There is little guidance from the literature as to appropriate patient selection for the varying procedures, and anonymously reported registries have yet to show that patients who undergo bariatric surgery have enhanced longevity. To date, the bariatric surgical community has not conducted adequately powered randomized prospective trials to elucidate key elements of the surgical procedure such as optimal bypass length, to determine whether mixed operations are superior to those that offer intake restriction only, and to define what constitutes success after bariatric surgery. As a public health measure, bariatric surgery in the United States is being pursued in an irrational manner, being concentrated in areas where there are fewer morbidly obese patients, and used disproportionately among the population of white obese females.

Systemic stress response after laparoscopic and open gastric bypass.

BACKGROUND: The magnitude of the systemic stress response is proportional to the degree of operative trauma. We hypothesized that laparoscopic gastric bypass (GBP) is associated with reduced operative trauma compared with open GBP, resulting in a lower systemic stress response. STUDY DESIGN: Forty-eight patients with a body mass index of 40 to 60 were randomly assigned to laparoscopic (n = 26) or open (n = 22) GBP Blood samples were measured at baseline and at 1, 24, 48, and 72 hours postoperatively. Metabolic (insulin, glucose, epinephrine, norepinephrine, dopamine, ACTH, cortisol), acute phase (C-reactive protein), and cytokine (interleukin [IL]-6, IL-8, tumor necrosis factor [TNF]-alpha) responses were measured. Catabolic response was also measured by calculating the nitrogen balance at 24 and 48 hours postoperatively. RESULTS: The two groups of patients were similar in terms of age, gender, and preoperative body mass index. The mean operative time was longer for laparoscopic GBP than for open GBP (229 +/- 50 versus 207 43 minutes). After laparoscopic and open GBP, plasma concentrations of insulin, glucose, epinephrine, dopamine, and cortisol increased; IL-8 and TNF-alpha remained unchanged; and negative nitrogen balances occurred at 24 and 48 hours. There was no significant difference in these parameters between groups. Concentrations of norepinephrine, ACTH, C-reactive protein, and IL-6 levels also increased, but these levels were significantly lower after laparoscopic GBP than after open GBP (p < 0.05). CONCLUSIONS: Systemic stress response after laparoscopic GBP is similar to that after open GBP, except that concentrations of norepinephrine, ACTH, C-reactive protein, and IL-6 are lower after laparoscopic than after open GBP. These findings may suggest a lower degree of operative injury after laparoscopic GBP.