Perianal thrombosis: no need for surgery.

AIM: There is little evidence for the best therapy for perianal thrombosis. No prospective trials exist. Even quality of retrospective data is low, due to low patient numbers or vague follow-up data. PATIENTS AND METHODS: Six hundred nineteen patients with thrombosis of internal or external hemorrhoids who presented in our clinic between March 2017 and August 2018 were enrolled in the study. All patients were treated conservatively, with sitz baths and oral pain medication, if needed. No surgery was performed. Follow-up data was obtained by personal examination. Data was gathered prospectively, and data analysis was retrospective. RESULTS: Five hundred four patients had perianal thrombosis (81.4%), and 115 patients had thrombosed hemorrhoids. Mean pain on a numerical rating scale (0-10) was 3.8 for perianal thrombosis and 5.2 for thrombosed hemorrhoids. Five hundred forty-eight patients (88.5%) did not need a sick leave. On follow-up, patients stated that their pain had largely resolved after 5 days and completely disappeared after 10 days. Local recurrence rate after perianal thrombosis was 6.3%. CONCLUSION: Perianal thrombosis and thrombosed hemorrhoids heal well without surgery. There is no evidence for advantages surgical therapy could offer.

Intraoperative Electron Radiation Therapy Combined with External Beam Radiation Therapy after Gross Total Resection in Extremity Soft Tissue Sarcoma: A European Pooled Analysis.

INTRODUCTION: We report a pooled analysis evaluating the combination of gross complete limb-sparing surgery, intraoperative electron radiation therapy (IOERT), and external beam radiation therapy (EBRT) in patients with extremity soft tissue sarcoma (STS). METHODS: Individual data of 259 patients (median follow-up 63 months) with extremity STS from three European expert centers were pooled. Median age was 55 years and median tumor size was 8 cm. Eighty percent of patients presented with primary disease, mainly located in the lower limb (81%). Union for International Cancer Control 7th edition stage at presentation was as follows: stage I: 9%; stage II: 47%; stage III: 39%; stage IV: 5%. Most patients showed high-grade lesions (91%), predominantly liposarcoma (31%). Median IOERT dose was 12 Gy, preceeded (17%) or followed (83%) by EBRT, with a median dose of 45 Gy. RESULTS: Surgery resulted in R0 resections in 71% of patients and R1 resections in 29% of patients. The 5-year local control (LC) rate was 86%, and significant factors in univariate analysis were disease status and resection margin. Only margin remained significant in multivariate analysis. The 5-year distant control rate was 69%, and significant factors in univariate analysis were histology, grading, resection margin, and metastases prior to/at IOERT. Only grading and metastases remained significant in multivariate analysis. Actuarial 5-year rates of freedom from treatment failure and OS were 61% and 78%, respectively. Significant factors for OS were grading and metastases prior to/at IOERT (univariate, multivariate). Limb preservation and good functional outcome were achieved in 95% and 81% of patients. CONCLUSIONS: Our pooled analysis confirmed prior reports of encouraging LC and survival, with excellent rates of preserved limb function with this treatment approach. Resection margin remained the most important factor for LC, while grading and metastases prior to/at IOERT mainly predicted survival.

Intraoperative Electron Radiation Therapy in Retroperitoneal Sarcoma.

PURPOSE: To report our experience with surgery, intraoperative radiation therapy (IORT), and external beam radiation therapy (EBRT) in retroperitoneal soft-tissue sarcoma. METHODS AND MATERIALS: We conducted a retrospective evaluation of 156 patients (69 primary, 87 recurrent) treated with IORT since 1991. The dominant histology was dedifferentiated liposarcoma (49%); 89% of lesions were high grade. Median tumor size was 11 cm. Surgery resulted in gross complete resection in 92%, and 65% had microscopically positive margins. Median IORT dose was 15 Gy. A total of 114 patients (73%) received additional EBRT (preoperatively n=38, postoperatively n=76, median dose 45 Gy). RESULTS: Median follow-up was 38 months (49 months in survivors). The 3- and 5-year local control (LC) rates were 57% and 50%, respectively. On univariate analysis, LC was significantly associated with primary versus recurrent status, histology, grade, Union for International Cancer Control (UICC) stage, resection margin, and addition of EBRT. The 5-year LC was 71% in the primary situation and 79% after R0 resection. On multivariate analysis only disease status, grade, resection margin, and addition of EBRT remained statistically significant. The 3- and 5-year overall survival (OS) rates were 66% and 56%. On univariate analysis, OS was significantly associated with primary versus recurrent status, histology, grade, UICC stage, resection margin, and timing of EBRT. The 5-year OS was 63% in the primary situation and 68% after R0 resection. On multivariate analysis only disease status, grade, and resection margin remained independent prognostic factors. Perioperative mortality was 1%, and major complications occurred in 34% (mainly wound complications). CONCLUSIONS: Treatment with surgery, IORT, and EBRT is feasible and resulted in good LC and OS, with acceptable morbidity in this unfavorable patient cohort. Incomplete resection and recurrent status resulted in clearly inferior outcomes. Reasonable efforts should be made during primary treatment to prevent the onset of a local recurrence.

Correction: Worldwide trends in volume and quality of published protocols of randomized controlled trials.

[This corrects the article DOI: 10.1371/journal.pone.0173042.].

Worldwide trends in volume and quality of published protocols of randomized controlled trials.

INTRODUCTION: Publishing protocols of randomized controlled trials (RCT) facilitates a more detailed description of study rational, design, and related ethical and safety issues, which should promote transparency. Little is known about how the practice of publishing protocols developed over time. Therefore, this study describes the worldwide trends in volume and methodological quality of published RCT protocols. METHODS: A systematic search was performed in PubMed and EMBASE, identifying RCT protocols published over a decade from 1 September 2001. Data were extracted on quality characteristics of RCT protocols. The primary outcome, methodological quality, was assessed by individual methodological characteristics (adequate generation of allocation, concealment of allocation and intention-to-treat analysis). A comparison was made by publication period (First, September 2001- December 2004; Second, January 2005-May 2008; Third, June 2008-September 2011), geographical region and medical specialty. RESULTS: The number of published RCT protocols increased from 69 in the first, to 390 in the third period (p<0.0001). Internal medicine and paediatrics were the most common specialty topics. Whereas most published RCT protocols in the first period originated from North America (n = 30, 44%), in the second and third period this was Europe (respectively, n = 65, 47% and n = 190, 48%, p = 0.02). Quality of RCT protocols was higher in Europe and Australasia, compared to North America (OR = 0.63, CI = 0.40-0.99, p = 0.04). Adequate generation of allocation improved with time (44%, 58%, 67%, p = 0.001), as did concealment of allocation (38%, 53%, 55%, p = 0.03). Surgical protocols had the highest quality among the three specialty topics used in this study (OR = 1.94, CI = 1.09-3.45, p = 0.02). CONCLUSION: Publishing RCT protocols has become popular, with a five-fold increase in the past decade. The quality of published RCT protocols also improved, although variation between geographical regions and across medical specialties was seen. This emphasizes the importance of international standards of comprehensive training in RCT methodology.

Targeting Fibroblast Growth Factor Receptor 1 for Treatment of Soft-Tissue Sarcoma.

Purpose: Altered FGFR1 signaling has emerged as a therapeutic target in epithelial malignancies. In contrast, the role of FGFR1 in soft-tissue sarcoma (STS) has not been established. Prompted by the detection and subsequent therapeutic inhibition of amplified FGFR1 in a patient with metastatic leiomyosarcoma, we investigated the oncogenic properties of FGFR1 and its potential as a drug target in patients with STS.Experimental Design: The frequency of FGFR1 amplification and overexpression, as assessed by FISH, microarray-based comparative genomic hybridization and mRNA expression profiling, SNP array profiling, and RNA sequencing, was determined in three patient cohorts. The sensitivity of STS cell lines with or without FGFR1 alterations to genetic and pharmacologic FGFR1 inhibition and the signaling pathways engaged by FGFR1 were investigated using viability assays, colony formation assays, and biochemical analysis.Results: Increased FGFR1 copy number was detected in 74 of 190 (38.9%; cohort 1), 13 of 79 (16.5%; cohort 2), and 80 of 254 (31.5%; cohort 3) patients. FGFR1 overexpression occurred in 16 of 79 (20.2%, cohort 2) and 39 of 254 (15.4%; cohort 3) patients. Targeting of FGFR1 by RNA interference and small-molecule inhibitors (PD173074, AZD4547, BGJ398) revealed that the requirement for FGFR1 signaling in STS cells is dictated by FGFR1 expression levels, and identified the MAPK-ERK1/2 axis as critical FGFR1 effector pathway.Conclusions: These data identify FGFR1 as a driver gene in multiple STS subtypes and support FGFR1 inhibition, guided by patient selection according to the FGFR1 expression and monitoring of MAPK-ERK1/2 signaling, as a therapeutic option in this challenging group of diseases. Clin Cancer Res; 23(4); 962-73. ©2016 AACR.

Long term follow up after resection emphasizes the role of surgery in Primary Hepatic Epithelioid Hemangioendothelioma.

BACKGROUND: Primary Hepatic Epithelioid Hemangioendothelioma is an extremely rare tumor of vascular origin. PATIENTS: In this work we present clinical data and long term results of eight patients who were surgically treated in our institution. Liver transplantation was performed in five patients (four cadaveric and one living related) and major liver resection in three patients. Three patients are alive with recurrent tumor. After a median follow-up of 100 months (48-266) all patients are alive. CONCLUSIONS: Only surgery can provide cure in HEH. If the extent of the disease prohibits primary resection liver transplantation might offer the most valuable option.

Duodenum-preserving pancreatic head resection: 10-year follow-up of a randomized controlled trial comparing the Beger procedure with the Berne modification.

BACKGROUND: Since the introduction of the duodenum-preserving pancreatic head resection for operative treatment of chronic pancreatitis, various modifications of the original Beger procedure have emerged. A randomized controlled trial comparing the Beger procedure and the Berne modification indicated that the latter is an equivalent alternative, but a comparison of the long-term results of both procedures has not yet been published. METHODS: Between December 2002 and January 2005, 65 patients were randomized intraoperatively to the Beger or the Berne procedure. For this 10-year follow-up, patients were contacted by phone and in writing to evaluate patient-relevant outcome parameters. Statistical analysis was made on an intention-to-treat basis. RESULTS: Median follow-up was 129 (111-137) months. Forty of 65 patients were available for follow-up; 11 of the original study cohort had died, and 14 were otherwise lost to follow-up. Quality of life, pain, occupational disability, exocrine and endocrine pancreatic function, endoscopic interventions, and redo operations were comparable in both groups. More than half of the patients were completely free of pain, and the majority in both groups judged that the index operation had improved their quality of life. CONCLUSION: Ten-year follow-up showed no differences in patient-relevant outcome parameters between the Beger and Berne procedures for treatment of chronic pancreatitis. Because short-term results have shown the Berne modification is superior in terms of operation time and duration of hospital stay, it should be preferred whenever possible, depending on the individual surgeon's expertise and the intraoperative findings.

Intraoperative electron radiation therapy combined with external beam radiation therapy and limb sparing surgery in extremity soft tissue sarcoma: a retrospective single center analysis of 183 cases.

BACKGROUND AND PURPOSE: To report our experience with limb-sparing surgery, IOERT and EBRT in extremity STS. MATERIALS AND METHODS: 183 patients were retrospectively analyzed. 78% presented in primary situation, with 80% located in the lower limb. Stage at presentation was: I: 6%, IIa: 25%, IIb: 21%, III: 42%, IV: 7%. The majority showed high-grade lesions (grade 1: 5%, 2: 31%, 3: 64%). IOERT was applied to the tumor bed (median 15Gy) and preceded (9%) or followed (91%) by EBRT (median 45Gy) in all patients. RESULTS: Median follow-up was 64months (78months in survivors). Surgery was complete in 68%, while 32% had microscopic residual disease. 5- and 10-year-LC was 86% and 84%, respectively. LC was significantly higher in primary compared to recurrent disease and tended to be higher after complete resection. Estimated 5- and 10-year-DC was 68% and 66%, while corresponding OS was 77% and 66%, respectively. OS was significantly affected by grading and stage. Severe postoperative complications and late toxicities were observed in 19% and 20%, respectively. Limb-preservation rate was 95% with good function in 83%. CONCLUSIONS: Combination of limb-sparing surgery, IOERT and EBRT achieved encouraging LC and OS in this unfavorable patient group with acceptable postoperative complications and low rates of late toxicities resulting in a high limb-preservation rate and good functional outcome.

Frequency of pneumothorax and haemothorax after primary open versus closed implantation strategies for insertion of a totally implantable venous access port in oncological patients: study protocol for a randomised controlled trial.

BACKGROUND: The insertion of central venous access devices, such as totally implantable venous access ports (TIVAPs), is routine in patients who need a safe and permanent venous access. The number of port implantations is increasing due to the development of innovative adjuvant and neo-adjuvant therapies. Currently, two different strategies are being routinely used: surgical cut-down of the cephalic vein (vena section) and direct puncture of the subclavian vein. The aim of this trial is to identify the strategy for the implantation of TIVAPs with the lowest risk of pneumothorax and haemothorax. METHODS/DESIGN: The PORTAS-3 trial is designed as a multicentre, randomised controlled trial to compare two implantation strategies. A total of 1,154 patients will be randomised after giving written informed consent. Patients must be over 18 years of age and scheduled for primary implantation of a TIVAP on the designated side. The primary endpoint will be the frequency of pneumothorax and haemothorax after insertion of a TIVAP by one of two different strategies. The experimental intervention is as follows: open strategy, defined as surgical cut-down of the cephalic vein, supported by a rescue technique if necessary, and in the case of failure, direct puncture of the subclavian vein. The control intervention is as follows: direct puncture of the subclavian vein using the Seldinger technique guided by sonography, fluoroscopy or landmark technique. The trial duration is approximately 36 months, with a recruitment period of 18 months and a follow-up period of 30 days. DISCUSSION: The PORTAS-3 trial will compare two different TIVAP implantation strategies with regard to their individual risk of postoperative pneumothorax and haemothorax. Since TIVAP implantation is one of the most common procedures in general surgery, the results will be of interest for a large community of surgeons as well as oncologists and general practitioners. The pragmatic trial design ensures that the results will be generalizable to a wide range of patients. TRIAL REGISTRATION: The trial protocol was registered on 28 August 2014 with the German Clinical Trials Register (DRKS00004900) . The World Health Organization's Universal Trial Number is U1111-1142-4420.

Outcome, complications, and mortality of an intrathoracic anastomosis in esophageal cancer in patients without a preoperative selection with a risk score.

BACKGROUND: Esophagectomy for esophageal cancer remains a challenge with relatively high morbidity. We analyzed outcome, complications, and mortality after abdominothoracic esophagectomy with intrathoracic anastomosis. No routine preoperative risk stratification was performed. METHODS: One hundred eighty-seven consecutive patients (105 AEG I, 21 AEG II, 58 SCC, and 3 other entities) underwent standardized right abdominothoracic esophagectomy with intrathoracic anastomosis and two field lymphadenectomy between 2003 and 2009. Reconstruction was performed mostly with a gastric tube (n = 126) or a fundus rotation gastroplasty (n = 57). Seventy-four patients underwent neoadjuvant treatment (36 patients chemotherapy; 38 patients chemoradiotherapy). RESULTS: Postoperative morbidity was high (73.2 %). Ninety-two patients (49.2 %) suffered from surgical complications, 50 patients had major (26.7 %), and 42 minor (22.5 %) complications. Thirty-day mortality was 9/187 (4.8 %) while in-hospital mortality was doubled with 9.6 %. Six of 19 of the patients died without surgical complications. Preoperative treatment did not increase morbidity or mortality. Surgical complications with subsequent death were tracheobronchial fistula (2/3), ischemia of the gastric tube (3/6), anastomotic leakage (6/30), chylothorax (1/6), and intraoperative bleeding from the aorta (1/1). The median overall survival was 25.0 months. The occurrence of surgical or medical complications did not influence overall survival. In multivariate analysis, cT-category, pN-category, R-category, and re-intubation were independent prognostic factors. CONCLUSIONS: Abdominothoracic esophagectomy with intrathoracic anastomosis without preoperative patient selection is associated with a high risk for complications and subsequent death but ranges still within the upper range of published data. Strict patient selection is accepted to reduce postoperative morbidity and mortality but excludes a subgroup of patients from potentially curative resection.

Clinical phase I/II trial to investigate preoperative dose-escalated intensity-modulated radiation therapy (IMRT) and intraoperative radiation therapy (IORT) in patients with retroperitoneal soft tissue sarcoma: interim analysis.

BACKGROUND: To report an unplanned interim analysis of a prospective, one-armed, single center phase I/II trial (NCT01566123). METHODS: Between 2007 and 2013, 27 patients (pts) with primary/recurrent retroperitoneal sarcomas (size > 5 cm, M0, at least marginally resectable) were enrolled. The protocol attempted neoadjuvant IMRT using an integrated boost with doses of 45-50 Gy to PTV and 50-56 Gy to GTV in 25 fractions, followed by surgery and IOERT (10-12 Gy). Primary endpoint was 5-year-LC, secondary endpoints included PFS, OS, resectability, and acute/late toxicity. The majority of patients showed high grade lesions (FNCLCC G1:18%, G2:52%, G3:30%), predominantly liposarcomas (70%). Median tumor size was 15 cm (6-31). RESULTS: Median follow-up was 33 months (5-75). Neoadjuvant IMRT was performed as planned (median dose 50 Gy, 26-55) in all except 2 pts (93%). Gross total resection was feasible in all except one patient. Final margin status was R0 in 6 (22%) and R1 in 20 pts (74%). Contiguous-organ resection was needed in all grossly resected patients. IOERT was performed in 23 pts (85%) with a median dose of 12 Gy (10-20 Gy).We observed 7 local recurrences, transferring into estimated 3- and 5-year-LC rates of 72%. Two were located outside the EBRT area and two were observed after more than 5 years. Locally recurrent situation had a significantly negative impact on local control. Distant failure was found in 8 pts, resulting in 3- and 5-year-DC rates of 63%. Patients with leiomyosarcoma had a significantly increased risk of distant failure. Estimated 3- and 5-year-rates were 40% for PFS and 74% for OS. Severe acute toxicity (grade 3) was present in 4 pts (15%). Severe postoperative complications were found in 9 pts (33%), of whom 2 finally died after multiple re-interventions. Severe late toxicity (grade 3) was scored in 6% of surviving patients after 1 year and none after 2 years. CONCLUSION: Combination of neoadjuvant IMRT, surgery and IOERT is feasible with acceptable toxicity and yields good results in terms of LC and OS in patients with high-risk retroperitoneal sarcomas. Long term follow-up seems mandatory given the observation of late recurrences. Accrual of patients will be continued with extended follow-up. TRIAL REGISTRATION: NCT01566123.

Endoscopic treatment of anastomotic leakage after esophagectomy or gastrectomy for carcinoma with self-expanding removable stents.

BACKGROUND/AIMS: Anastomotic leakage is a feared complication after gastrectomy and esophagectomy. We report our experience in the treatment with endoscopic stent placement. METHODOLOGY: Seventeen patients with anastomotic leakage after resection of a malignant tumor of the stomach or the distal esophagus have been long-term followed-up. RESULTS: In 10 patients the implanted stent did successfully close the leakage in the first attempt. In 3 out of 7 patients with unsuccessfully sealed leakage a stent-in-stent-manoeuvre did successfully seal the leakage. We had no major complications upon implantation of the stents. We did have no recurrence of a once sealed leakage. CONCLUSIONS: Endoscopic stent placement is a safe procedure in the treatment of anastomotic leakage after gastrectomy and esophagectomy. It should be performed in any clinically relevant leakage if possible. In cases where stent placement is not successful at first, correction of position, stent replacement or a stent-in-stent manoeuvre can be performed, with promising results.

TERT promoter hotspot mutations are recurrent in myxoid liposarcomas but rare in other soft tissue sarcoma entities.

BACKGROUND: Recently, recurrent point mutations in the telomerase reverse transcriptase (TERT) promoter region have been found in many human cancers, leading to a new transcription factor binding site, increased induction of TERT and subsequently to telomere maintenance. We determined the prevalence of TERT promoter mutations in soft tissue sarcomas of 341 patients comprising 16 entities and in 16 sarcoma cell lines covering 7 different soft tissue sarcoma types. METHODS: The sarcoma tissue samples were collected from the archives of the Institute of Pathology, University of Heidelberg and were composed of 39 myxoid liposarcomas (MLS), 61 dedifferentiated liposarcomas, 15 pleomorphic liposarcomas, 27 leiomyosarcomas, 25 synovial sarcomas (SS), 35 malignant peripheral nerve sheath tumors (MPNST), 40 undifferentiated pleomorphic sarcomas, 17 myxofibrosarcomas, 9 low grade fibromyxoid sarcomas, 10 cases of dermatofibrosarcoma protuberans, 31 solitary fibrous tumors (SFT), 8 extraskeletal myxoid chondrosarcomas, 9 angiosarcomas, 6 alveolar soft part sarcomas, 5 clear cell sarcomas and 4 epithelioid sarcomas. Sarcoma cell lines were obtained from the raising laboratories. A 193 bp fragment of the TERT promoter region covering the hot-spot mutations C228T and C250T was amplified, and direct sequencing of the PCR products was performed. RESULTS: TERT promoter mutations were detected in 36/341 sarcomas. They were highly recurrent in MLS (29/39; 74%) and were in the present MLS series not associated with the phenotype (myxoid vs. round cell variant), tumor grade, tumor site and patients' median age or gender. In the remaining cases, TERT promoter mutations were found only in 7/302 sarcoma samples and confined to SFTs (4/31; 13%), MPNSTs (2/35; 6%), and SSs (1/25; 4%). Within the collection of sarcoma cell lines examined, TERT promoter mutations were detected in two MLS and in one of three MPNST cell lines. CONCLUSIONS: TERT promoter mutations are frequent in MLSs including their round cell variants, representing the most prevalent mutation identified in this sarcoma entity to date, and in a minor fraction of SFTs, MPNSTs and SSs. The majority of sarcomas are devoid of TERT promoter hotspot mutations. These data suggest that telomere maintenance through increased expression of telomerase plays an important role in the pathogenesis especially of MLS.

Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas.

BACKGROUND: High-grade soft tissue sarcomas are a heterogeneous, complex group of aggressive malignant tumors showing mesenchymal differentiation. Recently, soft tissue sarcomas have increasingly been classified on the basis of underlying genetic alterations; however, the role of aberrant DNA methylation in these tumors is not well understood and, consequently, the usefulness of methylation-based classification is unclear. RESULTS: We used the Infinium HumanMethylation27 platform to profile DNA methylation in 80 primary, untreated high-grade soft tissue sarcomas, representing eight relevant subtypes, two non-neoplastic fat samples and 14 representative sarcoma cell lines. The primary samples were partitioned into seven stable clusters. A classification algorithm identified 216 CpG sites, mapping to 246 genes, showing different degrees of DNA methylation between these seven groups. The differences between the clusters were best represented by a set of eight CpG sites located in the genes SPEG, NNAT, FBLN2, PYROXD2, ZNF217, COL14A1, DMRT2 and CDKN2A. By integrating DNA methylation and mRNA expression data, we identified 27 genes showing negative and three genes showing positive correlation. Compared with non-neoplastic fat, NNAT showed DNA hypomethylation and inverse gene expression in myxoid liposarcomas, and DNA hypermethylation and inverse gene expression in dedifferentiated and pleomorphic liposarcomas. Recovery of NNAT in a hypermethylated myxoid liposarcoma cell line decreased cell migration and viability. CONCLUSIONS: Our analysis represents the first comprehensive integration of DNA methylation and transcriptional data in primary high-grade soft tissue sarcomas. We propose novel biomarkers and genes relevant for pathogenesis, including NNAT as a potential tumor suppressor in myxoid liposarcomas.

Long-term vacuum-assisted closure in open abdomen due to secondary peritonitis: a retrospective evaluation of a selected group of patients.

BACKGROUND/AIMS: Vacuum-assisted closure (VAC) leads to a high fascial closure rate in open abdomen within the first week of treatment. However, little data exist on the role of long-term VAC treatment in patients with peritonitis, where fascial closure cannot be accomplished within the first days. METHODS: We reviewed the medical records of 49 patients with open abdomen for more than 7 days due to secondary peritonitis, who underwent a VAC-treatment. Nonparametric analysis was performed using chi(2) test or Fisher's exact test. RESULTS: Fascial closure could be accomplished in only 11 patients (22%), whereas complications occurred in 43 patients (88%). Re-explorations after starting VAC were associated with the occurrence of enterocutaneous fistula (p < 0.001) and were also of prognostic value regarding the rate of fascial closure (p = 0.033). CONCLUSIONS: If fascial closure cannot be accomplished within the first days, patients show a dramatically lower fascial closure and an increased complication rate with VAC. Further studies are needed to evaluate whether this subgroup really benefits from VAC.

Prognostic significance of immunohistochemical RhoA expression on survival in pancreatic ductal adenocarcinoma: a high-throughput analysis.

Among all human carcinomas, pancreatic cancer has one of the worst survival rates. Most patients will die of this cancer shortly after diagnosis, and currently, surgery is the only potential cure. Ductal adenocarcinoma is the most common histologic type. The search for prognostic parameters has progressed from mere physical or histomorphological tumor properties to molecular parameters. These, in turn, might point toward new therapeutic strategies. The K-ras oncogene is known to play a role in early stages of ductal adenocarcinoma carcinogenesis, and ras homologues are differentially expressed in cancerous versus normal ductal cells. RhoA belongs to a family of ras homologues comprising RhoA, RhoB, and RhoC. It is a guanosine triphosphatase associated with the cytoskeleton that seems to be involved in epithelial mesenchymal transition, a process of dedifferentiation. Immunohistologic RhoA expression was studied in a tissue microarray of 94 pancreatic ductal adenocarcinomas and correlated with clinicopathologic parameters and follow-up. RhoA protein expression, measured as labeling intensity or evaluated as percentage of reactive tumor cells, correlated with overall survival. A multivariate analysis demonstrated that RhoA protein expression is independent from other known prognostic parameters such as tumor size or grade. Moreover, a score combining RhoA expression with tumor size and grade resulted in a highly significant increase in the prognostic value for the overall survival of patients with pancreatic ductal adenocarcinoma.

Complications and treatment of migrated biliary endoprostheses: a review of the literature.

Endoscopic biliary stent insertion is a well-established procedure. It is especially successful in treating postoperative biliary leaks, and may prevent surgical intervention. A routine change of endoprostheses after 3 mo is a common practice but this can be prolonged to 6 mo. We reported a colonic perforation due to biliary stent dislocation and migration to the rectosigmoid colon, and reviewed the literature.

Complete remission of a metastatic pancreatic carcinoma after modified G-FLIP therapy.

This is a report about a patient who had a complete remission of a metastatic pancreatic adenocarcinoma after a modified G-FLIP therapy administered in an outpatient setting. The patient underwent surgery and the complete remission could be proven histologically. The administered chemotherapy was very effective and is even more attractive since it could be administered without admission to hospital.

Prognosis and treatment of primary deep soft tissue sarcomas.

UNLABELLED: The objective of this study was to define the prognostic factors for survival of patients with soft tissue sarcomas (STS) of the extremities located below the muscular fascia. PATIENTS AND METHODS: One hundred and twenty-seven consecutive patients, resected in our Institution between March 1988 and December 2002, were reviewed. RESULTS: On univariate analysis, the prognostic factors for survival were tumor size, nodal status, adequate surgery, tumor malignancy grade and administered chemotherapy. Additionally, local failure, metastasis after resection and residual tumor after incomplete resection followed by complete resection were adverse prognostic factors for survival. The tumor size, nodal status and metastasis after resection were factors indicating worse survival on multivariate analysis. CONCLUSION: Our results indicate that most factors influencing the course of the disease cannot be controlled by the surgeon. Complete resection is imperative for local control and allows the patient the chance of a cure. New treatment procedures should be evaluated in prospective trials to optimize therapy. Surgery without sufficient information on the malignancy or expansion of the tumor might be detrimental for the patient.