Transplant Nephrectomy: A Comparative Study of Timing and Techniques in a Single Institution.

BACKGROUND Transplant nephrectomy (TN) has historically been associated with high morbidity and mortality rates. Our objective is to share our own experience and compare indications and surgical outcomes between early and late TN and intracapsular (ICAN) and extracapsular allograft nephrectomy (ECAN) techniques. MATERIAL AND METHODS Our study included all 69 TN procedures performed between January 2010 and February 2021. Of these, 17 TN procedures were performed within the first 60 days after transplantation (referred to as 'early'), while the remaining 52 procedures were performed later ('late'). Within the late allograft nephrectomy (AN) group, we compared the outcomes of intracapsular (ICAN) and extracapsular (ECAN) techniques. We conducted a statistical analysis using the chi-square test and the 2-sample t test. RESULTS The primary indication for early TN was surgical transplant complications (94.1%), with 58.8% of these cases requiring emergency surgery. Morbidity (major complications) occurred in 47.1% of cases, and mortality was 5.9%. In contrast, graft intolerance syndrome was the leading indication for late TN (76.9%), with elective surgery performed in 88.5% of cases. Morbidity (major complications) occurred in 11.5% of cases, and mortality was 3.8%. Within the late TN group, 82.7% of cases were treated with ICAN and 17.3% with ECAN. Blood transfusion was required during surgery in 17.3% of cases, with no significant difference between the groups. Multivariate logistic regression analysis revealed that the timing of surgery was the only statistically significant predictor of complication occurrence. CONCLUSIONS Our data suggest that TN can be performed with relatively low morbidity. However, early TN remains the only independent risk factor for developing adverse outcomes.

Three-year follow-up analysis of the short-stitch versus long-stitch technique for elective midline abdominal closure randomized-controlled (ESTOIH) trial.

BACKGROUND: Clinical trials have shown reduced incisional hernia rates 1 year after elective median laparotomy closure using a short-stitch technique. With hernia development continuing beyond the first postoperative year, we aimed to compare incisional hernias 3 years after midline closure using short or long stitches in patients from the ESTOIH trial. METHODS: The ESTOIH trial was a prospective, multicenter, parallel-group, double-blind, randomized-controlled study of primary elective midline closure. Patients were randomized to fascia closure using a short- or long-stitch technique with a poly-4-hydroxybutyrate-based suture. A predefined 3-year follow-up analysis was performed with the radiological imaging-verified incisional hernia rate as the primary endpoint. RESULTS: The 3-year intention-to-treat follow-up cohort consisted of 414 patients (210 short-stitch and 204 long-stitch technique) for analysis. Compared with 1 year postoperatively, incisional hernias increased from 4.83% (20/414 patients) to 9.02% (36/399 patients, p = 0.0183). The difference between the treatment groups at 3 years (short vs. long stitches, 15/198 patients (7.58%) vs. 21/201 (10.45%)) was not significant (OR, 1.4233; 95% CI [0.7112-2.8485]; p = 0.31). CONCLUSION: Hernia rates increased significantly between one and 3 years postoperatively. The short-stitch technique using a poly-4-hydroxybutyrate-based suture is safe in the long term, while no significant advantage was found at 3 years postoperatively compared with the standard long-stitch technique. TRIAL REGISTRY: NCT01965249, registered on 18 October 2013.

Impact of IDH1 mutation on clinical course of patients with intrahepatic cholangiocarcinoma: a retrospective analysis from a German tertiary center.

PURPOSE: IDH1 mutation is a known biomarker for targeted therapy of intrahepatic cholangiocarcinoma (iCCA), while its prognostic relevance for current palliative chemotherapy is still unclear. Aim of this study was to analyze clinicopathological characteristics of patients with IDH1 mutations and to outline a potential impact on the outcome after state-of-the-art palliative chemotherapy regimens. METHODS: All patients with iCCA receiving large panel molecular profiling and follow-up treatment at Frankfurt University Hospital until 04/2022 were retrospectively analyzed. Clinicopathological characteristics were assessed for IDH1 mutated (mut) and IDH1 wild type (wt) patients, and progression-free survival (PFS) and overall survival (OS) were determined. RESULTS: In total, 75 patients with iCCA received molecular profiling. Of the patients with available DNA data, pathogenic mutations in IDH1 were found in 14.5% (n = 10). IDH1 mut status was associated with lower serum CA-19/9 (p = 0.023), lower serum lactate dehydrogenase (p = 0.006), and a higher proportion of primary resectability (p = 0.028) as well as response to chemotherapy after recurrence (p = 0.009). Median PFS was 5.9 months (95% CI 4.4-7.3 months) for IDH1 wt in comparison to 9.8 months (95% CI 7.7-12 months) for patients with IDH1 mut (p = 0.031). IDH1 wt was a significant risk factor for shortened PFS in univariate (p = 0.043), but not in multivariate analysis (p = 0.061). There was no difference in OS between both groups. CONCLUSION: Patients with IDH1 mutated iCCA seem to have a favorable tumor biology including a longer PFS for palliative chemotherapy regimens compared to IDH1 wild type.

Site of analysis matters - Ongoing complete response to Nivolumab in a patient with HIV/HPV related metastatic anal cancer and MLH1 mutation.

Anal cancer is a rare disease with increasing incidence. In patients with locally recurrent or metastatic disease which cannot be treated with chemoradiotherapy or salvage surgery systemic first-line chemotherapy with carboplatin and paclitaxel is standard of care. For patients who progress after first-line therapy and are still eligible for second-line therapy Programmed cell death protein 1 (PD-1) antibodies are potential therapeutic options. However, prediction of response to immunotherapy is still challenging including anal cancer. We report here to our knowledge the first anal cancer case with microsatellite instability (MSI) due to MLH1 mutation and a deep and ongoing response to Nivolumab treatment. Namely, thorough analysis of the primary tumor as well as metastatic sites by next generation sequencing (NGS) revealed that MSI was formally only found in the metastatic sites but not in the primary tumor. Concomitantly, tumor mutational burden (TMB) was higher in the metastatic site than in the primary tumor. Therefore, we conclude that all anal cancer patients should be tested for MSI and whenever possible molecular analysis should be performed rather from metastatic sites than from the primary tumor.

Effects of the short stitch technique for midline abdominal closure on incisional hernia (ESTOIH): randomized clinical trial.

BACKGROUND: Incisional hernia remains a frequent problem after midline laparotomy. This study compared a short stitch to standard loop closure using an ultra-long-term absorbent elastic suture material. METHODS: A prospective, multicentre, parallel-group, double-blind, randomized, controlled superiority trial was designed for the elective setting. Adult patients were randomly assigned by computer-generated sequence to fascial closure using a short stitch (5 to 8 mm every 5 mm, USP 2-0, single thread HR 26 mm needle) or long stitch technique (10 mm every 10 mm, USP 1, double loop, HR 48 mm needle) with a poly-4-hydroxybutyrate-based suture material (Monomax®). Incisional hernia assessed by ultrasound 1 year after surgery was the primary outcome. RESULTS: The trial randomized 425 patients to short (n = 215) or long stitch technique (n = 210) of whom 414 (97.4 per cent) completed 1 year of follow-up. In the short stitch group, the fascia was closed with more stitches (46 (12 s.d.) versus 25 (7 s.d.); P < 0.001) and higher suture-to-wound length ratio (5.3 (2.2 s.d.) versus 4.0 (1.3 s.d.); P < 0.001). At 1 year, seven of 210 (3.3 per cent) patients in the short and 13 of 204 (6.4 per cent) patients in the long stitch group developed incisional hernia (odds ratio 1.97, 95 per cent confidence interval 0.77 to 5.05; P = 0.173). CONCLUSION: The 1-year incisional hernia development was relatively low with clinical but not statistical difference between short and long stitches. Registration number: NCT01965249 (http://www.clinicaltrials.gov).

A 55-Year-Old Man with Recurrent Gastrointestinal Bleeding Due to Stricture of the Portal Vein Anastomotic Site 12 Years After Combined Pancreas and Kidney Transplantation.

BACKGROUND Varices of the upper gastrointestinal tract are due to portal hypertension and can result from occlusion of the portal venous system. This report is of a 55-year-old man with recurrent gastrointestinal bleeding due to stricture of the portal vein anastomotic site to inferior vena cava (IVC) 12 years after combined pancreas and kidney transplantation. CASE REPORT A 55-year-old man presented bleeding episodes requiring transfusion of more than 70 units of red blood cells (RBCs), complicated by bacterial and viral infection episodes including cytomegalovirus (CMV) reactivation and hepatitis E and transient impairment of function of the renal allograft. Endoscopy, computed tomography (CT) scan, and angiography revealed jejunal varices due to anastomotic stricture at the portal vein to IVC as the cause of the hemorrhage. Neither conservative therapy nor an anastomosis between the splenic vein of the graft and the internal iliac vein as a bypass could stop the life-threatening bleeding. During the recurrent bleeding, CD4 T lymphocytes were low, indicating immunodeficiency despite paused immunosuppressive therapy. After the hemorrhage resolved and immunosuppression was restarted, CD4 T lymphocyte levels normalized. Finally, to stop the hemorrhage and save the transplanted kidney and the patient's life, graft pancreatectomy was performed. Long-term damage to the renal transplant was not found. CONCLUSIONS This report is of a rare case of portal hypertension as a long-term complication of transplant surgery. Although acute venous thrombosis at the anastomotic site is a recognized postoperative complication of pancreatic transplant surgery, this case highlights the importance of post-transplant follow-up and diagnostic imaging.

Sequence Therapy with FOLFIRINOX and Gemcitabine/Nab-Paclitaxel for Patients with Advanced Pancreatic Cancer: A Monocentre Retrospective Cohort Study.

BACKGROUND AND AIMS: While irresectable pancreatic cancer has still a dismal overall prognosis, evidence about the optimal chemotherapy sequence is scarce. After treatment with FOLFIRINOX in first-line, gemcitabine monotherapy was established for years. As a potential treatment alternative after failure of FOLFIRINOX therapy, combination of gemcitabine and nab-paclitaxel is used. However, this combination has formally not yet been approved for second-line treatment and investigation of efficiency and treatment tolerance is the aim of this trial. METHODS: Therefore, we investigated 225 patients with histologically confirmed local advanced or metastatic pancreatic cancer in this retrospective monocentre study (November 2010 - July 2019). Of this, 44 patients received FOLFIRINOX therapy and outcome was further analysed. The primary end point of this cohort was overall survival (OS), and secondary end points included progression-free survival (PFS), response rate, and safety. RESULTS: In most of the patients, FOLFIRINOX as first-line treatment of irresectable pancreatic cancer resulted in temporary cancer control (partial response [PR]: 50% and stable disease [SD]: 18%), whereas tumour progression was observed in 23% of the patients. The median PFS time for FOLFIRINOX treatment was 7.3 months and median OS 10.3 months. Seven (16%) patients received additional local radio chemotherapy of the pancreatic tumour. During first-line therapy, in 8 (18%) patients, laparotomy was performed to proof resectability of the tumour. Hereby, in 3 patients R0- and in 3 patients R1 resection was achieved, whereas 2 patients stayed irresectable. Twenty-five of the 44 patients (57%) received second-line therapy, namely, 24 patients gemcitabine/nab-paclitaxel and 1 patient gemcitabine and erlotinib. Hereby, gemcitabine/nab-paclitaxel led again to temporary tumour control in 46% of the patients (PR: 21%, SD: 25%), while in 29% of the patients, disease progression was observed. Corresponding median PFS for gemcitabine and nab-paclitaxel treatment was 3.5 months. Patients who received second-line treatment with nab-paclitaxel and gemcitabine had a more favourable prognosis (median OS: 17 vs. 9.2 months; HR 0.32 [0.14-0.70], p < 0.001) than patients who were not eligible for second-line treatment. Moreover, in multivariate analyses association with patients' survival and tumour response to chemotherapy in both therapeutic lines and µGT concentrations below 100 IU/L in first-line FOLFIRINOX chemotherapy were observed. CONCLUSION: These real-world data suggest that gemcitabine/nab-paclitaxel may be feasible after FOLFIRINOX therapy in patients with irresectable pancreatic cancer. However, prospective randomized data about the superiority to gemcitabine monotherapy are needed.

[Introduction of an interdisciplinary tumor board leads to improvement of treatment outcome of cholangiocarcinoma (bile duct cancer)]. / Einführung eines interdisziplinären Tumorboards führt zur Verbesserung der Behandlungsergebnisse von Cholangio- und Gallenblasenkarzinomen.

BACKGROUND: Cholangiocarcinoma (CCA, bile duct cancer) is a rare malignant disease with a poor prognosis. For several years interdisciplinary tumor boards (TuB) with the participation of experts from various disciplines have been organized to optimize medical treatment for patients suffering from oncological diseases. OBJECTIVE: This study addressed the question whether the introduction of TuB leads to a better life expectancy and quality of life for patients with CCA. MATERIAL AND METHODS: In this retrospective study 161 patients treated for CCA were investigated. The patient collective was divided in two groups (TuB+ vs. TuB-) and a propensity score matching was carried out. RESULTS: The patient group TuB+ included 109 patients (67.7%) and the control group (TuB-) included 52 patients (32.3%). Using propensity score matching 84 patients in the TuB+ and 50 in the TuB group were identified and matched. The survival rates of the matched patients demonstrated an advantage for patients in the TuB+ group (1-year survival rate 61.9%, 5­year survival rate 23.6%, 10-year survival rate 18.0%) over patients in the TuB-group (1-year survival rate 32.0%, 5­year survival rate 8.0%, 10-year survival rate 0%) with p < 0.001. The results of the univariate (hazard ratio, HR 0.513, 95% confidence interval, CI 0.350-0.751, p = 0.001) and the multivariate Cox proportional hazard models (HR 0.459, 95% CI 0.303-0.694, p < 0.001) showed a significant benefit in survival for patients in the TuB+ group. CONCLUSION: This article shows that the introduction of a TuB meeting can provide a measurable benefit for patients with CCA. Hence it is recommended that all cases of patients with CCA should be discussed in a TuB.

Anti-EGF Receptor-Based Conversion Chemotherapy in RAS Wild-Type Colorectal Cancer Patients: Impact on Survival and Resection Rates.

BACKGROUND: Initially unresectable colorectal liver metastases can become resectable after chemotherapy. Combination chemotherapy with epidermal growth factor receptor (EGFR) antibodies has shown consistent high response rates in patients with all rat sarcoma (RAS) wild-type tumors. METHODS: Out of a cohort of 424 patients with metastatic colorectal cancer, we identified 30 patients with initially unresectable Kirsten RAS (KRAS) exon 2 wild-type colorectal liver metastases who received neoadjuvant chemotherapy with anti-EGFR agents between January 2008 and February 2014. In all patients, extended RAS analysis (KRAS and NRAS exon 3 codon 59/61 and exon 4 codon 117/146) was carried out retrospectively. RESULTS: RAS mutation analysis identified further KRAS mutations in 4/30 patients (13.3%). In none of these 4 patients a R0 resection was achieved. In contrast, 15/26 (57.7%) RAS wild-type patients were R0 resected. Median overall survival was > 63.3 months in R0-resected patients versus 30.0 months in those with a R1 or R2 resection (HR 0.23; [95% CI 0.10-0.75; p = 0.008). CONCLUSION: Our data suggest that a RAS wild-type and a R0 resection are the strongest predictors for overall survival.

Circulating hypoxia marker carbonic anhydrase IX (CA9) in patients with hepatocellular carcinoma and patients with cirrhosis.

BACKGROUND AND AIMS: Expression of carbonic anhydrase IX (CA9), an enzyme expressed in response to hypoxia, acidosis and oncogenic alterations, is reported to be a prognostic factor in HCC patients. Here we evaluated serum CA9 levels in HCC and cirrhosis patients. METHODS: HCC and cirrhosis patients were prospectively recruited and CA9 levels were determined. CA9 levels were compared to stages of cirrhosis and HCC stages. The association of the CA9 levels and overall survival (OS) was assessed. Furthermore, immunohistochemical CA9 expression in HCC and cirrhosis was evaluated. RESULTS: 215 patients with HCC were included. The median serum CA9 concentration in patients with HCC was 370 pg/ml and significantly higher than in a healthy cohort. Patients with advanced cancer stages (BCLC and ALBI score) had hid significant higher levels of CA9 in the serum. HCC patients with high serum CA9 concentrations (>400 pg/ml) had an increased mortality risk (hazard ratio (HR) 1.690, 95% confidence interval (CI) 1.017-2.809, P = 0.043). Serum CA9 concentration in cirrhotic patients did not differ significantly from HCC patients. Higher CA9 levels in cirrhotic patients correlated with portal hypertension and esophageal varices. Patients with ethanol induced cirrhosis had the highest CA9 levels in both cohorts. Levels of CA9 did not correlate with immunohistochemical expression. CONCLUSIONS: We conclude that a high CA9 level is a possible prognostic indicator for a poor outcome in HCC patients. The high CA9 levels are probably mainly associated with portal hypertension. Ductular reactions might be a possible source of serum CA9.