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.

Identification of myeloid-derived growth factor as a mechanically-induced, growth-promoting angiocrine signal for human hepatocytes.

Recently, we have shown that after partial hepatectomy (PHx), an increased hepatic blood flow initiates liver growth in mice by vasodilation and mechanically-triggered release of angiocrine signals. Here, we use mass spectrometry to identify a mechanically-induced angiocrine signal in human hepatic endothelial cells, that is, myeloid-derived growth factor (MYDGF). We show that it induces proliferation and promotes survival of primary human hepatocytes derived from different donors in two-dimensional cell culture, via activation of mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3). MYDGF also enhances proliferation of human hepatocytes in three-dimensional organoids. In vivo, genetic deletion of MYDGF decreases hepatocyte proliferation in the regenerating mouse liver after PHx; conversely, adeno-associated viral delivery of MYDGF increases hepatocyte proliferation and MAPK signaling after PHx. We conclude that MYDGF represents a mechanically-induced angiocrine signal and that it triggers growth of, and provides protection to, primary mouse and human hepatocytes.

Optimizing Growth of the Future Liver Remnant and Making In-Situ Liver Transsection Safe-A Standardized Approach to ISLT or ALPPS.

In-situ splitting of the liver before extended resection has gained broad attention. This two-step procedure requires several measures to make an effective and safe procedure. Although the procedure is performed in many institutions, there is no consensus on a uniform technique. The two steps can be divided into different parts and a standardized technique may render the procedure safer and the results will be easier to evaluate. In this paper, we describe a detailed approach to in-situ splitting that allows making both procedures safe, avoids liver necrosis, and is easily reproducible. In the first procedure the portal branches to segments I and IV to VIII are divided, the arterial branches and bile ducts to these segments are preserved and encircled and the parenchyma between segments II/III and IVa/b is divided. This avoids necrosis and bile leaks of segments I and IV and avoids urgent completion operations. In particular, the handling of vital structures close to the dissection line seems important to us. Complete splitting and securing the right and middle hepatic vein will make the second step of this procedure a minimal-risk procedure at a stage where the patient is still recovering from the more demanding first step.

A single center comparative retrospective study of in situ split plus portal vein ligation versus conventional two-stage hepatectomy for cholangiocellular carcinoma.

INTRODUCTION: Cholangiocellular carcinoma (CCA) has a poor prognosis and the goldstandard even in locally advanced cases remains radical surgical resection. This approach however is limited by the future liver remnant volume (FLRV) after extensive parenchymal dissection leading to post-operative liver failure and high mortality rates. The aim of this study was to compare the outcome of in situ liver transection with portal vein ligation (ISLT) procedure and conventional two-stage hepatectomy with portal vein embolization (PVE/TSH) in patients with CCA. METHODS: All patients with CCA and insufficient FLR considered for either ISLT or PVE/TSH were analyzed for outcomes including post-operative morbidity, mortality, and overall survival rates (OS). RESULTS: Sixteen patients received ISLT and eight patients underwent PVE/TSH. The completion rate of the second stage in the PVE/TSH group was 62% and 100% in the ISLT group (p = 0.027). The overall 90-day morbidity rates including severe complications (Clavien-Dindo ≥3b) were comparable (PVE/TSH 40% vs. ISLT 69%, p = 0.262). The median OS (PVE/TSH 7 months vs. ISLT 3 months) and the 90-day mortality rates (PVE/TSH 0% vs. ISLT 50%) did not significantly differ between the two groups (p > 0.05). In multivariate analysis, biliary resection and reconstruction was the only risk factor independently associated with 90-day post-operative morbidity [HR = 20.0; 95%CI (1.68-238.63); p = 0.018]. CONCLUSION: Our results demonstrate comparable outcomes in both groups in a rather prognostically unfavorable disease. The completion rate in the ISLT group was significantly higher than in the PVE/TSH cohort. This work encourages specialized hepato-biliary-pancreatic centers in applying the ISLT procedure in selected cases with CCA.

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.

Vertical traction device prevents abdominal wall retraction and facilitates early primary fascial closure of septic and non-septic open abdomen.

PURPOSE: One of the major challenges in the management of patients with septic and non-septic open abdomen (OA) is to control abdominal wall retraction. The aim of this study was to evaluate the impact of a novel vertical traction device (VTD) on primary fascial closure (PFC) and prevention of fascial retraction. METHODS: Twenty patients treated with OA were included in this retrospective multicenter study. All patients were initially stabilized with laparostomy and the abdomen temporarily sealed either with a Bogotá bag or a negative pressure wound therapy system (NPWT). RESULTS: The mean duration of OA and fascia-to-fascia distance (FTF) prior to the VTD application were 3 days and 15 cm, respectively. At relook laparotomy 48 h after VTD implementation, the mean FTF distance significantly decreased to 10 cm (p = 0.0081). In all cases, PFC was achieved after a mean period of 7 days. Twelve patients received the VTD in combination with a NPWT, whereas in eight patients, the device was combined with an alternative temporary abdominal closure system (TAC). Although not statistically significant, the FTF distance remarkably decreased in both groups at relook laparotomy 48 h following the device implementation. The mean periods of PFC for patients with septic and non-septic OA were comparable (7.5 vs. 7 days). During follow-up, two patients developed an incisional hernia. CONCLUSION: Vertical traction device prevents fascial retraction and facilitates early PFC in OA. In combination with NPWT, rapid fascial closure of large abdominal defects can be achieved.

Peridural Anesthesia and Cancer-Related Survival after Surgery for Pancreatic Cancer-A Retrospective Cohort Study.

BACKGROUND: In patients with prostatic and breast cancer the application of peridural anesthesia (PDA) showed a beneficial effect on prognosis. This was explained by reduced requirements for general anesthetics and perioperative opioids as well as a lower perioperative stress level. The impact of PDA in patients with more aggressive types of cancer has not been completely elucidated. Here, we analyzed the prognostic influence of PDA on overall survival after surgery as primary in patients that underwent radical resection of pancreatic adenocarcinoma. METHODS: Records of 98 consecutive patients were reviewed. In 70 of these cases PDA was applied. Patient characteristics such as demographics, TNM stage, and operative data were retrospectively collected from medical records and analyzed. Survival data were analyzed by Cox's proportional hazard regression model. RESULTS: Overall, no significant prognostic influence of PDA on recurrence or overall survival (p = 0.762, Hazard Ratio [HR] 0.884, 95% confidence interval [CI] 0.398-1.961) was found. However, there was a trend towards a longer overall survival (p = 0.069, HR 0.394, 95% CI 0.144-1.078) associated with PDA in a subgroup of patients with better differentiation of pancreatic adenocarcinoma. CONCLUSION: The observation of longer survival associated with PDA in our subgroup of patients with better-differentiated pancreatic carcinomas is in line with previous reports on various other less aggressive tumor entities. Our results indicate that PDA might improve the oncological outcome of patients with pancreatic adenocarcinoma.

Repeated resection for recurrent intrahepatic cholangiocarcinoma: A retrospective German multicentre study.

BACKGROUND: Tumour recurrence is common after resection of intrahepatic cholangiocarcinoma (ICC). Repeated resection is a potential curative treatment, but outcomes are not well-defined thus far. The aim of this retrospective multicentre cohort study was to show the feasibility and survival of repeated resection of ICC recurrence. METHODS: Data were collected from 18 German hepato-pancreatico-biliary centres for patients who underwent repeated exploration of recurrent ICC between January 2008 and December 2017. Primary end points were overall (OS) and recurrence-free survival from the day of primary and repeated resection. RESULTS: Of 156 patients who underwent repeated exploration for recurrent ICC, 113 underwent re-resection. CA19-9 prior to primary resection, R status of first liver resection and median time to recurrence were significant determinants of repeated resectability. Median OS in the repeated resection group was 65.2 months, with consecutive 1-, 3- and 5-year OS of 98%, 78% and 57% respectively. After re-exploration, median OS from primary resection was 46.7 months, with a consecutive 1-, 3- and 5-year OS of 95%, 55% and 22% respectively. From the day of repeated resection, the median OS was 36.8 months, with a consecutive 1-, 3- and 5-year OS of 86%, 51% and 34% respectively. Minor morbidity (grade I+II) was present in 27%, grade IIIa-IVb morbidity in 20% and mortality in 3.5% of patients. CONCLUSION: Repeated resection of ICC has acceptable morbidity and mortality and seems to be associated with improved long-term survival. Structured follow-up after resection of ICC is necessary for early identification of these patients.

The "impossible" rectal anastomosis: a novel use for endoluminal vacuum-assisted therapy.

PURPOSE: Low rectal anastomoses can safely be performed, usually secured by a diverting ostomy. However, in cases of inflammation, extensive scarring, after extensive radiation, or after severe stapler dysfunction the risk for an anastomotic leak may become prohibitively high. We present a novel use for endoluminal vacuum-assisted therapy (EVAT) for otherwise "impossible" low rectal anastomoses. METHODS: Our initial series consisted of 14 consecutive patients who underwent prophylactic EVAT treatment due to unsafe low colorectal anastomosis. The vacuum sponge was placed intraoperatively in cases otherwise calling for a Hartmann's procedure. An open-pored polyurethane sponge was placed prophylactically transanally for a mean duration of 11 days. Patient characteristics, complications, and risk factors were prospectively collected from medical records and analyzed. RESULTS: Between March 2017 and September 2019, we performed this novel technique in 14 patients enabling us to perform an anastomosis. Our collective consisted of 4 female (29%) and 10 male (71%) patients with a medium age of 59 years. Underlying disease was colorectal cancer in 10 patients, ovarian cancer, perforated sigmoid diverticulitis, ischemic colitis and sarcoma in one patient each. Dominant factors putting the anastomosis at extremely high risk were acute inflammation (n = 2), frozen pelvis (n = 2), intraoperative local chemotherapy (n = 2), stapler dysfunction (n = 2), non-closable rectal stump (n = 2), empty pelvis (n = 1) and ultra-low anastomosis (n = 3). Prophylactic EVAT was successful in 92% and gastrointestinal continuity was preserved in all patients. CONCLUSION: This is the first description of prophylactic EVAT treatment. It seems to be a simple and safe method to enforce the high-risk low rectal anastomosis.

Negative Pressure Wound Therapy vs Conventional Wound Treatment in Subcutaneous Abdominal Wound Healing Impairment: The SAWHI Randomized Clinical Trial.

Importance: Negative pressure wound therapy (NPWT) is an established treatment option, but there is no evidence of benefit for subcutaneous abdominal wound healing impairment (SAWHI). Objective: To evaluate the effectiveness and safety of NPWT for SAWHI after surgery in clinical practice. Design, Setting, and Participants: The multicenter, multinational, observer-blinded, randomized clinical SAWHI study enrolled patients between August 2, 2011, and January 31, 2018. The last follow-up date was June 11, 2018. The trial included 34 abdominal surgical departments of hospitals in Germany, Belgium, and the Netherlands, and 539 consecutive, compliant adult patients with SAWHI after surgery without fascia dehiscence were randomly assigned to the treatment arms in a 1:1 ratio stratified by study site and wound size using a centralized web-based tool. A total of 507 study participants (NPWT, 256; CWT, 251) were assessed for the primary end point in the modified intention-to-treat (ITT) population. Interventions: Negative pressure wound therapy and conventional wound treatment (CWT). Main Outcomes and Measures: The primary outcome was time until wound closure (delayed primary closure or by secondary intention) within 42 days. Safety analysis comprised the adverse events (AEs). Secondary outcomes included wound closure rate, quality of life (SF-36), pain, and patient satisfaction. Results: Of the 507 study participants included in the modified ITT population, 287 were men (56.6%) (NPWT, 155 [60.5%] and CWT, 132 [52.6%]) and 220 were women (43.4%) (NPWT, 101 [39.5%] and CWT 119 [47.4%]). The median (IQR) age of the participants was 66 (18) years in the NPWT arm and 66 (20) years in the CWT arm. Mean time to wound closure was significantly shorter in the NPWT arm (36.1 days) than in the CWT arm (39.1 days) (difference, 3.0 days; 95% CI 1.6-4.4; P < .001). Wound closure rate within 42 days was significantly higher with NPWT (35.9%) than with CWT (21.5%) (difference, 14.4%; 95% CI, 6.6%-22.2%; P < .001). In the therapy-compliant population, excluding study participants with unauthorized treatment changes (NPWT, 22; CWT, 50), the risk for wound-related AEs was higher in the NPWT arm (risk ratio, 1.51; 95% CI, 0.99-2.35). Conclusions and Relevance: Negative pressure wound therapy is an effective treatment option for SAWHI after surgery; however, it causes more wound-related AEs. Trial Registration: ClinicalTrials.gov Identifier: NCT01528033.

In situ split plus portal vein ligation (ISLT) - a salvage procedure following inefficient portal vein embolization to gain adequate future liver remnant volume prior to extended liver resection.

BACKGROUND: Right extended liver resection is frequently required to achieve tumor-free margins. Portal venous embolization (PVE) of the prospective resected hepatic segments for conditioning segments II/III does not always induce adequate hypertrophy in segments II and III (future liver remnant volume (FLRV)) for extended right-resection. Here, we present the technique of in situ split dissection along segments II/III plus portal disruption to segments IV-VIII (ISLT) as a salvage procedure to overcome inadequate gain of FLRV after PVE. METHODS: In eight patients, FLRV was further pre-conditioned following failed PVE prior to hepatectomy (ISLT-group). We compared FLRV changes in the ISLT group with patients receiving extended right hepatectomy following sufficient PVE (PVEres-group). Survival of the ISLT-group was compared to PVEres patients and PVE patients with insufficient FLRV gain or tumor progress who did not receive further surgery (PVEnores-group). RESULTS: Patient characteristics and surgical outcome were comparable in both groups. The mean FLRV-to-body-weight ratio in the ISLT group was smaller than in the PVEres-group pre- and post-PVE. One intraoperative mortality due to a coronary infarction was observed for an ISLT patient. ISLT was successfully completed in the remaining seven ISLT patients. Liver function and 2-year survival of ~ 50% was comparable to patients with extended right hepatectomy after efficient PVE. Patients who received a PVE but who were not subsequently resected (PVEnores) demonstrated no survival beyond 4 months. CONCLUSION: Despite extended embolization of segments I and IV-VIII, ISLT should be considered if hypertrophy was not adequate. Liver function and overall survival after ISLT was comparable to patients with trisectionectomy after efficient PVE.

Hepatopancreatoduodenectomy -a controversial treatment for bile duct and gallbladder cancer from a European perspective.

BACKGROUND: Hepatopancreatoduodenectomy (HPD) is an aggressive operation for treatment of advanced bile duct and gallbladder cancer associated with high perioperative morbidity and mortality, and uncertain oncological benefit in terms of survival. Few reports on HPD from Western centers exist. The purpose of this study was to evaluate safety and efficacy for HPD in European centers. METHOD: Members of the European-African HepatoPancreatoBiliary Association were invited to report all consecutive patients operated with HPD for bile duct or gallbladder cancer between January 2003 and January 2018. The patient and tumor characteristics, perioperative and survival outcomes were analyzed. RESULTS: In total, 66 patients from 19 European centers were included in the analysis. 90-day mortality rate was 17% and 13% for bile duct and gallbladder cancer respectively. All factors predictive of perioperative mortality were patient and disease-specific. The three-year overall survival excluding 90-day mortality was 80% for bile duct and 30% for gallbladder cancer (P = 0.013). In multivariable analysis R0-resection had a significant impact on overall survival. CONCLUSION: HPD, although being associated with substantial perioperative mortality, can offer a survival benefit in patient subgroups with bile duct cancer and gallbladder cancer. To achieve negative resection margins is paramount for an improved survival outcome.

ALPPS in neuroendocrine liver metastases not amenable for conventional resection - lessons learned from an interim analysis of the International ALPPS Registry.

BACKGROUND: Surgery is the most effective treatment option for neuroendocrine liver metastases (NELM). This study investigated the role of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) as a novel strategy in treatment of NELM. METHODS: The International ALPPS Registry was reviewed to study patients who underwent ALPPS for NELM. RESULTS: From 2010 to 2017, 954 ALPPS procedures from 135 international centers were recorded in the International ALPPS Registry. Of them, 24 (2.5%) were performed for NELM. Twenty-one patients entered the final analysis. Overall grade ≥3b morbidity was 9% after stage 1 and 27% after stage 2. Ninety-day mortality was 5%. R0 resection was achieved in 19 cases (90%) at stage 2. Median follow-up was 28 (19-48) months. Median disease free survival (DFS) was 17.3 (95% CI: 7.1-27.4) months, 1-year and 2-year DFS was 73.2% and 41.8%, respectively. Median overall survival (OS) was not reached. One-year and 2-year OS was 95.2% and 95.2%, respectively. CONCLUSIONS: ALPPS appears to be a suitable strategy for inclusion in the multimodal armamentarium of well-selected patients with neuroendocrine liver metastases. In light of the morbidity in this initial series and a high rate of disease-recurrence, the procedure should be taken with caution.

Dorsal Track Control (DTC): A Modified Surgical Technique for Atraumatic Handling of the Distal Esophagus in Esophagojejunostomy.

Surgical therapy for adenocarcinoma of the esophagogastric junction II requires distal esophagectomy, in which a transhiatal management of the lower esophagus is critical. The 'dorsal track control' (DTC) maneuver presented here facilitates the atraumatic handling of the distal esophagus, in preparation for a circular-stapled esophagojejunostomy. It is based on a ventral semicircular incision in the distal esophagus, with an intact dorsal wall for traction control of the esophagus. The maneuver facilitates the proper placement of the purse-string suture, up to its tying (around the anvil), thus minimizing the manipulation of the remaining esophagus. Furthermore, the dorsally-exposed inner wall surface of the ventrally-opened esophagus serves as a guiding chute that eases anvil insertion into the esophageal lumen. We performed this novel technique in 21 cases, enabling a safe anastomosis up to 10 cm proximal to the Z-line. No anastomotic insufficiency was observed. The DTC technique improves high transhiatal esophagojejunostomy.