The Expression of the Claudin Family of Proteins in Colorectal Cancer.

Claudins (CLDN1-CLDN24) are a family of tight junction proteins whose dysregulation has been implicated in tumorigeneses of many cancer types. In colorectal cancer (CRC), CLDN1, CLDN2, CLDN4, and CLDN18 have been shown to either be upregulated or aberrantly expressed. In the normal colon, CLDN1 and CLDN3-7 are expressed. Although a few claudins, such as CLDN6 and CLDN7, are expressed in CRC their levels are reduced compared to the normal colon. The present review outlines the expression profiles of claudin proteins in CRC and those that are potential biomarkers for prognostication.

Increased Pathologic Downstaging with Induction versus Consolidation Chemotherapy in Patients with Locally Advanced Rectal Cancer Treated with Total Neoadjuvant Therapy-A National Cancer Database Analysis.

Total neoadjuvant therapy (TNT) is the recommended treatment for locally advanced rectal cancer. The optimal sequence of TNT is debated: induction (chemotherapy first) or consolidation (chemoradiation first)? We aim to evaluate the practice patterns and clinical outcomes of total neoadjuvant therapy with either induction or consolidation regiments in the United States for patients with locally advanced rectal cancer. METHODS: This is a retrospective analysis of the National Cancer Database for patients with clinical stage II or stage III rectal cancer, diagnosed between 2006 and 2017, who underwent total neoadjuvant therapy followed by surgery. RESULTS: From 2006 to 2017, we identified 8999 patients and found that the utilization of induction chemotherapy increased from 2.0% to 35.0%. TNT resulted in pathologic downstaging 46.7% of the time and a pathologic complete response 11.6% of the time. Induction chemotherapy lead to higher pathologic downstaging (58% vs. 44.7%, p < 0.001) and pathologic complete responses (16.8% vs. 10.7%, p < 0.001). Similar trends held true in a multivariate analysis and subset analysis of stage II and III disease. CONCLUSIONS: These findings suggest that induction chemotherapy may be preferred over consolidation chemotherapy when downstaging prior to oncologic resection is desired. The optimal treatment plan for total neoadjuvant therapy is multi-factorial and requires further elucidation.

Autologous Fat Grafting: an Emerging Treatment Option for Complex Anal Fistulas.

BACKGROUND: Autologous fat grafting (AFG) has shown promise in the treatment of complex wounds, with trials reporting good healing rates and safety profile. We aim to investigate the role of AFG in managing complex anorectal fistulas. METHODS: This was a retrospective review of a prospectively maintained IRB-approved database. We examined the rates of symptom improvement, clinical closure of fistula tracts, recurrence, complications, and worsening fecal incontinence. Perianal disease activity index (PDAI) was obtained for patients undergoing combination of AFG and fistula plug treatment. RESULTS: In total, 52 unique patients underwent 81 procedures, of which Crohn's was present in 34 (65.4%) patients. The majority of patients previously underwent more common treatments such as endorectal advancement flap or ligation of intersphincteric fistula tract. Fat-harvesting sites and processing technique were selected by the plastic surgeons based on availability of trunk fat deposits. When analyzing patients by their last procedure, 41 (80.4%) experienced symptom improvement, and 29 (64.4%) experienced clinical closure of all fistula tracts. Recurrence rate was 40.4%, and complication rate was 15.4% (7 postoperative abscesses requiring I&D and 1 bleeding episode ligated at bedside). The abdomen was the most common site of lipoaspirate harvest at 63%, but extremities were occasionally used. There were no statistically significant differences in outcomes when comparing single graft treatment to multiple treatments, Crohn's and non-Crohn's, different methods of fat preparation, and diversion. CONCLUSION: AFG is a versatile procedure that can be done in conjunction with other therapies and does not interfere with future treatments if recurrence occurs. It is a promising and affordable method to safely address complex fistulas.

Specific Targeting and Labeling of Colonic Polyps in CPC-APC Mice with Mucin 5AC Fluorescent Antibodies: A Model for Detection of Early Colon Cancer.

Poor visualization of polyps can limit colorectal cancer screening. Fluorescent antibodies to mucin5AC (MUC5AC), a glycoprotein upregulated in adenomas and colorectal cancer, could improve screening colonoscopy polyp detection rate. Adenomatous polyposis coli flox mice with a Cdx2-Cre transgene (CPC-APC) develop colonic polyps that contain both dysplastic and malignant tissue. Mice received MUC5AC-IR800 or IRdye800 as a control IV and were sacrificed after 48 h for near-infrared imaging of their colons. A polyp-to-background ratio (PBR) was calculated for each polyp by dividing the mean fluorescence intensity of the polyp by the mean fluorescence intensity of the background tissue. The mean 25 µg PBR was 1.70 (±0.56); the mean 50 µg PBR was 2.64 (±0.97); the mean 100 µg PBR was 3.32 (±1.33); and the mean 150 µg PBR was 3.38 (±0.87). The mean PBR of the dye-only control was 2.22 (±1.02), significantly less than the 150 µg arm (p-value 0.008). The present study demonstrates the ability of fluorescent anti-MUC5AC antibodies to specifically target and label colonic polyps containing high-grade dysplasia and intramucosal adenocarcinoma in CPC-APC mice. This technology can potentially improve the detection rate and decrease the miss rate of advanced colonic neoplasia and early cancer at colonoscopy.

The Mucin Family of Proteins: Candidates as Potential Biomarkers for Colon Cancer.

Mucins (MUC1-MUC24) are a family of glycoproteins involved in cell signaling and barrier protection. They have been implicated in the progression of numerous malignancies including gastric, pancreatic, ovarian, breast, and lung cancer. Mucins have also been extensively studied with respect to colorectal cancer. They have been found to have diverse expression profiles amongst the normal colon, benign hyperplastic polyps, pre-malignant polyps, and colon cancers. Those expressed in the normal colon include MUC2, MUC3, MUC4, MUC11, MUC12, MUC13, MUC15 (at low levels), and MUC21. Whereas MUC5, MUC6, MUC16, and MUC20 are absent from the normal colon and are expressed in colorectal cancers. MUC1, MUC2, MUC4, MUC5AC, and MUC6 are currently the most widely covered in the literature regarding their role in the progression from normal colonic tissue to cancer.

Perianal Basal Cell Carcinoma: 35-Year Experience.

BACKGROUND: Basal cell carcinoma of the perianal region is a rare anorectal disease. This condition is not related to exposure to ultraviolet radiation. Because of the low prevalence and poor detection, there is a paucity of data relating to this condition in the literature. Perianal basal cell carcinoma presents surgical challenges different from other anatomic locations and may not share the same prevalence or natural history. Here, we describe the largest series to date on the surgical management of perianal basal cell carcinoma. OBJECTIVE: We aimed to present our 35-year experience in managing perianal basal cell carcinoma in this study. DESIGN: This was a retrospective single-center analysis. SETTING: The study was conducted at a large tertiary referral academic health care system. PATIENTS: All patients undergoing surgical management of pathology confirmed perianal basal cell carcinoma. INTERVENTIONS: All patients underwent surgical management of their disease. MAIN OUTCOME MEASURES: The primary outcomes were disease recurrence, mortality, and wound complications. RESULTS: A total of 29 patients were identified with an average follow-up of 5.5 years. At index presentation, 27.6% of patients had multiple basal cell carcinoma in other anatomic locations. Ninety-three percent of patients were adequately treated with local excision, but 60% had wound dehiscence at the time of their first follow-up visit. Ultimately, there were no recurrences or disease-related mortality during the follow-up period. LIMITATIONS: Limitations to our study include its nonrandomized retrospective nature, single-institution experience, and small patient sample size. CONCLUSIONS: Perianal basal cell carcinoma carries a high rate of synchronous presentation in other locations and should prompt a thorough evaluation. Perianal basal cell carcinomas can and should be successfully treated with local excision despite the high rate of wound complications. See Video Abstract at http://links.lww.com/DCR/B883 .Carcinoma perianal de células basales: 35 años de experienciaANTECEDENTES:El carcinoma de células basales de la región perianal es una enfermedad anorrectal rara. Esta condición no está relacionada con la exposición a la radiación ultravioleta. Debido a la baja prevalencia y detección pobre, hay escasez de datos relacionados con esta condición en la literatura. El carcinoma de células basales perianal presenta diferentes desafíos quirúrgicos en otras ubicaciones anatómicas y puede no compartir la misma prevalencia o historia natural. A continuación, describimos la serie más grande hasta la fecha sobre el tratamiento quirúrgico del carcinoma de células basales perianal.OBJETIVO:Presentar nuestra experiencia de 35 años en el manejo del carcinoma de células basales perianal.DISEÑO:Este fue un análisis retrospectivo de un solo centro.ENTORNO CLINICO:El estudio se llevó a cabo en un gran centro de salud académico de referencia terciaria.PACIENTES:Todos los pacientes sometidos a tratamiento quirúrgico con patología confirmatoria de carcinoma basocelular perianal.INTERVENCIONES:Todos los pacientes fueron sometidos a tratamiento quirúrgico de su enfermedad.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados primarios fueron la recurrencia de la enfermedad, mortalidad, y complicaciones de la herida.RESULTADOS:Se identificaron un total de 29 pacientes con un seguimiento promedio de 5.5 años. El 27,6% de los pacientes tenían carcinoma basocelular múltiple en otras localizaciones anatómicas en la presentación inicial. El 93% de los pacientes fueron tratados adecuadamente con escisión local, pero el 60% tuvo dehiscencia de la herida en el momento de la primera visita de seguimiento. En última instancia, no hubo recurrencias ni mortalidad relacionada con la enfermedad durante el período de seguimiento.LIMITACIONES:Las limitaciones de nuestro estudio incluyen su naturaleza retrospectiva no aleatorizada, la experiencia de una sola institución y el tamaño pequeño de la muestra de pacientes.CONCLUSIONES:El carcinoma de células basales perianal tiene una alta tasa de presentación sincrónica en otras localizaciones y debe dar lugar a una evaluación exhaustiva. Los CBC perianales pueden y deben ser tratados exitosamente con escisión local a pesar de la alta tasa de complicaciones de herida. Consulte Video Resumen en http://links.lww.com/DCR/B883 . (Tradducción-Dr. Francisco M. Abarca-Rendon ).

Current trends in nonoperative management for rectal adenocarcinoma: An unequal playing field?

BACKGROUND AND OBJECTIVES: Increasing evidence suggests patient-oriented benefits of nonoperative management (NOM) for rectal cancer. However, vigilant surveillance requires excellent access to care. We sought to examine patient, socioeconomic, and facility-level factors associated with NOM over time. METHODS: Using the National Cancer Database (2006-2017), we examined patients with Stage II-III rectal adenocarcinoma, who received neoadjuvant chemoradiation and received NOM versus surgery. Factors associated with NOM were assessed using multivariable logistic regression with backward stepwise selection. RESULTS: There were 59,196 surgical and 8520 NOM patients identified. NOM use increased from 12.9% to 15.9% between 2006 and 2017. Patients who were Black (adjusted odds ratio [aOR]: 1.36, 95% confidence interval [CI]: 1.26-1.47), treated at community cancer centers (aOR: 1.22, 95% CI: 1.12-1.30), without insurance (aOR: 1.87, 95% CI: 1.68-2.09), and with less education (aOR: 1.53, 95% CI: 1.42-1.65) exhibited higher odds of NOM. Patients treated at high-volume centers (aOR: 0.79, 95% CI: 0.74-0.84) and those who traveled >25.6 miles for care (aOR: 0.59, 95% CI: 0.55-0.64) had lower odds of NOM. CONCLUSIONS: Vulnerable groups who traditionally have difficulty accessing comprehensive cancer care were more likely to receive NOM, suggesting that healthcare disparities may be driving utilization. More research is needed to understand NOM decision-making in rectal cancer treatment.

Factors associated with refusing surgery versus planned nonoperative management for rectal cancer.

BACKGROUND: Increasingly, patients with rectal cancer receive nonoperative management. A growing body of retrospective evidence supporting the safety of this approach has likely contributed to its growing popularity. However, patients may also undergo nonoperative management because of refusal of surgical resection. We hypothesize that patients who refuse surgery are more likely to be from groups who traditionally face barriers accessing care. METHODS: We used the National Cancer Database (2006-2017) to analyze patients with nonmetastatic rectal adenocarcinoma who underwent nonoperative management following radiation. We identified 2 groups: (1) planned nonoperative management and (2) nonoperative management because of refusal of surgery. We performed logistic regression to compare the groups along patient, socioeconomic, and facility-level factors. RESULTS: In total, 9,613 and 2,039 patients were included in the planned nonoperative management and refused nonoperative management groups, respectively. Of the total study cohort (ie, planned nonoperative management + refused nonoperative management), 21% of these patients diagnosed in 2017 underwent refused nonoperative management, versus 12% in 2006. Patients who were Black (adjusted odds ratio 1.47, 95% confidence interval 1.26-1.71) or Asian/Pacific Islander (adjusted odds ratio 1.51, 95% confidence interval 1.18-1.92), age ≥65 years (adjusted odds ratio 1.55, 95% confidence interval 1.37-1.77), with more advanced disease stage (stage III adjusted odds ratio 1.30, 95% confidence interval 1.10-1.53), and government insurance (adjusted odds ratio 1.19, 95% confidence interval 1.04-1.36) were associated with increased utilization of refused nonoperative management. Conversely, lower education (adjusted odds ratio 0.62, 95% confidence interval 0.50-0.76) and female sex (adjusted odds ratio 0.88, 95% confidence interval 0.79-0.97) were associated with planned nonoperative management. CONCLUSION: Our findings suggest that the refused nonoperative management group is demographically distinct. Outreach efforts to better understand the rationale behind patient decision making in rectal cancer will be paramount to ensuring appropriate implementation of nonoperative management.

Robotic transanal minimally invasive surgery: a single institutional experience.

Robotic transanal minimally invasive surgery (R-TAMIS) is a novel and evolving technique with limited reported outcomes in the literature. Compared to the laparoscopic approach, R-TAMIS provides enhanced optics, increased degrees of motion, superior ergonomics, and easier maneuverability in the confines of the rectum. We report a single institution experience at a large quaternary referral academic medical center with R-TAMIS using the da Vinci Xi® platform. This is a retrospective review of electronic medical records at the Mayo Clinic from September 2017 to April 2020. It includes all available clinical documentations for patients undergoing R-TAMIS at our institution. Patient demographics, intraoperative data (procedure time, tumor size and distance), complications, and pathology reports were reviewed. A total of 28 patients underwent R-TAMIS. Median follow-up was 23.65 months. Sixteen patients underwent R-TAMIS for endoscopically unresectable rectal polyps, eight for rectal adenocarcinoma, two for rectal gastrointestinal stromal tumor, and two for rectal carcinoid tumor. The mean size of the lesions was 4.1 cm (range 0.2-13.8 cm). The mean location of lesions was 7.8 cm (range 0-16 cm) from the anal verge. The mean operative time was 132.5 ± 46.8 min. There was one 30-day complication, and no deaths. Twenty-three (82%) patients were discharged the day of surgery. R-TAMIS is a safe, feasible, and effective technique for the surgical treatment of a variety of rectal pathology. A hybrid technique can be used for the resecting tumors extending into the anal canal.

State-of-the-art surgery for ulcerative colitis.

Ulcerative colitis (UC) is an autoimmune-mediated colitis which can present in varying degrees of severity and increases the individual's risk of developing colon cancer. While first-line treatment for UC is medical management, surgical treatment may be necessary in up to 25-30% of patients. With an increasing armamentarium of biologic therapies, patients are presenting for surgery much later in their course, and careful understanding of the complex interplay of the disease, its management, and the patient's overall health is necessary when considering he appropriate way in which to address their disease surgically. Surgery is generally a total proctocolectomy either with pelvic pouch reconstruction or permanent ileostomy; however, this may need to be spread across multiple procedures given the complexity of the surgery weighed against the overall state of the patient's health. Minimally invasive surgery, employing either laparoscopic, robotic, or transanal laparoscopic approaches, is currently the preferred approach in the elective setting. There is also some emerging evidence that appendectomy may delay the progression of UC in some individuals. Those who treat these patients surgically must also be familiar with the numerous potential pitfalls of surgical intervention and have plans in place for managing problems such as pouchitis, cuffitis, and anastomotic complications.

Flexible Endoscopic Zenker's Diverticulotomy with an Articulating Bipolar Energy Sealer.

The surgical management of Zenker's diverticula is performed through open or endoscopic approaches. The purpose of this report is to review our early experience with flexible endoscopic diverticulotomy with an articulating bipolar energy sealer for cricopharyngeal and diverticular wall division in a series of 5 patients where transoral rigid access was not possible. In addition to technical details, safety and efficacy data are included. The average diverticulum size was 2.5 cm. All patients reported symptom resolution, and there were no surgical complications. Liquid diet was initiated on postoperative day 1 for all patients and solids on day 11.8 ± 14.4 (mean ± SD) per protocol. Results demonstrate that treatment of Zenker's diverticula can safely and successfully be performed with flexible endoscopic visualization and utilization of an articulating bipolar energy sealer to perform diverticulotomy in a population of patients where transoral diverticulotomy would not otherwise be feasible due to anatomic constraints. Early results support obtaining further experience to study this technology as an alternative to open surgery, especially when visualization and access are suboptimal with rigid endoscopy.

Robotic transanal minimally invasive surgery (TAMIS) with the newest robotic surgical platform: a multi-institutional North American experience.

BACKGROUND: Transanal minimally invasive surgery (TAMIS) offers intra-luminal full-thickness excision of rectal neoplasia. Robotic TAMIS (RT) allows for greater versatility in motion while operating in the limited space of the rectum. We present our experience with this technique in practice using the DaVinci Xi™ platform. METHOD: This is a multi-institutional retrospective analysis for patient undergoing Robotic TAMIS for resection of rectal lesions at two tertiary referral hospitals in the United States. Morbidity, mortality, anatomic measurement, and final pathology were analyzed. RESULTS: Thirty-four patients planned for Robotic TAMIS were identified. Average follow-up was 188 days. The average BMI was 29.5 ± 5.9. All patients had an American Society of Anesthesiologist (ASA) Class of 2 or greater and 21 (62%) were ASA 3 or greater. Rectal lesions located from 2 to 15 cm from the dentate line were successfully resected. Lesions up to 4.5 cm in the longest dimension were successfully resected. The average operative time was 100 ± 70 min, which correlated to a robotic console time of 76 ± 67 min. Patients were placed in Lithotomy in 32 (94%) cases and were prone in only 2 (6%) cases. There were no intraoperative complications or conversions to another technique. The only postoperative complication was a medically managed Clostridium difficile infection in 1 patient. Three patients were upstaged to T2 on final pathology and underwent successful formal resections. BMI was a statistically significant predictor of a longer operation. CONCLUSIONS: With increased reach and operative range of motion, Robotic TAMIS is a safe and effective method for excising low-risk rectal neoplasia with a wide range of anatomical measurements. Higher BMI is a significant predictor of a longer and likely more challenging operation.

Preventing Rescue Surgeries by Endoscopic Clipping: A Valuable Resource in the Surgeon's Toolbox.

AIM: Over-the-scope-clip (OTSC) System is a relatively new endoluminal intervention for gastrointestinal (GI) leaks, fistulas, and bleeding. Here, we present a single center experience with the device over the course of 4 years. METHODS: Retrospective chart review was conducted for patients who received endoscopic OTSC treatment. Primary outcome is the resolution of the original indication for clip placement. Secondary outcomes are complications and time to resolution. RESULTS: Forty-one patients underwent treatment with the OTSC system from 2011 to 2015 with average follow-up of 152 days. The average age is 53.7. The most common site of clip placement was in the stomach (44%). Clips were placed after surgical complication for 28 patients (68%), endoscopic complications for 8 patients (19%), and spontaneous presentation in 5 patients (12%). Technical success was achieved in all patients. Overall, 34 patients (83%) were successfully treated. Nine patients required multiple clips and three patients required additional treatment modalities after OTSC. Four patients used the OTSC as a bridging therapy to surgery. Using OTSC for palliation versus nonpalliative indications was associated with lower rates of treatment success (50% versus 86%, P = .028). Using OTSC for symptoms <6 months had higher rates of treatment success than those experiencing longer symptoms (88% versus 65%, P = .045). There were no major morbidities or mortalities directly associated with the OTSC system. Complications from clip use were pain in two patients (5%) and hematemesis in one patient (3%). CONCLUSIONS: The OTSC System can be a very successful treatment for iatrogenic or spontaneous GI leaks and bleeds. Treatment success is more likely in patients treated within 6 months of diagnosis and less likely to when used for palliation. It was also successfully used as bridging therapy in several patients.

How bariatric surgery affects liver volume and fat density in NAFLD patients.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is an epidemic in the obese population. Bariatric surgery is known to reverse multiple metabolic complications of obesity such as diabetes, dyslipidemia, and NAFLD, but the timing of liver changes has not been well described. MATERIALS AND METHODS: This was an IRB-approved, two-institutional prospective study. Bariatric patients received MRIs at baseline and after a pre-operative liquid diet. Liver biopsies were performed during surgery and if NAFLD positive, the patients received MRIs at 1, 3, and 6 months. Liver volumes and proton-density fat fraction (PDFF) were calculated from offline MRI images. Primary outcomes were changes in weight, body mass index (BMI), percent excess weight loss (EWL%), liver volume, and PDFF. Resolution of steatosis, as defined as PDFF < 6.4% based on previously published cutoffs, was assessed. Secondarily, outcomes were compared between patients who underwent laparoscopic sleeve gastrectomy (LSG) versus laparoscopic Roux-en-Y gastric bypass (LRYGB). RESULTS: From October 2010 to June 2015, 124 patients were recruited. 49 patients (39.5%) completed all five scans. EWL% at 6 months was 55.6 ± 19.0%. BMI decreased from 45.3 ± 5.9 to 34.4 ± 5.1 kg/m2 and mean liver volume decreased from 2464.6 ± 619.4 to 1874.3 ± 387.8 cm3 with a volume change of 21.4 ± 11.4%. PDFF decreased from 16.6 ± 7.8 to 4.4 ± 3.4%. At 6 months, 83.7% patients had resolution of steatosis. Liver volume plateaued at 1 month, but PDFF and BMI continued to decrease. There were no statistically significant differences in liver volume or PDFF reduction from baseline to 6 months between the LSG versus LRYGB subgroups. CONCLUSION: Patients with NAFLD undergoing bariatric surgery can expect significant decreases in liver volume and hepatic steatosis at 6 months, with 83.7% of patients achieving resolution of steatosis. Liver volume reduction plateaus 1-month post-bariatric surgery, but PDFF continues to decrease. LSG and LRYGB did not differ in efficacy for inducing regression of hepatosteatosis.

Solving the surgeon ergonomic crisis with surgical exosuit.

INTRODUCTION: The widespread adoption of laparoscopic surgery has put new physical demands on the surgeon leading to increased musculoskeletal disorders and injuries. Shoulder, back, and neck pains are among the most common complaints experienced by laparoscopic surgeons. Here, we evaluate the feasibility and efficacy of a non-intrusive progressive arm support exosuit worn by surgeons under the sterile gown to reduce pain and fatigue during surgery. METHODS AND PROCEDURES: This is a prospective randomized crossover study approved by the Internal Review Board (IRB). The study involves three phases of testing. In each phase, general surgery residents or attendings were randomized to wearing the surgical exosuit at the beginning or at the crossover point. The first phase tests for surgeon manual dexterity wearing the device using the Minnesota Dexterity test, the Purdue Pegboard test, and the Fundamentals of Laparoscopic Surgery (FLS) modules. The second phase tests the effect of the device on shoulder pain and fatigue while operating the laparoscopic camera. The third phase rates surgeon experience in the operating room between case-matched operating days. RESULTS: Twenty subjects were recruited for this study. Surgeons had the similar dexterity scores and FLS times whether or not they wore the exosuit (p value ranges 0.15-0.84). All exosuit surgeons completed 15 min of holding laparoscopic camera compared to three non-exosuit surgeons (p < 0.02). Exosuit surgeons experienced significantly less fatigue at all time periods and arm pain (3.11 vs 5.88, p = 0.019) at 10 min. Surgeons wearing the exosuit during an operation experienced significant decrease in shoulder pain and 85% of surgeons reported some form of pain reduction at the end of the operative day. CONCLUSION: The progressive arm support exosuit can be a minimally intrusive device that laparoscopic surgeons wear to reduce pain and fatigue of surgery without significantly interfering with operative skills or manual dexterity.

Laparoscopic Gastropleural Fistula Repair: A Minimally Invasive Solution for a Complex Problem.

INTRODUCTION: Gastropleural fistula (GPF) is a complex pathology that can present as a result of surgery, trauma, peptic ulcer disease, malignancies, radiation, or chemotherapy. Management typically includes endoscopic or surgical intervention along with intraabdominal or intrathoracic drainage of pre-existing infection. Traditionally, surgical approaches have been through exploratory laparotomy or thoracotomy, subjecting already ill patients to additional morbidity. CASE REPORT: We describe and demonstrate a laparoscopic minimally invasive approach to the management of a GPF with a wedge resection of the stomach, along with a review of the current literature regarding GPF treatment. CONCLUSION: GPF repair can be performed through laparoscopy and may lead to improved patient outcomes and faster recovery.

Quality of polyp resection during colonoscopy: are we achieving polyp clearance?

BACKGROUND AND STUDY AIM: Currently colonoscopy quality indicators emphasize our ability to improve polyp detection (e.g., preparation quality, withdrawal times of ≥6 min). The completeness of a polyp resection may also be an important determinant of quality and efficient colonoscopy. The primary aim of this study was to determine the incidence of an incomplete polyp resection despite a perceived complete polypectomy. PATIENTS AND METHODS: This was a retrospective quality assurance project conducted at the San Diego Veterans Affair Medical Center and University of California San Diego Medical Center from July 2007 to April 2008. The patients recruited to this study were undergoing surveillance and screening colonoscopy. The resection quality was evaluated in 65 polyps of 47 patients. Twenty-two polyps were removed with standard biopsy forceps, jumbo forceps (18), hot snare (18), and cold snare (7). Biopsies were taken from the post-polypectomy site base and perimeter for histologic examination in order to confirm histologic absence of all polypoid appearing mucosa. RESULTS: The post-polypectomy sites of ten polyps (15%) were found to have residual polypoid tissue. Six were removed by standard biopsy forceps, jumbo forceps (2), hot snare (1), and cold snare (1). When compared to other polypectomy devices, standard biopsy forceps were more likely to result in an incomplete resection (27 vs. 9%; P = 0.076). CONCLUSIONS: The endoscopist may not be visually accurate in determining when a polyp is completely resected, and alternative devices and techniques for polyp resection should be considered.

U.S. multicenter pilot study of daily consensus interferon (CIFN) plus ribavirin for "difficult-to-treat" HCV genotype 1 patients.

BACKGROUND: Patients with chronic hepatitis C genotype 1 (HCV-1) and difficult-to-treat characteristics respond poorly to pegylated interferon alfa and ribavirin (RBV), and could benefit from an interferon with increased activity (consensus interferon or CIFN), favorable viral kinetics from daily dosing, and a longer duration of therapy. The purpose of this pilot study was to determine the efficacy and safety of daily CIFN + RBV for initial treatment of patients with HCV-1 infection. METHODS: Patients with difficult-to-treat characteristics (92% male, 33% African American, 78% Veterans Affairs [VA]; 67% high viral load, 59% stage 3-4 fibrosis, and mean weight of 204 lbs) were enrolled at seven VA and two community medical centers. They were randomized to daily CIFN (15 mcg/day SQ) and RBV (1-1.2 g/d PO) given for either 52 weeks (group A, n = 33) or 52-72 weeks (from time of viral response +48 weeks) (group B, n = 31). RESULTS: Intention to treat analysis for treatment groups A and B demonstrated 33% (11/33) and 32% (10/31) sustained virologic response (SVR), respectively. Only 2/31 patients in group B received more than 52 weeks of treatment. The overall group demonstrated a 31% (20/64) rapid virologic response rate (RVR), 54% (34/64) end of treatment virologic response and a 33% (21/64) SVR. Patients with RVR at 4 weeks, early virologic response from 8-12 weeks, and late virologic response from 16-24 weeks demonstrated SVR of 75% (15/20), 31% (4/13), and 22% (2/9), respectively. Overall early non-protocol discontinuation occurred in 26/64 (40%) patients. CONCLUSION: Daily CIFN and ribavirin for initial treatment of HCV-1 patients has potential for achieving a relatively high RVR rate, but discontinuations are frequent and successful use of this regimen is highly dependent on adequate patient support to maintain adherence.

Molecular mechanisms underlying Ca2+-mediated motility of human pancreatic duct cells.

We recently reported that transforming growth factor-ß (TGF-ß) induces an increase in cytosolic Ca(2+) ([Ca(2+)](cyt)) in pancreatic cancer cells, but the mechanisms by which TGF-ß mediates [Ca(2+)](cyt) homeostasis in these cells are currently unknown. Transient receptor potential (TRP) channels and Na(+)/Ca(2+) exchangers (NCX) are plasma membrane proteins that play prominent roles in controlling [Ca(2+)](cyt) homeostasis in normal mammalian cells, but little is known regarding their roles in the regulation of [Ca(2+)](cyt) in pancreatic cancer cells and pancreatic cancer development. Expression and function of NCX1 and TRPC1 proteins were characterized in BxPc3 pancreatic cancer cells. TGF-ß induced both intracellular Ca(2+) release and extracellular Ca(2+) entry in these cells; however, 2-aminoethoxydiphenyl borate [2-APB; a blocker for both inositol 1,4,5-trisphosphate (IP(3)) receptor and TRPC], LaCl(3) (a selective TRPC blocker), or KB-R7943 (a selective inhibitor for the Ca(2+) entry mode of NCX) markedly inhibited the TGF-ß-induced increase in [Ca(2+)](cyt). 2-APB or KB-R7943 treatment was able to dose-dependently reverse membrane translocation of PKCα induced by TGF-ß. Transfection with small interfering RNA (siRNA) against NCX1 almost completely abolished NCX1 expression in BxPc3 cells and also inhibited PKCα serine phosphorylation induced by TGF-ß. Knockdown of NCX1 or TRPC1 by specific siRNA transfection reversed TGF-ß-induced pancreatic cancer cell motility. Therefore, TGF-ß induces Ca(2+) entry likely via TRPC1 and NCX1 and raises [Ca(2+)](cyt) in pancreatic cancer cells, which is essential for PKCα activation and subsequent tumor cell invasion. Our data suggest that TRPC1 and NCX1 may be among the potential therapeutic targets for pancreatic cancer.