First-in-class MKK4 inhibitors enhance liver regeneration and prevent liver failure.

Diminished hepatocyte regeneration is a key feature of acute and chronic liver diseases and after extended liver resections, resulting in the inability to maintain or restore a sufficient functional liver mass. Therapies to restore hepatocyte regeneration are lacking, making liver transplantation the only curative option for end-stage liver disease. Here, we report on the structure-based development and characterization (nuclear magnetic resonance [NMR] spectroscopy) of first-in-class small molecule inhibitors of the dual-specificity kinase MKK4 (MKK4i). MKK4i increased liver regeneration upon hepatectomy in murine and porcine models, allowed for survival of pigs in a lethal 85% hepatectomy model, and showed antisteatotic and antifibrotic effects in liver disease mouse models. A first-in-human phase I trial (European Union Drug Regulating Authorities Clinical Trials [EudraCT] 2021-000193-28) with the clinical candidate HRX215 was conducted and revealed excellent safety and pharmacokinetics. Clinical trials to probe HRX215 for prevention/treatment of liver failure after extensive oncological liver resections or after transplantation of small grafts are warranted.

Effect of Hyperthermic Intraperitoneal Chemotherapy on Cytoreductive Surgery in Gastric Cancer With Synchronous Peritoneal Metastases: The Phase III GASTRIPEC-I Trial.

PURPOSE: In patients with peritoneal metastasis (PM) from gastric cancer (GC), chemotherapy is the treatment of choice. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are still being debated. This randomized, controlled, open-label, multicenter phase III trial (EudraCT 2006-006088-22; ClinicalTrials.gov identifier: NCT02158988) explored the impact on overall survival (OS) of HIPEC after CRS. PATIENTS AND METHODS: Adult patients with GC and histologically proven PM were randomly assigned (1:1) to perioperative chemotherapy and CRS alone (CRS-A) or CRS plus HIPEC (CRS + H). HIPEC comprised mitomycin C 15 mg/m2 and cisplatin 75 mg/m2 in 5 L of saline perfused for 60 minutes at 42°C. The primary end point was OS; secondary endpoints included progression-free survival (PFS), other distant metastasis-free survival (MFS), and safety. Analyses followed the intention-to-treat principle. RESULTS: Between March 2014 and June 2018, 105 patients were randomly assigned (53 patients to CRS-A and 52 patients to CRS + H). The trial stopped prematurely because of slow recruitment. In 55 patients, treatment stopped before CRS mainly due to disease progression/death. Median OS was the same for both groups (CRS + H, 14.9 [97.2% CI, 8.7 to 17.7] months v CRS-A, 14.9 [97.2% CI, 7.0 to 19.4] months; P = .1647). The PFS was 3.5 months (95% CI, 3.0 to 7.0) in the CRS-A group and 7.1 months (95% CI, 3.7 to 10.5; P = .047) in the CRS + H group. The CRS + H group showed better MFS (10.2 months [95% CI, 7.7 to 14.7] v CRS-A, 9.2 months [95% CI, 6.8 to 11.5]; P = .0286). The incidence of grade ≥3 adverse events (AEs) was similar between groups (CRS-A, 38.1% v CRS + H, 43.6%; P = .79). CONCLUSION: This study showed no OS difference between CRS + H and CRS-A. PFS and MFS were significantly better in the CRS + H group, which needs further exploration. HIPEC did not increase AEs.

Regional hyperthermia with cisplatin added to gemcitabine versus gemcitabine in patients with resected pancreatic ductal adenocarcinoma: The HEAT randomised clinical trial.

BACKGROUND: Regional hyperthermia (RHT) with cisplatin added to gemcitabine showed efficacy in gemcitabine-pre-treated patients with advanced pancreatic ductal adenocarcinoma. We conducted a randomised clinical trial to investigate RHT with cisplatin added to gemcitabine (GPH) compared with gemcitabine (G) in the adjuvant setting of resected pancreatic ductal adenocarcinoma. METHODS: This randomised, multicentre, open-label trial randomly assigned patients to either GPH (gemcitabine 1000 mg/m2 on day 1, 15 and cisplatin 25 mg/m2 with RHT on day 2, 3 and 15,16) or to G (gemcitabine 1000 mg/m2 on day 1,8,15), four-weekly over six cycles. Disease-free survival (DFS) was the primary end-point. Secondary end-points included overall survival (OS) and safety. RESULTS: A total of 117 eligible patients (median age, 63 years) were randomly allocated to treatment (57 GPH; 60 G). With a follow-up time of 56.6 months, the median DFS was 12.7 compared to 11.2 months for GPH and G, respectively (p = 0.394). Median post-recurrence survival was significantly prolonged in the GPH-group (15.3 versus 9.8 months; p = 0.031). Median OS reached 33.2 versus 25.2 months (p = 0.099) with 5-year survival rates of 28.4% versus 18.7%. Excluding eight patients who received additional capecitabine in the G-arm (investigators choice), median OS favoured GPH (p = 0.052). Adverse events CTCAE (Common Terminology Criteria for Adverse Events) grade ≥3 occurred in 61.5% (GPH) versus 63.6% (G) of patients. Two patients in the G-group died because of treatment-related toxic effects. CONCLUSIONS: The randomised controlled Hyperthermia European Adjuvant Trial study failed to demonstrate a significant difference in DFS. However, it suggests a difference in post-recurrence survival and a trend for improved OS. CLINICALTRIALS: gov, number NCT01077427.

Beware of gastric tube in esophagectomy after gastric radiotherapy: A case report.

BACKGROUND: Gastric tube formation and pull-up is the most common technique of reconstruction following esophagectomy for esophageal cancer. If previous treatment with radiotherapy for gastric mucosa-associated lymphoid tissue (MALT)-lymphoma restricts suitability of the stomach for anastomosis to the esophagus is unknown. CASE SUMMARY: A 57-year-old man underwent sequential chemotherapy and radiotherapy for gastric MALT-lymphoma seven years prior to diagnosis of esophageal adenocarcinoma. Esophagectomy without neoadjuvant treatment was recommended by the multidisciplinary tumor board due to early tumor stage [uT1 (sm2) uN+ cM0 according to TNM-classification of malignant tumors, 8th edition] without lymph node involvement. Minimal invasive esophageal resection with esophagogastrostomy was performed. Due to gastric tube necrosis with anastomotic leakage on the twelfth postoperative day, diverting resection with construction of a cervical salivary fistula was necessary. Rapid recovery facilitated colonic interposition without any complications six months afterwards. CONCLUSION: This case report may represent the start for further investigation to know if it is reasonable to refrain from esophagogastrostomy in patients with a long interval between gastric radiotherapy and surgery.

Urinary Tract Infections in Kidney Transplant Recipients-Is There a Need for Antibiotic Stewardship?

(1) Background: Urinary tract infections (UTI) are the most common infections after kidney transplantation. Given the risk of urosepsis and the potential threat to the graft, the threshold for treating UTI and asymptomatic bacteriuria with broad spectrum antibiotics is low. Historically fluoroquinolones were prescription favorites for patients that underwent kidney transplantation (KT). After the recent recommendation to avoid them in these patients, however, alternative treatment strategies need to be investigated (2) Methods: We retrospectively analyzed the charts of 207 consecutive adult kidney transplantations that were performed at the department of General, Visceral and Transplantation Surgery of the University Hospital of Tuebingen between January 2015 and August 2020. All charts were screened for the diagnosis and treatment of asymptomatic bacteriuria (ASB) and urinary tract infections (UTI) and the patients' clinical characteristics and outcomes were evaluated. (3) Results: Of the 207 patients, 68 patients suffered from urinary tract infections. Patients who developed UTI had worse graft function at discharge (p = 0.024) and at the 12 months follow-up (p < 0.001). The most commonly prescribed antibiotics were Ciprofloxacin and Piperacillin/Tazobactam. To both, bacterial resistance was more common in the study cohort than in the control group. (4) Conclusions: Urinary tract infections appear to be linked to worse graft functions. Thus, prevention and treatment should be accompanied by antibiotic stewardship teams.

Alveolar Echinococcosis-A Challenging Task for the Hepatobiliary Surgeon.

(1) Background: Alveolar echinococcosis (AE) is an ultimately fatal disease, whose only curative treatment is surgery. Due to its late presentation extended liver resections are often necessary. The true benefit of extensive surgery has yet to be established; (2) Methods: We present a single center experience of 33 cases of Echinococcus multilocularis that have been treated at a high-volume hepatobiliary surgery center between 2004 and 2021. (3) Results: Of the 33 patients 24 patients underwent major liver resection (73%). In addition to the liver resection patients frequently underwent complex extrahepatic procedures such as lymphadenectomy (n = 21, 61%), vascular resections and reconstructions (n = 9, 27%) or resections and reconstruction of the extrahepatic bile duct (n = 11, 33%). Seven patients suffered from ≥ grade III complications (21%). Complete resection was achieved in 17 patients. Fourteen patients had R1 resections and two had macroscopic parasitic remnant (R2). Progressive disease was reported in three patients (The two R2 patients and one R1 resected patient). At a median follow-up of 54 months no mortality has occurred in our cohort; (4) Conclusions: Liver resection remains the gold standard for AE. Even in extensive disease the combination of complex resection and perioperative benzimidazoles can achieve favorable long-term outcomes.

Applying the Delphi process for development of a hepatopancreaticobiliary robotic surgery training curriculum.

BACKGROUND: Robotic hepatopancreaticobiliary (HPB) procedures are performed worldwide and establishing processes for safe adoption of this technology is essential for patient benefit. We report results of the Delphi process to define and optimize robotic training procedures for HPB surgeons. METHODS: In 2019, a robotic HPB surgery panel with an interest in surgical training from the Americas and Europe was created and met. An e-consensus-finding exercise using the Delphi process was applied and consensus was defined as 80% agreement on each question. Iterations of anonymous voting continued over three rounds. RESULTS: Members agreed on several points: there was need for a standardized robotic training curriculum for HPB surgery that considers experience of surgeons and based on a robotic hepatectomy includes a common approach for "basic robotic skills" training (e-learning module, including hardware description, patient selection, port placement, docking, troubleshooting, fundamentals of robotic surgery, team training and efficiency, and emergencies) and an "advanced technical skills curriculum" (e-learning, including patient selection information, cognitive skills, and recommended operative equipment lists). A modular approach to index procedures should be used with video demonstrations, port placement for index procedure, troubleshooting, and emergency scenario management information. Inexperienced surgeons should undergo training in basic robotic skills and console proficiency, transitioning to full procedure training of e-learning (video demonstration, simulation training, case observation, and final evaluation). Experienced surgeons should undergo basic training when using a new system (e-learning, dry lab, and operating room (OR) team training, virtual reality modules, and wet lab; case observations were unnecessary for basic training) and should complete the advanced index procedural robotic curriculum with assessment by wet lab, case observation, and OR team training. CONCLUSIONS: Optimization and standardization of training and education of HPB surgeons in robotic procedures was agreed upon. Results are being incorporated into future curriculum for education in robotic surgery.

Oncological outcome of carcinomas in the rectosigmoid junction compared to the upper rectum or sigmoid colon - A retrospective cohort study.

INTRODUCTION: Although carcinomas of the rectosigmoid junction are frequent, specific data on these tumors are sparse because assignment either to the colon or rectum is common. The objective of this study is to determine whether carcinomas of the rectosigmoid junction can be assigned to the sigmoid colon or to the upper rectum in terms of tumor characteristics and oncological outcome. MATERIALS AND METHODS: 337 consecutive patients undergoing resection of carcinomas in the sigmoid colon, the rectosigmoid junction and the upper third of the rectum were analyzed retrospectively and additionally followed-up for oncological outcome. RESULTS: 185 patients (54.9%) showed carcinoma in the sigmoid colon, 41 (12.2%) in the rectosigmoid junction and 111 (32.9%) in the upper rectum. Synchronous liver metastases (rectosigmoid junction 31.7%, sigmoid colon 16.2%, upper rectum 11.7%; P = 0.01), lymphovascular invasion (rectosigmoid junction 46.3%, sigmoid colon 25.4%, upper rectum 32.4%; P = 0.03) and pN2 (rectosigmoid junction 31.7%, sigmoid colon 10.3%, upper rectum 13.5%; P = 0.002) were more common in carcinomas of the rectosigmoid junction. The median follow-up period was 44 (22-75.5) months. Five-year overall survival was 44.6% in patients with carcinomas in the rectosigmoid junction, 70.9% in the sigmoid colon, and 70.2% in the upper rectum. CONCLUSION: Carcinomas of the rectosigmoid junction reveal a deviant behavioral pattern compared to its adjacent bowel segments.

Anorectal malignant melanoma: curative abdominoperineal resection: patient selection with 18F-FDG-PET/CT.

BACKGROUND: Anorectal malignant melanomas (ARMM) are rare tumors, characterized by an early lymphatic spread and distant metastasis, resulting in an extremely poor overall survival. The objective of this study was to determine the pattern of regional lymph node metastasis (LNM) by computed tomography (CT) and 18F-FDG-PET/CT in patients undergoing abdominoperineal resection (APR) and its impact on oncologic outcome. METHODS: A retrospective analysis of six consecutive patients who underwent APR due to primary ARMM was performed. Patients were staged by CT and PET/CT. RESULTS: Four out of six patients had preoperative LNM involvement (two patients inguinal and perirectal, one iliacal, one perirectal), with two of them presenting with distant metastases additionally. Inguinal/iliacal LNM in two patients as well as liver metastasis in one patient was seen in PET/CT and missed by CT. The three patients with initial inguinal/iliacal LNM died during the observation period (overall survival: 10 (6-18) months). The three patients without inguinal/iliacal LNM involvement are currently alive, one patient showing a slowly progressive disease since 5 years, and two patients are tumor-free since 8.5 and 1.5 years (the patients had initial perirectal LNM). CONCLUSIONS: In ARMM, PET/CT is superior to CT in detection of LNM and distant metastasis. APR is possibly a curative approach if the PET/CT shows exclusively perirectal LNM despite locally advanced tumor growth.

Compliance of Clinical Pathways in Elective Laparoscopic Cholecystectomy: Evaluation of Different Implementation Methods.

BACKGROUND: Clinical pathways aim to standardize perioperative and postoperative care of surgical procedures and are shown to result in a significant optimization associated with cost reduction. The aim of this study was to establish the impact of two different implementations forms of clinical pathways on the pathway compliance and resulting costs. METHODS: Data of patients undergoing elective cholecystectomy for symptomatic cholecystolithiasis were collected over two different periods: using a clinical pathway in the form of a paper-based checklist, or a clinical pathway integrated into the paper-based medical treatment and nursing documentation. Outcome measures were compliance of the clinical pathway and total costs per case. RESULTS: The compliance was significantly higher using integrated pathways compared to paper-based checklists (n = 117 of 123, 95 % vs 54 of 118, 46 %; p < 0.001). Mean total costs (€2206 vs €2458, p = 0.027) and length of hospital stay (2.13 vs 2.77 days, p < 0.001) were significantly reduced by the integrated clinical pathway compared to checklists. Further, the variation of costs per case and variation of length of hospital stay were significantly smaller with integrated clinical pathway (±€440 vs ±€538, p = 0.039 and ±0.53 vs ±0.68 days, p < 0.001, respectively). No difference regarding postoperative complication was observed (n = 3 vs. 4 events; p = 0.67). CONCLUSION: Integrated clinical pathways display a significant higher compliance compared to checklists resulting in reduced total costs, shorter hospital stay and a smaller variation of cost, making it a useful tool in process controlling and planning.

Rapid thyroid nodule growth is not a marker for well-differentiated thyroid cancer.

BACKGROUND: Rapid growth of thyroid nodules is described as being associated with thyroid cancer. The objective of the study was to determine how the growth rate of thyroid nodules during follow-up is associated with the risk of thyroid cancer. METHODS: Retrospective analysis of patients undergoing thyroid surgery for nodular disease and a repetitive preoperative ultrasound work-up of at least 6 months was done. Nodule growth was considered relevant when a volume increase >49% was detected. Growth patterns were described as rapid for a volume increase present over 6 to 24 months. RESULTS: Of the 297 analysed patients, 226 (76%) displayed relevant nodule growth and 71 (24%) no relevant growth. A rapid growth pattern was seen in 73 patients (32%). Well-differentiated thyroid cancer was diagnosed in 33 patients (11%; 27 papillary, 6 follicular) with a relevant nodule growth in 2 and no relevant growth in 31 patients. No rapid growth pattern was observed in any case of well-differentiated thyroid cancer. A rapid growth pattern occurred only in benign nodules (70 patients) and in 1 patient each with a lymphoma, a metastasis of a renal cell cancer and a metastasis of a gastric adenocarcinoma. Therapy with levothyroxine and/or iodine was administered to 129 patients (43%) and was significantly inversely correlated with nodule growth (odds ratio 0.27; CI 95 % 0.14-0.53, p < 0.001). CONCLUSIONS: Thyroid nodule growth alone and especially a rapid growth pattern during follow-up for thyroid nodular disease is not a marker for well-differentiated thyroid cancer and should not be used as a stand-alone argument for thyroid surgery.

Preoperative assessment of peritoneal carcinomatosis: intraindividual comparison of 18F-FDG PET/CT and MRI.

OBJECTIVE: Exact determination of localization and extent of peritoneal carcinomatosis (PC) before peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC) is crucial for the clinical outcome. Our study compares dynamic contrast enhanced 3D MRI (T1wDCE) and 18F-FDG PET/CT regarding diagnostic accuracy in correlation with surgical exploration (SE) and histological (HI) results. MATERIALS AND METHODS: 15 patients with PC were examined on a 1.5T MRI and 16 slice PET/CT. MRI: coronal T1wDCE covering the complete abdomen (0.15 mmol Gd-chelate/kg BW, 2000 mL mannitol solution p.o., 40 mg buscopan i.v.). PET-CT: contrast enhanced 16slice CT (120 mL ultravist 370 i.v., 1000 mL mannitol solution p.o., 40 mg buscopan i.v.), PET: 350 MBq 18-FDG i.v., 3 min acquisition time/bed, 60 min after tracer injektion). Assessment by two independent, experienced observers in correlation with results of SE and HI for each abdominal segment based on the peritoneal cancer index (PCI) proposed by Sugarbaker and co-authors. RESULTS: MRI and PET/CT provided reliable detection of PC. One patient had to be excluded from statistical analysis. In summary, 182 segments were assessed (13/patient, 14 patients, one patient excluded from statistical analysis). PC was found in 118 by MRI, 124 by PET/CT. 4 segments were classified false positive for MRI, 2 for PET/CT. False negative segments (MRI: 17, PET/CT: 9) did not result in irresectability. Positive predictive value for PC/segment was 97/98%, negative predictive value 73/84%, sensitivity 87/93%, specificity 92/96%, and diagnostic accuracy 88/94% (MRI/PET/CT). CONCLUSION: With high diagnostic accuracy for PC of both, MRI and PET/CT, PET/CT provides better diagnostic accuracy and especially better NPV.

Peritoneal carcinomatosis: comparison of dynamic contrast-enhanced magnetic resonance imaging with surgical and histopathologic findings.

OBJECTIVE: In patients with peritoneal carcinomatosis (PC) accurate preoperative assessment is essential to determine indication and surgical procedure to ensure optimal outcome. Purpose of our study was to assess the diagnostic accuracy (DA) of multiphasic dynamic contrast-enhanced MRI to determine the extent of PC in correlation with surgical and histopathological findings. MATERIALS AND METHODS: 14 Patients with proven PC were examined on a 1.5T system before peritonectomy and hyperthermic intraperitoneal chemotherapy. Patient preparation included oral application of 2000 mL mannitol solution and 40 mg butylscopolaminiumbromid i.v. Coronal contrast-enhanced multiphasic dynamic T1w 3D gre sequences (T1W DCE) (0.15 mmol Gd-chelate/kg bw) covering the whole abdomen were acquired (TR 2.9 ms, TE 1.1 ms, resolution 2.0 × 2.0 × 1.8 mm, FOV 400 × 400 mm). MRI was assessed by two radiologists and correlated with surgical exploration (SE) and histopathology for each segment based on the peritoneal cancer index proposed by Sugarbaker et al. RESULTS: In total, 182 segments were evaluated. PC was found in 118/121 of 182 segments (reader 1/2) by MRI and in 131 segments by SE. In 4/7 segments MRI was false positive. False negative segments 17/17 in MRI did not result in irresectability. The positive predictive value for PC per segment of MRI was 97%/94%, the negative predictive value 73%/72%, the sensitivity 87%/87% and the specificity 92%/86%. The DA was 88%/87%. CONCLUSION: T1W DCE is an accurate and clinical valuable tool for the preoperative assessment of peritoneal tumor spread.

Circadian expression of clock- and tumor suppressor genes in human oral mucosa.

PURPOSE: Circadian rhythms are daily oscillations of multiple biological processes driven by endogenous clocks. Imbalance of these rhythms has been associated with cancerogenesis in humans. To further elucidate the role circadian clocks have in cellular growth control, tumor suppression and cancer treatment, it is revealing to know how clock genes and clock-controlled genes are regulated in healthy humans. MATERIALS AND METHODS: Therefore comparative microarray analyses were conducted investigating the relative mRNA expression of clock genes throughout a 24-hour period in cell samples obtained from oral mucosa of eight healthy diurnally active male study participants. Differentially expressed selected genes of interest were additionally evaluated using qRT-PCR. RESULTS: Microarray analysis revealed 33 significant differentially regulated clock genes and clock- controlled genes, throughout a one day period (6.00h, 12.00h, 18.00h, 24.00h). Hereof were 16 clock genes and 17 clock- controlled genes including tumor suppressor- and oncogenes. qRT-PCR of selected genes of interest, such as hPER2, hCRY1, hBMAL1, hCCRN4L and hSMAD5 revealed significant circadian regulations. CONCLUSION: Our study revealed a proper circadian regulation profile of several clock- and tumor suppressor genes at defined points in time in the participants studied. These findings could provide important information regarding genes displaying the same expression profile in the gastrointestinal tract amounting to a physiological expression profile of healthy humans. In the future asynchronous regulations of those genes might be an additional assistant method to detect derivations distinguishing normal from malignant tissue or assessing risk factors for cancer.

Postoperative complications have little influence on long-term quality of life in Crohn's patients.

PURPOSE: The purpose of the study was to determine the influence of postoperative complications on long-term quality of life in patients after abdominal operations for Crohn's disease. MATERIALS AND METHODS: From 1996 to 2002, 305 Crohn's patients underwent abdominal surgery, and 66 patients developed postoperative complications. Quality of life was studied using a standardized questionnaire and four quality of life instruments. Sixty-six Crohn's patients with uneventful postoperative course matched for age, and follow-up time served as controls. RESULTS: Forty-eight patients (81%) in the complication group (32 major and 16 minor) and 43 patients (75%) in the control group answered the questionnaire. Postoperative follow-up time was 42 (10-94) and 41 months (13-94; median (range)). Quality of life was comparable between groups, except on the subscale "physical functioning" of the Short-form 36 on which patients with minor and major complications showed impaired quality of life compared to controls (67+/-6, 69+/-4, and 84+/-2%; mean+/-standard error of the mean; both p<0.05 vs controls). The incidence of Crohn's disease-related symptoms at follow-up was unaffected by complications (minor 63%, major 56% vs controls 70%; both not significant). CONCLUSION: Postoperative complications after abdominal operations for Crohn's disease do not impair long-term quality of life in general but may affect specific dimensions of quality of life like patients' physical function.

Long-term quality of life in patients with Crohn's disease and perianal fistulas: influence of fecal diversion.

PURPOSE: Symptomatic perianal fistulas impair quality of life in patients with Crohn's disease. Fecal diversion improves symptoms but may impair quality of life. This study was designed to compare long-term quality of life in patients with Crohn's disease with symptomatic perianal fistulas who were treated with or without fecal diversion. METHODS: From 1996 to 2002, perianal fistulas were treated in 116 patients with Crohn's disease. A questionnaire, including four quality of life instruments, was mailed to each patient (Short-Form General Health Survey, Gastrointestinal Quality of Life Index, Cleveland Global Quality of Life Score, Short Inflammatory Bowel Disease Questionnaire). RESULTS: Questionnaires were returned by 77 of 116 patients (66 percent). Thirty-four of these patients had undergone fecal diversion, whereas 43 had not. Median follow-up was 49 (range, 18-97) months in diverted and 44 (range, 14-98) months in undiverted patients (not significant). In the diverted group, 44 percent complained of Crohn's disease-related symptoms, which was less compared with 79 percent in undiverted patients (P < 0.05). Diverted patients achieved 68 +/- 1 percent of the maximum possible score on the Gastrointestinal Quality of Life Index compared with 60 +/- 2 percent in undiverted patients (mean +/- standard error of the mean; P < 0.001); diverted patients scored better on the subscale "gastrointestinal symptoms" of the Gastrointestinal Quality of Life Index (81 +/- 1 percent vs. 67 +/- 2 percent; P < 0.001). There was no difference in the Short Inflammatory Bowel Disease Questionnaire between diverted and undiverted patients except for the subscale "bowel function" (91 +/- 2 percent vs. 76 +/- 2 percent; P < 0.0001). No difference in quality of life was detected by the Short-Form General Health Survey and Cleveland Global Quality of Life Score. CONCLUSIONS: In the investigated population of patients with Crohn's disease, quality of life seems to be similar or potentially superior in diverted patients suffering from perianal fistulas compared with undiverted patients. A diverting stoma, therefore, may improve quality of life in patients with severe perianal Crohn's disease.

Sentinel lymph node biopsy in colon cancer: a prospective multicenter trial.

INTRODUCTION: The clinical impact of sentinel lymph node biopsy (SLNB) in colon cancer is still controversial. The purpose of this prospective multicenter trial was to evaluate its clinical value to predict the nodal status and identify factors that influence these results. METHODS: Colon cancer patients without prior colorectal surgery or irradiation were eligible. The sentinel lymph node (SLN) was identified intraoperatively by subserosal blue dye injection around the tumor. The SLN underwent step sections and immunohistochemistry (IHC), if classified free of metastases after routine hematoxylin and eosin examination. RESULTS: At least one SLN (median, n = 2) was identified in 268 of 315 enrolled patients (detection rate, 85%). Center experience, lymphovascular invasion, body mass index (BMI), and learning curve were positively associated with the detection rate. The false-negative rate to identify pN+ patients by SLNB was 46% (38 of 82). BMI showed a significant association to the false-negative rate (P < 0.0001), the number of tumor-involved lymph nodes was inversely associated. If only slim patients (BMI < or =24) were investigated in experienced centers (>22 patients enrolled), the sensitivity increased to 88% (14 of 16). Moreover, 21% (30 of 141) of the patients, classified as pN0 by routine histopathology, revealed micrometastases or isolated tumor cells (MM/ITC) in the SLN. CONCLUSIONS: The contribution of SLNB to conventional nodal staging of colon cancer patients is still unspecified. Technical problems have to be resolved before a definite conclusion can be drawn in this regard. However, SLNB identifies about one fourth of stage II patients to reveal MM/ITC in lymph nodes. Further studies must clarify the clinical impact of these findings in terms of prognosis and the indication of adjuvant therapy.

Postoperative colonic motility after tropisetron and a standardized meal in patients undergoing conventional colorectal surgery.

BACKGROUND: Early postoperative enteral nutrition is advantageous for the recovery of colonic motility but may be limited by abdominal distension, nausea, and vomiting. We aimed to investigate the tolerance of a standardized meal after pretreatment with the 5-hydroxytryptamine-3-receptor antagonist tropisetron and to study the concomitant colonic motility. METHODS: Colonic motility and tone were recorded on postoperative day 1 to 3 with a combined manometry/barostat recording catheter in 12 patients who underwent open colorectal surgery with an anastomosis in the distal colon or rectum. The study protocol consisted of 30 min of baseline recordings followed by 5 mg of tropisetron intravenously. Then, motility was recorded for another 30 min before patients ingested a standardized meal to trigger the gastrocolonic response. Postprandial motility was recorded for the subsequent 60 min. RESULTS: The colonic motility index increased after administration of tropisetron on all three postoperative days (day 1: 34+/-11 vs 122+/-48, day 2: 55+/-19 vs 101+/-25, and day 3: 42+/-16 vs 93+/-33 mmHg/min; p<0.05). No further increase of the motility index was observed postprandially. Frequency and amplitude of contractions were virtually unaffected by tropisetron and the meal. Barostat bag volume decreased postprandially in the proximal bag on the third, and in the distal bag on the first and second postoperative day (p<0.05). Patients' condition was unaffected by the standardized meal after tropisetron administration. CONCLUSIONS: Tropisetron may enhance colonic motility in the early postoperative period; however, the gastrocolonic response was impaired thereafter. High caloric food intake is well tolerated early after surgery after tropisetron pretreatment.