Human papillomavirus, radiation dose and survival of patients with anal cancer.

Purpose: To determine if anal cancer patients with HPV positive disease have different overall survival (OS) compared to those with HPV negative disease, and to elucidate differences in the association between radiation dose and OS.Patients and methods: We utilized the National Cancer Database (NCDB) registry to identify a cohort of non-metastatic anal cancer patients treated with curative intent between 2008 and 2014. Propensity score matching was used to account for potential selection bias between patients with HPV positive and negative disease. Multivariable Cox regression was used to determine the association between HPV status and OS. Kaplan-Meier methods were used to compare actuarial survival estimates.Results: We identified 5927 patients with tumor HPV status for this analysis, 3523 (59.4%) had HPV positive disease and 2404 (40.6%) had HPV negative disease. Propensity-matched analysis demonstrated that patients with HPV positive locally advanced (T3-4 or node positive) anal cancer had better OS (HR = 0.81 (95%CI: 0.68-0.96), p=.018). For patients with early stage disease (T1-2 and node negative) there was no difference in OS (HR = 1.11 (95%CI: 0.86-1.43), p=.43). In the unmatched cohort, we found a significant improvement in OS with increasing radiation dose only for patients with locally advanced, HPV negative disease (p<.001). In those patients, significant improvement in OS compared to the group receiving 30-45 Gy was seen for increasing doses up to 55-60 Gy, but not beyond 60 Gy.Conclusion: We found HPV to be a significant prognostic marker in anal tumors, especially for locally advanced disease. We further found that higher radiation dose up to 55-60 Gy was associated with better OS, but only for patients with locally advanced, HPV negative disease.

Outcomes in 132 patients following laparoscopic total mesorectal excision (TME) for rectal cancer with greater than 5-year follow-up.

INTRODUCTION: The role of laparoscopic TME for rectal cancer is still questioned as a safe and adequate cancer operation. Currently, multicenter randomized prospective trials are underway to evaluate this. We analyze our long-term results using laparoscopic TME in the treatment of rectal cancer to evaluate its oncologic outcomes. METHODS: A prospective laparoscopic database was queried to identify all patients operated upon for rectal cancer from April 1997 to September 2007. In total, 151 patients were identified. Metastatic disease excluded 19 patients, leaving 132 patients to be analyzed for perioperative and 5-year oncologic outcomes. Procedures included LAR, n = 35; transanal abdominal transanal proctosigmoidectomy, n = 77; and APR, n = 20. All surgeries were TME or pTME. RESULTS: Laparoscopic TME was performed on 89 men (67%), mean age 61 (22-85). Preoperative chemoradiation was administered in 119 (90.2 %) with median dose of 5500 cGy (3800-10,080). Mean EBL was 300 ml, and 4.5% were transfused. Seven patients (5.3%) underwent conversion, 5 to lap-assisted, with a 1.5% conversion rate to open. Pathologic stage of disease: complete response: 24%; I: 36%; II: 22%; III: 18%. There were no mortalities. Overall morbidity was 23.5%, with no anastomotic leaks and 5 (3.8%) delayed anastomotic stricture/fistula. There were no port site recurrences. Mean follow-up was 69.4 months (7.6-168.0). Overall LR was 5.3% (n = 7). There was only one isolated LR (0.8%). Mean time to local recurrence was 13.9 months. Metastatic rate was 18.2%. By stage, disease-specific survival was: CR 86.3%; I: 87.4%; II: 86.4%; III: 77.4%. Overall, 5-year survival was 84.8%. CONCLUSION: The long-term data confirm that laparoscopic TME can be performed with lasting low local recurrence (5.3 %) and excellent 5-year survival (84.8%). This report's importance stems from it representing one of the largest experiences of rectal cancer treated by laparoscopic TME with greater than 5-year follow-up reported in the literature.

Short-term Outcomes of Laparoscopic Versus Open Treatment of Internal Enteric Fistulae: A Logistic Regression Analysis.

Although laparoscopy improves outcomes for common general surgical procedures, its role in complex colorectal procedures is not clearly defined. We sought to evaluate whether laparoscopy retains its short-term benefits when used for treatment of complex intra-abdominal fistulae. A retrospective analysis was conducted including patients undergoing surgeries for enteric fistulas over a 7-year period. The χ tests, the Fisher exact tests, and Student t tests were used. Logistic regression models were used to assess the relationship between outcome and predictors. A total of 74 patients (31 open, 43 laparoscopic) were included. There was no difference in age, sex, body mass index, and comorbidities between the 2 groups. The laparoscopic group had significantly shorter length of stay, estimated blood loss, and significantly lower incidence of major complications compared with open group. Our findings suggest that laparoscopy is safe and retains its short-term benefits for treatment of complex colorectal and small bowel procedures.

Single surgeon experience with laparoscopic surgery in pediatric patients with inflammatory bowel disease.

PURPOSE: Laparoscopic management of inflammatory bowel disease (IBD) has been well established in adults. Its efficacy and safety are less defined in pediatrics. We reviewed our single surgeon laparoscopic experience with pediatric IBD patients. PATIENTS AND METHODS: All consecutive patients 17 years old or younger with IBD who underwent initial laparoscopic surgery for management of disease from May 2002 to May 2011 were identified. Patients were analyzed retrospectively with respect to age, gender, weight, American Society of Anesthesiologists classification, history of prior abdominal surgery, operative time, need for conversion to open procedure, estimated blood loss, need for blood transfusion, length of hospitalization, need for intensive care unit monitoring, and patient outcomes within 30 days. RESULTS: In total, 44 pediatric patients underwent 52 laparoscopic surgeries. Forty-two patient cases (80.8%) had had no prior abdominal surgery. Mean operative time was 132 minutes. Two patients (3.8%) underwent conversion from a laparoscopic to open approach. Mean estimated blood loss was 64 mL. The average hospitalization was 5.5 days. Postoperative complications occurred in 10 patients (19.2%): 2 were treated for wound infection or abscess, 7 required re-admission, and 1 required return to the operating room for exploratory laparotomy. CONCLUSIONS: Laparoscopic management of IBD has not routinely been implemented in the pediatric population. We demonstrate acceptable perioperative morbidity and rate of conversion to open with an overall successful laparoscopic approach in pediatric patients. This may have particular long-term benefits in a population faced with longer life expectancy. An initial laparoscopic approach is a feasible and safe option for pediatric IBD patients.

Laparoscopic approach in patients with recurrent Crohn's disease.

The purpose of this study is to review our experience with laparoscopic management of Crohn's disease including patients with prior Crohn's-related abdominal surgery. All cases of Crohn's patients who underwent laparoscopic attempt for management of disease from April 2005 to October 2010 (n = 130) at a single institution were retrospectively reviewed. Evaluated datapoints include: prior abdominal surgery for Crohn's disease, operative time, rate of conversion, and complication rate. Of the 130 patients, 82 (63.1%) patients had no prior abdominal surgery and 48 (36.9%) patients had previous bowel surgery with mean age of 35.3 (3.5-79) and 41.3 (15-66) years, respectively. Operative time with no prior surgery was 106 (23-245) minutes, and with prior surgery was 100 (26-229) minutes. Estimated blood loss with no prior surgery was 116 (5-800) mL, and with prior surgery was 123 (5-800) mL. Conversion from laparoscopic to open surgery in those with no prior surgery was 17.1 per cent and in those with prior surgery, 20.8 per cent (P = 0.64). Postoperative complications were found in 13 patients (15.9%) without prior abdominal surgery and 13 patients (27.1%) with prior surgery (P = 0.17). The most common postoperative complication in both groups was infection/abscess (8.5%). The laparoscopic management of recurrent Crohn's disease is a safe and technically feasible option, even in those patients with prior history of Crohn's-related abdominal surgery, with a low complication rate and low conversion rate. The utility of the laparoscopic approach in Crohn's patients faced with repeat abdominal procedures may be beneficial in the long-term and should be considered as a method to limit morbidity.

Development of a robust and sensitive LC-MS/MS method for the determination of adenine in plasma of different species and its application to in vivo studies.

A simple, robust, and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the measurement of endogenous adenine in mouse, rat, cynomolgus monkey, and human plasma. A "surrogate analyte" strategy was adopted by employing [(13)C(U)]-adenine as the surrogate analyte. The plasma samples were processed by protein precipitation, and the extracted supernatant samples were subjected directly to LC-MS/MS analysis. The analysis was carried out in the negative ion detection mode using selected-reaction monitoring (SRM). The method achieved a lower limit of quantification (LLOQ) of 5.0nM with a signal-to-noise ratio of 10. The intra- and inter-day assay coefficients of variation (CV) were ≤6.67% in rat plasma, and the mean recoveries and matrix effects across species and at various concentrations ranged from 88.8% to 104.2% and 86.0% to 110.8%, respectively. Using this methodology, the endogenous concentration of adenine in plasma of four species was found to range from 8.7nM in human to 93.1nM in cynomolgus monkey plasma. The assay was further applied to both an adenine pharmacokinetic study and a pivotal pharmacodynamic study evaluating the plasma concentration of adenine after a dose of 5'-deoxy-5'-methylthioadenosine (MTA).