Correction: Fibroblast growth factor receptor 4 induced resistance to radiation therapy in colorectal cancer.

[This corrects the article DOI: 10.18632/oncotarget.12099.].

FGF8 induces therapy resistance in neoadjuvantly radiated rectal cancer.

PURPOSE: Therapy response to neoadjuvant radiochemotherapy (nRCT) of locally advanced rectal cancer varies widely so that markers predicting response are urgently needed. Fibroblast growth factor (FGF) and FGF receptor (FGFR) signaling is involved in pro-survival signaling and thereby may result in radiation resistance. METHODS: In a cohort of 43 rectal cancer patients, who received nRCT, we analyzed protein levels of FGF 8 and its downstream target Survivin by immunohistochemistry to assess their impact on nRCT response. In vitro resistance models were created by exposing colorectal cancer cell lines to fractionated irradiation and selecting long-term survivors. RESULTS: Our findings revealed significantly higher FGF8 and Survivin staining scores in pre-treatment biopsies as well as in surgical specimens of non-responsive compared to responsive patients. Functional studies demonstrated dose-dependent induction of FGF8 mRNA expression in mismatch-incompetent DLD1 cells already after one dose of irradiation. Surviving clones after one or two series of radiation were more resistant to an additional radiation fraction than non-irradiated controls and showed a significant increase in expression of the FGF8 receptor FGFR3 and of Survivin on both the RNA and the protein levels. CONCLUSION: The results of this study suggest that FGF8 and Survivin contribute to radiation resistance in rectal cancer and may serve as markers to select patients who may not benefit from neoadjuvant radiotherapy.

Outcome after liver transplantation in elderly recipients (>65 years) - A single-center retrospective analysis.

BACKGROUND: Liver transplantation (LT) in elderly recipients is controversially discussed in the literature with only little data on long-term outcome available. We aimed to evaluate the safety and efficiency of LT in elderly recipients (>65 years). METHODS: Between 1989-2016, 139 patients >65 years-old were listed for liver transplantation, and 76 (55%) were transplanted. Patient outcome and characteristics were evaluated separately for the time period before (1989-2004) and after (2005-2016) MELD-implementation. Post-transplant outcome was compared between the elderly cohort and LT-recipients aged 18-65 years (n = 1395). RESULTS: Overall survival of patients >65 years was better in the MELD-era compared to the earlier period (1- and 5-year-survival: 73%, 60% vs. 69%, 37%, respectively; p = 0.055). The main differences between the two groups included higher recipient age (p = 0.001) and BMI (p = 0.001), higher donor age (p < 0.001), less need of intraoperative red blood cells (p = 0.008) and a lower number of postoperative rejections (p = 0.03) after 2004. Comparing the overall survival of patients transplanted in the MELD-era aged 18-65 years vs. >65 years displayed comparable 1- and 5 year-survival rates (81%, 68% vs. 73% and 60%, respectively, p = 0.558). CONCLUSION: In the modern era, outcome of patients receiving LT with >65 years is comparable to <65 year-old patients. After careful evaluation, patients >65 years old should be considered for LT.

A siphon-like retrogastric transverse colon: A case report.

INTRODUCTION: Intestinal interposition is a term that describes rare anatomic variations where parts of the colon deviate from their normal intraabdominal position, attaching between two organs. Most patients with colonic interpositions are asymptomatic and diagnosed incidentally by computed tomography or ultrasound. Here we present a case of a symptomatic restrogastric colon, interposing kinked between stomach and pancreas. PRESENTATION OF CASE: A 66-year old female patient presented with an eight-year history of intermittent spastic bowel movements, epigastralgia and nausea. Consecutively, the patient lost 12 kg. Physical examination was unremarkable and routine blood tests were within normal limits. Subsequently performed colonoscopy and cross-sectional imaging diagnosed a retrogastric colon. Finally, the patient underwent surgical treatment. The intraoperative findings were consistent with the computed tomography images and showed a kinked retrogastric protrusion of the transverse colon into the lesser sac, adhering to both, the posterior wall of the stomach, and the anterior surface of the pancreas. After adhesiolysis and mobilization, the transverse colon slipped back to the normal position within the abdominal cavity. The patient recovered well after surgery and was discharged on the sixth postoperative day. Six-month follow-up revealed cured bowel function, weight regain and no signs of recurrence. DISCUSSION & CONCLUSION: These rare cases of intestinal interpositions are very often difficult to diagnose, as symptoms are misleading. In case of diagnosis adequate surgical treatment strategies should be considered.

Multimodality locoregional treatment strategies for bridging HCC patients before liver transplantation.

BACKGROUND: It is current practice that patients with hepatocellular carcinoma (HCC) listed for liver transplantation should receive locoregional treatment if the suspected waiting time for transplantation is longer than 6 months, even in the absence of prospective randomized data. Aim of this study was the comparison of single versus multimodality locoregional treatment strategies on outcomes after liver transplantation. METHODS: This is a retrospective analysis of 150 HCC patients listed for liver transplantation at our center between 2004 and 2011. Outcomes were analyzed according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) in relation to intention-to-treat and overall survival after liver transplantation. RESULTS: Overall, 92 patients (63%) were transplanted in this cohort. The intention-to-treat 1­, 3­, 5­year waiting list survival was 80, 59, and 50% respectively. In RFA-(radiofrequency ablative) and TACE-(transarterial chemoembolisation)-based regimens, rates of transplanted patients were comparable (69 vs. 58%, p = ns). No difference was seen in overall survival after liver transplantation when comparing TACE- and RFA-based regimens. Patients receiving multimodality locoregional therapy had lower overall survival after transplantation (p = 0.05). CONCLUSION: TACE- and RFA-based regimens showed equal outcomes in terms of transplantation rate, tumor response, and post-transplant survival. Patients in need of more than one treatment modality might identify a cohort with poorer post-transplant survival. POINTS OF NOVELTY: Direct comparison of TACE and RFA in a multimodality setting, analysis according to mRECIST.

The post-transplant course of patients undergoing liver transplantation for nonalcoholic steatohepatitis versus cryptogenic cirrhosis: a retrospective case-control study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) can be considered the hepatic manifestation of the metabolic syndrome with nonalcoholic steatohepatitis (NASH) as its progressive form. With increasing prevalence of the metabolic syndrome, NASH cirrhosis is becoming a leading cause for liver transplantation. Some cases of orthotopic liver transplantation (OLT) due to cryptogenic cirrhosis (CC) might show typical features of NASH cirrhosis. Therefore, our aim was to assess recurrence of liver fibrosis in patients transplanted for NASH versus CC after OLT. PATIENTS AND METHODS: Patients transplanted for CC or NASH between 1 January 2004 and 30 September 2015 were included. The histological NAFLD activity score and the NAFLD fibrosis score (NFS) were assessed. RESULTS: In total, 15 and 12 patients underwent OLT because of NASH and CC, respectively. The case load for OLT because of NASH was constantly increasing (n=2 in 2004-2007 vs. n=9 in 2012-2015) whereas decreasing for CC (n=6 in 2004-2007 vs. n=2 in 2012-2015). Patient characteristics at OLT were similar, except for an older age and a higher BMI in NASH patients (59.1±2.2 vs. 51.8±2.9 years, P=0.05; 27.7±1.2 vs. 24.3±0.8 kg/m, P=0.035). Although post-OLT plasma lipid levels and incidence of de-novo hypertension, diabetes, and hyperlipidemia were similar between groups, the post-transplant NFS re-increased in the NASH group (but not in the CC: -0.1317 vs. -1.3645 at 12 months post-OLT, P=0.0400). Post-transplant survival was similar in NASH and CC patients. CONCLUSION: According to the NFS, some NASH patients show recurrence of fibrosis as early as 6-12 months after OLT.

Fibroblast growth factor receptor 4 induced resistance to radiation therapy in colorectal cancer.

In colorectal cancer (CRC), fibroblast growth factor receptor 4 (FGFR4) is upregulated and acts as an oncogene. This study investigated the impact of this receptor on the response to neoadjuvant radiotherapy by analyzing its levels in rectal tumors of patients with different responses to the therapy. Cellular mechanisms of FGFR4-induced radioresistance were analyzed by silencing or over-expressing FGFR4 in CRC cell line models. Our findings showed that the FGFR4 staining score was significantly higher in pre-treatment biopsies of non-responsive than responsive patients. Similarly, high expression of FGFR4 inhibited radiation response in cell line models. Silencing or inhibition of FGFR4 resulted in a reduction of RAD51 levels and decreased survival in radioresistant HT29 cells. Increased RAD51 expression rescued cells in the siFGFR4-group. In radiosensitive SW480 and DLD1 cells, enforced expression of FGFR4 stabilized RAD51 protein levels resulting in enhanced clearance of γ-H2AX foci and increased cell survival in the mismatch repair (MMR)-proficient SW480 cells. MMR-deficient DLD1 cells are defective in homologous recombination repair and no FGFR4-induced radioresistance was observed. Based on our results, FGFR4 may serve as a predictive marker to select CRC patients with MMR-proficient tumors who may benefit from pre-operative radiotherapy.

Endoscopic versus surgical management of biliary complications - Outcome analysis after 1188 orthotopic liver transplantations.

BACKGROUND AND AIM: After liver transplantation, the endoscopic approach has become the standard treatment modality for biliary complications. Aim of this study was to compare primary endoscopic with primary surgical management. PATIENTS AND METHODS: A retrospective review on 1188 consecutive liver transplant patients between 1989 and 2009 was performed. Management strategies (endoscopic, surgical or combined approach) were evaluated for treatment success as well as patient survival. RESULTS: Biliary complications after liver transplantation were diagnosed in 211 (18%) patients. Initial endoscopic approach (N=162, 77%) was successful in 97 of 162 (60%) patients. In 80% of patients, success was achieved within a median of four ERCPs. Sixty-one patients (38%) were referred to surgery after non-successful ERCP. Initial surgical approach was performed in 49/211 patients (23%) with successful management in 38/49 (78%) of patients. Patients presenting with intraluminal objects needed a significantly higher number of ERCPs to reach treatment success (median 3 versus 2 interventions, p=0.001) but had an equal endoscopic success rate (p=0.427). Patients with successful endoscopic treatment showed lower mortality compared to patients with primary surgical treatment (p=0.029). CONCLUSIONS: Endoscopic management should be considered as the primary approach for biliary complications after liver transplantation.

Long-term oncologic outcomes for simultaneous resection of synchronous metastatic liver and primary colorectal cancer.

BACKGROUND: Twenty-five percent of patients with colorectal cancer present with simultaneous liver metastasis. Complete resection is the only potential curative treatment. Due to improvements in operative and perioperative management, simultaneous liver and colon resections are an accepted procedure at specialized centers for selected patients. Nevertheless, little is known about the long-term, oncologic results of simultaneous operative procedures compared with those of staged operations. METHODS: Patients with colorectal cancer and simultaneous liver metastases presenting for complete resection at a tertiary cancer center were identified. Patients who received the primary colon resection at an outside institution were excluded from analysis. RESULTS: Between 1984 and 2008, 429 patients underwent operative treatment for colorectal cancer with simultaneous liver metastasis. Of these, 320 (75%) had simultaneous resection and 109 had staged resection. There was no difference in the distribution of primary tumor locations between the 2 groups. Mean size of the hepatic metastases was significantly greater in the staged group (median 4 cm vs 2.5 cm; P < .01). Neither disease-free nor overall survival differed significantly between the 2 treatment strategies. The extent of the liver procedure (more than 3 segments) was identified as a risk factor for decreased disease-free and overall survival (both P < .01). CONCLUSION: Simultaneous liver and colorectal resections for metastatic colorectal cancer are associated with similar long-term cancer outcome compared with staged procedures.

Impact of dynamic changes in MELD score on survival after liver transplantation - a Eurotransplant registry analysis.

BACKGROUND & AIMS: With restricted numbers of available organs, futility in liver transplantation has to be avoided. The concept of dynamic changes in MELD score (DeltaMELD) has previously been shown to be a simple tool to identify patients with the greatest risk of death after transplantation. Aim was to validate this concept with the Eurotransplant (ET) database. METHODS: A retrospective registry analysis was performed on all patients listed for liver transplantation within ET between 2006 and 2011. Patients <18 years of age, acute liver failure, malignancy and patients listed for retransplantation were excluded. Influence of MELD at listing (MELDon), MELD at transplantation (MELDoff), DeltaMELD, age, sex, underlying disease and time on the waiting list on overall survival after liver transplantation were evaluated. RESULTS: A total of 16 821 patients were listed for liver transplantation, 8096 met the inclusion criteria. Age, MELD on and DeltaMELD showed significant influence on survival on the waiting list. Age and DeltaMELD showed influence on survival after liver transplantation, with DeltaMELD>10 showing a 1.6-fold increased risk of death. CONCLUSION: The concept of DeltaMELD was validated in a large, prospective data set. It provides a simple tool to identify patients with increased risk of death after liver transplantation and might help improve long-term results.

Abdominal drainage after liver transplantation from deceased donors.

PURPOSE: Traditionally, abdominal drainage (AD) is routinely inserted in patients after liver transplantation (LT) to drain ascites and to detect postoperative hemorrhage and bile leakage. However, the benefit of this surgical practice remains a matter of debate regarding potential drainage-associated morbidities. METHODS: In a retrospective pair-matched analysis in a 1:1 ratio, 116 patients after LT were assessed with regards to benefits and risks of abdominal drainage under immunosuppression, respecting model for end-stage liver disease (MELD), age, and gender. RESULTS: The indications for LT were comparable between the drain and the no-drain group. There was an increased rate of early bile leakage in patients with abdominal drainage (13.8 vs. 1.7%, p = 0.032). In addition, a significantly higher incidence of infections requiring antibiotic therapy was observed in the drain group (63.8 vs. 39.7%, p = 0.015). The contribution of drains as a diagnostic tool was marginal, as in the drain group, other diagnostic tools than the drain itself confirmed 50% of all early bile leakages and 60% of postoperative hemorrhages. Overall, there was no difference regarding the incidence of incisional hernia after LT (8.6 vs. 10.3%, p = 1.000), length of hospital stay (22.9 ± 18.7 vs. 18.6 ± 18.6 days, p = 0.215), and 1- and 5-year patient (p = 0.981) and graft survival (p = 0.092). CONCLUSIONS: Equal results can be achieved with or without an abdominal drain in recipients with whole-liver grafts in spite of an increased risk of postoperative infection and biliary leakage in the former group. A benefit of AD as a diagnostic tool could not be demonstrated.

Simultaneous resection for rectal cancer with synchronous liver metastasis is a safe procedure.

BACKGROUND: One quarter of colorectal cancer patients will present with liver metastasis at the time of diagnosis. Recent studies have shown that simultaneous resections are safe and feasible for stage IV colon cancer. Limited data are available for simultaneous surgery in stage IV rectal cancer patients. METHODS: One hundred ninety-eight patients underwent surgical treatment for stage IV rectal cancer. In 145 (73%) patients, a simultaneous procedure was performed. Fifty-three (27%) patients underwent staged liver resection. A subpopulation of 69 (35%) patients underwent major liver resection (3 segments or more) and 30 (44%) patients with simultaneous surgery. RESULTS: The demographics of the 2 groups were similar. Complication rates were comparable for simultaneous or staged resections, even in the group subjected to major liver resection. Total hospital stay was significantly shorter for the simultaneously resected patients (P < .01). CONCLUSIONS: Simultaneous resection of rectal primaries and liver metastases is a safe procedure in carefully selected patients at high-volume institutions, even if major liver resections are required.

Vacuum inversion and securing of distal colonic pseudodiverticula with novel spiked O-rings.

BACKGROUND: Diverticular disease is increasingly prevalent in Western societies and is associated with significant morbidity. OBJECTIVE: Two-stage endoscopic device development for inversion and secured ligation of colonic diverticula; first, human cadaver studies were performed to measure forces required for diverticular inversion; second, a novel set of devices (elastic spiked O-ring with delivery system) was tested in animals. DESIGN: Prospective, observational study of human cadavers and prospective, interventional study of a porcine model. SETTING: University hospital pathology laboratory and animal facility. INTERVENTION: Full-thickness inversion of the colonic wall with a pipelike delivery instrument to produce an inverted pseudodiverticulum that was secured with a spiked O-ring. MAIN OUTCOME MEASUREMENTS: The forces required for diverticular inversion, the secured closure of inverted pseudodiverticula, and the time until necrotic tissue falls off. RESULTS: A total of 248 of 248 of cadaveric sigmoid diverticula could be inverted by means of vacuum or forceps. The forces required for inversion ranged from 0.28 to 0.47 N (median, 0.37 N). Twenty-four spiked O-rings were delivered in 6 living pigs to produce 24 inverted pseudodiverticula. One animal died the day after the procedure of a pulmonary thromboembolism. In the remaining 5 pigs, all delivered spiked O-rings remained in place for 7 to 22 days. At necropsy, none of the inverted sites showed signs of perforation but rather full-thickness reparative scarring with ingrowth of connective tissue. LIMITATIONS: Animal model, stiff pipelike delivery instrument, variations in diverticular location, diameter, and size. CONCLUSIONS: Endoluminal inversion and securing of colonic diverticula induces tissue necrosis, diverticular sloughing, and full-thickness scarring.

[Surgical aspects of peritoneal dialysis]. / Chirurgische Aspekte der Peritonealdialyse.

Peritoneal dialysis (PD) has wide clinical range since die 70ies. Clinical data report a significantly higher 2 year survival rate for PD compared to patients treated with hemodialysis. Nevertheless, currently only about 10 % of patients suffering from end-stage renal disease are treated with PD. Long-term function of the catheter is based on patient's compliance as well as optimal surgical catheter implantation. Beside the classic "open" surgical approach by mini laparotomy new minimal invasive techniques of catheter implantation were developed during the last years. Advantages of laparoscopic techniques are the possibility for combined intraperitoneal procedures and optimal placement of the catheter. Most of surgery-related complications are caused by leakage or migration, infection is very rare. Several studies did not find an advantage of minimal invasive procedures regarding complications.This review should give an overview on currently established surgical techniques for PD-catheter implantation.

Imaging characteristics, tissue distribution, and spread of a novel oncolytic vaccinia virus carrying the human sodium iodide symporter.

INTRODUCTION: Oncolytic viruses show promise for treating cancer. However, to assess therapy and potential toxicity, a noninvasive imaging modality is needed. This study aims to determine the in vivo biodistribution, and imaging and timing characteristics of a vaccinia virus, GLV-1h153, encoding the human sodium iodide symporter (hNIS. METHODS: GLV-1h153 was modified from GLV-1h68 to encode the hNIS gene. Timing of cellular uptake of radioiodide (131)I in human pancreatic carcinoma cells PANC-1 was assessed using radiouptake assays. Viral biodistribution was determined in nude mice bearing PANC-1 xenografts, and infection in tumors confirmed histologically and optically via Green Fluorescent Protein (GFP) and bioluminescence. Timing characteristics of enhanced radiouptake in xenografts were assessed via (124)I-positron emission tomography (PET). Detection of systemic administration of virus was investigated with both (124)I-PET and 99m-technecium gamma-scintigraphy. RESULTS: GLV-1h153 successfully facilitated time-dependent intracellular uptake of (131)I in PANC-1 cells with a maximum uptake at 24 hours postinfection (P<0.05). In vivo, biodistribution profiles revealed persistence of virus in tumors 5 weeks postinjection at 10(9) plaque-forming unit (PFU)/gm tissue, with the virus mainly cleared from all other major organs. Tumor infection by GLV-1h153 was confirmed via optical imaging and histology. GLV-1h153 facilitated imaging virus replication in tumors via PET even at 8 hours post radiotracer injection, with a mean %ID/gm of 3.82 ± 0.46 (P<0.05) 2 days after intratumoral administration of virus, confirmed via tissue radiouptake assays. One week post systemic administration, GLV-1h153-infected tumors were detected via (124)I-PET and 99m-technecium-scintigraphy. CONCLUSION: GLV-1h153 is a promising oncolytic agent against pancreatic cancer with a promising biosafety profile. GLV-1h153 facilitated time-dependent hNIS-specific radiouptake in pancreatic cancer cells, facilitating detection by PET with both intratumoral and systemic administration. Therefore, GLV-1h153 is a promising candidate for the noninvasive imaging of virotherapy and warrants further study into longterm monitoring of virotherapy and potential radiocombination therapies with this treatment and imaging modality.

Bariatric surgery in morbidly obese adolescents: long-term follow-up.

OBJECTIVE: Morbid obesity is an increasingly common disease in the industrialized world and poses a great challenge to the medical community. Many obese adolescents have undergone various conservative treatment methods without adequate success so that a surgical approach became necessary. We report on 18 patients who underwent bariatric surgery as well as a long-term follow-up program. METHODS: Eight patients received a laparoscopic adjustable gastric banding (LAGB). Four of these had to undergo a gastric bypass surgery (GByp) as second procedure due to insufficient weight loss. Nine patients primarily received a gastric bypass. RESULTS: LAGB: Mean weight loss after 24 months was 20 ± 6.3 kg. Four of the patients showed a regain in weight leading to a mean weight loss of 9 kg compared to initial weight after 53.3 months mean in this group. These patients had to undergo an additional gastric bypass procedure and lost 31 ± 18.3 kg after 18 months. GByp: Mean weight loss in nine patients after gastric bypass (primary procedure) was 31 ± 10.2 kg after 12 months and 36 ± 30.1 kg at the end of the observation time. Sleeve: Initial weight in this patient was 232 kg with a weight loss of 38 kg after 24 months. DISCUSSION AND CONCLUSION: It is remarkable that in four of eight patients who underwent LAGB had to undergo a second surgical procedure (GByp). No previous indicator, neither from a psychological nor from a medical point of view, could be detected. More long-term studies including psychological aspects seem to be necessary.

Long-term results after laparoscopic adjustable gastric banding in adolescent patients: follow-up of the Austrian experience.

BACKGROUND: During the last 30 years a threefold increase in the number of overweight children has been reported in Western countries. More than 15% of adolescents have a body mass index (BMI) higher than the 95th percentile. The use of surgical strategies in adolescent patients is still controversial due to the impact on the continuing maturing process. Laparoscopic adjustable gastric banding (LAGB) is considered a minimal invasive procedure that does not alter the physiological behavior of the bowel and has already shown promising results in short-term studies. METHODS: Between 1998 and 2004, 50 adolescent patients above the 99.5th age- and gender-adjusted growing percentile were treated with LAGB. The surgical procedure was performed at three highly experienced centers for bariatric surgery. Mean age was 17.1 ± 2.2 years (range = 9-19 years) at the time of surgery. Follow-up investigations were performed in the outpatient clinic of the treating hospitals. Psychological changes were analyzed using the BAROS questionnaire. RESULTS: The mean BMI decreased from 45.2 ± 7.6 kg/m(2) at the time of surgery to 38.3 ± 6.2 kg/m(2) 1 year after surgery, 31.5 ± 6.6 kg/m(2) after 3 years, and 27.3 ± 5.3 kg/m(2) after 5 years. Mean excessive weight loss was 49.7 ± 29.2, 76.8 ± 27.5, and 92.6 ± 24.5% at 1, 3, and 5 years after surgery. Quality of life showed a further significant improvement between 3 and 5 years after surgery (BAROS: 5.5 ± 1.9 increased to 6.3 ± 2.2, p = 0.01). All preoperative comorbidities resolved in patients with a functional band after 5 years of follow-up. CONCLUSION: LAGB shows promising results in the long-term follow-up with continuous weight loss in patients with a functional band. Nevertheless, most of the weight loss is within the first 3 years after surgery. Thereafter, further weight reduction is about 10% over the following 2 years. Perioperative comorbidities resolve within the first 5 years after treatment.

Genetically engineered oncolytic Newcastle disease virus effectively induces sustained remission of malignant pleural mesothelioma.

Malignant pleural mesothelioma is a highly aggressive tumor. Alternative treatment strategies such as oncolytic viral therapy may offer promising treatment options in the future. In this study, the oncolytic efficacy and induction of tumor remission by a genetically engineered Newcastle disease virus [NDV; NDV(F3aa)-GFP; GFP, green fluorescent protein] in malignant pleural mesothelioma is tested and monitored by bioluminescent tumor imaging. The efficacy of NDV(F3aa)-GFP was tested against several mesothelioma cell lines in vitro. Firefly luciferase-transduced MSTO-211H* orthotopic pleural mesothelioma tumor-bearing animals were treated with either single or multiple doses of NDV(F3aa)-GFP at different time points (days 1 and 10) after tumor implantation. Tumor burden was assessed by bioluminescence imaging. Mesothelioma cell lines exhibited dose-dependent susceptibility to NDV lysis in the following order of sensitivity: MSTO-211H > MSTO-211H* > H-2452 > VAMT > JMN. In vivo studies with MSTO-211H* cells showed complete response to viral therapy in 65% of the animals within 14 days after treatment initiation. Long-term survival in all of these animals was >50 days after tumor installation (control animals, <23 d). Multiple treatment compared with single treatment showed a significantly better response (P = 0.005). NDV seems to be an efficient viral oncolytic agent in the therapy of malignant pleural mesothelioma in an orthotopic pleural mesothelioma tumor model.

A novel endoscopic device for repeated right-side colonic access during colonoscopy (with video).

BACKGROUND: Megachannel is a newly developed colonic access system allowing rapid and multiple passes of the colonoscope to the right side of the colon. OBJECTIVE: The aim of this study was to evaluate the safety and clinical feasibility of placing a 100 cm Megachannel prototype in the right side of the colon. SETTING: Six centers, international, both surgeons and gastroenterologists performing endoscopy. DESIGN AND INTERVENTION: Patients scheduled for colonoscopy with suspected right-side colonic polypoid lesions were included. The prototype was loaded onto a 160 cm lower GI endoscope and introduced via colonoscopic guidance. MAIN OUTCOME MEASUREMENT: The ability to place this device in the right side of the colon. RESULTS: The Megachannel prototype was introduced in 41 patients (19 female, mean age 54 years) undergoing colonoscopy. The cecum was reached in 27 cases (66%) within 18 minutes (range, 3-35 minutes) and with 73 cm (range, 40-100 cm) of the device being inserted into the colon. Mild tissue bruises and mild pain were observed in 5 and 3 patients, respectively. In 14 patients, the device assisted the removal of multiple polyps (2-12) as tissue was repeatedly retrieved through the channel. The device also allowed delivery of an endoscopic US scope or suction caps to the right side of the colon. LIMITATIONS: Prototype performance may differ from the actual product (80 cm in length, redesigned introducer plugs). Small number of patients, difficult in diverticular disease. CONCLUSIONS: This newly developed colonic access system can be safely placed in the right side of the colon and is useful for a variety of advanced procedures that require repeated insertion of the colonoscope or delivery of bulky instruments. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT00987896.).

The value of protecting the longitudinal staple line with invaginating sutures during esophageal reconstruction by gastric tube pull-up.

BACKGROUND: Radical surgery with lymphadenectomy offers the best chance of curing esophageal cancer, but it carries considerable risks. Generally, the resected esophagus is replaced with a gastric tube. Rupture of the gastric tube staple line is a rare but serious surgical complication. One unresolved issue is whether oversewing of the longitudinal gastric staple line is necessary to avoid staple line rupture or insufficiency. PATIENTS AND METHODS: Between 2000 and February 2008, 199 patients underwent esophageal resection for cancer or perforation at the Vienna General Hospital, Medical University of Vienna. Data were collected prospectively. Of these patients, 151 (75.9%) underwent reconstruction by pulling up a gastric tube. These comprised the study population. In 83 patients (55.0%) the longitudinal gastric staple line was not oversewn (group A). In 68 patients (45.0%) the staple line was reinforced by invaginating sutures (group B). RESULTS: The mean age of the patients was 62.0 +/- 10.6 years (median: 63.1 years). Males comprised 75.5% of the population. Adenocarcinoma was diagnosed in 77 patients (51.0%), 63 patients (41.7%) suffered from a squamous cell carcinoma, 10 patients (6.6%) had esophageal perforation, and in 1 patient (0.7%) a gastrointestinal stromal tumor was diagnosed. In group A, a leak within the staple line was observed in 4 of 83 patients (4.9%). No leak was found in group B (p = 0.09). Major surgical complications included anastomotic leakage (21 patients; 13.9%), gastric tip necrosis (3 patients; 2%), postoperative ileus (3 patients; 2.0%) and chylothorax (7 patients; 4.6%). Two major intraoperative complications (1.3%) were splenic injury and aortic bleeding. CONCLUSION: A remarkable but not statistically significant difference was found regarding staple line rupture between study groups. However, all leaks were seen in patients without a staple line suture.