Comparative study of short-and long-term results in patients with perihilar cholangiocarcinoma undergoing surgical resection: does the extent and side of resection really affect outcome?

BACKGROUND: The surgical management of perihilar carcinoma (pCCA) is still subject of ongoing debate. To provide more clarity, this study was conducted to evaluate outcomes related to the side and extent of heatectomy in patients with pCAA. METHODS: A total of 32 patients with curative resection for pCCA were identified from our prospective database. Short-and long-term clinical outcome data and histopathological results were compared between right-sided (R-H) and left-sided (L-H) hepatectomy. RESULTS: Nine patients (28.13%) underwent left-sided hepatectomy while a right-sided hepatectomy was accomplished in 23 patients (71.87%). In the R-H group hepatic conditioning of the future liver remnant (FLR) prior to extended resection was necessary in 13 cases (56.52%), and simultaneous pancreaticoduodenectomy was performed in 5 patients (21.74%). The arterial and portal venous reconstruction rates were 17.39% and 11.11% (P=1.00), and 60.87% and 33.33% (P=0.243) in the R-H and L-H groups, respectively. No statistically significant differences in short-term morbidity and mortality between both groups were observed. The rate of R0 resections was comparable (R-H: 78.26% versus L-H: 66.67%; P=0.654) resulting in similar long-term overall and disease-free survival rates after right-and left hepatectomy. CONCLUSIONS: In patients with pCCA, both right- and left-sided resections appear to be safe and feasible options with similar postoperative morbidity and oncologic outcomes. Consecutively, the ideal surgical approach should be patient-tailored based on anatomical considerations and the functional future liver capacity.

Predictive factors of 90-day mortality after curative hepatic resection for hepatocellular carcinoma: a western single-center observational study.

PURPOSE: The aim of this study was to identify predictive risk factors associated with 90-day mortality after hepatic resection (HR) in hepatocellular carcinoma (HCC). METHODS: All patients undergoing elective resection for HCC from a single- institutional and prospectively maintained database were included. Multivariate regression analysis was conducted to identify pre- and intraoperative as well as histopathological predictive factors of 90-day mortality after elective HR. RESULTS: Between August 2004 and October 2021, 196 patients were enrolled (148 male /48 female). The median age of the study cohort was 68.5 years (range19-84 years). The rate of major hepatectomy (≥ 3 segments) was 43.88%. Multivariate analysis revealed patient age ≥ 70 years [HR 2.798; (95% CI 1.263-6.198); p = 0.011], preoperative chronic renal insufficiency [HR 3.673; (95% CI 1.598-8.443); p = 0.002], Child-Pugh Score [HR 2.240; (95% CI 1.188-4.224); p = 0.013], V-Stage [HR 2.420; (95% CI 1.187-4.936); p = 0.015], and resected segments ≥ 3 [HR 4.700; (95% 1.926-11.467); p = 0.001] as the major significant determinants of the 90-day mortality. CONCLUSION: Advanced patient age, pre-existing chronic renal insufficiency, Child-Pugh Score, extended hepatic resection, and vascular tumor involvement were identified as significant predictive factors of 90-day mortality. Proper patient selection and adjustment of treatment strategies could potentially reduce short-term mortality.

Which factors predict tumor recurrence and survival after curative hepatectomy in hepatocellular carcinoma? Results from a European institution.

BACKGROUND: High tumor recurrence and dismal survival rates after curative intended resection for hepatocellular carcinoma (HCC) are still concerning. The primary goal was to assess predictive factors associated with disease-free (DFS) and overall survival (OS) in a subset of patients with HCC undergoing hepatic resection (HR). METHODS: Between 08/2004-7/2021, HR for HCC was performed in 188 patients at our institution. Data allocation was conducted from a prospectively maintained database. The prognostic impact of clinico-pathological factors on DFS and OS was assessed by using uni- and multivariate Cox regression analyses. Survival curves were generated with the Kaplan Meier method. RESULTS: The postoperative 1-, 3- and 5- year overall DFS and OS rates were 77.9%, 49.7%, 41% and 72.7%, 54.7%, 38.8%, respectively. Tumor diameter ≥ 45 mm [HR 1.725; (95% CI 1.091-2.727); p = 0.020], intra-abdominal abscess [HR 3.812; (95% CI 1.859-7.815); p < 0.0001], and preoperative chronic alcohol abuse [HR 1.831; (95% CI 1.102-3.042); p = 0.020] were independently predictive for DFS while diabetes mellitus [HR 1.714; (95% CI 1.147-2.561); p = 0.009), M-Stage [HR 2.656; (95% CI 1.034-6.826); p = 0.042], V-Stage [HR 1.946; (95% CI 1.299-2.915); p = 0.001, Sepsis [HR 10.999; (95% CI 5.167-23.412); p < 0.0001], and ISGLS B/C [HR 2.008; (95% CI 1.273-3.168); p = 0.003] were significant determinants of OS. CONCLUSIONS: Despite high postoperative recurrence rates, an acceptable long-term survival in patients after curative HR could be achieved. The Identification of parameters related to OS and DFS improves patient-centered treatment and surveillance strategies.

Quality of Life in Patients with Pancreatic Cancer before and during the COVID-19 Pandemic.

BACKGROUND: Coronavirus disease 19 (COVID-19) substantially affects cancer patients due to adverse outcomes and disruptions in cancer care. Recent studies have indicated the additional stress and anxiety burden arising from the pandemic and impairing quality of life in this vulnerable group of patients. However, patients with cancer represent a heterogenous group. Therefore, we conducted a study on patients with pancreatic cancer, requiring demanding surgical interventions and chemotherapy regimens due to its aggressive tumor biology, to explore the pandemic's impact on quality of life within this homogenous cohort. METHODS: In a descriptive observational study, the quality of life of patients who had undergone pancreatic surgery for tumor resection at our institution between 2014 and the beginning of the pandemic in March 2020 was assessed. For HRQoL measurement, we used the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30), comparing their situation before the pandemic and since its beginning. An additional self-developed questionnaire was applied to assess the life circumstances during the pandemic. RESULTS: Our cohort included 26 patients. Scores from the survey in HRQoL revealed no significant changes over time between before and during the pandemic. A medium deterioration in HRQoL was apparent in social functioning, as well as a small deterioration in role functioning and emotional functioning. Worries concerning a potential impact of COVID-19 on personal health were expressed. Psychological limitations in QoL were mainly attributed to the pandemic, whereas physical limitations in QoL were rather associated with the underlying disease of pancreatic cancer. CONCLUSION: The COVID-19 pandemic is causing considerable social and emotional distress among pancreatic cancer patients. These patients will benefit from psychological support during the pandemic and beyond. Long-time survivors of pancreatic cancer, such as those included in our cohort, appear to have improved resilience facing the psychosocial challenges of the pandemic. For pancreatic cancer, surgical care is considered the cornerstone of treatment. Prolonged delays in healthcare cause serious damage to mental and physical health. To date, the longer-term clinical consequences are not known and can only be estimated. The potential tragic outcome for the vulnerable group of pancreatic cancer patients highlights the urgency of timely healthcare decisions to be addressed in the future.

Repeated liver resection for recurrent hepatocellular carcinoma.

BACKGROUND AND AIM: Tumor recurrence after liver resection occurs in the majority of patients with hepatocellular carcinoma (HCC). This study was conducted to clarify the safety and effectiveness of repeated liver resection as a curative option for intrahepatic HCC recurrence. METHODS: Between July 1990 and January 2009, 483 patients underwent 514 curative hepatic resections for HCC in our institution. Among this collective, 27 patients underwent 31 repeated resections due to recurrent HCC (27 s resections, three third resections and one forth resection). The outcome of these patients was retrospectively reviewed using a prospective database. RESULTS: Perioperative morbidity and mortality was 11% (three of 27) and 0%. Six patients showed multiple liver lesions, 23 underwent minor liver resections (fewer than three segments) and five patients underwent major resections (three or more segments). The majority of the patients showed no signs of chronic liver disease (16 of 27). The median tumor free margin was 1.5 mm (range: 0 to 20 mm). The median tumor diameter was 40 mm (range: 10 to 165 mm). Tumor dedifferentiations at time of tumor recurrence were not observed. The 1-, 3- and 5-year overall survival rates after second liver resection were 96%, 70% and 42%. CONCLUSIONS: Repeated liver resection is a valid and safe curative therapy option for recurrent HCC and results in significant prolongation of survival in comparison to interventional treatment strategies in selected patients. However, due to impaired liver function, multifocal intrahepatic or extrahepatic recurrence repeated resection is only feasible in a minority of patients.

The gene polymorphism of the angiotensin I-converting enzyme correlates with tumor size and patient survival in colorectal cancer patients.

We studied the putative significance of angiotensin I-converting enzyme (ACE) in colorectal cancer (CRC) biology. Local expression of ACE was investigated by quantitative reverse transcription-polymerase chain reaction and by immunohistochemistry in CRCs and adenomas. ACE insertion (I)/deletion (D) polymorphism was studied in 141 CRC patients and 189 controls. ACE mRNA was upregulated in CRCs compared to corresponding nonlesional tissues (2.5-fold; P = .009). ACE protein was more commonly expressed in adenomas [17 (81%)] and cancer epithelial cells [22 (100%)] than in corresponding non-neoplastic crypt and surface epithelium [2 (10%) and 2 (9%), respectively]. Thirty-seven CRC patients (26%) carried II genotype, 69 (49%) carried ID genotype, and 35 (25%) carried DD genotype. The distribution of the genotypes did not differ from that of controls. Female CRC patients more commonly carried the ID genotype and less frequently the II and DD genotypes compared with male patients (P = .033). Men heterozygous or homozygous for the D-allele had larger tumors compared to carriers of the II genotype (P < .01). Women homozygous for the D-allele lived longer than carriers of the ID and II genotypes. Our study shows that ACE is differentially expressed in CRCs and that gene polymorphism is associated with gender-specific differences in primary tumor size and patient survival.

Intravenous administration of glutathione protects parenchymal and non-parenchymal liver cells against reperfusion injury following rat liver transplantation.

AIM: To investigated the effects of intravenous administration of the antioxidant glutathione (GSH) on reperfusion injury following liver transplantation. METHODS: Livers of male Lewis rats were transplanted after 24 h of hypothermic preservation in University of Wisconsin solution in a syngeneic setting. During a 2-h reperfusion period either saline (controls, n=8) or GSH (50 or 100 micromol/(h/kg), n=5 each) was continuously administered via the jugular vein. RESULTS: Two hours after starting reperfusion plasma ALT increased to 1457+/-281 U/L (mean+/-SE) in controls but to only 908+/-187 U/L (P<0.05) in animals treated with 100 microGSH/(h/kg). No protection was conveyed by 50 micromol GSH(h/kg). Cytoprotection was confirmed by morphological findings on electron microscopy: GSH treatment prevented detachment of sinusoidal endothelial cells (SEC) as well as loss of microvilli and mitochondrial swelling of hepatocytes. Accordingly, postischemic bile flow increased 2-fold. Intravital fluorescence microscopy revealed a nearly complete restoration of sinusoidal blood flow and a significant reduction of leukocyte adherence to sinusoids and postsinusoidal venules. Following infusion of 50 micromol and 100 micromol GSH/(h/kg), plasma GSH increased to 65+/-7 mol/L and 97+/-18 mol/L, but to only 20+/-3 mol/L in untreated recipients. Furthermore, plasma glutathione disulfide (GSSG) increased to 7.5+/-1.0 mol/L in animals treated with 100 micro(h/kg) GSH but did not raise levels of untreated controls (1.8+/-0.5 mol/L) following infusion of 50 microGSH/(h/kg) (2.2+/-0.2 mol/L). CONCLUSION: Plasma GSH levels above a critical level may act as a "sink" for ROS produced in the hepatic vasculature during reperfusion of liver grafts. Therefore, GSH can be considered a candidate antioxidant for the prevention of reperfusion injury after liver transplantation, in particular since it has a low toxicity in humans.