Proximal gastrectomy and double-tract reconstruction vs total gastrectomy in gastric and gastro-esophageal junction cancer patients - a systematic review and meta-analysis protocol (PROSPERO registration number: CRD42021291500).

BACKGROUND: In Germany and Western Europe, gastroesophageal junction cancer (AEG) and proximal gastric cancer are currently treated with (transhiatal-extended) total gastrectomy (TG) according to the latest treatment guidelines. TG leads to a severe and long-lasting impairment of postoperative health-related quality of life (HRQoL) of the treated patients. Recent studies have suggested that HRQoL of these patients could be improved by proximal gastrectomy with double-tract reconstruction (PG-DTR) without compromising oncologic safety. Our aim is therefore to conduct a randomized controlled non-inferiority trial comparing PG-DTR with TG in AEG II/III and gastric cancer patients with overall survival as primary endpoint and HRQoL as key secondary endpoint. METHODS: This protocol is written with reference to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P 2015) statement. We will conduct searches in the electronic databases MEDLINE, Web of Science Core Collection, ScienceDirect, and Cochrane Library. We will also check references of relevant studies and perform a cited reference research. Titles and abstracts of the records identified by the searches will be screened, and full texts of all potentially relevant articles will be obtained. We will consider randomized trials and non-randomized studies. The selection of studies, data extraction, and assessment of risk of bias of the included studies will be conducted independently by two reviewers. Meta-analysis will be performed using RevMan 5.4 (Review Manager (RevMan) Version 5.4, The Cochrane Collaboration). DISCUSSION: This systematic review will identify the current study pool concerning the comparison of TG and PG-DTR and help to finally refine the research questions and to allow an evidence-based trial design of the planned multicenter randomized-controlled trial. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review. Study findings will be shared by publication in a peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021291500.

Systematic review and meta-analysis comparing proximal gastrectomy with double-tract-reconstruction and total gastrectomy in gastric and gastroesophageal junction cancer patients: Still no sufficient evidence for clinical decision-making.

BACKGROUND: To compare proximal gastrectomy with double-tract reconstruction and total gastrectomy in patients with gastroesophageal junction (AEG II-III) and gastric cancer. METHODS: We conducted systematic searches in Medline, Web of Science, and Cochrane Library until December 20, 2021 (PROSPERO registration number: CRD42021291500). Risk of bias was assessed using the revised Cochrane risk of bias tool and the ROBINS-I tool, as applicable. Evidence was rated by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: One randomized controlled trial (RCT) and 13 non-RCTs with 1,317 patients (715 patients with total gastrectomy and 602 patients with proximal gastrectomy with double-tract reconstruction) were included. Patients treated by total gastrectomy had a significantly higher proportion of advanced cancer stages International Union Against Cancer IB-III (odds ratio: 0.68, 95% confidence interval: 0.51-0.91, P = .01). This heterogeneity biases the observed improved overall survival of patients after proximal gastrectomy with double-tract reconstruction (odds ratio: 0.67, 95% confidence interval: 0.44-1.01, P = .05). Both procedures were comparably efficient regarding perioperative parameters. Postoperative/preoperative bodyweight ratio (mean difference: 3.56, 95% confidence interval: 1.32-5.79, P = .002), postoperative/preoperative serum-hemoglobin ratio (mean difference 3.73, 95% confidence interval: 1.59-5.88, P < .001), and postoperative serum vitamin B12 levels (mean difference 42.46, 95% confidence interval: 6.37-78.55, P = .02) were superior after proximal gastrectomy with double-tract reconstruction, while postoperative/preoperative serum-albumin ratio (mean difference 1.24, 95% confidence interval: -4.76 to 7.24, P = .69) and postoperative/preoperative serum total protein ratio (mean difference 1.12, 95% confidence interval: -2.77 to 5.00, P = .57) were not different. Health-related quality of life data were reported in only 2 studies, which found no significant advantages for proximal gastrectomy with double-tract reconstruction. CONCLUSION: Proximal gastrectomy with double-tract reconstruction offers advantages in postoperative nutritional parameters compared to total gastrectomy (GRADE: moderate quality of evidence). Oncological effectiveness of proximal gastrectomy with double-tract reconstruction cannot be assessed (GRADE: very low quality of evidence). Further thoroughly planned randomized controlled trials in Western patient cohorts are necessary to improve treatment for gastric cancer patients.

Clinical characteristics and outcome of patients with acute mesenteric ischemia: a retrospective cohort analysis.

BACKGROUND: Acute mesenteric ischemia (AMI) is an uncommon, but life-threatening clinical entity due to late diagnosis resulting in irreversible ischemic bowel necrosis. The most common causes of AMI are the embolic occlusion and the acute thrombosis of the mesenteric circulation. Typical treatment is composed of an early revascularization of the mesenteric circulation followed by abdominal surgery for resection of nonviable intestine and restoration of the intestinal continuity, but the mortality rates remain high. METHODS: A retrospective cohort analysis was conducted, aiming to evaluate clinical characteristics, performed surgical procedures and outcomes of patients with acute mesenteric ischemia who underwent emergency abdominal surgery at a high volume surgical center in Germany. RESULTS: Overall, 53 patients were identified with the intraoperatively proven diagnosis of AMI. Overall hospital mortality was with 62% comparable to the literature. Nineteen patients presented with an intraoperatively verified complete and non-reversible intestinal infarction without any angiographic or surgical option for a revascularization of the mesenteric circulation or an option for intestinal resection. From the rest of the patients, 14 underwent intestinal resection of the ischemic area without restoration of intestinal continuity; the other 20 underwent resection with a primary anastomosis to restore intestinal continuity. The mortality rate of these patients with curative-intended surgery remained high (41% of patients died). Pre- and postoperative hyperlactatemia were associated with lower survival of these patients. CONCLUSION: AMI remains a life-threatening abdominal emergency. Therapeutic approaches are highly depended on acting surgeon's decision, being affected by subjectively rated bowel viability and physical condition of the affected patient. Only selected patients with good bowel viability appear to be suitable for receiving primary anastomosis. The results clearly indicate the need for further research to develop therapeutic approaches for a better management of AMI and to improve outcome of affected patients.

Cytopathological Heterogeneity of Circulating Tumor Cells in Non-metastatic Esophageal Adenocarcinoma.

BACKGROUND/AIM: The presence of circulating tumor cells (CTC) has been reported to have an impact on prognosis in different tumor entities. Little is known about CTC morphology and heterogeneity. PATIENTS AND METHODS: In a multicenter setting, pre-therapeutic peripheral blood specimens were drawn from patients with non-metastatic esophageal adenocarcinoma (EAC). CTCs were captured by size-based filtration (ScreenCell®), subsequently Giemsa-stained and evaluated by two trained readers. The isolated cells were categorized in groups based on morphologic criteria. RESULTS: Small and large single CTCs, as well as CTC-clusters, were observed in 69.2% (n=81) of the 117 specimens; small CTCs were observed most frequently (59%; n=69), followed by large CTCs (40%; n=47) and circulating cancer-associated macrophage-like cells (CAMLs; 34.2%, n=40). Clusters were rather rare (12%; n=14). CTC/CAML were heterogeneous in the cohort, but also within one specimen. Neither the presence of the CTC subtypes/CAMLs nor the exact cell count were associated with the primary clinical TNM stage. CONCLUSION: Morphologically heterogenic CTCs and CAMLs are present in patients with non-metastatic, non-pretreated EAC.

Circulating Tumor Cells in Pancreatic Cancer: Current Perspectives.

Pancreatic cancer is the fourth leading cause of cancer-related death in the USA and Europe; early symptoms and screenings are lacking, and it is usually diagnosed late with a poor prognosis. Circulating tumor cells (CTCs) have been promising new biomarkers in solid tumors. In the last twenty years (1999-2019), 140 articles have contained the key words "Circulating tumor cells, pancreatic cancer, prognosis and diagnosis." Articles were evaluated for the use of CTCs as prognostic markers and their correlation to survival in pancreatic ductal adenocarcinoma (PDAC). In the final selected 17 articles, the CTC detection rate varied greatly between different enrichment methodologies and ranged from 11% to 92%; the majority of studies used the antigen-dependent CellSearch© system for CTC detection. Fifteen of the reviewed studies showed a correlation between CTC presence and a worse overall survival. The heterogeneity of CTC-detection methods and the lack of uniform results hinder a comparison of the evaluated studies. However, CTCs can be detected in pancreatic cancer and harbor a hope to serve as an early detection tool. Larger studies are needed to corroborate CTCs as valid biomarkers in pancreatic cancer.

Non-Metastatic Esophageal Adenocarcinoma: Circulating Tumor Cells in the Course of Multimodal Tumor Treatment.

BACKGROUND: Isolation of circulating tumor cells (CTC) holds the promise to improve response-prediction and personalization of cancer treatment. In this study, we test a filtration device for CTC isolation in patients with non-metastatic esophageal adenocarcinoma (EAC) within recent multimodal treatment protocols. METHODS: Peripheral blood specimens were drawn from EAC patients before and after neoadjuvant chemotherapy (FLOT)/chemoradiation (CROSS) as well as after surgery. Filtration using ScreenCell® devices captured CTC for cytologic analysis. Giemsa-stained specimens were evaluated by a cytopathologist; the cut-off was 1 CTC/specimen (6 mL). Immunohistochemistry with epithelial (pan-CK) and mesenchymal markers (vimentin) was performed. RESULTS: Morphologically diverse malignant CTCs were found in 12/20 patients in at least one blood specimen. CTCs were positive for both vimentin and pan-CK. More patients were CTC positive after neoadjuvant therapy (6/20 vs. 9/15) and CTCs per/ml increased in most of the CTC-positive patients. After surgery, 8/13 patients with available blood specimens were still CTC positive. In clinical follow-up, 5/9 patients who died were CTC-positive. CONCLUSIONS: Detection of CTC by filtration within multimodal treatment protocols of non-metastatic EAC is feasible. The rate of CTC positive findings and the quantity of CTCs changes in the course of multimodal neoadjuvant chemoradiation/chemotherapy and surgery.

Surgical outcomes of renal transplant recipients after abdominal surgery not connected with transplantation. A retrospective case-control study.

BACKGROUND: Due to the increasing number of patients after kidney transplantation, elective and emergency surgery of transplanted patients is becoming a relevant challenge in clinical routine. The current data on complication rate of patients after kidney transplantation, which must undergo another elective or emergency abdominal surgery, is inhomogeneous. Therefore, the aim of our study was to evaluate the outcome of renal transplant patients undergoing abdominal and abdominal wall surgery. MATERIAL AND METHODS: We performed an observational study of patients after kidney transplantation undergoing graft-unrelated abdominal surgery between 2005 and 2015. We randomly created a non-transplanted control for a case-matched controlled analysis. Primary endpoint was the comparison of complication rate. Secondary, a risk analysis of all patients was performed and differences in mortality, length of hospital stay and reoperation rates were calculated. RESULTS: Overall 101 kidney transplanted patients were eligible for inclusion. 20 (19.8%) died after graft-unrelated surgery and 60 (59.4%) suffered from postoperative complications. Case-matched analysis could be performed for 84 out of these 101 patients. We found no significant difference in morbidity rate (58.3% vs. 45.2%, p = 0.090). Transplanted patients had, however, a significantly higher mortality (19% vs. 2.4%, p = 0.001), a longer hospital stay (28.2 vs. 16.9 days, p = 0.020) and a higher rate of re-operations (38.1% vs. 20.2%, p = 0.017). . CONCLUSIONS: Patients after renal transplantation undergoing graft-unrelated abdominal surgery have a significantly increased mortality risk, are more frequently re-operated and have to stay significantly longer in hospital than non-transplanted patients.

Author Correction: Pancreatic cancer: Circulating Tumor Cells and Primary Tumors show Heterogeneous KRAS Mutations.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

Clinical Characteristics and Outcomes of Surgical Patients with Intensive Care Unit Lengths of Stay of 90 Days and Greater.

BACKGROUND: The aim of this study was to evaluate the influence of prolonged length of stay in an intensive care unit (ICU) on the mortality and morbidity of surgical patients. METHODS: We performed a monocentric and retrospective observational study in the surgical critical care unit of the department of surgery at the Medical Center of the University of Freiburg, Germany. Clinical data was collected from patients assigned to the ICU with a length of stay (LOS) of 90 days and greater. RESULTS: From the total of the 19 patients with ICU LOS over 90 days, ten patients died in the ICU whereas nine patients were discharged to the normal ward. The ICU mortality rate was 52%. The overall survival one year after ICU discharge was 32%. Regarding factors affecting mortality of the patients, significantly higher mortality was associated with age of the patients at the time point of the ICU admission and with postoperative need of renal replacement therapy. CONCLUSIONS: We found a high but in our opinion acceptable mortality rate in surgical patients with ICU LOS of 90 days and greater. We identified age and the need of renal replacement therapy as risk factors for mortality.

Pancreatic cancer: Circulating Tumor Cells and Primary Tumors show Heterogeneous KRAS Mutations.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease. Circulating tumor cells (CTC) in the blood are hypothesized as the means of systemic tumor spread. Blood obtained from healthy donors and patients with PDAC was therefore subject to size-based CTC-isolation. We additionally compared Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in pancreatic CTC and corresponding tumors, and evaluated their significance as prognostic markers. Samples from 68 individuals (58 PDAC patients, 10 healthy donors) were analyzed; CTCs were present in patients with UICC stage IA-IV tumors and none of the controls (p < 0.001). Patients with >3 CTC/ml had a trend for worse median overall survival (OS) than patients with 0.3­3 CTC/ml (P = 0.12). Surprisingly, CTCs harbored various KRAS mutations in codon 12 and 13. Patients with a KRAS G12V mutation in their CTC (n = 14) had a trend to better median OS (24.5 months) compared to patients with other (10 months), or no detectable KRAS mutations (8 months; P = 0.04). KRAS mutations in CTC and corresponding tumor were discordant in 11 of 26 "tumor-CTC-pairs" (42%), while 15 (58%) had a matching mutation; survival was similar in both groups (P = 0.36). Genetic characterization, including mutations such as KRAS, may prove useful for prognosis and understanding of tumor biology.