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The present manuscript aimed to review the historical development and most important contributions regarding Lynch Syndrome since its first description, more than a century ago. In 1895, a reputed pathologist from Michigan University, Dr. Aldred Scott Warthin, got intrigued by the family history of a local seamstress called Pauline Gross. According to her prevision, she would present an early death due to cancer, which actually happened (from the uterus). Historically, her family was designated "Family G", comprising a group recognized as the longest and most detailed cancer genealogy that has ever been studied. Warthin concluded that its members had genetic susceptibility for cancer, and they are, nowadays, considered the first reported Lynch Syndrome family. At that time, however, the medical cancer community was far less receptive to the association between heredity and cancer, despite the description of other families with similar heredograms. Unfortunately, this historical fact remained somewhat dormant until another investigator inaugurated a new era in the understanding of family cancer clusters. After reports and studies from this family and many others, the condition initially called Cancer Family Syndrome was changed to the eponym Lynch Syndrome. This was a recognition of the extensive and dedicated work developed by Dr. Henry Lynch in describing various characteristics of the disease, and his efforts to establish the correct recommendations for its diagnosis and treatment. Although the future announces there is still far to go for a complete understanding of Lynch Syndrome, the remarkable contributions of Pauline's intuition, Warthin's perseverance, and Lynch's work consistency must never be forgotten by those who already have or will still benefit from this knowledge.

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ABSTRACT The present manuscript aimed to review the historical development and most important contributions regarding Lynch Syndrome since its first description, more than a century ago. In 1895, a reputed pathologist from Michigan University, Dr. Aldred Scott Warthin, got intrigued by the family history of a local seamstress called Pauline Gross. According to her prevision, she would present an early death due to cancer, which actually happened (from the uterus). Historically, her family was designated "Family G", comprising a group recognized as the longest and most detailed cancer genealogy that has ever been studied. Warthin concluded that its members had genetic susceptibility for cancer, and they are, nowadays, considered the first reported Lynch Syndrome family. At that time, however, the medical cancer community was far less receptive to the association between heredity and cancer, despite the description of other families with similar heredograms. Unfortunately, this historical fact remained somewhat dormant until another investigator inaugurated a new era in the understanding of family cancer clusters. After reports and studies from this family and many others, the condition initially called Cancer Family Syndrome was changed to the eponym Lynch Syndrome. This was a recognition of the extensive and dedicated work developed by Dr. Henry Lynch in describing various characteristics of the disease, and his efforts to establish the correct recommendations for its diagnosis and treatment. Although the future announces there is still far to go for a complete understanding of Lynch Syndrome, the remarkable contributions of Pauline's intuition, Warthin's perseverance, and Lynch's work consistency must never be forgotten by those who already have or will still benefit from this knowledge.

RESUMO O objetivo do presente manuscrito foi fazer uma revisão histórica do desenvolvimento e das mais importantes contribuições em relação à Síndrome de Lynch, desde sua primeira descrição há mais de um século atrás. Em 1895, o reputado patologista Dr. Aldred Scott Warthin ficou intrigado com a história familiar de uma costureira local, chamada Pauline Gross. De acordo com a sua previsão, ela morreria precocemente devido a um câncer, o que realmente aconteceu (do útero). Historicamente, sua família foi designada como Família "G", caracterizando um grupo reconhecido como a maior e mais longa árvore genealógica relacionada ao câncer familiar jamais estudada. Warthin concluiu que os membros dessa família tinham susceptibilidade genética para câncer, e ainda hoje são considerados a primeira família com Síndrome de Lynch reportada na literatura. Entretanto, naquela época a comunidade médica oncológica não era receptiva à associação entre hereditariedade e câncer, a despeito da descrição de outras famílias com heredogramas similares. Infelizmente, esse fato histórico permaneceu esquecido até que outro investigador inaugurou uma nova era para a melhor compreensão da agregação familiar do câncer. Após diversas descrições dessa mesma agregação de casos de câncer em outras famílias, essa condição inicialmente denominada Síndrome de Câncer Familial foi mudada para o epônimo Síndrome de Lynch. Esse foi um reconhecimento ao extenso e dedicado trabalho desenvolvido pelo Dr. Henry Lynch na descrição de diversas características da doença e seus esforços para estabelecer as recomendações corretas para o seu diagnóstico e tratamento. Embora o futuro anuncie que ainda teremos um longo caminho a percorrer para a completa compreensão da Síndrome de Lynch, as contribuições extraordinárias da intuição de Pauline, da perseverança de Warthin e da consistência do trabalho de Lynch nunca devem ser esquecidas por àqueles que já se beneficiaram, bem como os que ainda irão se beneficiar de todo esse conhecimento.

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Purpose: Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare primary liver malignancy often diagnosed at advanced stages. While there are limited data on the efficacy of specific agents, we aim to report outcomes of patients treated with systemic therapies and explore prognostic factors. Patients and Methods: Medical records of patients treated between 2010 and 2022 were reviewed. Treatments were defined after multidisciplinary assessment. Descriptive statistics were used for baseline demographics. Time-to-event outcomes were estimated using the Kaplan-Meier method, compared by log-rank and adjusted by a regression model. Radiomic features (including size, shape, and texture) of the primary lesion were extracted and dimensionality reduced. An unsupervised Gaussian Mixture Model (GMM) clustering was performed, and survival was compared between clusters. Results: We identified 23 patients: 12 males, with a median age of 23.6 years. At diagnosis, 82.6% had metastases, most frequently to the lungs (39.1%), lymph nodes (39.1%), and peritoneum (21.7%). Patients received a median of three lines (1-8) of treatment, including different regimens. Sorafenib (39.1%), capecitabine (30.4%), and capecitabine/interferon (13%) were the most used first-line regimens. The median time-to-failure was 3.8 months (95% CI: 3.2-8.7). Capecitabine + interferon (42.1%) and platinum combinations (39.1%) were the most used second-line regimens, with a time-to-failure of 3.5 months (95% CI: 1.5-11.6). Median overall survival was 26.7 months (95% CI: 15.1-40.4). A high baseline neutrophil-to-lymphocyte ratio (NLR) was associated with worse survival (p=0.02). Radiomic features identified three clusters, with one cluster (n=6) having better survival (40.4 vs 22.6 months, p=0.039). Tumor sphericity in the arterial phase was the most relevant characteristic associated with a better prognosis (accuracy=0.93). Conclusion: FLHCC has unique features compared to conventional HCC, including young onset, gender balance, and absence of hepatopathy. Systemic therapies can provide encouraging survival, but lack of uniformity precludes defining a preferable regimen. Radiomics and NLR were suggested to correlate with prognosis and warrant further validation.

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BACKGROUND: Hepatosplenic schistosomiasis is an endemic disease prevalent in tropical countries and is associated with a high incidence of portal vein thrombosis. Inflammatory changes caused by both parasitic infection and portal thrombosis can lead to the development of chronic liver disease with potential carcinogenesis. AIMS: To assess the incidence of portal vein thrombosis and hepatocellular carcinoma in patients with schistosomiasis during long-term follow-up. METHODS: A retrospective study was conducted involving patients with schistosomiasis followed up at our institution between 1990 and 2021. RESULTS: A total of 126 patients with schistosomiasis were evaluated in the study. The mean follow-up time was 16 years (range 5-31). Of the total, 73 (57.9%) patients presented portal vein thrombosis during follow-up. Six (8.1%) of them were diagnosed with hepatocellular carcinoma, all with portal vein thrombosis diagnosed more than ten years before. CONCLUSIONS: The incidence of hepatocellular carcinoma in patients with schistosomiasis and chronic portal vein thrombosis highlights the importance of a systematic long-term follow-up in this group of patients.

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BACKGROUND: The impact of cirrhosis and portal hypertension on perioperative outcomes of minimally invasive left lateral sectionectomies remains unclear. We aimed to compare the perioperative outcomes between patients with preserved and compromised liver function (noncirrhotics versus Child-Pugh A) when undergoing minimally invasive left lateral sectionectomies. In addition, we aimed to determine if the extent of cirrhosis (Child-Pugh A versus B) and the presence of portal hypertension had a significant impact on perioperative outcomes. METHODS: This was an international multicenter retrospective analysis of 1,526 patients who underwent minimally invasive left lateral sectionectomies for primary liver malignancies at 60 centers worldwide between 2004 and 2021. In the study, 1,370 patients met the inclusion criteria and formed the final study group. Baseline clinicopathological characteristics and perioperative outcomes of these patients were compared. To minimize confounding factors, 1:1 propensity score matching and coarsened exact matching were performed. RESULTS: The study group comprised 559, 753, and 58 patients who did not have cirrhosis, Child-Pugh A, and Child-Pugh B cirrhosis, respectively. Six-hundred and thirty patients with cirrhosis had portal hypertension, and 170 did not. After propensity score matching and coarsened exact matching, Child-Pugh A patients with cirrhosis undergoing minimally invasive left lateral sectionectomies had longer operative time, higher intraoperative blood loss, higher transfusion rate, and longer hospital stay than patients without cirrhosis. The extent of cirrhosis did not significantly impact perioperative outcomes except for a longer duration of hospital stay. CONCLUSION: Liver cirrhosis adversely affected the intraoperative technical difficulty and perioperative outcomes of minimally invasive left lateral sectionectomies.

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Given the frequent co-existence of an aggressive tumor and underlying chronic liver disease, the management of hepatocellular carcinoma (HCC) patients requires experienced multidisciplinary team discussion. Moreover, imaging plays a key role in the diagnosis, staging, restaging, and surveillance of HCC. Currently, imaging assessment of HCC entails the assessment of qualitative characteristics which are prone to inter-reader variability. Radiomics is an emerging field that extracts high-dimensional mineable quantitative features that cannot be assessed visually with the naked eye from medical imaging. The main potential applications of radiomic models in HCC are to predict histology, response to treatment, genetic signature, recurrence, and survival. Despite the encouraging results to date, there are challenges and limitations that need to be overcome before radiomics implementation in clinical practice. The purpose of this article is to review the main concepts and challenges pertaining to radiomics, and to review recent studies and potential applications of radiomics in HCC.

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BACKGROUND: Resection for colorectal liver metastases has evolved significantly and, currently, there are no limits to the number of resected nodules. This study aimed to evaluate the outcomes and prognostic factors after liver resection for patients with ≥4 colorectal liver metastases, emphasizing long-term survival. METHODS: The study population consisted of 137 patients with ≥4 colorectal liver metastases out of a total of 597 patients with colorectal liver metastases who underwent curative intent liver resection from January 2010 to July 2019 in a single hepatobiliary center. RESULTS: The probability of overall and disease-free survival at 1, 3, and 5 years was 90.8%, 64.5%, 40.6%, and 37.7%, 19.3%, 18.1%, respectively. In a multivariate analysis for overall survival, the size of the largest metastatic nodule was the only unfavorable factor (P = .001). For disease-free survival, complete pathological response was a favorable factor (P = .04), and the following were negative factors: number of nodules ≥7 (P = .034), radiofrequency ablation during surgery (P = .04), positive primary tumor lymph nodes (P = .034), R1 resection (P = .011), and preoperative carcinoembryonic antigen >20 ng/mL (P = .015). After the first and second years of follow-up, 59 patients (45.3%) and 45 patients (34.6%), respectively, were not receiving chemotherapy. After 5 years of follow-up, 21 (16.1%) multimetastatic patients were chemotherapy-free. CONCLUSION: A significant number of patients with multiple colorectal liver metastases will present long-term survival and should not be denied surgery. The long-term survival rates, even in the presence of recurrence, characterize a chronic neoplastic disease.

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ABSTRACT BACKGROUND: Hepatosplenic schistosomiasis is an endemic disease prevalent in tropical countries and is associated with a high incidence of portal vein thrombosis. Inflammatory changes caused by both parasitic infection and portal thrombosis can lead to the development of chronic liver disease with potential carcinogenesis. AIMS: To assess the incidence of portal vein thrombosis and hepatocellular carcinoma in patients with schistosomiasis during long-term follow-up. METHODS: A retrospective study was conducted involving patients with schistosomiasis followed up at our institution between 1990 and 2021. RESULTS: A total of 126 patients with schistosomiasis were evaluated in the study. The mean follow-up time was 16 years (range 5-31). Of the total, 73 (57.9%) patients presented portal vein thrombosis during follow-up. Six (8.1%) of them were diagnosed with hepatocellular carcinoma, all with portal vein thrombosis diagnosed more than ten years before. CONCLUSIONS: The incidence of hepatocellular carcinoma in patients with schistosomiasis and chronic portal vein thrombosis highlights the importance of a systematic long-term follow-up in this group of patients.

RESUMO RACIONAL: A esquistossomose hepatoesplênica é uma doença endêmica prevalente em países tropicais e está associada a uma alta incidência de trombose da veia porta. Alterações inflamatórias causadas tanto pela infecção parasitária quanto pela trombose portal podem levar ao desenvolvimento de doença hepática crônica com potencial carcinogênico. OBJETIVOS: Avaliar a incidência de trombose da veia porta e carcinoma hepatocelular em pacientes com esquistossomose durante um seguimento de longo prazo. MÉTODOS: Foi realizado estudo retrospectivo envolvendo pacientes com esquistossomose acompanhados em nossa instituição entre 1990 e 2021. RESULTADOS: Um total de 126 pacientes com esquistossomose foram avaliados no estudo. O tempo médio de acompanhamento foi de 16 anos (variando de 5 a 31). Do total, 73 (57,9%) pacientes apresentaram trombose da veia porta durante o seguimento e seis (8,1%) deles foram diagnosticados com carcinoma hepatocelular, todos com trombose da veia porta diagnosticada há mais de 10 anos. CONCLUSÕES: A incidência de carcinoma hepatocelular em pacientes com esquistossomose e trombose da veia porta crônica destaca a importância de um acompanhamento sistemático de longo prazo nesse grupo de pacientes.

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OBJECTIVE: The aim of the present study was to evaluate the clinical features, Hepatocellular Carcinoma (HCC) screening, treatment modalities, and Overall Survival (OS) in a series of Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma (NAFLD-HCC) Brazilian patients. METHODS: This was a cross-sectional study at the Instituto do Cancer do Estado de São Paulo, at the Faculdade de Medicina da Universidade de São Paulo with the approval of the local research ethics committee. NAFLD patients with HCC diagnosed, from May 2010 to May 2019, were included. RESULTS: A total of 131 patients were included. Risk factors for NAFLD were present in 94.7% of the patients. Only 29% of patients were in the HCC screening program before diagnosis. HCC treatment was performed in 84.7% of patients. Cumulative survival at the end of the first year was 72%, second-year 52%, and fifth-year 32%. HCC screening before diagnosis was not significantly associated with higher cumulative survival. The independent factors associated with shorter general survival were BCLC C-D, p < 0.001, and the size of the largest nodule > 42 mm, p = 0.039. CONCLUSIONS: Although the efficacy of screening in our population regarding overall survival was hampered due to the sample size (29% had screening), BCLC stages C‒D and the size of the largest nodule larger than 42 mm were identified as independent factors of worse prognosis.

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