Recent outcomes of liver transplantation for Budd-Chiari syndrome: A study of the European Liver Transplant Registry (ELTR) and affiliated centers.

BACKGROUND AND AIMS: Management of Budd-Chiari syndrome (BCS) has improved over the last decades. The main aim was to evaluate the contemporary post-liver transplant (post-LT) outcomes in Europe. APPROACH AND RESULTS: Data from all patients who underwent transplantation from 1976 to 2020 was obtained from the European Liver Transplant Registry (ELTR). Patients < 16 years, with secondary BCS or HCC were excluded. Patient survival (PS) and graft survival (GS) before and after 2000 were compared. Multivariate Cox regression analysis identified predictors of PS and GS after 2000. Supplemental data was requested from all ELTR-affiliated centers and received from 44. In all, 808 patients underwent transplantation between 2000 and 2020. One-, 5- and 10-year PS was 84%, 77%, and 68%, and GS was 79%, 70%, and 62%, respectively. Both significantly improved compared to outcomes before 2000 ( p < 0.001). Median follow-up was 50 months and retransplantation rate was 12%. Recipient age (aHR:1.04,95%CI:1.02-1.06) and MELD score (aHR:1.04,95%CI:1.01-1.06), especially above 30, were associated with worse PS, while male sex had better outcomes (aHR:0.63,95%CI:0.41-0.96). Donor age was associated with worse PS (aHR:1.01,95%CI:1.00-1.03) and GS (aHR:1.02,95%CI:1.01-1.03). In 353 patients (44%) with supplemental data, 33% had myeloproliferative neoplasm, 20% underwent TIPS pre-LT, and 85% used anticoagulation post-LT. Post-LT anticoagulation was associated with improved PS (aHR:0.29,95%CI:0.16-0.54) and GS (aHR:0.48,95%CI:0.29-0.81). Hepatic artery thrombosis and portal vein thrombosis (PVT) occurred in 9% and 7%, while recurrent BCS was rare (3%). CONCLUSIONS: LT for BCS results in excellent patient- and graft-survival. Older recipient or donor age and higher MELD are associated with poorer outcomes, while long-term anticoagulation improves both patient and graft outcomes.

Integrating a microRNA signature as a liquid biopsy-based tool for the early diagnosis and prediction of potential therapeutic targets in pancreatic cancer.

INTRODUCTION: Pancreatic cancer is a highly aggressive cancer, and early diagnosis significantly improves patient prognosis due to the early implementation of curative-intent surgery. Our study aimed to implement machine-learning algorithms to aid in early pancreatic cancer diagnosis based on minimally invasive liquid biopsies. MATERIALS AND METHODS: The analysis data were derived from nine public pancreatic cancer miRNA datasets and two sequencing datasets from 26 pancreatic cancer patients treated in our medical center, featuring small RNAseq data for patient-matched tumor and non-tumor samples and serum. Upon batch-effect removal, systematic analyses for differences between paired tissue and serum samples were performed. The robust rank aggregation (RRA) algorithm was used to reveal feature markers that were co-expressed by both sample types. The repeatability and real-world significance of the enriched markers were then determined by validating their expression in our patients' serum. The top candidate markers were used to assess the accuracy of predicting pancreatic cancer through four machine learning methods. Notably, these markers were also applied for the identification of pancreatic cancer and pancreatitis. Finally, we explored the clinical prognostic value, candidate targets and predict possible regulatory cell biology mechanisms involved. RESULTS: Our multicenter analysis identified hsa-miR-1246, hsa-miR-205-5p, and hsa-miR-191-5p as promising candidate serum biomarkers to identify pancreatic cancer. In the test dataset, the accuracy values of the prediction model applied via four methods were 94.4%, 84.9%, 82.3%, and 83.3%, respectively. In the real-world study, the accuracy values of this miRNA signatures were 82.3%, 83.5%, 79.0%, and 82.2. Moreover, elevated levels of these miRNAs were significant indicators of advanced disease stage and allowed the discrimination of pancreatitis from pancreatic cancer with an accuracy rate of 91.5%. Elevated expression of hsa-miR-205-5p, a previously undescribed blood marker for pancreatic cancer, is associated with negative clinical outcomes in patients. CONCLUSION: A panel of three miRNAs was developed with satisfactory statistical and computational performance in real-world data. Circulating hsa-miRNA 205-5p serum levels serve as a minimally invasive, early detection tool for pancreatic cancer diagnosis and disease staging and might help monitor therapy success.

Robotic Versus Laparoscopic Liver Resection in Various Settings: An International Multicenter Propensity Score Matched Study of 10.075 Patients.

OBJECTIVE: To compare the perioperative outcomes of robotic liver surgery (RLS) and laparoscopic liver surgery (LLS) in various settings. BACKGROUND: Clear advantages of RLS over LLS have rarely been demonstrated, and the associated costs of robotic surgery are generally higher than those of laparoscopic surgery. Therefore, the exact role of the robotic approach in minimally invasive liver surgery remains to be defined. METHODS: In this international retrospective cohort study, the outcomes of patients who underwent RLS and LLS for all indications between 2009 and 2021 in 34 hepatobiliary referral centers were compared. Subgroup analyses were performed to compare both approaches across several types of procedures: (1) minor resections in the anterolateral (2, 3, 4b, 5, and 6) or (2) posterosuperior segments (1, 4a, 7, 8), and (3) major resections (≥3 contiguous segments). Propensity score matching was used to mitigate the influence of selection bias. The primary outcome was textbook outcome in liver surgery (TOLS), previously defined as the absence of intraoperative incidents ≥grade 2, postoperative bile leak ≥grade B, severe morbidity, readmission, and 90-day or in-hospital mortality with the presence of an R0 resection margin in case of malignancy. The absence of a prolonged length of stay was added to define TOLS+. RESULTS: Among the 10.075 included patients, 1.507 underwent RLS and 8.568 LLS. After propensity score matching, both groups constituted 1.505 patients. RLS was associated with higher rates of TOLS (78.3% vs 71.8%, P < 0.001) and TOLS+ (55% vs 50.4%, P = 0.026), less Pringle usage (39.1% vs 47.1%, P < 0.001), blood loss (100 vs 200 milliliters, P < 0.001), transfusions (4.9% vs 7.9%, P = 0.003), conversions (2.7% vs 8.8%, P < 0.001), overall morbidity (19.3% vs 25.7%, P < 0.001), and microscopically irradical resection margins (10.1% vs. 13.8%, P = 0.015), and shorter operative times (190 vs 210 minutes, P = 0.015). In the subgroups, RLS tended to have higher TOLS rates, compared with LLS, for minor resections in the posterosuperior segments (n = 431 per group, 75.9% vs 71.2%, P = 0.184) and major resections (n = 321 per group, 72.9% vs 67.5%, P = 0.086), although these differences did not reach statistical significance. CONCLUSIONS: While both produce excellent outcomes, RLS might facilitate slightly higher TOLS rates than LLS.

N-glycosylation Regulates Intrinsic IFN-γ Resistance in Colorectal Cancer: Implications for Immunotherapy.

BACKGROUND & AIMS: Advanced colorectal carcinoma (CRC) is characterized by a high frequency of primary immune evasion and refractoriness to immunotherapy. Given the importance of interferon (IFN)-γ in CRC immunosurveillance, we investigated whether and how acquired IFN-γ resistance in tumor cells would promote tumor growth, and whether IFN-γ sensitivity could be restored. METHODS: Spontaneous and colitis-associated CRC development was induced in mice with a specific IFN-γ pathway inhibition in intestinal epithelial cells. The influence of IFN-γ pathway gene status and expression on survival was assessed in patients with CRC. The mechanisms underlying IFN-γ resistance were investigated in CRC cell lines. RESULTS: The conditional knockout of the IFN-γ receptor in intestinal epithelial cells enhanced spontaneous and colitis-associated colon tumorigenesis in mice, and the loss of IFN-γ receptor α (IFNγRα) expression by tumor cells predicted poor prognosis in patients with CRC. IFNγRα expression was repressed in human CRC cells through changes in N-glycosylation, which decreased protein stability via proteasome-dependent degradation, inhibiting IFNγR-signaling. Downregulation of the bisecting N-acetylglucosaminyltransferase III (MGAT3) expression was associated with IFN-γ resistance in all IFN-γ-resistant cells, and highly correlated with low IFNγRα expression in CRC tissues. Both ectopic and pharmacological reconstitution of MGAT3 expression with all-trans retinoic acid increased bisecting N-glycosylation, as well as IFNγRα protein stability and signaling. CONCLUSIONS: Together, our results demonstrated that tumor-associated changes in N-glycosylation destabilize IFNγRα, causing IFN-γ resistance in CRC. IFN-γ sensitivity could be reestablished through the increase in MGAT3 expression, notably via all-trans retinoic acid treatment, providing new prospects for the treatment of immune-resistant CRC.

Evaluation of the effect of sleeve gastrectomy versus Roux-en-Y gastric bypass in patients with morbid obesity: multicenter comparative study.

INTRODUCTION: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the two most performed techniques in bariatric surgery. The aim of this study is to compare two surgical procedures in terms of weight loss and the development of comorbidities such as type II diabetes mellitus T2D, arterial hypertension, sleep apnea (OSAS), and gastroesophageal reflux disease (GERD). METHODS: Data from the German Bariatric Surgery Registry (GBSR) from 2005 to 2021 were used. 1,392 RYGB and 1,132 SG primary surgery patients were included. Minimum age 18 years; five-year follow-up data available. Tests were performed with a 5% significance level. RESULTS: Loss of follow-up 95.41% within five years. Five years after surgery, the RYGB showed significant advantages in terms of excess weight loss (%EWL 64.2% vs. 56.9%) and remission rates of the studied comorbidities: hypertension (54.4% vs. 47.8%), OSAS (64.5% vs. 50.1%), and GERD (86.1% vs. 66.9%). Compared to the pre-test, individuals diagnosed with insulin-dependent T2D showed significant improvements with RYGB over a five-year period (remission rate: 75% vs. 63%). In contrast, non-insulin-dependent T2D showed no significant difference between the two approaches (p = 0.125). CONCLUSION: Both surgical procedures resulted in significant weight loss and improved comorbidities. However, the improvement in comorbidities was significantly greater in patients who underwent RYGB than in those who underwent SG, suggesting that the RYGB technique is preferable. Nevertheless, RYGB requires a high degree of surgical skill. Therefore, acquiring expertise in the technical facets of the surgery is essential to achieving favorable outcomes.

Standardization of the Definition and Surgical Management of Splenic Flexure Carcinoma by an International Expert Consensus Using the Delphi Technique: Room for Improvement?

BACKGROUND: Surgical management of splenic flexure carcinoma remains controversial. OBJECTIVE: This study aimed to establish an expert international consensus on splenic flexure carcinoma management. DESIGN: A 3-round online-based Delphi study was conducted between September 2020 and April 2021. SETTING: The first round included 18 experts from 12 different countries. For the second and third rounds, each expert in the first round was asked to invite 2 more colorectal surgeons (n = 47). Out of 47 invited experts, 89% (n = 42) participated in the second and third rounds of the consensus. INTERVENTIONS: A total of 35 questions were created and sent via the online questionnaire tool. MAIN OUTCOME MEASURES: Levels of recommendation based on voting concordance were graded as follows: more than 75% agreement was defined as strong, between 50% and 75% as moderate, and below 50% as weak. RESULTS: There was moderate consensus on the definition of splenic flexure (55%) as 10 cm from either side where the distal transverse colon turns into the proximal descending colon. Also, experts recommended an abdominopelvic CT scan plus intraoperative exploration (moderate consensus, 72%) for tumor localization and cancer registry. Segmental colectomy was the preferred technique for the management of splenic flexure carcinoma in the elective setting (72%). Moderate consensus was achieved on the technique of complete mesocolic excision and central vascular ligation principles for splenic flexure carcinoma (74%). Only strong consensus was achieved on the surgical approach for minimally invasive surgery (88%). LIMITATIONS: Subjective decisions are based on individual expert clinical experience and not evidence based. CONCLUSIONS: This is the first internationally conducted Delphi consensus study regarding splenic flexure carcinoma. The definition of splenic flexure remains ambiguous. To more effectively compare oncologic outcomes among different cancer registries, guidelines need to be developed to standardize each domain and avoid arbitrary definitions. See Video Abstract at http://links.lww.com/DCR/C143 . ESTANDARIZACIN DE LA DEFINICIN Y MANEJO QUIRRGICO DEL CARCINOMA DE NGULO ESPLNICO ESTABLECIDO POR UN CONSENSO INTERNACIONAL DE EXPERTOS UTILIZANDO LA TCNICA DELPHI ESPACIO PARA MEJORAR: ANTECEDENTES:El tratamiento quirúrgico del cáncer de ángulo esplénico sigue siendo controvertido.OBJETIVO:Establecer un consenso internacional de expertos sobre el manejo del cáncer del ángulo esplénico.DISEÑO:Se condujo un estudio Delphi en línea de 3 rondas entre septiembre de 2020 y febrero de 2021.ESCENARIO:La primera ronda incluyó a 18 expertos de 12 países distintos. Para la segunda y tercera rondas, a cada experto de la primera ronda se le pidió que invitara a 2 cirujanos colorrectales más de su región (n = 47). De los 47 expertos invitados, el 89% (n = 42) participó en la segunda y tercera ronda del consenso.INTERVENCIONES:Se crearon y enviaron un total de 35 preguntas a través de la herramienta de cuestionario en línea.PRINCIPALES MEDIDAS DE RESULTADO:Los niveles de recomendación basados en la concordancia de votos fueron jerarquizados de la siguiente manera: más del 75% de acuerdo se definió como fuerte, entre 50 y 75% como moderado y por debajo del 50% como débil.RESULTADOS:Hubo un consenso moderado sobre la definición de ángulo esplénico (55%) como 10 cm desde cualquier lado donde el colon transverso distal se convierte en el colon descendente proximal. Así también, los expertos recomendaron la tomografía computarizada abdominopélvica más la exploración intraoperatoria (consenso moderado, 72%) para la localización del tumor y el registro del ángulo esplénico. La colectomía segmentaria fue la técnica preferida para el tratamiento del cáncer de ángulo esplénico en el caso de ser electivo (72%). Se logró un consenso moderado sobre la técnica de escisión completa del mesocolon y los principios de ligadura vascular a nivel central para el cáncer de ángulo esplénico (74%). Solo se logró un fuerte consenso sobre el abordaje quirúrgico para la cirugía mínimamente invasiva (88%).LIMITACIONES:Decisiones subjetivas basadas en la experiencia clínica de expertos individuales y no basadas en evidencia.CONCLUSIONES:Este es el primer estudio internacional de consenso Delphi realizado sobre el cáncer de ángulo esplénico. Si bien encontramos un consenso moderado sobre las modalidades de diagnóstico preoperatorio y el manejo quirúrgico, la definición de ángulo esplénico sigue siendo ambigua. Para comparar de manera más efectiva los resultados oncológicos entre diferentes registros de cáncer, se deben desarrollar pautas para estandarizar cada dominio y evitar definiciones arbitrarias. Consulte Video Resumen en http://links.lww.com/DCR/C143 . (Traducción-Dr. Osvaldo Gauto ).

Rapid, label-free classification of glioblastoma differentiation status combining confocal Raman spectroscopy and machine learning.

Label-free identification of tumor cells using spectroscopic assays has emerged as a technological innovation with a proven ability for rapid implementation in clinical care. Machine learning facilitates the optimization of processing and interpretation of extensive data, such as various spectroscopy data obtained from surgical samples. The here-described preclinical work investigates the potential of machine learning algorithms combining confocal Raman spectroscopy to distinguish non-differentiated glioblastoma cells and their respective isogenic differentiated phenotype by means of confocal ultra-rapid measurements. For this purpose, we measured and correlated modalities of 1146 intracellular single-point measurements and sustainingly clustered cell components to predict tumor stem cell existence. By further narrowing a few selected peaks, we found indicative evidence that using our computational imaging technology is a powerful approach to detect tumor stem cells in vitro with an accuracy of 91.7% in distinct cell compartments, mainly because of greater lipid content and putative different protein structures. We also demonstrate that the presented technology can overcome intra- and intertumoral cellular heterogeneity of our disease models, verifying the elevated physiological relevance of our applied disease modeling technology despite intracellular noise limitations for future translational evaluation.

Previous antibiotic therapy as independent risk factor for the presence of vancomycin-resistant enterococci in surgical inpatients. Results from a matched case-control study.

BACKGROUND: Investigation of risk factors for the presence of vancomycin-resistant enterococci (VRE) in inpatients on surgical wards and associated intensive care units of a German tertiary care hospital. METHODS: A single-centre retrospective matched case-control study was performed with surgical inpatients admitted between July 2013 and December 2016. Patients with in-hospital detection of VRE later than 48 h after admission were included and comprised 116 VRE-positive cases and 116 VRE-negative matched controls. VRE isolates of cases were typed by multi-locus sequence typing. RESULTS: ST117 was identified as the dominant VRE sequence type. Next to length of stay in hospital or on an intensive care unit and previous dialysis the case-control study revealed previous antibiotic therapy as a risk factor for the in-hospital detection of VRE. The antibiotics piperacillin/tazobactam, meropenem, and vancomycin were associated with the highest risks. After taking into account length of stay in hospital as possible confounder other potential contact-related risk factors such as previous sonography, radiology, central venous catheter, and endoscopy were not significant. CONCLUSIONS: Previous dialysis and previous antibiotic therapy were identified as independent risk factors for the presence of VRE in surgical inpatients.

Current status of metabolic surgery in patients with type I diabetes mellitus and obesity: a nationwide multicenter study.

PURPOSE: While obesity is prevalent among patients with type I diabetes mellitus (T1DM), the effects of metabolic surgery on patients with T1DM have not been adequately investigated. The study aims to investigate the perioperative outcomes and the improvement of comorbidity 1 year following metabolic surgery amongst this patient population. METHODS: In this study, we evaluated the effects of sleeve gastrectomy (SG) and Roux-Y gastric bypass (RYGB) on patients with T1DM and insulin resistance. RESULTS: One hundred forty-nine patients (SG n = 91 and RYGB n = 58) with obesity, T1DM, and insulin resistance were analyzed. There was no significant difference in BMI reduction and %EWL 1 year after surgery between the two groups. In the SG group, BMI reduction was 6.5 kg/m2 versus 5.9 kg/m2 in the RYGB group (p=0.406). The %EWL was 68.2 ± 25.2 in the RYGB group and 64.3 ± 21.5 in SG (p=0.332). There was also no significant difference in weight loss between the two groups (14.9 ± 5.4 kg in SG vs. 14.2 ± 7 kg in RYGB; p=0.548). In all patients, insulin requirements decreased after surgery, and in 22% of patients, insulin requirements were equivalent to those of normal-weight individuals. There was a significantly higher rate of remission of reflux in RYGB patients than in SG patients (94·44% vs 29·41; p<0.001). CONCLUSION: Patients with obesity and T1DM may benefit from metabolic surgery. Both methods produce satisfactory results in this group of patients regarding daily insulin requirements and treatment of obesity-related diseases. However, the decision of which procedure should be carried out still depends on the patient's general condition and the surgeon's technical ability.

Neoadjuvant radiochemotherapy with cisplatin/5-flourouracil or carboplatin/paclitaxel in patients with resectable cancer of the esophagus and the gastroesophageal junction - comparison of postoperative mortality and complications, toxicity, and pathological tumor response.

PURPOSE: In 2012, the CROSS trial implemented a new neoadjuvant radiochemotherapy protocol for patients with locally advanced, resectable cancer of the esophagus prior to scheduled surgery. There are only limited studies comparing the CROSS protocol with a PF-based (cisplatin/5-fluorouracil) nRCT protocol. METHODS: In this retrospective, monocentric analysis, 134 patients suffering from esophageal cancer were included. Those patients received either PF-based nRCT (PF group) or nRCT according to the CROSS protocol (CROSS group) prior to elective en bloc esophagectomy. Perioperative mortality and morbidity, nRCT-related toxicity, and complete pathological regression were compared between both groups. Logistic regression analysis was performed in order to identify independent factors for pathological complete response (pCR). RESULTS: Thirty-day/hospital mortality showed no significant differences between both groups. Postoperative complications ≥ grade 3 according to Clavien-Dindo classification were experienced in 58.8% (PF group) and 47.6% (CROSS group) (p = 0.2) respectively. nRCT-associated toxicity ≥ grade 3 was 30.8% (PF group) and 37.2% (CROSS group) (p = 0.6). There was no significant difference regarding the pCR rate between both groups (23.5% vs. 30.5%; p = 0.6). In multivariate analysis, SCC (OR 7.7; p < 0.01) and an initial grading of G1/G2 (OR 2.8; p = 0.03) were shown to be independent risk factors for higher rates of pCR. CONCLUSION: We conclude that both nRCT protocols are effective and safe. There were no significant differences regarding toxicity, pathological tumor response, and postoperative morbidity and mortality between both groups. Squamous cell carcinoma (SCC) and favorable preoperative tumor grading (G1 and G2) are independent predictors for higher pCR rate in multivariate analysis.

Acute epiploic appendagitis - a rare differential diagnosis of acute abdomen.

BACKGROUND: Acute epiploic appendagitis is a rare differential diagnosis of unclear or acute abdomen. AIM: To describe - by means of a scientific case report - the extraordinary diagnosis of acute epiploic appendagitis along with contained diverticulitis and incarcerated herniation of the greater omentum into the hernial sac of a former trocar site (medical history, significant for laparoscopic ovarian cyst removal) in a 29-year-old female based on experiences obtained in the successful clinical case management, and on selective references from medical scientific literature. CASE SUMMARY: Medical history: A 29-year-old female was admitted with abdominal pain in the lower left quadrant. She reported a laparoscopic ovarian cyst removal 3 years prior. Physical examination of the abdomen revealed tenderness in the lower left quadrant without a palpable mass.Leading diagnoses were found using transabdominal ultrasound and confirmed by an abdominal CT scan; namely, incarcerated trocar hernia, diverticulitis of sigmoid colon, and acute epiploic appendagitis. Therapeutic approach was comprised of an explorative laparoscopy (because of the incarcerated hernia), adhesiolysis, removal of a tip of the greater omentum out of the hernial sac, closure of the hernial orifice, and removal of an unclear, inflamed, and bloody fatty tissue from the wall of the descending colon (histopathological investigation confirmed acute epiploic appendagitis). This was flanked by conservative treatment of diverticulitis of the sigmoid colon.Further clinical course was uneventful, with discharge on the 3rd postoperative day with favorable long-term outcome, characterized by no further complaints for 15 months. DISCUSSION: Acute epiploic appendagitis is an inflammatory, usually self-limiting condition of the epiploic appendages of the colon. It typically manifests with abdominal pain in the lower left quadrant. Imaging is an important diagnostic tool to determine whether the patient has, in fact, acute epiploic appendagitis, so recognizing the characteristic oval lesions with the surrounding inflammation and central fat attenuation on CT, as well as the hyperechoic oval lesions with a hypoechoic peripheral band on ultrasound images is crucial. Nevertheless, it is often overlooked in patients and confused with other differential diagnoses, such as appendicitis or diverticulitis. Although the condition appears infrequently, it is essential to be proficient in the diagnostic evaluation, as a misdiagnosis may lead to unnecessary treatment and even surgical intervention. IN CONCLUSION: , the patient was initially diagnosed with an incarcerated abdominal hernia, and therefore subsequently underwent surgery. The inflamed epiploic appendage was discovered in laparoscopic exploration, removed, and confirmed through the histopathology report. This is an approach to be performed with great caution so as not to 1. : misinterpret an inflamed diverticula or covered perforation of it as well as not 2. : overlooking a peritoneal tumor lesion.

Robot-assisted transthoracic hybrid esophagectomy versus open and laparoscopic hybrid esophagectomy: propensity score matched analysis of short-term outcome.

PURPOSE: Minimally invasive en-bloc esophagectomy is associated with a reduction of postoperative morbidity. This was demonstrated for both total minimally invasive and hybrid esophagectomy. However, little is known about any benefits of robotic assistance compared to the conventional minimally invasive technique, especially in hybrid procedures. METHODS: For this retrospective study, all consecutive patients who had undergone elective esophagectomy with circular stapled intrathoracic anastomosis using the open and the minimally invasive hybrid technique at the University Hospital Magdeburg, from January 2010 to March 2021 were considered for analysis. RESULTS: In total, 137 patients (60.4%) had undergone open esophagectomy. In 45 patients (19.8%), the laparoscopic hybrid technique and in 45 patients (19.8%), the robot-assisted hybrid technique were applied. In propensity score matching analysis comparing the open with the robotic hybrid technique, significant differences were found in favor of the robotic technique (postoperative morbidity, p < 0.01; hospital length of stay, p < 0.01; number of lymph nodes retrieved, p = 0.048). In propensity score matching analysis comparing the laparoscopic with the robotic hybrid technique, a significant reduction of the rate of postoperative delayed gastric emptying (p = 0.02) was found for patients who had undergone robotic esophagectomy. However, the operation time was significantly longer (p < 0.01). CONCLUSIONS: En-bloc esophagectomy using the robotic hybrid technique is associated with a significant reduction of postoperative morbidity and of the hospital length of stay when compared to the open approach. However, when compared to the laparoscopic hybrid technique, only few advantages could be demonstrated.

Low skeletal muscle mass and post-operative complications after surgery for liver malignancies: a meta-analysis.

PURPOSE: To assess the influence of low skeletal muscle mass (LSMM) on post-operative complications in patients with hepatic malignancies grade (Clavien Dindo ≥ 3) undergoing resection. METHODS: MEDLINE, Cochrane, and SCOPUS databases were screened for associations between sarcopenia and major post-operative complications (≥ grade 3 according to Clavien-Dindo classification) after resection of different malignant liver tumors. RevMan 5.3 software was used to perform the meta-analysis. The methodological quality of the included studies was assessed according to the QUIPS instrument. RESULTS: The analysis included 17 studies comprising 3157 patients. Subgroup analyses were performed for cholangiocarcinoma (CCC), colorectal cancer (CRC) liver metastases, and hepatocellular carcinoma (HCC). LSMM as identified on CT was present in 1260 patients (39.9%). Analysis of the overall sample showed that LSMM was associated with higher post-operative complications grade Clavien Dindo ≥ 3 (OR 1.56, 95% CI 1.25-1.95, p < 0.001). In the subgroup analysis, LSMM was associated with post-operative complications in CRC metastases (OR 1.60, 95% CI 1.11-2.32, p = 0.01). In HCC and CCC sub-analyses, LSMM was not associated with post-operative complications in simple regression analysis. CONCLUSION: LSMM is associated with major post-operative complications in patients undergoing surgery for hepatic metastases and it does not influence major post-operative complications in patients with HCC and CCC.

Laparoscopic cholecystectomy during the COVID-19 pandemic in a tertiary care hospital in Germany: higher rates of acute and gangrenous cholecystitis in elderly patients.

BACKGROUND: The COVID-19 pandemic caused a global health crisis in 2020. This pandemic also had a negative impact on standard procedures in general surgery. Surgeons were challenged to find the best treatment plans for patients with acute cholecystitis. The aim of this study is to investigate the impact of the COVID-19 pandemic on the outcomes of laparoscopic cholecystectomies performed in a tertiary care hospital in Germany. PATIENTS AND METHODS: We examined perioperative outcomes of patients who underwent laparoscopic cholecystectomy during the pandemic from March 22, 2020 (first national lockdown in Germany) to December 31, 2020. We then compared these to perioperative outcomes from the same time frame of the previous year. RESULTS: A total of 182 patients who underwent laparoscopic cholecystectomy during the above-mentioned periods were enrolled. The pandemic group consisted of 100 and the control group of 82 patients. Subgroup analysis of elderly patients (> 65 years old) revealed significantly higher rates of acute [5 (17.9%) vs. 20 (58.8%); p = 0.001] and gangrenous cholecystitis [0 (0.0%) vs. 7 (20.6%); p = 0.013] in the "pandemic subgroup". Furthermore, significantly more early cholecystectomies were performed in this subgroup [5 (17.9%) vs. 20 (58.8%); p = 0.001]. There were no significant differences between the groups both in the overall and subgroup analysis regarding the operation time, intraoperative blood loss, length of hospitalization, morbidity and mortality. CONCLUSION: Elderly patients showed particularly higher rates of acute and gangrenous cholecystitis during the pandemic. Laparoscopic cholecystectomy can be performed safely in the COVID-19 era without negative impact on perioperative results. Therefore, we would assume that laparoscopic cholecystectomy can be recommended for any patient with acute cholecystitis, including the elderly.

Surgeons' requirements for a surgical support system to improve laparoscopic access.

Creating surgical access is a critical step in laparoscopic surgery. Surgeons have to insert a sharp instrument such as the Veress needle or a trocar into the patient's abdomen until the peritoneal cavity is reached. They solely rely on their experience and distorted tactile feedback in that process, leading to a complication rate as high as 14% of all cases. Recent studies have shown the feasibility of surgical support systems that provide intraoperative feedback regarding the insertion process to improve laparoscopic access outcomes. However, to date, the surgeons' requirements for such support systems remain unclear. This research article presents the results of an explorative study that aimed to acquire data about the information that helps surgeons improve laparoscopic access outcomes. The results indicate that feedback regarding the reaching of the peritoneal cavity is of significant importance and should be presented visually or acoustically. Finally, a solution should be straightforward and intuitive to use, should support or even improve the clinical workflow, but also cheap enough to facilitate its usage rate. While this study was tailored to laparoscopic access, its results also apply to other minimally invasive procedures.

The Advances in Computer Vision That Are Enabling More Autonomous Actions in Surgery: A Systematic Review of the Literature.

This is a review focused on advances and current limitations of computer vision (CV) and how CV can help us obtain to more autonomous actions in surgery. It is a follow-up article to one that we previously published in Sensors entitled, "Artificial Intelligence Surgery: How Do We Get to Autonomous Actions in Surgery?" As opposed to that article that also discussed issues of machine learning, deep learning and natural language processing, this review will delve deeper into the field of CV. Additionally, non-visual forms of data that can aid computerized robots in the performance of more autonomous actions, such as instrument priors and audio haptics, will also be highlighted. Furthermore, the current existential crisis for surgeons, endoscopists and interventional radiologists regarding more autonomy during procedures will be discussed. In summary, this paper will discuss how to harness the power of CV to keep doctors who do interventions in the loop.

In Vitro Validation of the Therapeutic Potential of Dendrimer-Based Nanoformulations against Tumor Stem Cells.

Tumor cells with stem cell properties are considered to play major roles in promoting the development and malignant behavior of aggressive cancers. Therapeutic strategies that efficiently eradicate such tumor stem cells are of highest clinical need. Herein, we performed the validation of the polycationic phosphorus dendrimer-based approach for small interfering RNAs delivery in in vitro stem-like cells as models. As a therapeutic target, we chose Lyn, a member of the Src family kinases as an example of a prominent enzyme class widely discussed as a potent anti-cancer intervention point. Our selection is guided by our discovery that Lyn mRNA expression level in glioma, a class of brain tumors, possesses significant negative clinical predictive value, promoting its potential as a therapeutic target for future molecular-targeted treatments. We then showed that anti-Lyn siRNA, delivered into Lyn-expressing glioma cell model reduces the cell viability, a fact that was not observed in a cell model that lacks Lyn-expression. Furthermore, we have found that the dendrimer itself influences various parameters of the cells such as the expression of surface markers PD-L1, TIM-3 and CD47, targets for immune recognition and other biological processes suggested to be regulating glioblastoma cell invasion. Our findings prove the potential of dendrimer-based platforms for therapeutic applications, which might help to eradicate the population of cancer cells with augmented chemotherapy resistance. Moreover, the results further promote our functional stem cell technology as suitable component in early stage drug development.

The initiation, standardization and proficiency (ISP) phases of the learning curve for minimally invasive liver resection: comparison of a fellowship-trained surgeon with the pioneers and early adopters.

BACKGROUND: Using the Ideal Development Exploration Assessment and Long-term study (IDEAL) paradigm, Halls et al. created risk-adjusted cumulative sum (RA-CUSUM) curves concluding that Pioneers (P) and Early Adopters (EA) of minimally invasive (MI) liver resection obtained similar results after fewer cases. In this study, we applied this framework to a MI Hepatic-Pancreatic and Biliary fellowship-trained surgeon (FT) in order to assess where along the curves this generation fell. METHODS: The term FT was used to designate surgeons without previous independent operative experience who went from surgical residency directly into fellowship. Three phases of the learning curve were defined using published data on EAs and Ps of MI Hepatectomy, including phase 1 (initiation) (i.e., the first 17 or 50), phase 2 (standardization) (i.e., cases 18-46 or 1-50) and phase 3 (proficiency) (i.e., cases after 46, 50 or 135). Data analysis was performed using the Social Science Statistics software ( www.socscistatistics.com ). Statistical significance was defined as p < .05. RESULTS: From November 2007 until April 2018, 95 MI hepatectomies were performed by a FT. During phase 1, the FT approached larger tumors than the EA group (p = 0.002), that were more often malignant (94.1%) when compared to the P group (52.5%) (p < 0.001). During phase 2, the FT operated on larger tumors and more malignancies (93.1%) when compared to the Ps (p = 0.004 and p = 0.017, respectively). However, there was no difference when compared to the EA. In the phase 3, the EAs tended to perform more major hepatectomies (58.7) when compared to either the FT (30.6%) (p = 0.002) or the P's cases 51-135 and after 135 (35.3% and 44.3%, respectively) (both p values < 0.001). When compared to the Ps cases from 51-135, the FT operated on more malignancies (p = 0.012), but this was no longer the case after 135 cases by the Ps (p = 0.164). There were no statistically significant differences when conversions; major complications or 30- and 90-day mortality were compared among these 3 groups. DISCUSSION: Using the IDEAL framework and RA-CUSUM curves, a FT surgeon was found to have curves similar to EAs despite having no previous independent experience operating on the liver. As in our study, FTs may tend to approach larger and more malignant tumors and do more concomitant procedures in patients with higher ASA classifications than either of their predecessors, without statistically significant increases in major morbidity or mortality. CONCLUSION: It is possible that the ISP (i.e., initiation, standardization, proficiency) model could apply to other innovative surgical procedures, creating different learning curves depending on where along the IDEAL paradigm surgeons fall.

The experience of the minimally invasive (MI) fellowship-trained (FT) hepatic-pancreatic and biliary (HPB) surgeon: could the outcome of MI pancreatoduodenectomy for peri-ampullary tumors be better than open?

BACKGROUND: Although early series focused on benign disease, minimally invasive pancreatoduodenectomy (MIPD) might be particularly suited for malignancy. Unlike their predecessors, fellowship-trained (FT) Hepatic-Pancreatic and Biliary (HPB) surgeons usually have equal skills in approaching peri-ampullary tumors (PT) either openly or via minimally invasive (MI) techniques. METHOD: We retrospectively reviewed a MI-HPB-FT surgeon's 10-year experience with PD. A sub-analysis of malignant PT was also done (MIPD-PT vs. OPD-PT). The primary endpoint was to assess postoperative mortality and morbidity. Secondary endpoints included operative parameters, length of hospital stay, and survival analysis. Moreover, we addressed practice pattern changes for a surgeon straight out of training with no previous experience of independent surgery. RESULTS: From December 2007-February 2018, one MI-HPB-FT performed a total of 100 PDs, including 57 MIPDs and 43 open PDs (OPDs). In both groups, over 70% of PDs were undertaken for malignancy. Eight patients with borderline resectable pancreatic ductal cancer (PDC) were in the OPD-PT group (as compared to only 2 in the MIPD-PT group) (p = 0.07). Estimated mean blood loss and length of stay were less in the MIPD-PT group (345 mL and 12 days) as compared to the OPD-PT group (971 mL and 16 days), p < 0.001 and p = 0.007, respectively. However, the mean operative time was longer for the MIPD-PT (456 min) as compared to the OPD-PT (371 min), p < 0.001. Thirty and 90-day mortality was 2.6%/5.1% after MIPD-PT compared to 0%/3.2% after OPD-PT, respectively, p = 1. Overall 30-/90-day morbidity rates were similar at 41.0%/43.6% after MIPD-PT and 35.5%/41.9% after OPD-PT, respectively, p = 0.8 and 1. Complete resection (R0) rates were not statistically different, 97.4% after MIPD-PT compared to 87.0% after OPD-PT (p = 0.2). After MIPD and OPD for malignant PT, overall 1, 3 and 5-year survival rates, and median survival were 82.5%, 59.6% and 46.3% and 38 months as compared to 52.5%, 15.7% and 10.5% and 13 months, respectively (p = 0.01). In the MIDP-PT group, recurrence free survival (RFS) at 1, 3 and 5 years and median RFS were 69.1%, 41.9% and 33.5% and 26 months as compared to 50.4%, 6.3% and 6.3% and 13 months, in the OPD-PT group, respectively (p = 0.03). CONCLUSION: FT HPB Surgeons who begin their practice with the ability to do both MI and OPD may preferentially approach resectable peri-ampullary tumors minimally invasively. This may result in decreased blood loss decreased length of hospital stays. Despite longer operative time, the improved visualization of MI techniques may enable superior R0 rates when compared to historical open controls. Moreover, combined with quicker initiation of adjuvant chemotherapeutic treatments, this may eventually result in improved survival.

Short-term outcome after robot-assisted hiatal hernia and anti-reflux surgery-is there a benefit for the patient?

PURPOSE: The robotic system was introduced to overcome the technical limitations of conventional laparoscopy. For complex oncological operations, it appears to offer further advantages. With regard to hiatal hernia repair, its role has yet to be determined. METHODS: All consecutive patients who received elective laparoscopic or robot-assisted hiatal hernia repair at a single institution between January 2016 and July 2020 were retrospectively evaluated. We compared both techniques with particular focus on their short-term outcome. A propensity score-matched comparison considering clinical and surgical covariates was also performed between the two groups. RESULTS: 140 patients were included, and 55 (39.3%) underwent a robot-assisted procedure. The baseline demographics and the frequency of previous abdominal operations were comparable for both groups. The size of the hiatal hernia did not differ significantly between the groups (p = 0.06). The mean operative time was significantly longer for the robot-assisted procedure (149 vs. 125 min; p < 0.01) but decreased markedly during the study period. By contrast, no significant differences were observed in terms of conversion rate (p = 1.0) and blood loss (p = 0.25). Likewise, the postoperative morbidity was comparable for both groups (10.9 vs. 12.9; p = 0.79). The hospital length of stay was not significantly different between the laparoscopic and robotic group (4.0 vs. 3.6 days; p = 0.2). After propensity score-matching, 48 patients were identified for each group. Except for the operative time, no other significant differences were found. Thus, the results of the univariate analysis were confirmed. CONCLUSION: Our initial results failed to demonstrate a clear advantage of the robotic technique in patients with refractory gastroesophageal reflux disease and/or symptomatic hiatal hernias.