Meta-analysis of outcomes following resection of the primary tumour in patients presenting with metastatic colorectal cancer.

BACKGROUND: It is not clear whether resection of the primary tumour (when there are metastases) alters survival and/or whether resection is associated with increased morbidity. This systematic review and meta-analysis assessed the prognostic value of primary tumour resection in patients presenting with metastatic colorectal cancer. METHODS: A systematic review of MEDLINE/PubMed was performed on 12 March 2016, with no language or date restrictions, for studies comparing primary tumour resection versus conservative treatment without primary tumour resection for metastatic colorectal cancer. The quality of the studies was assessed using the MINORS and STROBE criteria. Differences in survival, morbidity and mortality between groups were estimated using random-effects meta-analysis. RESULTS: Of 37 412 initially screened articles, 56 retrospective studies with 148 151 patients met the inclusion criteria. Primary tumour resection led to an improvement in overall survival of 7·76 (95 per cent c.i. 5·96 to 9·56) months (risk ratio (RR) for overall survival 0·50, 95 per cent c.i. 0·47 to 0·53), but did not significantly reduce the risk of obstruction (RR 0·50, 95 per cent c.i. 0·16 to 1·53) or bleeding (RR 1·19, 0·48 to 2·97). Neither was the morbidity risk altered (RR 1·14, 0·77 to 1·68). Heterogeneity between the studies was high, with a calculated I2 of more than 50 per cent for most outcomes. CONCLUSION: Primary tumour resection may provide a modest survival advantage in patients presenting with metastatic colorectal cancer.

[Delayed complications after pancreatic surgery: Pancreatic insufficiency, malabsorption syndrome, pancreoprivic diabetes mellitus and pseudocysts]. / Spätkomplikationen nach Pankreaseingriffen : Pankreasinsuffizienz, Malabsorptionssyndrom, pankreopriver Diabetes mellitus, Pseudozysten.

BACKGROUND: Benign and malignant pathologies of the pancreas can result in a relevant chronic disease burden. This is aggravated by morbidities resulting from surgical resections as well as from progression of the underlying condition. OBJECTIVE: The aim was to summarize the current evidence regarding epidemiology, pathophysiology, diagnosis and treatment of endocrine and exocrine pancreatic insufficiency, as well as of pancreatic pseudocysts. MATERIAL AND METHODS: A selective literature search was performed and a summary of the currently available data on the surgical sequelae after pancreatic resection is given. RESULTS: Reduction of healthy pancreatic parenchyma down to 10-15 % leads to exocrine insufficiency with malabsorption and gastrointestinal complaints. Orally substituted pancreatic enzymes are the therapy of choice. Loss of pancreatic islets and/or islet function leads to endocrine insufficiency and pancreoprivic diabetes mellitus. Inflammatory, traumatic and iatrogenic injuries of the pancreas can lead to pancreatic pseudocysts, which require endoscopic, interventional or surgical drainage if symptomatic. Finally, pancreatic surgery harbors the long-term risk of gastrointestinal anastomotic ulcers, bile duct stenosis, portal vein thrombosis and chronic pain syndrome. CONCLUSION: As the evidence is limited, an interdisciplinary and individually tailored approach for delayed pancreatic morbidity is recommended.

Strategies to improve the outcome in locally advanced pancreatic cancer.

Pancreatic cancer is associated with the worst prognosis of all gastrointestinal malignancies. The major reasons for the dismal outcome are late diagnosis due to unspecific symptoms and aggressive tumor biology. Although highly effective chemotherapeutic options have emerged within the last decade, radical resection offers the only chance of cure. Only 10-20% of patients are resectable at presentation, and 30-40% present with borderline resectable or locally advanced/unresectable tumors. Even if resectable, the 5-year-survival rate after complete resections remains unsatisfactory, with less than 25%. This article gives an overview on current therapy standards as well as on new approaches especially for locally advanced tumors and outlines the importance of ongoing research to improve prognosis.

Could hyponatremia be a marker of anastomotic leakage after colorectal surgery? A single center analysis of 1,106 patients over 5 years.

PURPOSE: The aim of this study is to define the significance of hyponatremia as a marker of anastomotic leakage after colorectal surgery. METHODS: All anastomoses in colorectal surgery performed at a single institution between July 2007 and July 2012 (n = 1,106) were retrospectively identified. Serum sodium levels and leukocyte values measured when an anastomotic leak was diagnosed by CT scan and/or surgical reintervention (n = 81) were compared to the values preferably on postoperative day 5 in the absence of an anastomotic leak (n = 1,025). RESULTS: The leak rate in anastomoses of the rectum was 9.0 %, while the leak rate of the other anastomoses was 5.4 %. Mean serum sodium level was 138.8 mmol/l in the group with an anastomotic leak and 140.5 mmol/l in the group without. Hyponatremia (<136 mmol/l) was present in 23 % of patients in the group with an anastomotic leak and in 15 % in the group without (p < 0.001). In multivariate analysis, leukocytes and serum sodium level remained as significant markers of an anastomotic leak. As a marker of an anastomotic leak, hyponatremia had a specificity of 93 % and a sensitivity of 23 %, while the presence of either leukocytosis or hyponatremia had a sensitivity of 68 %, a specificity of 75 %, a positive predictive value of 18 %, and a negative predictive value of 97 %. CONCLUSIONS: Hyponatremia could be a specific and relevant marker of anastomotic leakage after colorectal surgery. If hyponatremia and leukocytosis are present after colorectal surgery, anastomotic leakage should be suspected and a CT scan with rectal contrast dye is recommended.

Molecular staging of lymph node-negative colon carcinomas by one-step nucleic acid amplification (OSNA) results in upstaging of a quarter of patients in a prospective, European, multicentre study.

BACKGROUND: Current histopathological staging procedures in colon carcinomas depend on midline division of the lymph nodes with one section of haematoxylin & eosin (H&E) staining only. By this method, tumour deposits outside this transection line may be missed and could lead to understaging of a high-risk group of stage UICC II cases, which recurs in ∼20% of cases. A new diagnostic semiautomated system, one-step nucleic acid amplification (OSNA), detects cytokeratin (CK) 19 mRNA in lymph node metastases and enables the investigation of the whole lymph node. The objective of this study was to assess whether histopathological pN0 patients can be upstaged to stage UICC III by OSNA. METHODS: Lymph nodes from patients who were classified as lymph node negative after standard histopathology (single (H&E) slice) were subjected to OSNA. A result revealing a CK19 mRNA copy number >250, which makes sure to detect mainly macrometastases and not isolated tumour cells (ITC) or micrometastases only, was regarded as positive for lymph node metastases based on previous threshold investigations. RESULTS: In total, 1594 pN0 lymph nodes from 103 colon carcinomas (median number of lymph nodes per patient: 14, range: 1-46) were analysed with OSNA. Out of 103 pN0 patients, 26 had OSNA-positive lymph nodes, resulting in an upstaging rate of 25.2%. Among these were 6/37 (16.2%) stage UICC I and 20/66 (30.3%) stage UICC II patients. Overall, 38 lymph nodes were OSNA positive: 19 patients had one, 3 had two, 3 had three, and 1 patient had four OSNA-positive lymph nodes. CONCLUSIONS: OSNA resulted in an upstaging of over 25% of initially histopathologically lymph node-negative patients. OSNA is a standardised, observer-independent technique, allowing the analysis of the whole lymph node. Therefore, sampling bias due to missing investigation of certain lymph node tissue can be avoided, which may lead to a more accurate staging.

Activation of the PI3K/AKT pathway correlates with prognosis in stage II colon cancer.

BACKGROUND: Patients with UICC/AJCC stage II colon cancer have a high 5-year overall survival rate after surgery. Nevertheless, a significant subgroup of patients develops tumour recurrence. Currently, there are no clinically established biomarkers available to identify this patient group. We applied reverse-phase protein arrays (RPPA) for phosphatidylinositide-3-kinase pathway activation mapping to stratify patients according to their risk of tumour recurrence after surgery. METHODS: Full-length proteins were extracted from formalin-fixed, paraffin-embedded tissue samples of 118 patients who underwent curative resection. RPPA technology was used to analyse expression and/or phosphorylation levels of six major factors of the phosphatidylinositide-3-kinase pathway. Oncogenic mutations of KRAS and BRAF, and DNA microsatellite status, currently discussed as prognostic markers, were analysed in parallel. RESULTS: Expression of phospho-AKT (HR=3.52; P=0.032), S6RP (HR=6.3; P=0.044), and phospho-4E-BP1 (HR=4.12; P=0.011) were prognostic factors for disease-free survival. None of the molecular genetic alterations were significantly associated with prognosis. CONCLUSIONS: Our data indicate that activation of the PI3K/AKT pathway evidenced on the protein level might be a valuable prognostic marker to stratify patients for their risk of tumour recurrence. Beside adjuvant chemotherapy targeting of upregulated PI3K/AKT signalling may be an attractive strategy for treatment of high-risk patients.

Specific activity of cyclin-dependent kinase I is a new potential predictor of tumour recurrence in stage II colon cancer.

BACKGROUND: There are no established biomarkers to identify tumour recurrence in stage II colon cancer. As shown previously, the enzymatic activity of the cyclin-dependent kinases 1 and 2 (CDK1 and CDK2) predicts outcome in breast cancer. Therefore, we investigated whether CDK activity identifies tumour recurrence in colon cancer. METHODS: In all, 254 patients with completely resected (R0) UICC stage II colon cancer were analysed retrospectively from two independent cohorts from Munich (Germany) and Leiden (Netherlands). None of the patients received adjuvant treatment. Development of distant metastasis was observed in 27 patients (median follow-up: 86 months). Protein expression and activity of CDKs were measured on fresh-frozen tumour samples. RESULTS: Specific activity (SA) of CDK1 (CDK1SA), but not CDK2, significantly predicted distant metastasis (concordance index=0.69, 95% confidence interval (CI): 0.55-0.79, P=0.036). Cutoff derivation by maximum log-rank statistics yielded a threshold of CDK1SA at 11 (SA units, P=0.029). Accordingly, 59% of patients were classified as high-risk (CDK1SA ≥11). Cox proportional hazard analysis revealed CDK1SA as independent prognostic variable (hazard ratio=6.2, 95% CI: 1.44-26.9, P=0.012). Moreover, CKD1SA was significantly elevated in microsatellite-stable tumours. CONCLUSION: Specific activity of CDK1 is a promising biomarker for metastasis risk in stage II colon cancer.

Penile and scrotal swelling in Crohn's disease: a case report.

Penile and scrotal swelling considered as metastatic Crohn's disease is described in a 23 years-old-man. Clinical features and therapeutic options of this rare manifeatation are reviewed.

[Changes in insulin-glucose quotients in a glucose tolerance test in the third trimester]. / Veränderungen der Insulin-Glukose-Quotienten während eines Glukosetoleranztests im III. Trimenon.

OBJECTIVE: In comparison a higher insulin-glucose-index is usually associated with an increased insulin resistance. In the present study changes in insulin-glucose-indices were examined in relation to a defined glucose tolerance in the last trimester of pregnancy. MATERIAL AND METHODS: 249 pregnant women were challenged with a 75 gm oral glucose tolerance test (oGTT). Serum samples for glucose (glucose-dehydrogenase-method) and insulin measurements (RIA) were drawn before and at 30, 60, 120, and 180 minutes after glucose load during oGTT. Patients were assigned to five groups with increasing glucose intolerance according to maximal glucose levels during the test. RESULTS: There were no significant differences in insulin-glucose-indices prior to glucose load. Pregnant women with gestational diabetes were shown to have significantly lower insulin-glucose-indices in the early and intermediate phase of the challenge test while the indices were higher in the final phase of the test. CONCLUSIONS: Women with gestational diabetes demonstrated an initial delay in insulin secretion in combination with a higher insulin-glucose-index, corresponding to an increased insulin resistance, only in the end of the test. These characteristics may possibly be a cause of the observed disorder in glucose metabolism in these patients.

Privacy and efficiency in patients focused health care processes.

Today's health care industry is striving to achieve the development and deployment of computer-based patient records for improvements in health care quality, cost, and access. This rapidly increasing use of computer techniques in the field of medicine and health care has created an urgent need for the dissemination of information on data protection. We present in this paper a workflow-based approach to ensure privacy and efficiency in clinical information systems and discuss the presented solution according to its practicability in daily clinical use.

[Rate of early abortion after in vitro fertilization and embryo transfer]. / Frühstabortrate nach In-vitro-Fertilisation und Embryotransfer.

The high rate of implantation failures in infertile patients after in vitro fertilization must be regarded as the major problem of the kind of treatment. Usually, no information on the development of the embryo can be obtained for the time between embryo replacement and rising beta-hCG levels. Own studies on the early pregnancy factor (EPF) showed a positive reaction few hours following the contact of a fertilized oocyte with the endometrial surface. Therefore, we used the EPF as a marker for the viability of the embryo in 82 patients after in vitro fertilization and embryo transfer. Within two days after embryo transfer the EPF was positive in 52 (63%) patients and negative in 30 (37%) patients. In these women the embryos may have been lost during handling or may have discontinued further development. Between day 3 and day 12 after transfer the EPF turned to negative values in 35 patients--especially between day 6 and 10. These cases must be regarded as true implantation failures. After day 12 following embryo transfer, rising beta-hCG levels could be measured in 17 women (21%), but only in 12 patients (15%) could a growing embryonic sac be detected by ultrasound. From these figures, we may conclude, that about half of the embryos are lost already during the step of embryo transfer and the other half during implantation. Therefore, more attention should be given to the handling of the embryos to increase the pregnancy rate after in vitro fertilization.