Henrique Alexandrino

Mitochondrial bioenergetics and posthepatectomy liver dysfunction

Liver regeneration requires an enormous energy supply. Experimental evidence suggests that mitochondrial function is of paramount importance for liver regeneration. However, this has not been investigated in the clinical setting. We aimed to: (i) evaluate changes in mitochondrial function during hepatectomy, especially after hepatic pedicle clamping; and (ii) correlate these changes with postoperative hepatocellular function and clinical outcome.

Functional hepatocellular regeneration in elderly patients undergoing hepatectomy

More than 50% of liver tumours occur in patients aged 65 years or more. Assessment of functional liver regeneration capacity is crucial to minimize postoperative liver failure. We aimed to study functional hepatocellular regeneration, through scintigraphic quantification of Mebrofenin hepatic extraction fraction (HEF), after partial hepatectomy, comparing elderly patients with younger ones.

Sinusoidal dilation increases the risk of complications in hepatectomy for CRCLM – Protective effect of bevacizumab and diabetes mellitus, serum gamma-glutamyltranspeptidase as predictive factor

INTRODUCTION Advances in neoadjuvant chemotherapy (NCT) have allowed surgical treatment in otherwise unresectable patients with colorectal liver metastases (CRLM). It is well known that NCT induces liver lesions such as sinusoidal obstruction syndrome (SOS) and steatohepatitis (SH). However, whether it affects postoperative morbidity remains controversial. The aim of this study was both to evaluate the impact of NCT on liver parenchyma and postoperative morbidity, and to identify preoperative predictive markers for liver injury. PATIENTS AND METHODS Among 140 patients undergoing liver resection for CRLM between 2010 and 2013, 70 underwent systemic NCT. Liver function tests, pathology, postoperative morbidity and mortality were compared between the two groups. RESULTS Univariate analysis revealed NCT as a cause of sinusoidal dilation (p = 0.09), peliosis (p = 0.028) and moderate and severe SOS (p = 0.004) and bevacizumab as a protective agent against moderate and severe SOS (p = 0.045). Diabetic patients were identified as having a lower incidence of sinusoidal dilation (p = 0.034) and a higher incidence of steatosis (p = 0.003). Multivariate analysis confirmed sinusoidal dilation as an independent cause for morbidity (p = 0.02) and liver-specific complications (p = 0.016). Preoperative level of GGT was identified as predictive factor for moderate and severe SOS and peliosis (p < 0.001 and p = 0.004, respectively). CONCLUSION The administration of NCT induces SOS-lesions, but can be partially prevented by bevacizumab and diabetes. Sinusoidal dilation is associated with increased postoperative morbidity. Preoperative GGT levels can be useful to predict the presence of SOS.

Rupture of splenic angiosarcoma: a rare cause of spontaneous haemoperitoneum

Primary splenic angiosarcoma, a very rare mesenchymal tumour of endothelial cell origin, comprises 2.6% of all cases of angiosarcoma and 10% of all primitive splenic tumours. Clinical presentation is usually unspecific, with abdominal pain and anaemia. Rupture is a rare complication and should prompt emergency splenectomy. Prognosis is usually poor because of liver, lung or bone metastases. We describe the case of an 80-year-old woman admitted to the emergency room with syncope, hypotension and vomiting. She stabilised after fluid resuscitation. Investigations showed anaemia, a large, heterogeneous spleen and free fluid in the abdominal cavity. She underwent emergency splenectomy. Pathology revealed primary splenic angiosarcoma. The postoperative period was complicated by respiratory failure but the patient made an otherwise uneventful course and was discharged 2 weeks after surgery. Six months after the operation she remains free of disease with no adjuvant treatment.

Mitochondria in Liver Regeneration: Energy Metabolism and Posthepatectomy Liver Dysfunction

Liver resection is the only curative therapy for most patients with hepatobiliary malignancies. Resection of a substantial amount of liver mass is only possible due to the liver’s remarkable capacity to regenerate. However, when this process is hampered Posthepatectomy Liver Failure (PHLF) ensues, resulting in increased postoperative mortality and morbidity. Being a highly energy dependent chain of events, liver regeneration is influenced by the energy status of the main parenchymal cell—the hepatocyte. Mitochondria are the powerhouses of eukaryote cells and key players in cell death. As such, they play a major role in the organ’s response to major resection. Although this subject has been the focus of investigation in the past, recent findings have led to a renewal of interest on disordered bioenergetics in liver surgery. In this Chapter we will scrutinize the experimental and clinical evidence supporting a major role for mitochondria in the liver’s response to resection, as well as the relevance of mitochondrial derangement in the pathophysiology of PHLF. Furthermore, as a significant proportion of patients undergoing hepatectomy have chronic liver diseases, namely cirrhosis, biliary obstruction, steatosis or sinusoidal obstruction syndrome, which are at increased risk of PHLF, we will recapitulate the disordered bioenergetics in the pathophysiology of these conditions. Finally, we will elaborate on the evidence for a definitive role of boosting energetic status of the liver parenchyma in improving the clinical results of hepatectomy.

Rewards and Challenges of Research in a Surgical Career

1. Faculdade de Medicina. Universidade de Coimbra. Coimbra. Portugal. 2. Serviço de Cirurgia A. Centro Hospitalar e Universitário de Coimbra. Coimbra. Portugal. 3. Editor-Associado. Acta Médica Portuguesa. Lisboa. Portugal.  Autor correspondente: Henrique Alexandrino. halexandrino123@gmail.com Recebido: 20 de abril de 2018 Aceite: 07 de maio de 2018 | Copyright

Locally advanced adenocarcinoma of the rectum presenting with necrotising fasciitis of the perineum: successful management with early aggressive surgery and multimodal therapy

Colorectal cancer is a common malignant neoplasm and its treatment usually involves surgery associated, in some cases, depending on the staging, with chemoradiotherapy. Necrotising fasciitis of the perineum is a highly lethal infection of the perineum, perirectal tissues and genitals, requiring emergency surgical debridement, broad-spectrum antibiotics and control of sepsis. We present the case of a 59-year-old man with necrotising fasciitis of the perineum as the first clinical manifestation of locally advanced adenocarcinoma of the rectum, in which successful management consisted of early and aggressive surgical debridement, followed by multimodal therapy with curative intent. 2 years and 6 months after surgery the patient is well, with no evidence of local or systemic relapse.