A machine learning predictive model for recurrence of resected distal cholangiocarcinoma: Development and validation of predictive model using artificial intelligence.

INTRODUCTION: Distal Cholangiocarcinoma (dCCA) represents a challenge in hepatobiliary oncology, that requires nuanced post-resection prognostic modeling. Conventional staging criteria may oversimplify dCCA complexities, prompting the exploration of novel prognostic factors and methodologies, including machine learning algorithms. This study aims to develop a machine learning predictive model for recurrence after resected dCCA. MATERIAL AND METHODS: This retrospective multicentric observational study included patients with dCCA from 13 international centers who underwent curative pancreaticoduodenectomy (PD). A LASSO-regularized Cox regression model was used to feature selection, examine the path of the coefficient and create a model to predict recurrence. Internal and external validation and model performance were assessed using the C-index score. Additionally, a web application was developed to enhance the clinical use of the algorithm. RESULTS: Among 654 patients, LNR (Lymph Node Ratio) 15, neural invasion, N stage, surgical radicality, and differentiation grade emerged as significant predictors of disease-free survival (DFS). The model showed the best discrimination capacity with a C-index value of 0.8 (CI 95 %, 0.77%-0.86 %) and highlighted LNR15 as the most influential factor. Internal and external validations showed the model's robustness and discriminative ability with an Area Under the Curve of 92.4 % (95 % CI, 88.2%-94.4 %) and 91.5 % (95 % CI, 88.4%-93.5 %), respectively. The predictive model is available at https://imim.shinyapps.io/LassoCholangioca/. CONCLUSIONS: This study pioneers the integration of machine learning into prognostic modeling for dCCA, yielding a robust predictive model for DFS following PD. The tool can provide information to both patients and healthcare providers, enhancing tailored treatments and follow-up.

Genomic and transcriptomic profiling of hepatocellular carcinoma reveals a rare molecular subtype.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide, occurring predominantly in patients with underlying chronic liver disease and cirrhosis. Here, we describe a case of a 62-year-old man that was admitted to our hospital and diagnosed with HCC where the cancer has already metastasized to the retroperitoneum and peritoneum. In order to better characterize the HCC, both the cancerous liver tissue and the adjacent normal liver tissue of the patient were collected and subjected to a genomic, transcriptomic and proteomic analysis. Our patient carries a highly mutated HCC, which is characterized by both somatic mutation in the following genes ALK, CDK6, TP53, PGR. In addition, we observe several molecular alterations that are associated with potential therapy resistance, for example the expression of the organic-anion-transporting polypeptide (OATP) family members B1 and B3, that mediate the transport of the anticancer drugs, has been found decreased. Overall, our molecular profiling potentially classify the patient with poor prognosis and possibly displaying resistance to pharmacological therapy.

Levels of Robotic Mesopancreas Dissection According to Malignancy and Vascular Anatomy: What Surgeons Need to Know.

INTRODUCTION: The robotic approach is attracting increasing interest among the surgical community, and more and more series describing robotic pancreatoduodenectomy have been reported. Thus, surgeons performing robotic pancreatoduodenectomy should be confident with this critical step's potential scenarios. MATERIALS AND METHODS: According to Yosuke et al., there are three different levels of mesopancreas dissection. We describe the main steps for a safe mesopancreas dissection by robotic approach. RESULTS: This multimedia article provides, for the first time in literature, a comprehensive step-by-step overview of the mesopancreas dissection during robotic pancreatoduodenectomy (PD) and its three different levels according to tumor type. CONCLUSIONS: Through the tips and indications presented in this multimedia article, we aim to familiarize surgeons with the mesopancreas dissections levels according to type of malignancy and vascular anatomy.

Current status of liver surgery for non-colorectal non-neuroendocrine liver metastases: the NON.LI.MET. Italian Society for Endoscopic Surgery and New Technologies (SICE) and Association of Italian Surgeons in Europe (ACIE) collaborative international survey.

Despite the increasing trend in liver resections for non-colorectal non-neuroendocrine liver metastases (NCNNLM), the role of surgery for these liver malignancies is still debated. Registries are an essential, reliable tool for assessing epidemiology, diagnosis, and therapeutic approach in a single hub, especially when data are dispersive and inconclusive, as in our case. The dissemination of this preliminary survey would allow us to understand if the creation of an International Registry is a viable option, while still offering a snapshot on this issue, investigating clinical practices worldwide. The steering committee designed an online questionnaire with Google Forms, which consisted of 37 questions, and was open from October 5th, 2022, to November 30th, 2022. It was disseminated using social media and mailing lists of the Italian Society of Endoscopic Surgery and New Technologies (SICE), the Association of Italian Surgeons in Europe (ACIE), and the Spanish Chapter of the American College of Surgeons (ACS). Overall, 141 surgeons (approximately 18% of the total invitations sent) from 27 countries on four continents participated in the survey. Most respondents worked in general surgery units (62%), performing less than 50 liver resections/year (57%). A multidisciplinary discussion was currently performed to validate surgical indications for NCNNLM in 96% of respondents. The most commonly adopted selection criteria were liver resectability, RECIST criteria, and absence of extrahepatic disease. Primary tumors were generally of gastrointestinal (42%), breast (31%), and pancreaticobiliary origin (13%). The most common interventions were parenchymal-sparing resections (51% of respondents) of metachronous metastases with an open approach. Major post-operative complications (Clavien-Dindo > 2) occurred in up to 20% of the procedures, according to 44% of respondents. A subset analysis of data from high-volume centers (> 100 cases/year) showed lower post-operative complications and better survival. The present survey shows that NCNNLM patients are frequently treated by surgeons in low-volume hospitals for liver surgery. Selection criteria are usually based on common sense. Liver resections are performed mainly with an open approach, possibly carrying a high burden of major post-operative complications. International guidelines and a specific consensus on this field are desirable, as well as strategies for collaboration between high-volume and low-volume centers. The present study can guide the elaboration of a multi-institutional document on the optimal pathway in the management of patients with NCNNLM.

Primary versus Salvage Liver Transplantation after Curative-Intent Resection or Radiofrequency Ablation for Hepatocellular Carcinoma: Long-Term Oncological Outcomes.

Liver transplantation for hepatocellular carcinoma (HCC) may be performed ab initio, primary liver transplantation (PLT), or for HCC recurrence after previous treatments such as liver resection (LR) or radiofrequency ablation (RFA), salvage liver transplantation (SLT). The aim of this study was to evaluate the oncological outcomes of SLT vs. PLT. For this, a retrospective study was carried out on patients undergoing liver transplantation for HCC. The outcomes of PLT were compared with those of SLT. The primary outcome was disease-free survival (DFS). The secondary outcomes included overall survival (OS), cancer-specific survival (CSS), and major postoperative complications. A sub-analysis of SLT-LR and SLT-RFA was also performed. In total, 141 patients were included: 96 underwent PLT and 45 SLT. Among the SLT group, 25 patients had undergone previous LR while 20 had had RFA. There were no differences in the major postoperative complications. Unadjusted DFS was significantly longer in the PLT group (p = 0.02), as were OS (p = 0.025) and CSS (p = 0.001). There was no difference in DFS between PLT and SLT-LR groups, while a significant difference was found between the PLT and SLT-RFA groups (p = 0.035). Nonetheless, DFS was no different between the SLT-LR and SLT-RFA groups. PLT appears to offer superior long-term oncological outcomes to SLT. Both SLT-LR and SLT-RFA offer acceptable OS and CSS. Further prospective studies are needed to confirm these results, but the re-direction of grafts and transplant philosophy towards PLT rather than SLT may need to be considered.

Liver-Specific Contrast-Enhanced Magnetic Resonance Cholangio-Pancreatography (Ce-MRCP) in Non-Invasive Diagnosis of Iatrogenic Biliary Leakage.

Current non-invasive diagnostic modalities of iatrogenic bile leak (BL) are not particularly sensitive and often fail to localise the BL origin. Percutaneous transhepatic cholangiography (PTC) and endoscopic retrograde cholangiopancreatography (ERCP) are considered the gold standard, yet are invasive studies with potential complications. Ce-MRCP has been not comprehensively studied in this setting but may prove particularly helpful given its non-invasive nature and the anatomical dynamic detail. This paper reports a monocentric retrospective study of BL patients referred between January 2018 and November 2022 submitted to Ce-MRCP followed by PTC. The primary outcome was the accuracy of Ce-MRCP in detecting and localising BL compared to PTC and ERCP. Blood tests, coexisting cholangitis features and time for leak resolution were also investigated. Thirty-nine patients were included. Liver-specific contrast-enhanced MRCP detected BL in 69% of cases. The BL localisation was 100% accurate. Total bilirubin above 4 mg/dL was significantly associated with false negative results of Ce-MRCP. Ce-MRCP is highly accurate in detecting and localising BL, but sensitivity is significantly reduced by a high bilirubin level. Ce-MRCP may be very useful in early BL diagnosis and in accurate pre-treatment planning, but can only be reliably used in selected patients with TB < 4 mg/dL. Non-surgical techniques, both radiological and endoscopic, are proven to be effective in terms of leak resolution.

Implementation of Blockchain Technology Could Increase Equity and Transparency in Organ Transplantation: A Narrative Review of an Emergent Tool.

In the last few years, innovative technology and health care digitalization played a major role in all medical fields and a great effort worldwide to manage this large amount of data, in terms of security and digital privacy has been made by different national health systems. Blockchain technology, a peer-to-peer distributed database without centralized authority, initially applied to Bitcoin protocol, soon gained popularity, thanks to its distributed immutable nature in several non-medical fields. Therefore, the aim of the present review (PROSPERO N° CRD42022316661) is to establish a putative future role of blockchain and distribution ledger technology (DLT) in the organ transplantation field and its role to overcome inequalities. Preoperative assessment of the deceased donor, supranational crossover programs with the international waitlist databases, and reduction of black-market donations and counterfeit drugs are some of the possible applications of DLT, thanks to its distributed, efficient, secure, trackable, and immutable nature to reduce inequalities and discrimination.

Minimally invasive pancreatic anastomosis after pancreaticoduodenectomy: multi-institutional step by step video description of the technique.

Minimally invasive pancreaticoduodenectomy (PD) is attracting increased interest in the pancreatic surgical community with more and more teams reporting their experience worldwide. The pancreatic anastomosis (PA) is one of the key steps and challenging manoeuvre of this procedure. Since the introduction of the minimally invasive approach for PD, several PA types have been proposed, ranging from high to low complexity, but none of them have been proven unequivocally superior to the others. Therefore, definitive consensus has not been reached yet. In the present multimedia manuscript, we report the most commonly adopted minimally invasive PA and we propose a "complexity classification" to guide the choice accordingly to different characteristics of the pancreatic stump. We describe five possible different PA that might be tailored to each different case, depending mainly on texture of pancreatic stump (soft/hard, lean/fatty) and the size and visibility of main duct. This manuscript presents a step-by-step portfolio of the most commonly used mini-invasive PA. This technique requires experience in pancreatic surgery and advanced minimally invasive skills. Knowledge of and proficiency in different types of PA could help reducing the incidence of postoperative pancreatic fistula.

Superior Mesenteric Artery First Approach for Minimally Invasive Pancreaticoduodenectomy: A Step-By-Step Surgical Technique Video.

INTRODUCTION: In the past decade, minimally invasive pancreaticoduodenectomy has been gaining interest. However, minimally invasive pancreaticoduodenectomy remains technically challenging and is associated with a steep learning curve. Additionally, the operating surgeon should be cognizant of replicating the same oncological steps as observed in the typical open approach. In view of this, there exist various maneuvers that are designed to achieve negative margins and a safer mesopancreatic dissection. One of these techniques is the superior mesenteric artery first approach, which is garnering interest among pancreatic surgeons. MATERIAL AND METHODS: According to existing literature, there are several superior mesenteric artery dissections approaches. We describes 5 different minimally invasive approaches. RESULTS: This multimedia manuscript provide, for the first time in literature, a comprehensive step-by-step overview of the superior mesenteric artery first approach for minimally invasive pancreaticoduodenectomy by a team of expert surgeons from various international institutions. CONCLUSIONS: Through the tips and indications presented in this article, we aim to guide the choice of this approach according to tumor location, type of minimally invasive approach and the operating surgeon's experience and increase familiarity with such a complex procedure.

Percutaneous Tibial Nerve Stimulation Improves Lower Urinary Tract Dysfunction and Infection Rate in a Kidney Transplant Recipient With Augmentation Cystoplasty: A Case Report and Literature Review.

Almost 20% of patients with congenital posterior urethral valves (PUV) reach end-stage kidney disease requiring kidney transplantation (KT). An augmentation cystoplasty (AC) is performed to treat significant lower urinary tract dysfunction (LUTD) which can persist afterwards due to residual valve bladder and lead to recurrent urinary tract infections (UTIs) and a worse graft survival. Percutaneous tibial nerve stimulation (PTNS) is a minimally invasive second-line neuromodulation therapy approved for the treatment of non-neurogenic LUTD performed in the outpatient setting. Herein, we reported the case of significant improvement of bladder voiding pattern and yearly UTI rates through PTNS in a 32-year-old male KT recipient with a history of congenital PUV and AC. The patient was referred to our institution at the beginning of 2019 for urgency, high post-void residual volume (PVR) and recurrent clinically significant UTIs (3 to 4/y). After assessment, the patient attended once-weekly 30-minute sessions of PTNS for 12 consecutive weeks. A significant improvement of urodynamic and infectious outcomes was observed through 3-day bladder diaries, questionnaires, and laboratory exams during the subsequent 3 years of regular follow-up. The present results might be significant for the prevention of antibiotic resistance and for better graft survival in KT recipients. We successfully treated a patient with AC, implying that the technique may be appliable also in this case. Neuromodulation in KT is still an unexplored field of research, we advocate for prospective assessment of the efficacy of PTNS in these patients, as reproducible results might lead to life-changing improvements.

Disappearing Colorectal Liver Metastases: Do We Really Need a Ghostbuster?

The development of new systemic treatment strategies has resulted in a significant increase in the response rates of colorectal liver metastases (CRLM) in the last few years. Although the radiological response is a favorable prognostic factor, complete shrinkage of CRLM, known as disappearing liver metastases (DLM), presents a therapeutic dilemma, and proper management is still debated in the literature. In fact, DLM is not necessarily equal to cure, and when resected, pathological examination reveals in more than 80% of patients a variable percentage of the tumor as residual disease or early recurrence in situ. Moreover, while a higher incidence of intrahepatic recurrence is documented in small series when surgery is avoided, its clinical significance for long-term OS is still under investigation. In light of this, a multidisciplinary approach and, in particular, radiologists' role is needed to assist the surgeon in the management of DLM, thanks to emerging technology and strategy. Therefore, the aim of this review is to provide an overview of the DLM phenomenon and current management.

Pancreatic Adeno-MiNEN, a Rare Newly Defined Entity with Challenging Diagnosis and Treatment: A Case Report with Systematic Literature Review and Pooled Analysis.

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) are a peculiar entity that can occur throughout the whole gastrointestinal trait, and pancreatic localization is rare. Their main characteristic is the presence of at least a neuroendocrine and an epithelial component, each accounting for at least 30% of the tumour mass. The presence of epithelial ductal component defines adeno-MiNEN. We report a case of a 59-year-old woman affected by pancreatic adeno-MiNEN with challenging diagnosis and successfully treated. A systematic literature review and pooled analysis was also performed, aiming to define the management and outcomes of pancreatic adeno-MiNEN. Out of 190 identified records, 15 studies including 28 patients affected by pancreatic-adeno-MiNEN were included in the analysis. Pancreatic adeno-MiNEN occurred mainly in males (82.8%) and at a mean age of 61.7 (range: 24-82) years. Pre-operative diagnosis was possible only in 14.2% of cases. At presentation, the majority had already advanced disease (TNM stage III (53.8%) and stage IV 19.3%). Adjuvant therapy was performed in 55% of patients, and the tumour recurrence rate was in 30% of cases. Median disease-free survival (DFS) was 12 months (range: 0-216 months) with a 5-year DFS of 16.6%, while the median overall survival (OS) was 12 months (range: 0-288 months) with a 5-year OS of 23.5%. Pancreatic adeno-MiNENs are rare; as they have very heterogenous behaviour, they are rarely diagnosed preoperatively and have poor prognosis. Treatment of localised MiNEN still relies on radical surgical resection, which seems essential to achieve a good oncological prognosis. International registry on MiNEN is necessary to improve the knowledge on this rare tumour and to improve its outcomes.

All the Routes for Laparoscopic Liver Segment VIII Resection: A Comprehensive Review of Surgical Techniques.

Liver surgery is highly demanding for anatomical, physiological and technical reasons, and minimally invasive approaches have been implemented at a slower rate. Today, laparoscopic liver resection is a standard of care in many occasions, yet specific operations remain particularly challenging and generally performed in open surgery. In particular, SVIII resection may be considered one of the most difficult due to anatomical characteristics including its sub-diaphragmatic position, the deep-lying Glissonean pedicle and the close contact with the inferior vena cava and right and middle hepatic veins. Many techniques have risen to overcome technical difficulties, and today laparoscopic SVIII resection has been demonstrated to be feasible. This review provides a complete picture of current approaches, focusing on all techniques reported so far with critical appraisal of each, discussing and explaining benefits and pitfalls.

KRAS Assessment Following ESMO Recommendations for Colorectal Liver Metastases. Is It Always Worth It?

BACKGROUND: Genetic evaluation is essential in assessing colorectal cancer (CRC) and colorectal liver metastasis (CRLM). The aim of this study was to determine the pragmatic value of KRAS on oncological outcomes after CRLM according to the ESMO recommendations and to query whether it is necessary to request KRAS testing in each situation. METHODS: A retrospective cohort of 126 patients who underwent surgery for hepatic resection for CRLM between 2009 and 2020 were reviewed. The patients were divided into three categories: wild-type KRAS, mutated KRAS and impractical KRAS according to their oncological variables. The impractical (not tested) KRAS group included patients with metachronous tumours and negative lymph nodes harvested. Disease-free survival (DFS), overall survival (OS) and hepatic recurrence-free survival (HRFS) were calculated by the Kaplan-Meier method, and a multivariable analysis was conducted using the Cox proportional hazards regression model. RESULTS: Of the 108 patients identified, 35 cases had KRAS wild-type, 50 cases had a KRAS mutation and the remaining 23 were classified as impractical KRAS. Significantly longer medians for OS, HRFS and DFS were found in the impractical KRAS group. In the multivariable analyses, the KRAS mutational gene was the only variable that was maintained through OS, HRFS and DFS. For HRFS (HR: 13.63; 95% confidence interval (CI): 1.35-100.62; p = 0.010 for KRAS), for DFS (HR: 10.06; 95% CI: 2.40-42.17; p = 0.002 for KRAS) and for OS (HR: 4.55%; 95% CI: 1.37-15.10; p = 0.013). CONCLUSION: Our study considers the possibility of unnecessary KRAS testing in patients with metachronous tumours and negative lymph nodes harvested. Combining the genetic mutational profile (i.e., KRAS in specific cases) with tumour characteristics helps patient selection and achieves the best prognosis after CRLM resection.

Laparoscopic Left Hemihepatectomy for Intrahepatic Cholangiocellular Carcinoma: An Adequate Lymphadenectomy is Also Possible in Artery Variation.

BACKGROUND: Laparoscopic liver resection (LLR) is becoming essential in the treatment of malignant liver tumors but only a few reports exist about LLR for intrahepatic cholangiocarcinoma (IHCC). METHODS: We present a video of a laparoscopic left hemihepatectomy with lymphadenectomy for IHCC. CASE PRESENTATION: A 67-year-old asymptomatic male underwent a routine abdominal ultrasound, revealing a 15 × 9 mm solid nodular iso-hyperechoic lesion, located in SIII, with SII/III biliary duct dilation. Magnetic resonance imaging confirmed a 32 × 22 mm lesion in SII/III, with mild hyper-intensity on T2-weighted images and strong hypo-intensity on T1-weighted images. After administration of contrast medium, the lesion showed light peripheral enhancement on the portal and delayed phases, and hypo-intensity on the hepatospecific phase. No relevant comorbidities were reported (KPS 100). Laboratory tests showed normal liver function and normal CA19-9 levels. A laparoscopic left hemihepatectomy was indicated. RESULTS: Operative time was 330 min. Four intermittent Pringle maneuver cycles were applied and no blood transfusions were administered. Intraoperative ultrasound confirmed preoperative findings and additionally highlighted involvement of the SIV duct. A full replacing right hepatic artery arising from the superior mesenteric artery was identified and was preserved during hilar dissection. Postoperative course was uneventful and the patient was discharged on postoperative day 3. The pathology report indicated cholangiocellular carcinoma pT1bN0. Twelve lymph nodes were retrieved. CONCLUSIONS: According to recent literature reports and our experience, laparoscopic surgery for intrahepatic cholangiocellular carcinoma should be considered feasible and safe in selected patients. Hepatic artery variations allow for adequate lymphadenectomy. Oncological long-term results require multicenter randomized studies in order to be validated.