Outcome of intraoperative brachytherapy as a salvage treatment for locally recurrent rectal cancer.

BACKGROUND: Locally advanced recurrent rectal cancer (RRC) requires a multimodal approach. Intraoperative high-dose-rate brachytherapy (HDR-BT) may reduce the risk of local recurrence. However, the optimal therapeutic regimen remains unclear. The aim of this retrospective monocentric study was to evaluate the toxicity of HDR-BT after resection of RRC. METHODS: Between 2018 and 2022, 17 patients with RRC received resection and HDR-BT. HDR-BT was delivered alone or as an anticipated boost with a median dose of 13 Gy (range 10-13 Gy) using an 192iridium microSelectron HDR remote afterloader (Elekta AB, Stockholm, Sweden). All participants were followed for assessment of acute and late adverse events using the Common Terminology Criteria for Adverse Events version 5.0 and the modified Late Effects in Normal Tissues criteria (subjective, objective, management, and analytic; LENT-SOMA) at 3­ to 6­month intervals. RESULTS: A total of 17 patients were treated by HDR-BT with median dose of 13 Gy (range 10-13 Gy). Most patients (47%) had an RRC tumor stage of cT3­4 N0. At the time of RRC diagnosis, 7 patients (41.2%) had visceral metastases (hepatic, pulmonary, or peritoneal) in the sense of oligometastatic disease. The median interval between primary tumor resection and diagnosis of RRC was 17 months (range 1-65 months). In addition to HDR-BT, 2 patients received long-course chemoradiotherapy (CRT; up to 50.4 Gy in 1.8-Gy fractions) and 2 patients received short-course CRT up to 36 Gy in 2­Gy fractions. For concomitant CRT, all patients received 5­fluorouracil (5-FU) or capecitabine. Median follow-up was 13 months (range 1-54). The most common acute grade 1-2 toxicities were pain in 7 patients (41.2%), wound healing disorder in 3 patients (17.6%), and lymphedema in 2 patients (11.8%). Chronic toxicities were similar: grade 1-2 pain in 7 patients (41.2%), wound healing disorder in 3 patients (17.6%), and incontinence in 2 patients (11.8%). No patient experienced a grade ≥3 event. CONCLUSION: Reirradiation using HDR-BT is well tolerated with low toxicity. An individualized multimodality approach using HDR-BT in the oligometastatic setting should be evaluated in prospective multi-institutional studies.

Non-antigen-specific Immunoadsorption Is a Risk Factor for Severe Postoperative Infections in ABO-Incompatible Kidney Transplant Recipients.

ABO-incompatible (ABOi) living kidney transplantation (KTx) is an established procedure to address the demand for kidney transplants with outcomes comparable to ABO-compatible KTx. Desensitization involves the use of immunoadsorption (IA) to eliminate preformed antibodies against the allograft. This monocentric retrospective study compares single-use antigen-selective Glycosorb® ABO columns to reusable non-antigen-specific Immunosorba® immunoglobulin adsorption columns regarding postoperative infectious complications and outcome. It includes all 138 ABOi KTx performed at Freiburg Transplant Center from 2004-2020. We compare 81 patients desensitized using antigen-specific columns (sIA) to 57 patients who received IA using non-antigen-specific columns (nsIA). We describe distribution of infections, mortality and allograft survival in both groups and use Cox proportional hazards regression to test for the association of IA type with severe infections. Desensitization with nsIA tripled the risk of severe postoperative infections (adjusted HR 3.08, 95% CI: 1.3-8.1) compared to sIA. nsIA was associated with significantly more recurring (21.4% vs. 6.2%) and severe infections (28.6% vs. 8.6%), mostly in the form of urosepsis. A significantly higher proportion of patients with sIA suffered from allograft rejection (29.6% vs. 14.0%). However, allograft survival was comparable. nsIA is associated with a two-fold risk of developing a severe postoperative infection after ABOi KTx.

Pancreatic head resection for carcinoma of the ampulla vateri - better long-term prognosis, but more postoperative complications.

BACKGROUND: Pancreatoduodenectomies are complex surgical procedures with a considerable morbidity and mortality even in high-volume centers. However, postoperative morbidity and long-term oncological outcome are not only affected by the surgical procedure itself, but also by the underlying disease. The aim of our study is an analysis of pancreatoduodenectomies for patients with pancreatic ductal adenocarcinoma (PDAC) and ampullary carcinoma (CAMP) concerning postoperative complications and long-term outcome in a tertiary hospital in Germany. METHODS: The perioperative and oncological outcome of 109 pancreatic head resections performed for carcinoma of the ampulla vateri was compared to the outcome of 518 pancreatic head resections for pancreatic ductal adenocarcinoma over a 20 year-period from January 2002 until December 2021. All operative procedures were performed at the University Hospital Freiburg, Germany. Patient data was analyzed retrospectively, using a prospectively maintained SPSS database. Propensity score matching was performed to adjust for differences in surgical and reconstruction technique. Primary outcome of our study was long-term overall survival, secondary outcomes were postoperative complications and 30-day postoperative mortality. Postoperative complications like pancreatic fistula (POPF), postpancreatectomy hemorrhage (PPH) and delayed gastric emptying (DGE) were graded following current international definitions. Survival was estimated using Kaplan Meier curves and log-rank tests. A p-value < 0.05 was considered statistically significant. RESULTS: Operation time was significantly longer in PDAC patients (432 vs. 391 min, p < 0.001). The rate of portal vein resections was significantly higher in PDAC patients (p < 0.001). In CAMP patients, a pancreatogastrostomy as reconstruction technique was performed more frequently compared to PDAC patients (48.6% vs. 29.9%, p < 0.001) and there was a trend towards more laparoscopic surgeries in CAMP patients (p = 0.051). After propensity score matching, we found no difference in DGE B/C and PPH B/C (p = 0.389; p = 0.517), but a significantly higher rate of clinically relevant pancreatic fistula (CR-POPF) in patients with pancreatoduodenectomies due to ampullary carcinoma (30.7% vs. 16.8%, p < 0.001). Long-term survival was significantly better in CAMP patients (42 vs. 24 months, p = 0.003). CONCLUSION: Patients with pancreatoduodenectomies due to ampullary carcinomas showed a better long-term oncological survival, by reason of the better prognosis of this tumor entity. However, these patients often needed a more elaborated postoperative treatment due to the higher rate of clinically relevant pancreatic fistula in this group.

[Reform proposal "Occasional surgical oncology" : Medical strategic analysis and ramifications of the draft bill within the framework of the Hospital Treatment Improvement Act (KHVVG) from the perspective of a university hospital]. / Reformvorhaben "Gelegenheits-Onkochirurgie" : Medizinstrategische Analyse und Auswirkungen der Gesetzesinitiative im Rahmen des Krankenhausversorgungsverbesserungsgesetzes (KHVVG) aus der Perspektive eines Universitätsklinikums.

BACKGROUND: Cancer remains the second most common cause of death in Germany. Performance management and specialization concepts in medicine have the potential to positively influence the care and chances of survival of patients. OBJECTIVE: From the perspective of the University Hospital Freiburg (UKF), the legislative initiative within the framework of the Hospital Treatment Improvement Act (KHVVG) results in a number of medical strategic implications. This article explains and discusses the background, objectives and contents of the reform project "Occasional surgical oncology" and provides perspectives on strategic fields of action. MATERIAL AND METHODS: Analysis and interpretation of the draft of the Act for improvement of the treatment quality in hospitals and on the reform of the remuneration structures (Federal Government draft act). RESULTS: From the point of view of the UKF hospitals should engage in cooperative discussions with neighboring hospitals at the earliest opportunity to shape regional healthcare with the goals of mapping the local allocation of oncology patients for optimal treatment, mitigating the loss of patients at affected locations and preparing for patient growth at facilities that will continue to provide treatment in surgical oncology. DISCUSSION: The ongoing legislative process and the fact that a reliable analysis of relevant treatment areas will be possible for hospitals in the first half of 2025, presents particular challenges for hospitals and the strategic planning of activities. The gaps in the bill presented in this article should be urgently addressed to avoid undermining the project's goals and to support the hospitals remaining in the healthcare system in their preparations.

Oncological survival in pancreatic head ductal carcinoma: hybrid minimally invasive versus open pancreatoduodenectomy - a single centre analysis.

BACKGROUND: Surgery remains the only curative treatment option for pancreatic head cancer. Laparoscopic surgical techniques are increasingly used, in line with the development of visceral surgery as a whole. The success of surgery is measured by the oncological outcome. Aim of this study is to evaluate the oncological outcome and survival after laparoscopic assisted resection of the pancreatic head compared to open surgery for ductal adenocarcinoma. MATERIALS AND METHODS: Data were collected in a prospectively maintained database. Perioperative and oncological outcomes of 182 laparoscopic pancreatic head resections for ductal carcinoma were compared with 585 open pancreatic head resections. The laparoscopic procedures were performed between 2010 and 2022, the open procedures between 2002 and 2022. RESULTS: Laparoscopic procedure was significantly superior in terms of intraoperative blood loss (575 vs. 600 mL, P=0.021) and operative time (413 vs. 427 min, P=0.033). Tumour size (25 vs. 27 mm, P=0.028), need for portal vein resection (P=0.009) and blood transfusion (P=0.004) were significantly greater in the open group (P=0.009). The resection margin remained negative significantly more often in the laparoscopic group (159 [87%] vs. 449 [77%], P<0.001). There was no difference in postoperative mortality and morbidity. Postoperative survival at 5 years was significantly better in the laparoscopic group (37% vs. 15%, P<0.001). CONCLUSION: In our cohort, patients who underwent hybrid laparoscopic resection of pancreatic head cancer showed a significantly improved oncological outcome. Most of these effects are due to selection bias, which is not captured by the clinical parameters used to date. Our results highlight the need for additional prognostic factors in pancreatic cancer.

Banded Versus Non-banded Sleeve Gastrectomy: 5-Year Results of a 3-Year Randomized Controlled Trial.

PURPOSE: Banded sleeve gastrectomy (BSG) has been shown to enable better weight loss than non-banded sleeve gastrectomy (SG) in retrospective analyses. These findings were supported by two randomized controlled trials (RCT). However, to date, mid-term prospective data is not available. MATERIALS AND METHODS: We invited all 94 patients of an RCT comparing banded to non-banded sleeve gastrectomy at 3 years (DRKS00007729) for a 5-year follow-up visit. Eighty-two patients (BSG n = 42; SG n = 40) came for evaluation. Outcome measures were identical with the RCT to allow longitudinal comparison. Data analysis was descriptive and focused on biometric data, development of comorbidities, mid-term complications, quality of life, and type of body contouring surgery (BCS). RESULTS: The per-protocol analysis revealed a treatment difference of 9% (CI - 1.5 to 19.6) excess weight loss (EWL). Total weight loss (TWL) was 27.4% (CI 23.5-31.3) after SG and 31.6% (CI 27.3-35.5) after BSG. Twenty percent of patients after SG and 11.9% following BSG had been converted to a gastric bypass. Type 2 diabetes went into remission in most patients (SG 66.7% vs. BSG 63.6%). Antihypertensive medication was stopped or reduced in 81.3% after SG and 80% after BSG. Reflux symptoms were similar in both groups (symptoms [Formula: see text] 1/ week: SG 28.2% vs. BSG 26.8%). Frequency of postprandial regurgitation was higher after BSG (SG 23% vs. BSG 59%). Forty percent of patients had undergone BCS at time of follow-up. CONCLUSION: Five-year weight loss after BSG was 9% EWL and 4.2% TWL higher compared to SG. The main added morbidity following BSG was postprandial regurgitation.

Association Between Body Composition and Survival in Patients With Gastroesophageal Adenocarcinoma: An Automated Deep Learning Approach.

PURPOSE: Body composition (BC) may play a role in outcome prognostication in patients with gastroesophageal adenocarcinoma (GEAC). Artificial intelligence provides new possibilities to opportunistically quantify BC from computed tomography (CT) scans. We developed a deep learning (DL) model for fully automatic BC quantification on routine staging CTs and determined its prognostic role in a clinical cohort of patients with GEAC. MATERIALS AND METHODS: We developed and tested a DL model to quantify BC measures defined as subcutaneous and visceral adipose tissue (VAT) and skeletal muscle on routine CT and investigated their prognostic value in a cohort of patients with GEAC using baseline, 3-6-month, and 6-12-month postoperative CTs. Primary outcome was all-cause mortality, and secondary outcome was disease-free survival (DFS). Cox regression assessed the association between (1) BC at baseline and mortality and (2) the decrease in BC between baseline and follow-up scans and mortality/DFS. RESULTS: Model performance was high with Dice coefficients ≥0.94 ± 0.06. Among 299 patients with GEAC (age 63.0 ± 10.7 years; 19.4% female), 140 deaths (47%) occurred over a median follow-up of 31.3 months. At baseline, no BC measure was associated with DFS. Only a substantial decrease in VAT >70% after a 6- to 12-month follow-up was associated with mortality (hazard ratio [HR], 1.99 [95% CI, 1.18 to 3.34]; P = .009) and DFS (HR, 1.73 [95% CI, 1.01 to 2.95]; P = .045) independent of age, sex, BMI, Union for International Cancer Control stage, histologic grading, resection status, neoadjuvant therapy, and time between surgery and follow-up CT. CONCLUSION: DL enables opportunistic estimation of BC from routine staging CT to quantify prognostic information. In patients with GEAC, only a substantial decrease of VAT 6-12 months postsurgery was an independent predictor for DFS beyond traditional risk factors, which may help to identify individuals at high risk who go otherwise unnoticed.

Effect of Intraoperative Blood Pressure Regulation on Postoperative Hemorrhage After Bariatric Surgery.

INTRODUCTION: With a rising number of bariatric procedures, the absolute number of postoperative complications is increasing, too. Postoperative bleeding, particularly along the staple line, is a recognized challenge. Numerous strategies including reinforcement of the staple line (SLR) have been proposed to improve bleeding rates, but no single technique has shown superiority over the others. In our bariatric center, we have implemented intraoperative blood pressure regulation alone, without SLR, to reduce hemorrhagic complications postoperatively. METHODS: This retrospective observational analysis compares the incidence of postoperative bleeding in two groups of consecutive patients (total n = 438 patients), one with and one without intraoperative blood pressure elevation to 150 mmHg systolic without the additional use of staple line reinforcement. This intervention was integrated into our standard bariatric surgical procedure, no randomization or matching was conducted. Significant postoperative bleeding was defined as drop of hemoglobin of more than 2.5 mg/dl in 48 h and one of the following symptoms: lactate ≥ 2 mmol/L, bloody drainage, quantity of drainage more than 200 ml and/or radiological signs. RESULTS: Defined postoperative bleeding occurred in 33 (7.5%) patients. We observed a decrease in bleeding rates from 10% to 5% (n = 22 vs. n = 11) after introducing intraoperative blood pressure increase (p = 0.034). The rate of revisional surgery for bleeding also decreased from 2.7% to 0.5% (n = 6 vs. n = 1). In multivariate analysis, the intervention with blood pressure elevation showed a significant decrease on bleeding rates (p = 0.038). CONCLUSION: The use of increased intraoperative blood pressure alone, without staple line reinforcement, appears to be an effective and suitable method for reducing post-bariatric hemorrhagic complications.

Association of parental obesity with the profile of metabolic-bariatric surgery patients: a cohort study of the German StuDoQ|MBE registry.

OBJECTIVES: To investigate the association of parental obesity (PO) with onset of obesity, pre-surgical disease duration and body mass index (BMI) at the time of surgery in patients undergoing metabolic-bariatric surgery (MBS). DESIGN: This is a cohort study of the German StuDoQ registry for metabolic-bariatric diseases. All surgical cases from initiation of the registry in September 2015 until August 2020 were screened for pertinent information. SETTING: The registry is based on participating German hospitals of various sizes. PARTICIPANTS: A total of 11 891 patients were included in this analysis, 74.2% of which were females and 25.8% males. Roux-en-Y gastric bypass was performed in 5652 (47.5%) cases, sleeve gastrectomy in 4618 (38.8%) cases and one-anastomosis gastric bypass in 1621 (13.6%) cases. RESULTS: One-sided and two-sided PO are independently associated with early-onset obesity (OR 1.61, [95% CI, 1.47 to 1.76], p<0.001 and OR 2.45, [95% CI, 2.22 to 2.71], p<0.001) and prolonged pre-surgical disease duration (regression coefficient 2.39, [95% CI, 1.93 to 2.83], p<0.001 and regression coefficient 4.27, [95% CI, 3.80 to 4.75], p<0.001). Unlike one-sided PO, two-sided PO had a significant association with BMI at the time of surgery (regression coefficient 0.49, [95% CI, 0.14 to 0.85], p=0.006). Age at the onset of obesity and disease duration had a negative association with BMI at the time of surgery (regression coefficient -0.13, [95% CI, -0.14 to -0.11], p<0.001 and regression coefficient -0.05, [95% CI, -0.07 to -0.04], p<0.001). CONCLUSIONS: This study established a clear association between PO status of patients undergoing MBS and their pre-surgical patient profile as well as known risk factors for poor postoperative response.

Partial hepatectomy accelerates colorectal metastasis by priming an inflammatory premetastatic niche in the liver.

Background: Resection of colorectal liver metastasis is the standard of care for patients with Stage IV CRC. Despite undoubtedly improving the overall survival of patients, pHx for colorectal liver metastasis frequently leads to disease recurrence. The contribution of this procedure to metastatic colorectal cancer at a molecular level is poorly understood. We designed a mouse model of orthograde metastatic colorectal cancer (CRC) to investigate the effect of partial hepatectomy (pHx) on tumor progression. Methods: CRC organoids were implanted into the cecal walls of wild type mice, and animals were screened for liver metastasis. At the time of metastasis, 1/3 partial hepatectomy was performed and the tumor burden was assessed longitudinally using MRI. After euthanasia, different tissues were analyzed for immunological and transcriptional changes using FACS, qPCR, RNA sequencing, and immunohistochemistry. Results: Mice that underwent pHx presented significant liver hypertrophy and an increased overall metastatic load compared with SHAM operated mice in MRI. Elevation in the metastatic volume was defined by an increase in de novo liver metastasis without any effect on the growth of each metastasis. Concordantly, the livers of pHx mice were characterized by neutrophil and bacterial infiltration, inflammatory response, extracellular remodeling, and an increased abundance of tight junctions, resulting in the formation of a premetastatic niche, thus facilitating metastatic seeding. Conclusions: Regenerative pathways following pHx accelerate colorectal metastasis to the liver by priming a premetastatic niche.

Single-cell deconvolution reveals high lineage- and location-dependent heterogeneity in mesenchymal multivisceral stage 4 colorectal cancer.

Metastasized colorectal cancer (CRC) is associated with a poor prognosis and rapid disease progression. Besides hepatic metastasis, peritoneal carcinomatosis is the major cause of death in Union for International Cancer Control (UICC) stage IV CRC patients. Insights into differential site-specific reconstitution of tumor cells and the corresponding tumor microenvironment are still missing. Here, we analyzed the transcriptome of single cells derived from murine multivisceral CRC and delineated the intermetastatic cellular heterogeneity regarding tumor epithelium, stroma, and immune cells. Interestingly, we found an intercellular site-specific network of cancer-associated fibroblasts and tumor epithelium during peritoneal metastasis as well as an autologous feed-forward loop in cancer stem cells. We furthermore deciphered a metastatic dysfunctional adaptive immunity by a loss of B cell-dependent antigen presentation and consecutive effector T cell exhaustion. Furthermore, we demonstrated major similarities of this murine metastatic CRC model with human disease and - based on the results of our analysis - provided an auspicious site-specific immunomodulatory treatment approach for stage IV CRC by intraperitoneal checkpoint inhibition.