LIVER TRANSPLANT FOR METASTATIC NEUROENDOCRINE TUMORS: A SINGLE-CENTER REPORT.

BACKGROUND: Neuroendocrine tumors are rare neoplasms of uncertain biological behavior. The liver is one of the most common sites of metastases, occurring in 50% of patients with metastatic disease. AIMS: To analyze a clinical series in liver transplant of patients with neuroendocrine tumors metastases. METHODS: A retrospective descriptive study, based on the review of medical records of patients undergoing liver transplants due to neuroendocrine tumor metastases in a single center in northeast Brazil, over a period of 20 years (January 2001 to December 2021). RESULTS: During the analyzed period, 2,000 liver transplants were performed, of which 11 were indicated for liver metastases caused by neuroendocrine tumors. The mean age at diagnosis was 45.09±14.36 years (26-66 years) and 72.7% of cases were females. The most common primary tumor site was in the gastrointestinal tract in 64% of cases. Even after detailed investigation, three patients had no primary tumor site identified (27%). Overall survival after transplantation at one month was 90%, at one year was 70%, and five year, 45.4%. Disease-free survival rate was 72.7% at one year and 36.3% at five years. CONCLUSIONS: Liver transplantation is a treatment modality with good overall survival and disease-free survival results in selected patients with unresectable liver metastases from neuroendocrine tumors. However, a rigorous selection of patients is necessary to obtain better results and the ideal time for transplant indication is still a controversial topic in the literature.

Liver transplant for metastatic neuroendocrine tumors: a single-center report / Transplante de fígado para tumores neuroendócrinos metastáticos: série de casos

ABSTRACT BACKGROUND: Neuroendocrine tumors are rare neoplasms of uncertain biological behavior. The liver is one of the most common sites of metastases, occurring in 50% of patients with metastatic disease. AIMS: To analyze a clinical series in liver transplant of patients with neuroendocrine tumors metastases. METHODS: A retrospective descriptive study, based on the review of medical records of patients undergoing liver transplants due to neuroendocrine tumor metastases in a single center in northeast Brazil, over a period of 20 years (January 2001 to December 2021). RESULTS: During the analyzed period, 2,000 liver transplants were performed, of which 11 were indicated for liver metastases caused by neuroendocrine tumors. The mean age at diagnosis was 45.09±14.36 years (26-66 years) and 72.7% of cases were females. The most common primary tumor site was in the gastrointestinal tract in 64% of cases. Even after detailed investigation, three patients had no primary tumor site identified (27%). Overall survival after transplantation at one month was 90%, at one year was 70%, and five year, 45.4%. Disease-free survival rate was 72.7% at one year and 36.3% at five years. CONCLUSIONS: Liver transplantation is a treatment modality with good overall survival and disease-free survival results in selected patients with unresectable liver metastases from neuroendocrine tumors. However, a rigorous selection of patients is necessary to obtain better results and the ideal time for transplant indication is still a controversial topic in the literature.

RESUMO RACIONAL: Os tumores neuroendócrinos são neoplasias raras de comportamento biológico incerto. O fígado é um local comum de metástase, ocorrendo em 50% dos pacientes com doença metastática. OBJETIVOS: Analisar casuística de transplante hepático por metástases de tumores neuroendócrinos. MÉTODOS: Estudo descritivo retrospectivo com revisão de prontuários de pacientes submetidos a transplante hepático por metástases de tumores neuroendócrinos em um único centro no Nordeste do Brasil durante 20 anos (janeiro de 2001 a dezembro de 2021). RESULTADOS: Durante o período analisado, foram realizados 2.000 transplantes hepático, sendo 11 indicados por metástases hepáticas de tumores neuroendócrinos. A média de idade ao diagnóstico foi de 45,09±14,36 anos (26-66 anos) e 72,7% dos casos eram do sexo feminino. O local do tumor primário mais comum foi o trato gastrointestinal (64% dos casos). Após detalhada investigação, três pacientes não tiveram o local do tumor primário identificado (27%). A sobrevida global um mês e após um ano do transplante foi de 90 e 70%, respectivamente. A sobrevida após 5 anos foi de 45,4%. A taxa de sobrevida livre de doença foi de 72,7% no primeiro ano e 36,3% em cinco anos. CONCLUSÕES: O transplante hepático é uma modalidade de tratamento com bons resultados de sobrevida global e sobrevida livre de doença, em pacientes selecionados com metástases hepáticas irressecáveis de tumores neuroendócrinos. No entanto, a seleção rigorosa dos pacientes é necessária para obter melhores resultados e o momento ideal para a indicação do transplante ainda é um tema controverso na literatura.

Estudo prospectivo da incidência, das características clínico-patológicas e da hiperalgesia na síndrome mão-pé induzida por capecitabina

INTRODUÇÃO: A capecitabina (CAP) é uma fluoropirimidina oral cuja toxicidademais comum é a síndrome mão-pé (SMP), caracterizada pela presença de disestesia, eritema e dor na região palmo-plantar. Apesar de a SMP acometer metade dos pacientes que utilizam a droga, pouco se sabe sobre seu mecanismo fisiopatogênico. OBJETIVO: Avaliar prospectivamente a incidência, as características clínicopatológicas e a hiperalgesia da SMP em pacientes tratados com CAP em monoterapia. MATERIAL E MÉTODOS: Foram incluídos 35 doentes com câncer de mama ou colorretal metastático. Os doentes foram tratados com CAP na dose de 2500 mg/m2/dia até máxima resposta ou toxicidade e acompanhados prospectivamente. A quantificação da resposta hiperalgésica cutânea foi realizada através da aferição do limiar mecânico da dor (LMD) com um analgesímetro digital do tipo von Frey antes do início de cada ciclo de tratamento. Os pacientes que apresentaram SMP de grau 2 ou 3 foram submetidos a biópsia cutânea palmar com punch de 4 mm, que foi comparada com amostras de cadáveres. As peças foram estudadas em hematoxilinaeosinae submetidas a pesquisa da expressão de IL-1, TNF-a, iNOS, substância P (SP)e CGRP por imunoistoquímica. RESULTADOS: 56% dos doentes tiveram toxicidade grau 3 ou 4, e 63% tiveram de ser submetidos a reduções da dose do quimioterápico. Nos pacientes com SMP houve uma redução média do LMD de 17,8% em relação aobasal, enquanto os doentes sem SMP apresentaram redução de 2,8% (p=0,014). A alteração do LMD foi tanto maior quanto mais intensas as manifestações clínicas, à exceção da síndrome grau 3. Observou-se uma associação entre o desenvolvimento de SMP e a presença de benefício clínico com a terapia (65% vs. 0%; p<0,001), assim como com uma maior sobrevida livre de progressão (7,7 meses vs. 1,9 mês; p=0,042). As peças de pacientes com SMP exibiram alterações inflamatórias, necrose de queratinócitos, espongiose, acantólise, disqueratose e degeneração hidrópica focal, enquanto...

INTRODUCTION: The most important adverse effect of capecitabine (CAP), an oral fluoropyrimidine, is the development of hand-foot syndrome (HFS), which is characterized by dysestesia, erythema and pain on the the palms and soles areas. Although described in half the patients treated with CAP, little is known about HFS pathogenesis. OBJECTIVE: To evaluate prospectively the incidence, the clinicalpathological characteristics and the hyperalgesia of HFS in patients on CAP monotherapy. MATERIAL AND METHODS: 35 patients with metastatic colorectal or breast cancer were included. The patients were treated with CAP at the dose of 2500 mg/m2/day until maximal response or toxicity and were followed prospectively. The cutaneous hyperalgesic response was quantified by the measurement of mechanical pain threshold (MPT) with a von Frey electronic analgesimeter beforeeach chemotherapy cycle. The patients that developed grade 2 or 3 HFS weresubmitted to palm biopsy with a 4-mm punch, which was compared to autopsysamples. The biopsies were studied in hematoxyllin-eosin stain and submitted to analysis of IL-1, TNF-a, iNOS, substance P (SP) and CGRP immunohistochemical expression. RESULTS: 56% of the patients had grade 3-4 adverse events, and 63% had to be submitted to dose reductions. The MPT of HFS patients had a mean duction of 17.8% compared to basal, while patients without HFS had a reduction of 2.8% (p=0.014). The change in MPT was higher as the clinical signs of HFS were more intense, with the exception of grade 3 HFS. There is a association between HFS development and the presence of clinical benefit with CAP (65% vs. 0%; p<0,001), as well as with longer progression free survival (7.7 months vs. 1.9 month; p=0.042).Pathologically, HFS patients had inflammatory changes, keratinocyte necrosis, spongiosis, acantholysis, dyskeratosis and focal hydropic degeneration, whereas no significant alterations were found in control group. It was detected hyperexpression of...