Jörg Tschmelitsch

Risk factors for anastomotic leakage after resection for rectal cancer

BACKGROUND Controversy still exists concerning the impact of patient and tumor characteristics on anastomotic dehiscence after resection for rectal cancer. METHODS Between January 1986 and July 2006, 472 patients underwent curative rectal resection. Patient and tumor characteristics, details of treatment, and postoperative results were recorded prospectively. Univariate and multivariate analysis were applied to identify risk factors for anastomotic leakage. RESULTS In our patients, the anastomotic leak rate was 10.4% (49 of 472 patients), and mortality was 2.2% (1 of 49 patients). In univariate analysis, tumor diameter and absence of a protective stoma were associated with increased anastomotic leak rate, whereas American Society of Anesthesiologists (ASA) score and tumor localization showed borderline significance. In multivariate analysis, tumor diameter, tumor localization, and absence of a protective stoma were significantly associated with anastomotic leakage. CONCLUSIONS Patients with large and low lying rectal tumors are at high risk for anastomotic leakage. A protective stoma significantly decreases the rate of clinical leaks and subsequent reoperation after low anterior resection.

Predictive Value of Urinary Neopterin in Patients with Lung Cancer

Concentrations of neopterin, which is produced by human monocytes/macrophages when stimulated by gamma-interferon, were measured in urine specimens from 72 patients with lung cancer at diagnosis. Other routine clinical and laboratory variables were concomitantly determined. Neither neopterin nor any other laboratory variable studied showed a significant correlation with clinical indicators of the disease (morphologic type, tumour stage, grading, lymph node status, presence of distant metastases). The cancer patients were followed up for up to 10 years, and the abilities of all variable to predict fatal outcome were assessed. In univariate survival analyses, all clinical indicators except morphologic type (P = 0.86) were significant predictors of survival (P < 0.002), but of all the laboratory variables studies, only neopterin was significantly predictive (P = 0.0013). By multivariate survival analysis, a combination of four variables was found to jointly predict survival: lymph node status (P = 0.003), multivariate model), tumour stage (P = 0.0006), grading (P = 0.0047) and neopterin (P = 0.0047). The data suggest that certain aspects of immune activation may have adverse consequences for the prognosis of patients with lung cancer.

Impact of postoperative complications on long-term survival after resection for rectal cancer.

BACKGROUND: The relevance of type and severity of postoperative complications after curative resection for rectal cancer on survival and recurrence rates is a matter of controversy. OBJECTIVE: The aim of this study was to investigate the impact of postoperative complications on long-term outcome after resection for rectal cancer. DESIGN: This study is a retrospective analysis of prospectively collected data. SETTINGS: The study was conducted at a university teaching hospital by a specialized colorectal team. PATIENTS: Between January 1984 and October 2008, 811 patients with rectal cancer underwent curative resection. Patients who experienced postoperative complications were divided into a minor complication group (grades I and II) and a major complications group (grades III and IV) according to the Clavien classification. MAIN OUTCOME MEASURES: The influence of several pathological and clinical factors, including complications in terms of overall and disease-free survival, was tested and compared in univariate and multivariate analyses. RESULTS: Curative resection was performed in 811 patients; median age was 65 years. The Kaplan-Meier estimates (± SE) for 5- and 10-year overall cumulative survival were 70.3% ± 1.8% and 54.5% ± 2.4%; Kaplan-Meier estimates for 5- and 10-year disease-free survival were 64.0% ± 1.8% and 50.9% ± 2.3%. One hundred sixty-five patients (20.3%) had minor complications, and 103 patients (12.7%) had major complications. Twelve patients (1.48%) died within 30 days after surgery. There was no significant difference between patients with no complications, patients with minor complications, and patients with major complications in terms of overall (p = 0.41) or disease-free survival (p = 0.32). LIMITATIONS: A possible limitation of our study is that the data represent a cohort study from a single center. CONCLUSION: Following resection for rectal cancer, the severity of postoperative complications (minor or major) according to a standardized classification system does not demonstrate a statistically significant effect on either overall or disease-free survival.

Survival and local recurrence after anterior resection and abdominoperineal excision for rectal cancer

The aim of this retrospective study is to compare the outcome of abdominoperineal excision (APE) and anterior resection (AR) for rectal cancer in 136 patients. Local recurrence rates and 5-year survival probabilities were estimated for the AR and APE group. Further comparisons were carried out between hand-sewn and stapled anastomoses after AR, and between patients after AR and APE for tumours 2 to 6 cm from the dentate line. Local recurrence after AR occurred in 14% and after APE in 10% of these cases. Five-year survival probabilities and local recurrence frequencies showed no statistically significant difference (P > 0.05). Local recurrence rates were 13.5% after hand-sewn anastomoses and 15% after the stapled procedure. No statistically significant difference was observed in the 5-year survival and recurrence rate (P > 0.05). Seventy-four of 136 patients had tumours located 2 to 6 cm from the dentata line. Local recurrence occurred in 21% after AR and 5% after APE, showing a statistically significant difference in frequency (P < 0.05). No significant difference was found in cumulative 5-year survival probabilities. APE for advanced low rectal cancer showed a significant reduction in local recurrences compared to AR.

TP53 Mutational Status and Prediction of Benefit from Adjuvant 5-Fluorouracil in Stage III Colon Cancer Patients.

We investigated the hypothesis that the varying treatment efficacy of adjuvant 5-fluorouracil (5FU) in stage III colon cancer is linked to the TP53 mutational status. ABCSG-90 was a prospective randomized trial in which effect of adjuvant 5FU was studied in stage III colon cancer patients. Tumor material of 70% of these patients (389/572) was available for analysis of the biomarker TP53 using a TP53-gene-specific Sanger sequencing protocol. Median follow-up was 88 months. TP53 mutation frequency was 33%. A significant interaction between TP53 status, outcomes and nodal category was found (P = 0.0095). In the N1 category, TP53 wildtype patients had significantly better overall survival than TP53 mutated (81.0% vs. 62.0% overall survival at 5 years; HR = 2.131; 95% CI: 1.344–3.378; P = 0.0010). In the N2 category, the TP53 status did not affect survival (P = 0.4992). In TP53 wildtype patients, the prognostic significance of N category was significantly enhanced (P = 0.0002). In TP53 mutated patients, survival curves of N1 and N2 patients overlapped and nodal category was no longer prognostic. The biomarker TP53 independently predicted effect of adjuvant 5FU in N1 colon cancer patients. TP53 was not predictive in N2 patients, in whom 5FU is known to have no effect.

In vivo Release of Vascular Endothelial Growth Factor from Colorectal Carcinomas

The formation of new blood vessels is essential for the growth of malignant tumors and their hematogenic spread. Tumor-induced neoangiogenesis occurs through sprouting of preexisting vessels. An alternative mechanism might be the recruitment of bone marrow-derived endothelial cells, or their precursors, to the tumor site by the release of vascular endothelial growth factor (VEGF) from cancer cells, i.e., tumor-induced postnatal vasculogenesis. To investigate if a significant amount of VEGF is released from malignant tumors in vivo, thus potentially mobilizing endothelial precursor cells (EPC) from the bone marrow, we measured plasma levels of soluble VEGF obtained from tumor-draining mesenteric veins (VEGF-M) during surgery and, simultaneously, in venous blood obtained distant from the tumor (VEGF-P). This analysis was performed in 29 patients with colorectal carcinoma. VEGF-M levels were substantially higher in patients with distant metastases (208 ± 61 pg/ml) compared to patients with nonmetastatic disease (99 ± 72 pg/ml, p = 0.003). Also, in patients with aggressive disease, i.e., histologically undifferentiated (G3) tumors, higher levels of VEGF-M were measured than in patients with tumors of lower histologic grading (196 ± 46 vs. 107 ± 80 pg/ml, p = 0.01). In conclusion, the release of significant amounts of soluble VEGF in vivo from clinically and/or histologically aggressive tumors might reflect their high angiogenic or vasculogenic potential, probably leading to the recruitment of EPC from the bone marrow.

Diverting ileostomy versus no diversion after low anterior resection for rectal cancer: A prospective, randomized, multicenter trial

BACKGROUND This study sought to determine whether a protective diverting ileostomy improves short-term outcomes in patients with rectal resection and colonic J-pouch reconstruction for low anastomoses. Criteria for the use of a proximal stoma in rectal resections with colonic J-pouch reconstruction have not been defined sufficiently. METHODS In a multicenter prospective study, rectal cancer patients with anastomoses below 8 cm treated with low anterior resection and colonic J-pouch were randomized to a defunctioning loop ileostomy or no ileostomy. The primary study endpoint was the rate of anastomotic leakage, and the secondary endpoints were surgical complications related to primary surgery, stoma, or stoma closure. RESULTS From 2004 to 2014, a total of 166 patients were randomized to 1 of the 2 study groups. In the intention-to-treat analysis, the overall leakage rate was 5.8% in the stoma group and 16.3% in the no stoma group (P = .0441). However, some patients were not treated according to randomization and only 70% of our patients with low anastomoses received a pouch. Therefore, we performed a second analysis as to actual treatment. In this analysis, as well, leakage rates (P = .044) and reoperation rates for leakage (P = .021) were significantly higher in patients without a stoma. In multivariate analysis, male gender (P = .0267) and the absence of a stoma (P = .0092) were significantly associated with anastomotic leakage. CONCLUSION Defunctioning loop ileostomy should be fashioned in rectal cancer patients with anastomoses below 6 cm, particularly in male patients, even if reconstruction was done with a J-pouch.

Influence of body mass index on postoperative complications after rectal resection for carcinoma.

Objectives The influence of obesity on postoperative complications after various surgical interventions remains controversial. The aim of this study was to evaluate the impact of overweight and obesity on the occurrence of postoperative complications for patients undergoing elective resection for rectal carcinoma. Methods We conducted a retrospective data analysis of 676 patients undergoing surgical treatment for rectal carcinoma. Depending on their body mass index (BMI), patients were grouped as follows: group I, patients up to BMI 24.9 kg/m2; group II patients, with a BMI between 25 and 29.9 kg/m2; and group III, all patients with a BMI >30 kg/m2. Complications were classified as minor and major with regard to severity grades (1–5). Statistical analysis was performed to evaluate the difference in complication rates between the different BMI groups. Results A total of 444 patients were included for analysis. Overall, 300 (67.6%) of the 444 patients did not develop postoperative complications, 82 (18.4%) patients had minor complications (grade 1 + 2), and 56 patients (12.6%) had major (grade 3 + 4) complications. Six (1.4%) patients died (grade 5). The Fisher exact test indicated no statistically significant difference of complication rates between the different BMI groups (P = 0.3716). Conclusions Compared with nonobese or normal-weight patients, obese patients do not have a statistically significant higher risk of developing postoperative complications after rectal resection for carcinoma.

Ileocecal intussusception caused by lung cancer metastasis.

ZusammenfassungDie Invagination von Darmabschnitten stellt im Erwachsenenalter ein seltenes Krankheitsbild dar. Der distale Dünndarm und der Dickdarm sind am häufigsten betroffen. Wir berichten über eine 65-jährige Patientin mit bekanntem nichtkleinzelligem Lungenkarzinom mit akutem Abdomen und ileusartigem Beschwerdebild. Die Computertomographie des Abdomens zeigte das Bild einer ileozökalen Invagination. Es erfolgte eine rechtsseitige Hemikolektomie mit histopathologischem Nachweis einer Metastase des Lungenkarzinoms als Ursache der Invagination. Die klassische Trias krampfartiger abdomineller Schmerzen, blutiger Diarrhö und einer tastbaren Resistenz, die bei Kindern in der Mehrzahl der Fälle beobachtet werden kann, ist bei Erwachsenen selten. Das Beschwerdebild ist nicht selten unspezifisch. Wegen der großen Zahl ursächlicher struktureller Veränderungen ist bei Erwachsenen mit Invagination eine chirurgische Versorgung anzustreben. Bei kolischer und ileokolischer Invagination besteht in der Mehrzahl der Fälle eine maligne Grunderkrankung, weshalb eine radikale onkologische Operation durchgeführt werden sollte. Bei Dünndarminvagination ist in den meisten Fällen eine Segmentresektion ausreichend.SummaryIntussusception is a rare clinical finding in adults. Most cases occur in the distal small bowel or large intestine. We report the case of a 65-year-old woman with known non-small-cell lung cancer (NSCLC) who presented with acute abdomen and ileus-like symptoms. Abdominal computed tomography suggested ileocecal intussusception. The patient underwent right hemicolectomy and the histopathological workup showed ileal NSCLC metastasis as the lead lesion of intussusception. The classic triad of cramping abdominal pain, bloody diarrhea and a palpable tender mass, which is present in the majority of pediatric patients, is only infrequently observed in adults. Thus, symptoms are often nonspecific and the clinical presentation may be inconspicuous. Because of the large proportion of structural anomalies, adult intussusception requires definitive treatment, of which surgical resection is the treatment of choice. In patients with colocolonic or ileocolonic intussusception, malignancy should be considered and therefore en bloc resection rather than reduction is the recommended surgical technique, whereas cases of enteric intussusceptions may be reduced by limited resection of the small intestine.

Heterotopic pancreatic tissue in the cystic duct: complicating factor or coexisting pathology.

The case of a 75-year-old female suffering from recurrent abdominal pain and nausea is presented. Ultrasound showed gallstones without inflammation of the gallbladder. The patient underwent laparoscopic cholecystectomy and her symptoms resolved. Histological examination of the operation specimen disclosed heterotopic pancreatic tissue within the cystic duct. An accurate clinical diagnosis of pancreatic heterotopia is difficult. The deep submucosal or intramural location of the lesion may hamper retrieval of representative biopsy material. Indications for surgery or endoscopic resection include symptomatic lesions as well as cases of unclear histological examination in order to distinguish pancreatic heterotopia from other tumors.