Textbook Outcomes in Solid Transplantation: A Systematic Review.

Background: The concept of TO is expanding across various surgical disciplines to establish a standardized, comprehensive quality benchmark. Traditional metrics such as 1-y patient and graft survival have been key for evaluating transplant program performance but are now deemed inadequate because of significant field advancements. This systematic review aims to provide a comprehensive understanding of the applicability and validity of textbook outcome (TO) in the setting of solid organ transplantation. Methods: A structured search, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, was conducted across PubMed, Embase, and Scopus databases on March 10, 2024. Results: Fourteen articles were identified for inclusion in this review. Of these, 2 studies addressed TO in heart transplantation, 3 in lung transplantation, 2 in kidney transplantation, and 7 in liver transplantation. A subgroup analysis was conducted to categorize the different definitions of TOs and identify the most common reasons for TO failure. Conclusions: Our systematic review highlights the ongoing efforts in the field of solid organ transplantation to define TO and emphasizes the importance of developing a universally recognized set of TO criteria for each type of transplant. TO provides a valuable framework for transplant centers to benchmark their performance against similar institutions on a risk-adjusted basis and to pinpoint specific areas for enhancing patient outcomes. Even the most successful programs may discover aspects within the composite outcome with scope for improvement.

Metroticket approach in a retrospective cohort study to predict overall survival after surgical resection for intermediate stage hepatocellular carcinoma.

BACKGROUND: Surgical resection is a curative therapy for early-stage hepatocellular carcinoma (HCC) patients meeting the Milan criteria as well as a widely used therapy in intermediate-stage HCC. However, intermediate-stage HCC encompasses a wide spectrum of disease and there is a lack of good predictive models for the long-term clinical outcome of HCC patients currently. Here, we adopt Mazzaferro's Metroticket 2.0 to create a robust survival prediction model for intermediate-stage HCC patients undergoing surgical resection. Our algorithm considers age, AFP levels, ALBI score, and nodule size/number to generate survival estimates in an accessible graph format. Importantly, our model surpasses the American Joint Committee on Cancer staging model and was validated with independent US patient data. METHODS: We conducted a retrospective analysis of OS and RFS in early- and intermediate-stage HCC patients treated with liver resection, including a training cohort in Singapore and a validation cohort in North Carolina, USA. RESULTS: We recorded 278 deaths (35.0%) and 428 patients (53.9%) in the first 5-years after surgical resection; higher ALBI score, higher lnAFP, more advanced age and higher tumour burden index were identified as significant parameters. The overall predictive capability of our model, with the inclusion of AFP, is reflected with a UNO's C-statistic of 0.655, which is 1.11 times better than the 0.5895 C-statistic of the 8th AJCC TNM Staging model. CONCLUSIONS: Our modified Metroticket model allows for more granular and better-informed prognostication. This will help surgeons and patients make accurate comparisons between the clinical outcomes of surgical resection and other non-surgical treatments.

Hepatic Resection as the Primary Treatment Method for Hepatocellular Carcinoma After Orthotopic Liver Transplantation.

BACKGROUND: Liver transplantation (LT) is the treatment of choice for end-stage liver disease and certain malignancies such as hepatocellular carcinoma (HCC). Data on the surgical management of de novo or recurrent tumors that develop in the transplanted allograft are limited. This study aimed to investigate the perioperative and long-term outcomes for patients undergoing hepatic resection for de novo or recurrent tumors after liver transplantation. METHODS: The study enrolled adult and pediatric patients from 12 centers across North America who underwent hepatic resection for the treatment of a solid tumor after LT. Perioperative outcomes were assessed as well as recurrence free survival (RFS) and overall survival (OS) for those undergoing resection for HCC. RESULTS: Between 2003 and 2023, 54 patients underwent hepatic resection of solid tumors after LT. For 50 patients (92.6 %), resection of malignant lesions was performed. The most common lesion was HCC (n = 35, 64.8 %), followed by cholangiocarcinoma (n = 6, 11.1 %) and colorectal liver metastases (n = 6, 11.1 %). The majority of the 35 patients underwent resection of HCC did not receive any preoperative therapy (82.9 %) or adjuvant therapy (71.4 %), with resection their only treatment method for HCC. During a median follow-up period of 50.7 months, the median RFS was 21.5 months, and the median OS was 49.6 months. CONCLUSION: Hepatic resection following OLT is safe and associated with morbidity and mortality rates that are comparable to those reported for patients undergoing resection in native livers. Hepatic resection as the primary and often only treatment modality for HCC following LT is associated with acceptable RFS and OS and should be considered in well selected patients.

Evolution of Initial Treatment for Desmoid Tumors.

INTRODUCTION: Desmoid tumors (DTs) are rare, fibroblastic cell proliferations that can exhibit locally aggressive behavior but lack metastatic potential. Initial management has traditionally involved upfront resection; however, contemporary guidelines and expert panels have increasingly advocated for prioritizing active surveillance strategies. METHODS: A single-institution, retrospective chart review identified all patients diagnosed with a primary DT at any site from 2007 to 2020. The primary outcome was the initial management strategy over time. Secondary outcomes included treatment-free survival (TFS) and time to treatment (TTT) for those undergoing active surveillance, as well as recurrence-free survival (RFS) and time to recurrence for those undergoing resection. RESULTS: Overall, 103 patients were included, with 68% female and a median follow-up of 44 months [24-74]. The most common tumor locations included the abdominal wall (27%), intra-abdominal/mesenteric (25%), chest wall (19%), and extremity (10%). Initial management included resection (60%), systemic therapy (20%), active surveillance (18%), and cryoablation (2%). Rates of surgical resection significantly decreased (p < 0.001) over time, from 69.6% prior to 2018 to 29.2% after 2018. For those treated with upfront resection, 5-year RFS was 41.2%, and for patients undergoing initial active surveillance, TFS was 66.7% at 2 years, with a median TTT of 4 months [4-10]. CONCLUSIONS: This single-institution cohort at a tertiary medical center spanning over a decade demonstrates the transition to active surveillance for initial management of DTs, and highlights salient metrics in the era of surveillance. This trend mirrors recommended treatment strategies by expert panels and consensus guidelines.

Cholangiocarcinoma of the Middle Bile Duct: A Narrative Review.

Resectable cholangiocarcinoma (CCA) arising from the middle of the extrahepatic biliary tree has historically been classified as perihilar or distal CCA, depending on the operation contemplated or performed, namely the associated hepatectomy or pancreaticoduodenectomy, respectively. Segmental bile duct resection is a less invasive alternative for select patients harboring true middle extrahepatic CCA (MCC). A small, yet growing body of literature has emerged detailing institutional experiences with bile duct resection versus pancreaticoduodenectomy or concomitant hepatectomy for MCC. Herein, we provide a brief overview of the epidemiology, preoperative evaluation, and emerging systemic therapies for MCC, and narratively review the existing work comparing segmental resection with pancreaticoduodenectomy or less commonly, hepatectomy, for MCC, with emphasis on the surgical management and oncologic implications of the approach used.

Benign Etiology for High-Risk Intraductal Papillary Mucinous Neoplasm: A Case Report and Literature Review.

Intraductal papillary mucinous neoplasms are relatively common and entail a variable risk of malignant potential. The Fukuoka guidelines present criteria for the risk of malignant transformation and are used for risk stratification and treatment decision-making. However, these guidelines entail some fallibility with limited sensitivity and specificity. In this case, we present an individual who had many of the hallmarks of malignant transformation but was found to have no evidence of malignancy or high-grade dysplasia. We discuss the suspected etiology of this individual's condition and how it might arise in others, as well as a brief review of the literature on risk factors in intraductal papillary mucinous neoplasms.

Downstaging strategies for unresectable hepatocellular carcinoma.

A significant number of patients with hepatocellular carcinoma (HCC) are usually diagnosed in advanced stages, that leads to inability to achieve cure. Palliative options are focusing on downstaging a locally advanced disease. It is well-supported in the literature that patients with HCC who undergo successful conversion therapy followed by curative-intent surgery may achieve a significant survival benefit compared to those who receive chemotherapy alone or those who are successfully downstaged with conversion therapy but not treated with surgery. Hepatic artery infusion chemotherapy can be a potential downstaging strategy, since recent studies have demonstrated excellent outcomes in patients with colorectal liver metastatic disease as well as primary liver malignancies.

Advances in Detecting, Prognosticating, and Treating Hepatocellular Carcinoma: Advances and Outcomes.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the ninth leading cause of cancer-related death in the United States [...].

Prolonged xenokidney graft survival in sensitized NHP recipients by expression of multiple human transgenes in a triple knockout pig.

Genetic modification of porcine donors, combined with optimized immunosuppression, has been shown to improve outcomes of experimental xenotransplant. However, little is known about outcomes in sensitized recipients, a population that could potentially benefit the most from the clinical implementation of xenotransplantation. Here, five highly allosensitized rhesus macaques received a porcine kidney from GGTA1 (α1,3-galactosyltransferase) knockout pigs expressing the human CD55 transgene (1KO.1TG) and were maintained on an anti-CD154 monoclonal antibody (mAb)-based immunosuppressive regimen. These recipients developed de novo xenoreactive antibodies and experienced xenograft rejection with evidence of thrombotic microangiopathy and antibody-mediated rejection (AMR). In comparison, three highly allosensitized rhesus macaques receiving a kidney from GGTA1, CMAH (cytidine monophospho-N-acetylneuraminic acid hydroxylase), and b4GNT2/b4GALNT2 (ß-1,4-N-acetyl-galactosaminyltransferase 2) knockout pigs expressing seven human transgenes including human CD46, CD55, CD47, THBD (thrombomodulin), PROCR (protein C receptor), TNFAIP3 (tumor necrosis factor-α-induced protein 3), and HMOX1 (heme oxygenase 1) (3KO.7TG) experienced significantly prolonged graft survival and reduced AMR, associated with dampened post-transplant humoral responses, early monocyte and neutrophil activation, and T cell repopulation. After withdrawal of all immunosuppression, recipients who received kidneys from 3KO.7TG pigs rejected the xenografts via AMR. These data suggest that allosensitized recipients may be suitable candidates for xenografts from genetically modified porcine donors and could benefit from an optimized immunosuppression regimen designed to target the post-transplant humoral response, thereby avoiding AMR.

Clinical Prediction Models for Prognosis of Colorectal Liver Metastases: A Comprehensive Review of Regression-Based and Machine Learning Models.

Colorectal liver metastasis (CRLM) is a disease entity that warrants special attention due to its high frequency and potential curability. Identification of "high-risk" patients is increasingly popular for risk stratification and personalization of the management pathway. Traditional regression-based methods have been used to derive prediction models for these patients, and lately, focus has shifted to artificial intelligence-based models, with employment of variable supervised and unsupervised techniques. Multiple endpoints, like overall survival (OS), disease-free survival (DFS) and development or recurrence of postoperative complications have all been used as outcomes in these studies. This review provides an extensive overview of available clinical prediction models focusing on the prognosis of CRLM and highlights the different predictor types incorporated in each model. An overview of the modelling strategies and the outcomes chosen is provided. Specific patient and treatment characteristics included in the models are discussed in detail. Model development and validation methods are presented and critically appraised, and model performance is assessed within a proposed framework.

Elective Appendectomy Following Antibiotics for Appendicitis.

This Viewpoint considers which may be the better long-term approach to appendicitis­interval elective appendectomy or nonsurgical treatment with antibiotics.

Endovascular Treatment of a Multi-visceral Aortic Conduit Blowout With Parallel Stent Grafts and Coils.

Multi-visceral transplantation (MVT) is a complex surgical procedure involving the transplantation of multiple abdominal organs as a single unit, typically used as bailout treatment of patients with devastating abdominal pathologies. Due to the complexity of the procedure, major and even life-threatening complications can happen. Vascular complications, including anastomotic breakdowns or pseudoaneurysms due to infections, can be universally lethal. Open surgical repair is often not an option due to the hostile operative field. We report a case of endovascular salvage of multi-visceral aortic conduit blowout utilizing parallel stent grafts and coils without sacrifice of the transplanted viscera. This combination can successfully control bleeding and maintain graft perfusion in this rare but devastating complication.

Regorafenib combined with a PD-1 inhibitor in the second-line setting for unresectable hepatocellular carcinoma in real-world practice.

Background: Most advanced hepatocellular carcinoma (HCC) cases administered molecular targeted agents and/or anti-programmed cell death-1 (PD-1) inhibitors have no response or develop resistance. Moreover, second-line therapies still cannot provide beneficial clinical outcomes. A pilot study assessing combined regorafenib and PD-1 inhibitor as second-line treatment of advanced HCC reported promising effectiveness. Methods: The current single-center, retrospective, real-world study was carried out between January 2019 and July 2021. Advanced HCC cases were administered second-line regorafenib combined with a PD-1 inhibitor or regorafenib alone were assessed. Progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were determined. Results: Totally 46 HCC cases were analyzed, most of whom underwent previous systemic treatment comprising targeted therapy and immunotherapy. Tumor response was evaluated in 25 and 21 individuals in the regorafenib + PD-1 inhibitor and regorafenib monotherapy groups, respectively: ORRs were 21.7% and 8.7%, and DCRs were 47.8% and 32.6%, respectively. Median PFS was markedly longer in the regorafenib plus PD-1 inhibitor group (11.5 months) compared with the regorafenib monotherapy group (5.1 months, P=0.049). Conclusions: This study suggested regorafenib and a PD-1 inhibitor in combination may provide significant clinical benefits in HCC cases showing progression following first-line treatment. Further analysis in real-world studies with large cohorts is warranted to confirm these findings.

Idiopathic Megaduodenum in a Teenager: A Case Report.

Megaduodenum is a rare clinical syndrome characterized by significant duodenal dilation, elongation, and hypertrophy. Given its rarity and nonspecific clinical manifestations, megaduodenum may be misdiagnosed, leading to delays in surgical care and increased morbidity. We describe a case of idiopathic megaduodenum in a teenage Caucasian female, who presented with a five-year history of halitosis, recurrent belching, bloating, nausea and vomiting, and postprandial epigastric abdominal pain. She was diagnosed with megaduodenum by dramatic findings on contrast radiography. She developed a duodenal volvulus necessitating emergency exploratory laparotomy, during which a duodenal plication and a side-to-side duodenojejunostomy were performed. Exploratory laparotomy and histopathological analysis were unrevealing of any definitive abnormalities to explain her megaduodenum. Postoperatively, she developed two early small bowel obstructions, both from subsequent adhesions requiring repeat laparotomy with adhesiolysis. She has subsequently recovered without incident. Diagnosis and accurate classification of megaduodenum requires surgical exploration with a full-thickness biopsy and subsequent histopathologic analysis to rule out obstructive or functional disorders of the duodenum. Treatment of megaduodenum depends on the underlying cause and degree of duodenal distention. It is crucial that clinicians are knowledgeable of the various surgical options, their indications, and the potential postoperative complications that may arise.