Immunotherapy for gastrointestinal malignancies.

BACKGROUND: Gastrointestinal (GI) cancers are the most common human tumors encountered worldwide. The majority of GI cancers are unresectable at the time of diagnosis, and in the subset of patients undergoing resection, few are cured. There is only a modest improvement in survival with the addition of modalities such as chemotherapy and radiation therapy. Due to an increasing global cancer burden, it is imperative to integrate alternative strategies to improve outcomes. It is well known that cancers possess diverse strategies to evade immune detection and destruction. This has led to the incorporation of various immunotherapeutic strategies, which enable reprogramming of the immune system to allow effective recognition and killing of GI tumors. METHODS: A review was conducted of the results of published clinical trials employing immunotherapy for esophageal, gastroesophageal, gastric, hepatocellular, pancreatic, and colorectal cancers. RESULTS: Monoclonal antibody therapy has come to the forefront in the past decade for the treatment of colorectal cancer. Immunotherapeutic successes in solid cancers such as melanoma and prostate cancer have led to the active investigation of immunotherapy for GI malignancies, with some promising results. CONCLUSIONS: To date, monoclonal antibody therapy is the only immunotherapy approved by the US Food and Drug Administration for GI cancers. Initial trials validating new immunotherapeutic approaches, including vaccination-based and adoptive cell therapy strategies, for GI malignancies have demonstrated safety and the induction of antitumor immune responses. Therefore, immunotherapy is at the forefront of neoadjuvant as well as adjuvant therapies for the treatment and eradication of GI malignancies.

Smoking History and the Development of Incisional Umbilical Hernia After Laparoscopic and Laparoendoscopic Single-Site Cholecystectomy.

The aim of this study was to analyze umbilical hernia occurrences in patients who underwent laparoscopic or laparoendoscopic single-sight (LESS) cholecystectomy. Patients who underwent cholecystectomy by a single surgeon between 2015 and 2020 were surveyed. Data are presented as median (mean +/- standard deviation). Two hundred and fifty-three patients were sent the survey and 130 (51%) patients responded. The overall age was 57 (31 +/- 18) and the overall BMI was 30 (31 +/- 7). Twelve (9%) patients developed an umbilical hernia. Seventeen patients were active smokers and four (24%) developed an umbilical hernia. One hundred and thirteen patients were inactive smokers and eight (7%) developed an umbilical hernia. There was a statistical significance between umbilical hernia occurrence and smoking history (P < .05). Active smokers have a higher risk of developing an umbilical hernia following a minimally invasive cholecystectomy, regardless of operative approach. Elective cholecystectomy should be reconsidered for current smokers.

Idiopathic Small Bowel Diaphragm Disease Without Use of Non-steroidal Anti-inflammatory Drugs: A Case Report and Review of the Literature.

Small bowel diaphragm disease is a rare condition that is characterized by the presence of diaphragm-like strictures that causes intermittent or complete small bowel obstruction. Most cases are asymptomatic until presented with severe abdominal pain due to small bowel obstruction or diagnosed during anemia workup as a cause of occult gastrointestinal bleeding. Small bowel diaphragm disease is usually associated with long-term use of non-steroidal anti-inflammatory drugs (NSAIDs). Here, we present the case of a 50-year-old male with no history of NSAID use who presented with abdominal pain and iron deficiency anemia. He was postoperatively diagnosed with idiopathic small bowel diaphragm disease.

Integrating 31-Gene Expression Profiling With Clinicopathologic Features to Optimize Cutaneous Melanoma Sentinel Lymph Node Metastasis Prediction.

National guidelines recommend sentinel lymph node biopsy (SLNB) be offered to patients with > 10% likelihood of sentinel lymph node (SLN) positivity. On the other hand, guidelines do not recommend SLNB for patients with T1a tumors without high-risk features who have < 5% likelihood of a positive SLN. However, the decision to perform SLNB is less certain for patients with higher-risk T1 melanomas in which a positive node is expected 5%-10% of the time. We hypothesized that integrating clinicopathologic features with the 31-gene expression profile (31-GEP) score using advanced artificial intelligence techniques would provide more precise SLN risk prediction. METHODS: An integrated 31-GEP (i31-GEP) neural network algorithm incorporating clinicopathologic features with the continuous 31-GEP score was developed using a previously reported patient cohort (n = 1,398) and validated using an independent cohort (n = 1,674). RESULTS: Compared with other covariates in the i31-GEP, the continuous 31-GEP score had the largest likelihood ratio (G2 = 91.3, P < .001) for predicting SLN positivity. The i31-GEP demonstrated high concordance between predicted and observed SLN positivity rates (linear regression slope = 0.999). The i31-GEP increased the percentage of patients with T1-T4 tumors predicted to have < 5% SLN-positive likelihood from 8.5% to 27.7% with a negative predictive value of 98%. Importantly, for patients with T1 tumors originally classified with a likelihood of SLN positivity of 5%-10%, the i31-GEP reclassified 63% of cases as having < 5% or > 10% likelihood of positive SLN, for a more precise, personalized, and clinically actionable SLN-positive likelihood estimate. CONCLUSION: These data suggest the i31-GEP could reduce the number of SLNBs performed by identifying patients with likelihood under the 5% threshold for performance of SLNB and improve the yield of positive SLNBs by identifying patients more likely to have a positive SLNB.

Diagnostic accuracy of nodal enhancement pattern of rectal cancer at MRI enhanced with ultrasmall superparamagnetic iron oxide: findings in pathologically matched mesorectal lymph nodes.

OBJECTIVE: The purpose of this study was to evaluate the diagnostic accuracy of the pattern of nodal enhancement at MRI enhanced with ultrasmall superparamagnetic iron oxide (USPIO) in the nodal classification of rectal cancer in pathologically matched mesorectal lymph nodes. SUBJECTS AND METHODS: Twenty-five patients with adenocarcinoma of the rectum underwent prospective evaluation with 3-mm axial T2-weighted and USPIO-enhanced T2*-weighted MRI before surgery. Mesorectal nodes visible at in vivo MRI were independently scored by two radiologists as malignant or nonmalignant according to morphologic criteria (irregular nodal contour, heterogeneous signal intensity) on T2-weighted MR images and according to USPIO enhancement pattern on T2*-weighted MR images. The sensitivity, specificity, and positive and negative predictive values of morphologic and USPIO criteria in identification of malignancy in the pathologically matched mesorectal nodes were compared by use of the McNemar test. Interobserver agreement was compared by use of kappa statistics. RESULTS: After surgery, radiologic-pathologic comparison of 126 mesorectal nodes (116 benign, 10 malignant) was possible. Use of morphologic criteria resulted in an average sensitivity of 65% (95% CI, 35-88%); specificity, 75% (67-83%); positive predictive value, 19% (8-34%); and negative predictive value, 96% (91-99%). Use of USPIO criteria resulted in an average sensitivity of 65% (95% CI, 35-88%); specificity, 93% (87-96%); positive predictive value, 43% (21-67%); and negative predictive value, 97% (92-99%). Use of USPIO MRI improved diagnostic specificity for both observers (p < 0.01). Interobserver agreement was fair for morphologic criteria (kappa = 0.39) but good for USPIO criteria (kappa = 0.68). CONCLUSION: Use of the pattern of USPIO enhancement had higher diagnostic specificity than but the same sensitivity as morphologic findings in pathologically matched mesorectal lymph nodes.

Surgery residency training programmes have greater impact on outcomes after pancreaticoduodenectomy than hospital volume or surgeon frequency.

BACKGROUND: Hospital volume of pancreaticoduodenectomy (PD) and surgeon frequency of PD have been shown to impact outcomes. The impact of surgery residency training programmes after PD is unknown. This study was undertaken to determine the impact of surgery training programmes on outcomes after PD, as well as their importance relative to hospital volume and surgeon frequency of PD. METHODS: The State of Florida Agency for Healthcare Administration Database was queried for patients undergoing PD during 2002-2007. Measures of outcome were compared for patients undergoing PD at centres with vs. without surgery residency training programmes. RESULTS: A total of 2345 PDs were identified, of which 1478 (63%) were undertaken at training centres and 867 (37%) were performed at non-training centres. Patients undergoing PD at training centres had shorter lengths of stay, lower hospital charges and lower in-hospital mortality. Relative to surgeon frequency of PD, training centres had a greater favourable impact on hospital length of stay, hospital charges and in-hospital mortality (P < 0.001 for each, ancova). Relative to hospital volume of PDs undertaken, training centres had a greater impact on hospital charges (P < 0.001, ancova). CONCLUSIONS: Surgery residency training programmes have a favourable effect on outcomes following PD and their impact on outcome is greater than the impact of hospital volume or surgeon frequency of PD.

Survival after pancreaticoduodenectomy is not improved by extending resections to achieve negative margins.

OBJECTIVE: This study was undertaken to determine the survival benefit of extending resections to obtain microscopically negative margins after positive intraoperative frozen sections. SUMMARY BACKGROUND DATA: The impact of residual microscopic disease after pancreaticoduodenectomy is currently a point of controversy. It is, however, generally believed that microscopically positive margins negatively impact survival and this may be improved by ultimately achieving negative margins. METHODS: Since 1995, patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma have been prospectively followed. Margin status has been codified as macro/microscopically negative (R0) or macroscopically negative/microscopically positive (R1). The impact of margin status on survival was evaluated utilizing survival curve analysis. Data are presented as median, mean +/- SD where appropriate. RESULTS: For pancreatic adenocarcinoma, 202 patients underwent pancreaticoduodenectomy. R0 resections were achieved in 158 patients, 17 of whom required extended resections to achieve complete tumor extirpation after an initially positive intraoperative frozen section (R1 --> R0). R1 resections were undertaken in 44 patients. Median survival for patients undergoing R0 resections was 21 months, 26 +/- 23.4 months versus 13 months, 17 +/- 21.0 months for patients undergoing R1 resections (P = 0.02). Median survival for patients undergoing R1 --> R0 resections was 11 months, 16 +/- 17.3, (P = 0.001). Margin status had a significant correlation with "N" stage and AJCC stage but not "T" stage. CONCLUSION: Survival after pancreaticoduodenectomy is not improved by extending pancreatic resections to achieve negative margins after initially positive intraoperative frozen sections. Tumor-specific factors beyond the presence of disease at a surgical margin are responsible for the abbreviated survival seen in patients undergoing R1 resections.

Resection of portovenous structures to obtain microscopically negative margins during pancreaticoduodenectomy for pancreatic adenocarcinoma is worthwhile.

Locally advanced pancreatic adenocarcinoma may require resections of the portal vein and/or its major tributaries to achieve tumor extirpation, albeit with the potential for increased morbidity and mortality. However, major venous resections can impart complete tumor extirpation and thereby a survival advantage compared with resections with residual microscopic disease. This study was undertaken to determine if resection of the portal vein and/or its splenic or superior mesenteric venous (SMV) tributaries is a worthwhile endeavor. Since 1995, patients undergoing pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma have been prospectively followed. The impact of portovenous resections (portal vein, SMV, and/or splenic vein) on survival was evaluated using survival curve analysis (Mantel-Cox test). Margins were codified as R0 or R1 and data are presented as median, mean +/- SD where appropriate. For 220 patients undergoing PD for pancreatic adenocarcinoma, survival was 17 months. Patients undergoing R0 resections had improved survival relative to patients undergoing R1 resections (20 vs 13 months, P < 0.03). Concomitant portovenous resections were undertaken in 48 patients. There was no difference in survival after PD without portovenous resection (17 months) versus PD with portovenous resection (18 months). Resections with complete tumor extirpation (i.e., R0 resections) provide superior long-term survival; all efforts to obtain R0 resections should be undertaken. Portovenous resections during pancreaticoduodenectomy can be undertaken safely and are worthwhile when complete tumor extirpation is attainable.

Laparoscopic Heller Myotomy with Anterior Fundoplication Improves Frequency and Severity of Symptoms of Achalasia, Regardless of Preoperative Severity Determined by Esophagography.

This study was undertaken to determine whether postoperative outcomes after laparoscopic Heller myotomy with anterior fundoplication could be predicted by preoperative findings on esophagography. Preoperative barium esophagograms of 135 patients undergoing laparoscopic Heller myotomy with anterior fundoplication were reviewed. The number of esophageal curves, esophageal width, and angulation of the gastroesophageal junction (GEJ) were determined; correlations between these determined parameters and symptoms were assessed using linear regression analysis. The number of esophageal curves correlated with the preoperative frequency of dysphagia, vomiting, chest pain, regurgitation, and heartburn. The width of the esophagus negatively correlated with the preoperative frequency of regurgitation. The angulation of the GEJ did not correlate with preoperative symptoms. Laparoscopic Heller myotomy with anterior fundoplication significantly reduced the frequency and severity of all symptoms, regardless of the number of esophageal curves, esophageal width, or angulation of the GEJ. Laparoscopic Heller myotomy with anterior fundoplication provides dramatic palliation for achalasia. More esophageal curves on preoperative esophagography correlate well with the frequency of a broad range of preoperative symptoms, including the frequency of dysphagia and regurgitation. Patients experience dramatically improved frequency and severity of symptoms after laparoscopic Heller myotomy with anterior fundoplication for achalasia regardless of the number of esophageal curves, esophageal width, or the angulation of the GEJ. Findings on barium esophagogram, in evaluating achalasia, should not deter the application of laparosocopic Heller myotomy with anterior fundoplication.

Sulfonylureas (not metformin) improve survival of patients with diabetes and resectable pancreatic adenocarcinoma.

Patients with pancreatic adenocarcinoma have an increased propensity for diabetes. Recent studies suggest patients with diabetes and pancreatic adenocarcinoma treated with metformin have increased survival. This study was undertaken to determine whether metformin use is associated with increased survival in patients with pancreatic adenocarcinoma. METHODS: Patients who underwent pancreaticoduodenectomy for pancreatic adenocarcinoma from 1991 to 2013 were included in this study. Survival was evaluated by Kaplan-Meier analysis. Median data are reported. Significance was accepted with 95% probability. RESULTS: Of 414 patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma, 132 (32%) were diabetic. Of patients with diabetes, 35 (27%) were diet-controlled, 34 (26%) were treated with insulin alone, 18 (14%) were treated with metformin alone, 14 (10%) were treated with sulfonylureas alone, 7 (5%) were taking sulfonylureas with insulin, and 24 (18%) patients were taking metformin with sulfonylureas and/or insulin. Patients with/without diabetes not taking sulfonylureas had survival of 16.4 months compared with patients taking sulfonylureas who achieved survival of 27.5 months after undergoing pancreaticoduodenectomy (P<0.05). CONCLUSIONS: Patients taking sulfonylureas with or without other therapy had improved survival compared with patients not taking sulfonylureas after pancreaticoduodenectomy. Metformin does not seem to be beneficial for patients with resectable disease, but may be beneficial for patients with unresectable and/or metastatic disease as shown in prior studies. The use of sulfonylureas is associated with a survival benefit for patients undergoing resection for pancreatic adenocarcinoma. Tumor staging and margin status continue to be the overriding predictors of survival in patients with resectable pancreatic adenocarcinoma, not metformin therapy.

Female urogenital dysfunction following total mesorectal excision for rectal cancer.

BACKGROUND: The effect of Total Mesorectal Excision (TME) on sexual function in the male is well documented. However, there is little literature in female patients. The aim of this study was to review the pelvic autonomic nervous anatomy in the female and to perform a retrospective audit of urinary and sexual function in women following surgery for rectal cancer where TME had been performed. Urogenital dysfunction was assessed through interview and questionnaire. METHOD: Twenty-three questionnaires, eighteen returned, were sent to women with a mean age 65.5 yrs (range 34-86). All had undergone total mesorectal excision for rectal cancer between 1998-2001. Mean follow-up was 18.8 months (range 3-35). RESULTS: Preoperatively 5/18 (28%) were sexually active, 3/18 (17%) of patients described urinary frequency and nocturia and 7/18 (39%) described symptoms of stress incontinence prior to surgery. Postoperatively all sexually active patients remained active although all described some discomfort with penetration. Two of the patients sexually active described reduced libido secondary to the stoma. Postoperative urinary symptoms developed with 59% reporting the development of nocturia, 18% developed stress incontinence and one patient required a permanent catheter. Of those with symptoms, 80% persisted longer than three months from surgery. Symptoms were predominant in those patients with low rectal cancers, particularly those undergoing abdomino-perineal excision and in those who had previously undergone abdominal hysterectomy. CONCLUSION: The treatment of rectal cancer involves surgery to the pelvic floor. Despite nerve preservation this is associated with the development of worsening nocturia and stress incontinence. This is most marked in those patients who had previously undergone a hysterectomy. Further studies are warranted to assess the interaction with previous gynaecological surgery.

Local staging and assessment of colon cancer with 1.5-T magnetic resonance imaging.

OBJECTIVE:: The aim of this study was to assess the accuracy of 1.5-T MRI in the pre-operative local T and N staging of colon cancer and identification of extramural vascular invasion (EMVI). METHODS:: Between 2010 and 2012, 60 patients with adenocarcinoma of the colon were prospectively recruited at 2 centres. 55 patients were included for final analysis. Patients received pre-operative 1.5-T MRI with high-resolution T2 weighted, gadolinium-enhanced T1 weighted and diffusion-weighted images. These were blindly assessed by two expert radiologists. Accuracy of the T-stage, N-stage and EMVI assessment was evaluated using post-operative histology as the gold standard. RESULTS:: Results are reported for two readers. Identification of T3 disease demonstrated an accuracy of 71% and 51%, sensitivity of 74% and 42% and specificity of 74% and 83%. Identification of N1 disease demonstrated an accuracy of 57% for both readers, sensitivity of 26% and 35% and specificity of 81% and 74%. Identification of EMVI demonstrated an accuracy of 74% and 69%, sensitivity 63% and 26% and specificity 80% and 91%. CONCLUSION:: 1.5-T MRI achieved a moderate accuracy in the local evaluation of colon cancer, but cannot be recommended to replace CT on the basis of this study. ADVANCES IN KNOWLEDGE:: This study confirms that MRI is a viable alternative to CT for the local assessment of colon cancer, but this study does not reproduce the very high accuracy reported in the only other study to assess the accuracy of MRI in colon cancer staging.

High-volume surgeons vs high-volume hospitals: are best outcomes more due to who or where?

BACKGROUND: High-volume hospitals are purported to provide "best" outcomes. We undertook this study to evaluate the outcomes after pancreaticoduodenectomy when high-volume surgeons relocate to a low-volume hospital (ie, no pancreaticoduodenectomies in >5 years). METHODS: Outcomes after the last 50 pancreaticoduodenectomies undertaken at a high-volume hospital in 2012 (ie, before relocation) were compared with the outcomes after the first 50 pancreaticoduodenectomies undertaken at a low-volume hospital (ie, after relocation) in 2012 to 2013. RESULTS: Patients undergoing pancreaticoduodenectomies at a high-volume vs a low-volume hospital were not different by age or sex. Patients who underwent pancreaticoduodenectomy at the low-volume hospital had shorter operations with less blood loss, spent less time in the intensive care unit, and had shorter length of stay (P < .05 for each); 30-day mortality and 30-day readmission rates were not different. CONCLUSIONS: The salutary benefits of undertaking pancreaticoduodenectomy at a high-volume hospital are transferred to a low-volume hospital when high-volume surgeons relocate. The "best" results follow high-volume surgeons.

The Effect of Product Safety Courses on the Adoption and Outcomes of LESS Surgery.

BACKGROUND AND OBJECTIVES: As technology in surgery evolves, the medical instrument industry is inevitability involved in promoting the use and appropriate (ie, effective and safe) application of its products. This study was undertaken to evaluate industry-supported product safety courses in laparoendoscopic single-site (LESS) surgery, by using the metrics of surgeons' adoption of the technique, safety of the procedure, and surgeons' perception of the surgery. METHODS: LESS surgery courses that involved didactic lectures, operative videos, operation observation, collaborative learning, and simulation, were attended by 226 surgeons. With Florida Hospital Tampa Institutional Review Board approval, the surgeons were queried before and immediately after the course, to assess their attitudes toward LESS surgery. Then, well after the course, the surgeons were contacted, repeatedly if necessary, to complete questionnaires. RESULTS: Before the course, 82% of the surgeons undertook more than 10 laparoscopic operations per month. Immediately after the course, 86% were confident that they were prepared to perform LESS surgery. Months after the course, 77% of the respondents had adopted LESS surgery, primarily cholecystectomy; 59% had added 1 or more trocars in 0-20% of their procedures; and 73% held the opinion that operating room observation was the most helpful learning experience. Complications with LESS surgery were noted 12% of the time. Advantages of the technique were better cosmesis (58%) and patient satisfaction (38%). Disadvantages included risk of complications (37%) and higher technical demand (25%). Seventy-eight percent viewed LESS surgery as an advancement in surgical technique. CONCLUSION: In multifaceted product safety courses, operating room observation is thought to provide the most helpful instruction for those wanting to undertake LESS surgery. The procedure has been safely adopted by surgeons who frequently perform laparoscopies. The tradeoff is in performing a more difficult technique to obtain better cosmesis for the patient. We must continue to conduct critical evaluations of product safety courses for the introduction of new technology in surgery.

Margin status impacts survival after pancreaticoduodenectomy but negative margins should not be pursued.

Negative margins are the goal with pancreaticoduodenectomy for pancreatic adenocarcinoma. Thereby, margins are assessed intraoperatively with frozen section analysis and negative margins are pursued. This study was undertaken to determine the impact of margin status with pancreaticoduodenectomy for pancreatic adenocarcinoma and the value of extending resections to achieve negative margins. The intraoperative frozen section analysis and final margins for 448 patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma were assessed and their impact on survival was determined. Median data are presented. Two hundred ninety-eight (67%) patients had negative margins (R0), an additional 110 (25%) patients had microscopically positive and macroscopically negative margins (R1), and an additional 40 (9%) patients had initially positive microscopic margins, which became negative with further resection (R1 → R0). R0 resections were more likely to have smaller tumors, earlier T grade, earlier N grade, lower American Joint Committee on Cancer stage, and less frequent extrapancreatic extension (P ≤ 0.03 for each). Survival was better with R0 resections than R1 resections (20 vs 12 months, P < 0.001); extending resections to achieve negative margins (i.e., R1 → R0) did not improve survival beyond R1 resections (14 vs 12 months, P = 0.19). Survival after pancreaticoduodenectomy is disappointing. Patients with initial negative margins do best. Positive microscopic margins reflect more aggressive tumor-specific factors and lead to abbreviated survival even with extended resections to achieve negative margins (i.e., R1 → R0). With an initial positive margin, pursuing negative margins does not improve survival and, thereby, negative margins should not be "chased."

Transoral incisionless fundoplication: is it as safe and efficacious as a Nissen or Toupet fundoplication?

Transoral incisionless fundoplication (TIF) was U.S. Food and Drug Administration-approved in 2007 to treat gastroesophageal reflux disease (GERD), but comparative data are lacking. This study was undertaken to compare outcomes for patients with GERD undergoing TIF versus laparoscopic Nissen or Toupet fundoplications. We undertook a case-controlled study of three cohorts of 20 patients undergoing TIF or laparoscopic Nissen or Toupet fundoplications from 2010 to 2013 controlling for age, body mass index, and preoperative DeMeester scores. All patients were prospectively followed. Median data are reported. Patients undergoing TIF had significantly shorter operative times (in minutes: 71 vs 119 and 85, respectively, P < 0.001) and length of stay (in days: 1, 2, and 1, respectively, P < 0.001). No matter the approach, patients reported dramatic and similar reduction in symptom frequency and severity (e.g., heartburn 8 to 0, P < 0.05). At follow-up, 83 per cent of patients after TIF, 80 per cent after Nissen, or 92 per cent after Toupet fundoplications had symptoms less than once per month (P = 0.12). TIF leads to dramatic symptom resolution, similar when compared with Nissen or Toupet fundoplications. TIF promotes shorter operative times and lengths of stay. Patient satisfaction and effective palliation of symptoms show that TIF is safe and efficacious in comparison to Nissen and Toupet fundoplications and support its continued application and evaluation.

Nontherapeutic celiotomy incidence is not affected by volume of pancreaticoduodenectomy for pancreatic adenocarcinoma.

Nontherapeutic celiotomy for pancreatic adenocarcinoma is detrimental to patients by delaying medical treatment as a result of unnecessarily incurred postoperative recovery time. This study was undertaken to evaluate whether surgeon volume of pancreaticoduodenectomy for pancreatic adenocarcinoma impacted the incidence of nontherapeutic celiotomy. All patients undergoing an intended pancreaticoduodenectomy for pancreatic adenocarcinoma were evaluated from 2003 to 2012. Survival was calculated using Kaplan-Meier analysis. The association between surgeon volume of pancreaticoduodenectomy and occurrence of nontherapeutic celiotomy was assessed using Fisher's exact test. Median data are presented. Eight surgeons undertook 443 intended pancreaticoduodenectomies for patients with pancreatic adenocarcinoma; 329 (74%) patients underwent pancreaticoduodenectomy, whereas 114 (26%) patients underwent nontherapeutic celiotomies. Two surgeons undertook 85 per cent of operations. Surgeon volume did not impact the incidence of nontherapeutic celiotomies (P = 0.26). Seventy-seven (68%) patients had metastatic disease at the time of the operation, whereas 37 (32%) patients had locally advanced unresectable disease. These patients had survivals of 5.0 and 6.0 months, respectively (P = 0.77). A high proportion of patients--one in four--undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma will ultimately undergo a nontherapeutic celiotomy. Surgeon volume of pancreaticoduodenectomy for pancreatic adenocarcinoma does not lessen the incidence of nontherapeutic celiotomies. Preoperative prediction of patients with imaging-occult metastatic or locally advanced disease remains a challenge, even for high-volume surgeons. Attempts to create algorithms for patients with high risk of imaging-occult metastatic or locally advanced disease to undergo staging laparoscopy and/or positron emission tomography scanning may decrease the burden of patients undergoing nontherapeutic celiotomies.

Intralesional injection of rose bengal induces a systemic tumor-specific immune response in murine models of melanoma and breast cancer.

Intralesional (IL) injection of PV-10 has shown to induce regression of both injected and non-injected lesions in patients with melanoma. To determine an underlying immune mechanism, the murine B16 melanoma model and the MT-901 breast cancer model were utilized. In BALB/c mice bearing MT-901 breast cancer, injection of PV-10 led to regression of injected and untreated contralateral subcutaneous lesions. In a murine model of melanoma, B16 cells were injected into C57BL/6 mice to establish one subcutaneous tumor and multiple lung lesions. Treatment of the subcutaneous lesion with a single injection of IL PV-10 led to regression of the injected lesion as well as the distant B16 melanoma lung metastases. Anti-tumor immune responses were measured in splenocytes collected from mice treated with IL PBS or PV-10. Splenocytes isolated from tumor bearing mice treated with IL PV-10 demonstrated enhanced tumor-specific IFN-gamma production compared to splenocytes from PBS-treated mice in both models. In addition, a significant increase in lysis of B16 cells by T cells isolated after PV-10 treatment was observed. Transfer of T cells isolated from tumor-bearing mice treated with IL PV-10 led to tumor regression in mice bearing B16 melanoma. These studies establish that IL PV-10 therapy induces tumor-specific T cell-mediated immunity in multiple histologic subtypes and support the concept of combining IL PV10 with immunotherapy for advanced malignancies.

Outcomes after transjugular intrahepatic portosystemic stent shunt: a "bridge" to nowhere.

BACKGROUND: Transjugular intrahepatic portosystemic stent shunt (TIPS) has become the modality of choice for complicated portal decompression. This study was undertaken to determine outcomes after TIPS and the usefulness of TIPS as a "bridge" to transplantation. METHODS: Patients undergoing TIPS from 2001 to 2010 at a teaching hospital with a transplant program were studied. The median data are presented. RESULTS: TIPS was undertaken in 256 patients. TIPS decreased portal vein-inferior vena cava (IVC) gradients from 17 to 5 mm Hg (P < .001). Reinterventions were undertaken in 54 patients (21%). Survival after TIPS was 26 months; liver transplantation was undertaken in 35 (14%) patients. CONCLUSIONS: TIPS effectively decompresses portal hypertension but leads to frequent reinterventions and short survival. After TIPS, liver transplantation is uncommonly undertaken. TIPS is a "bridge" to transplantation that is seldom "crossed," and TIPS continues to be plagued by frequent reinterventions. Outcomes after TIPS and the infrequency of transplantation after TIPS make it difficult to recommend on merit.