Characterization of Perioperative Serotonin in Patients Undergoing Orthotopic Liver Transplantation.

Background: Platelets were shown to be relevant for liver regeneration. In particular, platelet-stored serotonin (5-HT) proved to be a pro-regenerative factor in this process. The present study aimed to investigate the perioperative course of 5-HT and evaluate associations with patient and graft outcomes after othotopic liver transplantation (OLT). Methods: 5-HT was quantified in plasma and serum of 44 OLT recipients perioperatively, and in their respective donors. Olthoff's criteria for early allograft dysfunction (EAD) were used to evaluate postoperative outcomes. Results: Patients with higher donor intra-platelet 5-HT per platelet (IP 5-HT PP) values had significantly lower postoperative transaminases (ASAT POD1: p = 0.006, ASAT POD5: p = 0.006, ASAT POD10: p = 0.02, ALAT POD1: p = 0.034, ALAT POD5: p = 0.017, ALAT POD10: p = 0.04). No significant differences were seen between postoperative 5-HT values and the occurrence of EAD. A tendency was measured that donor IP 5-HT PP is lower in donor-recipient pairs that developed EAD (p = 0.07). Conclusions: Donor IP 5-HT PP might be linked to the postoperative development of EAD after OLT, as higher donor levels are correlated with a more favorable postoperative course of transaminases. Further studies with larger cohorts are needed to validate these findings.

MELD-Na Alterations on the Liver Transplant Waiting List and Their Impact on Listing Outcome.

BACKGROUND: Dynamic MELD deterioration (Delta MELD) during waiting time was shown to have significant impact on post-transplant survival. The aim of this study was to analyze the impact of MELD-Na score alterations on waiting list outcomes in liver transplant candidates. METHOD: 36,806 patients listed at UNOS for liver transplantation in 2011-2015 were analyzed according to their delisting reasons. Several different MELD-Na alterations during waiting time were analyzed (e.g., maximal change, last change before delisting/transplantation). Outcome estimates were calculated according to MELD-Na scores at listing and Delta MELD. RESULTS: Patients who died while on the waiting list showed a significantly higher deterioration in MELD-Na during the waiting time (6.8 ± 8.4 points) than stable patients who remained actively listed (-0.1 ± 5.2 points; p < 0.01). Patients who were considered too healthy for transplantation improved by more than 3 points on average during the waiting time. The mean peak MELD-Na alteration during the waiting time was 10.0 ± 7.6 for patients who died on the waiting list, compared to 6.6 ± 6.1 in the group of patients who finally underwent transplantation. CONCLUSIONS: Deterioration of MELD-Na during waiting time and maximal MELD-Na deterioration have a significant negative impact on the liver transplant waiting list outcome.

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.

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.

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.

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.

The difficulty in defining extended donor criteria for liver grafts: the Eurotransplant experience.

Donor criteria for liver grafts have been expanded because of organ shortage. Currently, no exact definitions for extended donor grafts have been established. The aim of this study was to analyze the impact of donor-specific risk factors, independent of recipient characteristics. In collaboration with Eurotransplant and European Liver Transplant Register, solely donor-specific parameters were correlated with 1-year survival following liver transplantation. Analyses of 4701 donors between 2000 and 2005 resulted in the development of a nomogram to estimate graft survival for available grafts. Predictions by nomogram were compared to those by Donor Risk Index (DRI). In the multivariate analysis, cold ischemic time (CIT), highest sodium, cause of donor death, γ-glutamyl transferase (γ-GT), and donor sex (female) were statistically significant factors for 3 months; CIT, γ-GT, and cause of donor death for 12-month survival. The median DRI of this study population was 1.45 (Q1: 1.17; Q3: 1.67). The agreement between the nomogram and DRI was weak (kappa = 0.23). Several donor-specific risk factors were identified for early survival after liver transplantation. The provided nomogram will support quick organ quality assessment. Nevertheless, this study showed the difficulties of determining an exact definition of extended criteria donors.

[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.

Dynamic changes in MELD score not only predict survival on the waiting list but also overall survival after liver transplantation.

The predictive value of MELD score for post-transplant survival has been under constant debate since its implementation in 2001. Aim of this study was to assess the impact of alterations in MELD score throughout waiting time (WT) on post-transplant survival. A single-centre retrospective analysis of 1125 consecutive patients listed for liver transplantation between 1997 and 2009 was performed. The impact of MELD score and dynamic changes in MELD score (DeltaMELD), as well as age, sex, year of listing and WT were evaluated on waiting list mortality and post-transplant survival. In this cohort, 539 (60%) patients were transplanted, 223 (25%) died on list and 142 (15%) were removed from the waiting list during WT. One-, three- and five-year survival after liver transplantation were 83%, 78% and 76% respectively. DeltaMELD as a continuous variable proved to be the only significant risk factor for overall survival after liver transplantation (hazard ratio (HR): 1.06, 95% confidence interval (CI) 1.02-1.1, P = 0.013). The highest risk of post-transplant death could be defined for patients with a DeltaMELD > 10 (HR: 4.87, 95% CI 2.09-11.35, P < 0.0001). In addition, DeltaMELD as well as MELD at listing showed a significant impact on waiting list mortality. DeltaMELD may provide an easy evaluation tool to identify patients on the liver transplant waiting list with a high mortality risk after transplantation in the current setting. Temporarily withholding and re-evaluating these patients might improve overall outcome after liver transplantation.

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.

Surgery for gastrointestinal stromal tumors of the stomach.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the main mesenchymal neoplasms in the gastrointestinal tract. Tumor size, mitotic rate, and location correlate with potential malignancy and recurrence rate. Results of surgical treatment of gastric GIST are analyzed with emphasis on recurrence of disease after intermediate follow-up. METHODS: From 1998 to 2006, a total of 63 patients (median age 62.1 +/- 14.1) underwent gastric resection for GIST. Fifty-five patients (93.6%) returned for follow-up investigations, which included computed tomography in 45, gastroscopy in 32, and endosonography in 29. Positron emission tomography was done in five patients. RESULTS: Mean tumor size was 5.3 +/- 3.8 cm. Open atypical gastric resection was done in 32, distal gastric resection in five, and remnant gastrectomy in four patients. Laparoscopic gastric resection was initiated in 22 patients; the conversion rate was four of 22 (18.2%). Overall, R0 resection was reached in 61/63 patients (96.8%). According to the Fletcher criteria, 33 tumors (52.4%) were classified as intermediate or high risk GIST. Six patients (9.5%) died of unrelated causes before follow-up. After a median follow-up of 2.5 years, overall recurrence rate was 7.0% after R0 resection. CONCLUSION: Histologically proven complete resection is an effective treatment for gastric GIST. Laparoscopic procedures were carried out successfully in selected patients.

CC chemokine and CC chemokine receptor profiles in visceral and subcutaneous adipose tissue are altered in human obesity.

BACKGROUND/AIMS: Obesity is associated with a low-grade inflammation, insulin resistance, and macrophage infiltration of adipose tissue. The role of CC chemokines and their respective receptors in human adipose tissue inflammation remains to be determined. METHODS: sc and visceral adipose tissue of obese patients (body mass index 53.1 +/- 11.3 kg/m(2)) compared with lean controls (body mass index 25.9 +/- 3.8 kg/m(2)) was analyzed for alterations in inflammatory gene expression. RESULTS: Macrophage infiltration was increased in sc and visceral adipose tissue of obese patients as determined by increased mRNA expression of a macrophage-specific marker (CD68) and by elevated macrophage infiltration. Gene expression of CC chemokines involved in monocyte chemotaxis (CCL2, CCL3, CCL5, CCL7, CCL8, and CCL11) and their receptors (CCR1, CCR2, CCR3, and CCR5) was higher in sc and visceral adipose tissue of obese patients. Serum concentrations of the inflammatory marker IL-6 and C-reactive protein were elevated in obese patients compared with lean controls. Obese patients revealed increased insulin resistance as assessed by the homeostasis model assessment of insulin resistance index and reduced plasma adiponectin concentrations. Adipose tissue expression of many CC chemokines and their receptors in the obese group positively correlated with CD68 expression. CONCLUSION: Up-regulation of the CC chemokines and their respective receptors in adipose tissue occurs in human obesity and is associated with increased systemic inflammation.