Robotic Complete ALPPS (rALPPS)-First German Experiences.

BACKGROUND: ALPPS leads to fast and effective liver hypertrophy. This enables the resection of extended tumors. Conventional ALPPS is associated with high morbidity and mortality. MILS reduces morbidity and the robot adds technical features that make complex procedures safe. MATERIAL AND METHODS: The MD-MILS was screened for patients who underwent rALPPS. Demographic and perioperative data were evaluated retrospectively. Ninety days postoperative morbidity was scored according to the CD classification. The findings were compared with the literature. RESULTS: Since November 2021, five patients have been identified. The mean age and BMI of the patients were 50.0 years and 22.7 kg/m2. In four cases, patients suffered from colorectal liver metastases and, in one case, intrahepatic cholangiocarcinoma. Prior to the first operation, the mean liver volume of the residual left liver was 380.9 mL with a FLR-BWR of 0.677%. Prior to the second operation, the mean volume of the residual liver was 529.8 mL with a FLR-BWR of 0.947%. This was an increase of 41.9% of the residual liver volume. The first and second operations were carried out within 17.8 days. The mean time of the first and second operations was 341.2 min and 440.6 min. The mean hospital stay was 27.2 days. Histopathology showed the largest tumor size of 39 mm in diameter with a mean amount of 4.7 tumors. The mean tumor-free margin was 12.3 mm. One complication CD > 3a occurred. No patient died during the 90-day follow up. CONCLUSION: In the first German series, we demonstrated that rALPPS can be carried out safely with reduced morbidity and mortality in selected patients.

Tumor visualization and fluorescence angiography with indocyanine green (ICG) in laparoscopic and robotic hepatobiliary surgery - valuation of early adopters from Germany.

OBJECTIVES: Indocyanine green (ICG) is a fluorescent dye which was initially used for liver functional assessment. Moreover, it is of value for intraoperative visualization of liver segments and bile ducts or primary and secondary liver tumors. Especially in minimally invasive liver surgery, this is essential to enhance the precision of anatomical guided surgery and oncological quality. As early adopters of ICG implementation into laparoscopic and robotic-assisted liver surgery in Germany, we summarize the current recommendations and share our experiences. METHODS: Actual strategies for ICG application in minimally invasive liver surgery were evaluated and summarized during a review of the literature. Experiences in patients who underwent laparoscopic or robotic-assisted liver surgery with intraoperative ICG staining between 2018 and 2020 from the Magdeburg registry for minimally invasive liver surgery (MD-MILS) were evaluated and the data were analyzed retrospectively. RESULTS: ICG can be used to identify anatomical liver segments by fluorescence angiography via direct or indirect tissue staining. Fluorescence cholangiography visualizes the intra- and extrahepatic bile ducts. Primary and secondary liver tumors can be identified with a sensitivity of 69-100%. For this 0.5 mg/kg body weight ICG must be applicated intravenously 2-14 days prior to surgery. Within the MD-MILS we identified 18 patients which received ICG for intraoperative tumor staining of hepatocellular carcinoma (HCC), cholangiocarcinoma, peritoneal HCC metastases, adenoma, or colorectal liver metastases. The sensitivity for tumor staining was 100%. In 27.8% additional liver tumors were identified by ICG fluorescence. In 39% a false positive signal could be detected. This occurred mainly in cirrhotic livers. CONCLUSIONS: ICG staining is a simple and useful tool to assess individual hepatic anatomy or to detect tumors during minimally invasive liver surgery. It may enhance surgical precision and improve oncological quality. False-positive detection rates of liver tumors can be reduced by respecting the tumor entity and liver functional impairments.

Robotic and laparoscopic liver surgery for colorectal liver metastases: an experience from a German Academic Center.

BACKGROUND: Minimally invasive liver surgery (MILS) in the treatment of colorectal liver metastases (CRLM) is increasing in incidence. The aim of this work was to present our experience by reporting short-term and long-term outcomes after MILS for CRLM with comparative analysis of laparoscopic (LLS) and robotic liver surgery (RLS). METHODS: Twenty-five patients with CRLM, who underwent MILS between May 2012 and March 2020, were selected from our retrospective registry of minimally invasive liver surgery (MD-MILS). Thirteen of these patients underwent LLS and 12 RLS. Short-term and long-term outcomes of both groups were analyzed. RESULTS: Operating time was significantly longer in the RLS vs. the LLS group (342.0 vs. 200.0 min; p = 0.004). There was no significant difference between the laparoscopic vs. the robotic group regarding length of postoperative stay (8.8 days), measured blood loss (430.4 ml), intraoperative blood transfusion, overall morbidity (20.0%), and liver surgery related morbidity (4%). The mean BMI was 27.3 (range from 19.2 to 44.8) kg/m2. The 30-day mortality was 0%. R0 resection was achieved in all patients (100.0%) in RLS vs. 10 patients (76.9%) in LLS. Major resections were carried out in 32.0% of the cases, and 84.0% of the patients showed intra-abdominal adhesions due to previous abdominal surgery. In 24.0% of cases, the tumor was bilobar, the maximum number of tumors removed was 9, and the largest tumor was 8.5 cm in diameter. The 1-, 3- and 5-year overall survival rates were 84, 56.9, and 48.7%, respectively. The 1- and 3-year overall recurrence-free survival rates were 49.6 and 36.2%, respectively, without significant differences between RLS vs. LLS. CONCLUSION: Minimally invasive liver surgery for CRLM is safe and feasible. Minimally invasive resection of multiple lesions and large tumors is also possible. RLS may help to achieve higher rates of R0 resections. High BMI, previous abdominal surgery, and bilobar tumors are not a barrier for MILS. Laparoscopic and robotic liver resections for CRLM provide similar long-term results which are comparable to open techniques.

Radioablation by Image-Guided (HDR) Brachytherapy and Transarterial Chemoembolization in Hepatocellular Carcinoma: A Randomized Phase II Trial.

BACKGROUND AND AIMS: The aim of this single-center, open-label phase II study was to assess the efficacy of image-guided high-dose-rate (HDR) brachytherapy (iBT) compared with conventional transarterial embolization (cTACE) in unresectable hepatocellular carcinoma. METHODS: Seventy-seven patients were treated after randomization to iBT or cTACE, as single or repeated interventions. Crossover was allowed if clinically indicated. The primary endpoint was time to untreatable progression (TTUP). Eligibility criteria included a Child-Pugh score of ≤ 8 points, absence of portal vein thrombosis (PVT) at the affected liver lobe, and ≤ 4 lesions. Survival was analyzed by using the Cox proportional hazard model with stratification for Barcelona Clinic Liver Cancer (BCLC) stages. RESULTS: Twenty patients were classified as BCLC-A (iBT/cTACE 8/12), 35 as BCLC-B (16/19), and 22 as BCLC-C (13/9). The 1-, 2-, and 3-year TTUP probabilities for iBT compared with cTACE were 67.5% versus 55.2%, 56.0% versus 27.4%, and 29.5% versus 11.0%, respectively, with an adjusted hazard ratio (HR) of 0.49 (95% confidence interval 0.27-0.89; p = 0.019). The 1-, 2-, and 3-year TTPs for iBT versus cTACE were 56.0% versus 28.2%, 23.9% versus 6.3%, and 15.9% versus 6.3%, respectively, with an adjusted HR of 0.49 (0.29-0.85; p = 0.011). The 1-, 2-, and 3-year OS rates were 78.4% versus 67.7%, 62.0% versus 47.3%, and 36.7% versus 27.0%, respectively, with an adjusted HR of 0.62 (0.33-1.16; p = 0.136). CONCLUSIONS: This explorative phase II trial showed a superior outcome of iBT compared with cTACE in hepatocellular carcinoma and supports proceeding to a phase III trial.

Staple Line Leak After Primary Sleeve Gastrectomy-Risk Factors and Mid-term Results: Do Patients Still Benefit from the Weight Loss Procedure?

BACKGROUND: Staple line leak after laparoscopic sleeve gastrectomy (LSG) still represents the most feared complication. The purpose of this study was to investigate whether there are factors that increase the risk for a leakage. Furthermore, we aimed to analyze the impact of a leak on weight change and resolution of comorbidities. METHODS: Since 2005, data from obese patients that undergo bariatric procedures in Germany are prospectively registered. For the current analysis, all adult subjects that had undergone primary LSG from 2005 to 2014 were considered. RESULTS: Overall, 241/15,756 (1.53%) patients experienced a leak. The occurrence of a leakage resulted in a significant increase of the mortality rate (3.7 vs. 0.2%; p < 0.01). Percent excess weight loss did not differ between leak and non-leak patients, both, at 12 (64.2 vs. 60.9%; p = 1.0) and 24 months (68.5 vs. 64.0%, p = 0.86). Similarly, no significant difference was observed for resolution rate of all comorbid conditions. Matched pair analysis confirmed these findings. Multivariable analysis identified operation time, conversion, intraoperative complications, and hypertension and degenerative joint disease as risk factors for a leak. Oversewing the staple line was associated with the lowest risk. CONCLUSION: The postoperative staple line leak after primary LSG significantly increases postoperative morbidity and mortality. We found that there are patient-related factors and operative variables that predispose to leakage after LSG. However, the occurrence of a leakage does not adversely impact the weight loss and resolution of comorbidities in the mid-term.

Significance of a Single-Time-Point Somatostatin Receptor SPECT/Multiphase CT Protocol in the Diagnostic Work-up of Gastroenteropancreatic Neuroendocrine Neoplasms.

UNLABELLED: This prospective study compared a 1-d SPECT/CT protocol with the commonly used 3-d protocol for somatostatin receptor scintigraphy in patients with gastroenteropancreatic neuroendocrine neoplasms. Additionally, the influence of SPECT/CT on patient management was evaluated. METHODS: From October 2011 to October 2012, all gastroenteropancreatic neuroendocrine neoplasm patients undergoing restaging with somatostatin receptor scintigraphy on a modern SPECT/CT device were enrolled in this study. The protocol consisted of planar imaging at 4, 24, and 48 h; low-dose SPECT/CT at 24 and 48 h; diagnostic CT at 24 h using a triple-phase delay after administration of contrast; and diagnostic SPECT/CT at 24 h. All components of the imaging data were reassessed by 3 masked interpreters. The results were compared with a reference standard based on all clinical, imaging, and histopathology follow-up data available (follow-up range, 24-36 mo; mean, 29.9 mo). The reference standard was defined by a study-specific interdisciplinary tumor board that also reassessed treatment decisions. RESULTS: Thirty-one patients were eligible for analysis (18 men and 13 women; mean age, 60.4 y). Ten had no imaging signs of disease and remained disease-free during follow-up. Twenty-one had persistent or recurrent disease (82 lesions: 24 in the liver, 21 in the lymph nodes, 16 in bone, 12 in the pancreas, and 9 in other locations). The respective lesion detection rates for interpreters 1, 2, and 3 were 51.9%, 49.4%, and 71.6% for low-dose SPECT/CT at 24 h; 51.9%, 55.6%, and 67.9% for low-dose SPECT/CT at 48 h; 63.0%, 70.4%, and 85.2% for diagnostic CT; and 77.8%, 84.0%, and 88.9% for diagnostic SPECT/CT. Interobserver agreement was moderate for diagnostic SPECT/CT (κ = 0.44), diagnostic CT (κ = 0.43), low-dose SPECT/CT at 48 h (κ = 0.61), and low-dose SPECT/CT at 24 h (κ = 0.55). For planar imaging, interobserver agreement was fair after 48 h (κ = 0.36) and 24 h (κ = 0.38) and moderate after 4 h (κ = 0.42). Every lesion detectable on planar imaging or low-dose SPECT/CT was also detectable on diagnostic SPECT/CT. The CT and SPECT components of diagnostic SPECT/CT strongly complemented each other, as 34 of 82 lesions (41.4%) were detected on only the CT component or only the SPECT component. Therapeutic management was influenced by the diagnostic SPECT/CT interpretation in 8 of 31 patients (25.8%). CONCLUSION: The highest detection rates were achieved by diagnostic SPECT/CT. Thus, a more patient-friendly 1-d protocol is feasible. Furthermore, multiphase SPECT/CT affected management in about a quarter of patients.

Malnutrition is a prognostic factor in patients with hepatocellular carcinoma (HCC).

BACKGROUND & AIMS: Malnutrition is a common, hence frequently underdiagnosed condition in patients with liver cirrhosis as well as in patients with cancer and has been shown to have a negative impact on survival in these patients. Frequently applied screening tools including anthropometric measurements or laboratory parameters to screen for malnutrition are not suitable for patients with liver cirrhosis with additional pathophysiological mechanisms leading to hypoalbuminemia and edema. Prospective data on the prevalence and prognostic impact of malnutrition in patients with HCC are scarce. METHODS: Fifty-one consecutive patients with hepatocellular carcinoma were prospectively enrolled into this study and screened for malnutrition by anthropometric measurements, the MNA score, the NRS score, laboratory work-up, and BIA measurement. The results of the different screening tools were compared to each other and with the BIA assessment and correlated with the outcome of patients. RESULTS: The calculation of a body mass index (BMI) was not suitable to identify malnourished patients with HCC. The MNA identified 19, the NRS score 17 patients at a risk for malnutrition. BIA revealed a reduction in relative body cell mass in 12 patients. Univariate Cox regression analyses identified tumor stage, MNA score, and phase angle obtained by BIA as significant factors with influence on survival. Multivariate analyses confirmed the phase angle at a cut-off of 4.8 to be an independent factor. CONCLUSIONS: A significant proportion of patients with HCC is malnourished or at risk for malnutrition. Screening questionnaires and BIA measurement are superior to pure anthropometric measurements to identify the condition that negatively influences survival. The phase angle derived from body impedance analysis is an independent prognostic factor in patients with HCC.

Characterization and prognosis of patients with hepatocellular carcinoma (HCC) in the non-cirrhotic liver.

BACKGROUND: HCC predominantly develops in the condition of chronic inflammation that has led to liver cirrhosis. A small proportion of patients with HCC is diagnosed in the non-cirrhotic liver (NCL). Data on patients with HCC in NCL in advanced stages are scarce. METHODS: A retrospective analysis was performed comparing 93 patients with HCC in NCL to 571 patients with HCC in liver cirrhosis (LC) with respect to clinical and demographic characteristics. Also factors influencing survival in patients with HCC in NCL were analyzed. RESULTS: Patients with HCC in NCL were diagnosed at older age and in more advanced tumor stages than patients with LC. More than 25% of patients with HCC in NCL presented with extrahepatic metastases. Only a minority of patients with HCC in NCL lacked any sign of hepatic damage. Risk factors for LC and risk factors for NAFLD are present in the majority of patients with HCC in NCL. The BCLC classification corresponded with the survival of patients with HCC in NCL although the therapeutic options differ from those for patients with liver cirrhosis. CONCLUSIONS: It will be one of the major challenges in the future to awake awareness of carrying a risk of hepatic malignancies in patients with chronic liver diseases apart from liver cirrhosis, especially in NAFLD. Surveillance programs need to be implemented if these are cost-effective.

Gastric high-risk gist and retroperitoneal liposarcoma--a challenging combination of two mesenchymal tumor lesions with regard to diagnosis and treatment.

Both gastrointestinal stromal tumors (GIST) and liposarcoma originate from mesenchymal tissue. Their coincidence requires a specific expertise in the diagnostic and therapeutic management. An unusual exemplary case is described representing a 47-year old female patient with a gastric GIST and a monstrous retroperitoneal liposarcoma with infiltration of the left kidney. The gastric tumor lesion was removed with a tangential resection of the gastric wall; the retroperitoneal tumor lesion was resected including the left kidney. Both tumors were resected with no macroscopic tumor residual. The technically difficult surgical intervention did not show any postoperative complication, and the postoperative course was also uneventful. The complete tumor resection is the treatment of choice in mesenchymal tumors (aim: R0). Depending on histologic tumor classification, resection status and tumor sensitivity, a subsequent radiation and/or chemotherapy is necessary, which allowed to achieve a postoperative tumor-free survival of 6 years including a good quality of life.

Clinical characteristics and time trends in etiology of hepatocellular cancer in Germany.

INTRODUCTION: The incidence of hepatocellular cancer (HCC) continues to rise in Europe with a shift of the primary cause towards alcoholic and non-alcoholic fatty liver disease. Metabolic factors like diabetes mellitus and overweight have been identified as significant risk factors for HCC development. PATIENTS AND METHODS: A retrospective analysis in a large single-center cohort of 650 patients diagnosed with HCC was performed. Demographic characteristics, risk factors, tumor stage at diagnosis and survival were evaluated. RESULTS: Among 650 patients (aged 17-87 years, with a male: female ratio of 4:1), 80.8% had underlying liver cirrhosis. Alcohol abuse was identified as the only risk factor for liver cirrhosis in 52.2% of patients. Viral infection with hepatitis C and hepatitis B was present in 13.7 and 3.6% of patients, respectively. 66.1% of patients with HCC were overweight with a body mass index exceeding 25, 25.5% even exceeding 30; 52% of patients had diabetes mellitus. CONCLUSION: Strategies aiming at prevention and surveillance of patients at risk to develop HCC in the future need to widen the focus from patients with chronic viral hepatitis and a history of alcohol abuse to patients with metabolic risk factors.

Delayed Diagnosis of HCC with Chronic Alcoholic Liver Disease.

BACKGROUND: Adherence to surveillance recommendations for patients at risk of developing hepatocellular carcinoma (HCC) is influenced by several factors, including the etiology of chronic liver disease. AIM: The aim of this study was to analyze whether tumor stage at diagnosis and prognosis differ in patients with alcohol-related HCC compared to those with chronic viral hepatitis-related HCC. PATIENTS AND METHODS: Medical records of 650 patients diagnosed with HCC between 1994 and 2011 were analyzed retrospectively. Groups were formed from patients having either alcohol abuse or viral hepatitis (chronic hepatitis B or C virus infection) as the only known HCC risk factors. Demographic data (age and gender), tumor stage at diagnosis, survival, liver function [Child-Pugh-Turcotte (CPT) score] in patients with liver cirrhosis, complications of liver cirrhosis, and serologic parameters were compared between the two groups. RESULTS: A total of 393 HCC cases (male 84%, median age 65 years) were identified, with alcohol abuse as the causative factor in 76.8% and chronic viral hepatitis in 23.2%. In patients with alcohol abuse, 278 (92.1%) were diagnosed with liver cirrhosis (CPT A 49.3%, CPT B 31.1%, CPT C 9.6%), while in patients with viral hepatitis, 84 (92.3%) suffered from liver cirrhosis (CPT A 59.3%, CPT B 23.1%, CPT C 8.8%). Tumor stage in patients with alcohol abuse was Barcelona Clinic Liver Cancer (BCLC) C in 43.7%, BCLC B in 30.5%, and BCLC A in 14.6%. Patients with viral hepatitis showed a trend toward diagnosis at an earlier tumor stage (BCLC B 35.2%, BCLC C 34.1%, BCLC A 22.2%). Etiology of liver cirrhosis did not significantly influence survival in intermediate and advanced tumor stages, but BCLC-A patients with alcohol-related disease demonstrated prolonged survival compared to patients with viral hepatitis. CONCLUSION: Tumor stage at diagnosis of HCC is influenced by the etiology of underlying chronic liver disease and is more progressed in patients having a disease with alcoholic etiology. Majority of HCC patients are not diagnosed at a curable stage, which underlines the need for specialized care for all patients with chronic liver disease, independent of etiology and consequent adherence to current surveillance guidelines.