Relevance of liver surface nodularity for preoperative risk assessment in patients with resectable hepatocellular carcinoma.

BACKGROUND: Quantification of liver surface nodularity (LSN) on routine preoperative CT images allows detection of cirrhosis and clinically significant portal hypertension. This study aimed to assess the relevance of LSN in preoperative assessment of operative risks for patients with resectable hepatocellular carcinoma (HCC). METHODS: All patients undergoing hepatectomy for HCC between 2012 and 2017 were analysed retrospectively. LSN was assessed at the liver-fat interface on the left liver lobe on preoperative CT images. The feasibility of LSN quantification was assessed. The association between LSN and outcomes (severe complications and posthepatectomy liver failure (PHLF)) was evaluated by multivariable analysis and after propensity score matching. RESULTS: Among 210 patients, LSN measurement was successful in 187 (89·0 per cent). Among these, the median LSN score was 2·42 (i.q.r. 2·21-2·66) and 52·9 per cent had severe fibrosis, including 33·7 per cent with cirrhosis. LSN score increased with hepatic venous pressure gradient (P = 0·048), severity of steatosis (P = 0·011) and fibrosis grade (P = 0·001). LSN score was independently associated with severe complications (odds ratio (OR) 5·25; P = 0·006) and PHLF (OR 6·78; P = 0·003). After matching with respect to model for end-stage liver disease, aspartate aminotransferase-to-platelet ratio index and fibrosis-4 score, patients with a LSN score of 2·63 or higher retained an increased risk of PHLF (OR 5·81; P = 0·018). In the subgroup of patients without severe fibrosis, LSN was accurate in predicting severe complications (P = 0·005). Patients with (P = 0·039) or without (P = 0·018) severe fibrosis with increased LSN score had a higher comprehensive complication index score. Among patients with cirrhosis who had clinically significant portal hypertension, a LSN value below 2·63 ruled out the risk of PHLF. CONCLUSION: LSN measurement represents a practical tool that may allow improvement in the preoperative evaluation and management of patients with HCC.

ANTECEDENTES: La cuantificación de la nodularidad de la superficie hepática (liver surface nodularity, LSN) en las imágenes de la tomografía computarizada (TC) de rutina preoperatoria permite detectar la cirrosis y la hipertensión portal clínicamente significativa (clinically significant portal hypertension, CSPH). Este estudio tuvo como objetivo evaluar la relevancia de la LSN en la evaluación preoperatoria del riesgo quirúrgico en pacientes con carcinoma hepatocelular resecable (hepatocellular carcinoma, HCC). MÉTODOS: Todos los pacientes sometidos a hepatectomía por HCC entre 2012 y 2017 fueron analizados de forma retrospectiva. La LSN se evaluó en la interfase hígado-grasa en el lóbulo hepático izquierdo en la TC preoperatoria. Se evaluó la viabilidad de la cuantificación de la LSN. La asociación entre la LSN y los resultados (complicaciones graves e insuficiencia hepática poshepatectomía (post-hepatectomy liver failure, PHLF) se analizó en un análisis multivariable y después del método de emparejamiento por puntaje de propensión. RESULTADOS: Del total de 210 pacientes, la medición de la LSN fue exitosa en 187 (89,0%). En estos pacientes, la mediana de LSN fue de 2,42 (rango intercuartílico 2,21-2,66) y el 53,0% tenía fibrosis severa, incluyendo un 33,7% con cirrosis. La LSN aumentó con el gradiente de presión venosa hepática (P = 0,048), la gravedad de la esteatosis (P = 0,011) y el grado de fibrosis (P = 0,001). La LSN se asoció de forma independiente con complicaciones graves (razón de oportunidades, odds ratio, OR = 5,25; P = 0,006) y PHLF (OR = 6,78; P = 0,003). Después de emparejar para el modelo de enfermedad hepática terminal, el índice de relación aspartato amino transferase-plaquetas y el grado de fibrosis-4, los pacientes con LSN ≥ 2,63 mantuvieron un mayor riesgo de PHLF (OR = 5,81; P = 0,018). Dentro del subgrupo de pacientes sin fibrosis severa, la LSN fue precisa en predecir complicaciones graves (P = 0,005). Los pacientes con (P = 0,039) y sin (P = 0,018) fibrosis severa con aumento de la LSN tuvieron un índice de complicación global más alto. De los pacientes cirróticos con CSPH, un valor de LSN de 2,63 descartó el riesgo de PHLF. CONCLUSIÓN: La LSN representa una herramienta práctica, que puede permitir mejorar la evaluación preoperatoria y el manejo de pacientes con HCC.

Metabolic syndrome and hepatic surgery.

In Europe, the prevalence of metabolic syndrome (MS) has reached the endemic rate of 25%. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of MS. Its definition is histological, bringing together the different lesions associated with hepatic steatosis (fat deposits on more than 5% of hepatocytes) without alcohol consumption and following exclusion of other causes. MS and NAFLD are implicated in the carcinogenesis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). At present, HCC and ICC involving MS represent 15-20% and 20-30% respectively of indications for hepatic resection in HCC and ICC. Moreover, in the industrialized nations NAFLD is tending to become the most frequent indication for liver transplantation. MS patients combine the operative risk associated with their general condition and comorbidities and the risk associated with the presence and/or severity of NAFLD. Following hepatic resection in cases of HCC and ICC complicating MS, the morbidity rate ranges from 20 to 30%, and due to cardiovascular and infectious complications, post-transplantation mortality is heightened. The operative risk incurred by MS patients necessitates appropriate management including: (i) precise characterization of the subjacent liver; (ii) an accurately targeted approach privileging detection and optimization of treatment taking into account the relevant cardiovascular risk factors; (iii) a surgical strategy adapted to the histology of the underlying liver, with optimization of the volume of the remaining (postoperative) liver.

Circumferential margin involvement after total mesorectal excision for mid or low rectal cancer: are all R1 resections equal?

AIM: Our aim was to assess the prognostic influence of the circumferential resection margin (CRM) exact value after total mesorectal excision for mid or low rectal cancer. METHODS: All patients (n = 321) who underwent total mesorectal excision from 2005 to 2013 were identified from a prospective database, including 49 (15%) who presented with a CRM ≤ 1 mm. Four groups were defined: group 1, CRM = 0 mm (n = 21); group 2, 0 < CRM ≤ 0.4 mm (n = 13); group 3, 0.4 < CRM ≤ 1 mm (n = 15); group 4, CRM > 1 mm (n = 272). RESULTS: After a mean follow-up of 42 ± 26 months, locoregional recurrence rates were 8/21 (38%) in group 1, 3/13 (23%) in group 2, 0/12 (0%) in group 3 and 26/272 (10%) in group 4 (P < 0.001), leading to significantly impaired 3-year locoregional recurrence-free survival in group 1 (57% ± 13%) and group 2 (56% ± 15%) compared to group 3 (85% ± 10%, vs group 1, P = 0.021, vs group 2, P = 0.049) and to group 4 (89% ± 2%, vs group 1, P < 0.001, vs group 2, P < 0.001). In multivariate Cox analysis, a CRM ≤ 0.4 mm was identified as an independent factor impairing both locoregional recurrence-free survival (OR 3.14, 95% CI 1.53-6.46; P = 0.002) and disease-free survival (OR 2.15, 95% CI 1.28-3.63; P = 0.004). CONCLUSION: Our study suggests that the prognosis after mid or low rectal cancer surgery was worse with a CRM ≤ 0.4 mm. The prognosis was similar in patients with a CRM > 0.4 mm or ≤ 1 mm and patients with an R0 resection.

Long-term intermittent glutamine supplementation repairs intestinal damage (structure and functional mass) with advanced age: assessment with plasma citrulline in a rodent model.

OBJECTIVE: Glutamine is the preferred fuel for the rat small intestine and promotes the growth of intestinal mucosa, especially in the event of gut injury. Quantitatively, glutamine is one important precursor for intestinal citrulline release. The aim of this study was to determine whether the effect of glutamine on the increase in intestinal villus height is correlated with an increase in both gut mass and citrulline plasma level in very old rats. METHODS: We intermittently supplemented very old (27-mo) female rats with oral glutamine (20% of diet protein). Intestinal histomorphometric analysis of the small bowel was performed. Amino acids, in particular citrulline, were measured in the plasma, liver and jejunum. Markers of renal (creatinine, urea) and liver (alanine aminotransferase [ALT]) and aspartate aminotransferase (AST) functions were measured to evaluate renal and liver functions in relation to aging and to glutamine supplementation. Liver glutathione was also determined to evaluate cellular redox state. RESULTS: Glutamine supplementation maintains the body weight of very old rats, not by limiting sarcopenia but rather by increasing the organ mass of the splanchnic area. Total intestine mass was significantly higher in glutamine-supplemented rats than in controls (15%). Measurement of villus height and crypt depth demonstrated that the difference between villus and crypt was significantly improved in glutamine pre-treated rats compared to controls (~ 11%). Plasma citrulline also increased by 15% in glutamine-supplemented rats compared to controls. CONCLUSION: Citrulline appears as a biomarker of enterocyte mass in villous atrophy associated with advanced age. Non-invasive measurement of this metabolite may be useful in following the state of the gastrointestinal tract in very old people, whose numbers are increasing worldwide and the care of whom is a major public health issue. The gut may contribute to the malnutrition caused by malabsorption frequently observed in the elderly.

Effect of intermittent glutamine supplementation on skeletal muscle is not long-lasting in very old rats.

BACKGROUND AND OBJECTIVE: Muscle is the major site for glutamine synthesis via glutamine synthetase (GS). This enzyme is increased 1.5-2 fold in 25-27-mo rats and may be a consequence of aging-induced stress. This stimulation is similar to the induction observed following a catabolic state such as glucocorticoid treatment (6 to 24 months). Although oral glutamine supply regulates the plasma glutamine level, nothing is known if this supplementation is interrupted before the experiment. DESIGN: Adult (8-mo) and very old (27-mo) female rats were exposed to intermittent glutamine supplementation for 50 % of their age lifetime. Treated rats received glutamine added to their drinking water and control rats water alone but the effect of glutamine supplementation was only studied 15 days after the last supplementation. RESULTS: Glutamine pretreatment discontinued 15 days before the experiment increased plasma glutamine to ~ 0.6 mM, a normal value in very old rats. However, it failed to decrease the up-regulated GS activity in skeletal muscle from very old rats. CONCLUSION: Our results suggest that long-term treatment with glutamine started before advanced age but discontinued 15 days before rat sacrifice is effective in increasing plasma glutamine to recover basal adult value and in maintaining plasma glutamine in very old rats, but has no long-lasting effect on the GS activity of skeletal muscle with advanced age.

[Prenatal diagnosis of cerebral tumors and differential diagnosis]. / Diagnostic anténatal des tumeurs cérébrales fœtales et diagnostics différentiels.

Fetal brain tumors are rare and have different histologies. Although the definitive diagnosis relies on the histopathology of the tumor, it is useful to distinguish the tumors potentially curable from the tumors rapidly fatal after birth. Nevertheless, some intracranial masses are not tumors. We report four cases of intracerebral masses diagnosed prenatally corresponding to different histological lesions: teratoma, fetus-in-fetu, chraniopharyngioma, hemangioma. We discuss the elements of the differential diagnosis, which can be identified prenatally.

Genotype-phenotype correlations in fetuses and neonates with autosomal recessive polycystic kidney disease.

The prognosis of autosomal recessive polycystic kidney disease is known to correlate with genotype. The presence of two truncating mutations in the PKHD1 gene encoding the fibrocystin protein is associated with neonatal death while patients who survive have at least one missense mutation. To determine relationships between genotype and renal and hepatic abnormalities we correlated the severity of renal and hepatic histological lesions to the type of PKHD1 mutations in 54 fetuses (medical pregnancy termination) and 20 neonates who died shortly after birth. Within this cohort, 55.5% of the mutations truncated fibrocystin. The severity of cortical collecting duct dilatations, cortical tubule and glomerular lesions, and renal cortical and hepatic portal fibrosis increased with gestational age. Severe genotypes, defined by two truncating mutations, were more frequent in patients of less than 30 weeks gestation compared to older fetuses and neonates. When adjusted to gestational age, the extension of collecting duct dilatation into the cortex and cortical tubule lesions, but not portal fibrosis, was more prevalent in patients with severe than in those with a non-severe genotype. Our results show the presence of two truncating mutations of the PKHD1 gene is associated with the most severe renal forms of prenatally detected autosomal recessive polycystic kidney disease. Their absence, however, does not guarantee survival to the neonatal period.

Prenatal diagnosis of thrombosis of the dural sinuses: report of six cases, review of the literature and suggested management.

OBJECTIVES: To describe and assess the sonographic findings, evolution and clinical implications of thrombosis of the fetal dural sinuses. METHODS: We compiled a multicenter report of the outcomes of five cases with a prenatal diagnosis of thrombosis of the dural sinuses, and one case in which thrombosis of the dural sinus was diagnosed at necroscopy after termination of pregnancy. Prognostic factors are discussed, and suggestions made for prenatal and postnatal management. RESULTS: The mean (range) gestational age at diagnosis of thrombosis of the dural sinuses in the five cases in which it was made prenatally was 25.2 (22-31) weeks. In these five cases, diagnosis was made by sonography and confirmed by magnetic resonance imaging (MRI), which showed a blood clot in the region of the torcular herophili. Three of the six cases delivered vaginally with favorable sonographic findings, and normal clinical neurological development. Two pregnancies were terminated at the request of the parents. In one of these cases the prognosis was poor, with signs of fetal decompensation or cardiac failure; the pregnancy was terminated and necropsy revealed thrombosis of the occipital dural sinuses associated with a hemangioma. One infant, in whom the thrombosis developed in conjunction with a dural sinus malformation, died at 4 months of age. CONCLUSIONS: Thrombosis of the cerebral venous circulation can occur antenatally and is detectable by fetal real-time and color Doppler ultrasound examination. A review of the literature supports targeted evaluation of the fetus by serial ultrasound imaging and MRI to help guide the diagnosis, and to improve the counseling and management of such cases. Partial or total regression, isolated abnormality, absence of fetal decompensation or signs of cardiac failure and favorable clinical evolution are suggestive of favorable prognosis. In such cases, non-interventional neonatal management is recommended.

Larsen-like phenotype associated with partial trisomy 3p and monosomy 5p.

BACKGROUND: We report on a fetus with radiographic features of Larsen Syndrome (LS) and unbalanced 3;5 translocation. Recently LS was shown to be caused by mutations in FLNB gene which maps on 3p14.3. METHODS: Comparative genomic hybridization (CGH) was performed to search for genomic imbalances. Fluorescence in situ analysis (FISH) was done with BAC clone RP11-754F19 probe from the FLNB gene region (3p14.3). RESULTS: CGH showed a large loss of the chromosome 5 short arm and a gain of half of the short arm of chromosome 3 resulting from a derivative chromosome 5. FISH analysis with FLNB probe demonstrated that it was not triplicated. Thus, we excluded the role of a gene dosage effect of FLNB in abnormal craniofacial development in this fetus. CONCLUSIONS: To our knowledge, this is the first report of Larsen-like phenotype associated with unbalanced translocation resulting in partial trisomy 3p and monosomy 5p.

[Pancreatic involvement in Wegener's granulomatosis: a rare and difficult diagnosis]. / Les atteintes pancréatiques au cours de la granulomatose de Wegener: une localisation rare et un diagnostic difficile.

INTRODUCTION: Pancreatic involvement in the course of wegener's granulomatosis is rarely reported. EXEGESIS: We report a case presenting as a pancreatic tumorlike lesion. We also discuss six further cases from the medical literature. Two of them had a tumorlike lesion, three had acute pancreatitis and the last had exocrine pancreatic insufficiency. CONCLUSION: Treatment, association of corticoid and cyclophosphamide, is efficient if it is started quickly. So we think that this unusual manifestation of Wegener's granulomatosis should be recognized.

Prenatal detection of mosaic isochromosome 20q: a fourth report with abnormal phenotype.

We described a new case of mosaic isochromosome 20q revealed by amniocentesis. The propositus presented with craniofacial dysmorphism, clubfeet, and vertebral abnormalities. A 46,XX,i(20)(q10)[14]/46,XX[1] karyotype was confirmed by FISH on cultured cells. The pregnancy was terminated. From review of literature, fetus with mosaic isochromosome 20q identified on amniocentesis are most likely to be phenotypically and cytogenetically normal after birth. So we performed CGH and array-CGH to exclude another possible imbalance. We discuss here the possible relation between this chromosomal abnormality and the abnormal phenotype.

[Recurrence of multiple chorio-angiomas: a case-report]. / Récurrence de chorio-angiomes multiples : à propos d'un cas.

Diffuse chorioangiomatosis is a rare placental pathology characterized by multiple chorioangiomas, inducing a high risk of fetal complications, especially cardiovascular, with a risk of fetal death. The physiopathology is not clearly established but seems to be related with an over-expression of vascular growth factors related to hypobaric-hypoxia. Here, we describe a case of recurrent chorioangiomatosis with fetal demise. No risk factors were identified (high altitude, genetic disease like Beckwith-Wiedemann, diabetes). Intra-amniotic, plasmatic values of alphafetoprotein and plasmatic beta gonadotrophin chorionic hormone remained low. Ultrasonographic assessment of placental thickness was in the normal range, at 22 and 32 weeks of gestation. In case of previous chorioangiomatosis, we recommend a weekly sonographic monitoring to diagnose fetal complications associated with an early inpatient hospitalization for daily surveillance at the age of previous accidents. Labor will be induced in case of fetal intolerance or systematically after 37-38 weeks of gestation.

First-trimester features of Fowler syndrome (hydrocephaly-hydranencephaly proliferative vasculopathy).

We describe the features of Fowler syndrome (proliferative vasculopathy and hydrocephaly-hydranencephaly) diagnosed in the first trimester. The pregnancy with no significant family history was referred for karyotyping and ultrasound examination after a cystic hygroma was seen at 12 weeks. At 13 weeks, ultrasound examination revealed hydrocephaly-hydranencephaly, fetal akinesia, and arthrogryposis associated with increased nuchal translucency. The parents opted for termination of pregnancy and the diagnosis of Fowler syndrome was confirmed by pathological examination of the fetus. Calcified necrotic lesions and proliferative vasculopathy were observed in the entire central nervous system including the brainstem and spinal cord. Cases previously reported in siblings suggest an autosomal recessive transmission but specific genetic antenatal diagnosis is not yet available. The diagnosis of proliferative vasculopathy and hydrocephaly-hydranencephaly (Fowler syndrome) should be considered whenever hydrocephaly-hydranencephaly associated with a fetal akinetic sequence are encountered at the end of the first trimester. Genetic counseling is recommended.

[Sudden unexpected death in an infant due to a ruptured coronary aneurysm revealing Kawasaki disease]. / Mort subite chez un nourrisson par rupture d'anévrisme coronarien révélatrice d'une maladie de Kawasaki.

UNLABELLED: The early mortality of Kawasaki disease is low, resulting from coronary complications, mainly aneurismal thrombosis with myocardial infarction. The aneurysmal rupture is an exceptional cause of death. CASE REPORT: We report on a six-month-old girl who died suddenly and unexpectedly. The autopsy showed a cardiac tamponade caused by an important ruptured aneurysm of the left coronary artery. Multiple aneurysms, with or without thrombosis, on the right coronary were also present. There was no ischaemic lesion. Three weeks before death, this infant demonstrated several clinical signs of Kawasaki disease whose diagnosis had not been done. CONCLUSION: Even if the rupture of coronary aneurysm is an exceptional initial complication of Kawasaki disease, a better knowledge of the atypical or incomplete forms, particularly below the age of one year, should allow an early diagnosis and treatment, decreasing the risks of coronary complications. This observation furthermore illustrates the interest of post-mortem examination in all sudden or unexpected infant deaths.

X-linked myopathy with excessive autophagy: a clinicopathological study of five new families.

In 1988, Kalimo et al. (Ann Neurol 23 (1988) 258)described a new type of X-linked myopathy in a Finnish family. The clinical course was characterized by slow progression of muscle weakness without loss of ambulation in childhood and no evidence of cardiac, respiratory, or central nervous system involvement. Muscle fibers were not necrotic and showed excessive autophagic activity and exocytosis of the phagocytosed material. These authors proposed the name X-linked myopathy with excessive autophagy. Subsequently, only one French family has been reported with similar clinical and histopathological data. We report here five new families with a total of eight affected boys with the same clinical and histopathological features as reported in the original families. Histopathological findings of an asymptomatic mother are also reported. Vacuolar changes in muscle fibers result both from invaginations of the sarcolemma along with a variable component of basal lamina and from an autophagic process. The complement C5b-9 membrane attack complex associated with MHC class 1 antigen and calcium deposits is involved in muscle fiber damage. Among the X-linked myopathies, the identification of this new type is of great interest because of its favorable prognosis and unique morphological findings.

[A familial case of chronic progressive external ophthalmoplegia associated with mitochondrial disease]. / Une observation familiale d'ophtalmoplégie externe chronique progressive liée à une mitochondriopathie.

Mitochondrial myopathies are rare hereditary diseases that affect the energy functions of the mitochondria. Clinical manifestations are variable and sometimes multisystemic. Progressive external ophthalmoplegia constitutes the most frequent clinical form. Unfortunately, the diagnosis and the treatment of these mitochondrial abnormalities stay, today, even difficult. We report ophthalmic findings and the course of the disease in members of a family with chronic progressive external ophthalmoplegia presenting with severe acquired blepharoptosis. From study at the family background, the inheritance seemed autosomal dominant. In one case, a comprehensive workup, including muscular biopsy and molecular genetics disclosed a mitochondrial myopathy. During the 30-year follow-up, the patients were operated on for their ptosis several times, because of recurrences and uneven results.

Fetal umbilical cord ligation under ultrasound guidance.

In a patient with severe twin-to-twin transfusion syndrome, ultrasound-guided umbilical cord ligation of the hydropic recipient twin was performed at 27 weeks' gestation. The procedure was successful in arresting the blood flow and was associated with improvement in the condition of the severely compromised donor fetus. At 29 weeks' gestation, premature onset of labor occurred and a healthy baby was delivered by emergency Cesarean section. This report demonstrates the feasibility of ultrasound-guided cord ligation for selective feticide in a case of severe twin-to-twin transfusion syndrome.