A study of the association between UGT1A1*28 variant allele of UGT1A1 gene and colonic phenotype of sporadic colorectal cancer.

INTRODUCTION: The transcriptional activity of the UGT1A1 gene is modulated by a variable number of repetitions of the dinucleotide (TA) within its promoter region. By comparison to the most common allele (TA)6 (UGT1A1*1), decreased activity is observed with increasing TA repetitions. The aim of this study was to determine whether the presence of the variant allele UGT1A1*28, harbouring seven TA repetitions, (TA)7, in the homozygous state, is associated with precancerous colonic lesions and/or with specific colorectal cancer characteristics. MATERIAL AND METHODS: All patients treated for colorectal cancer in a tertiary care centre, between January 2009 and December 2013, who had routine UGT1A1 genotyping for irinotecan dose-adjustment were included. Data were retrospectively collected. RESULTS: 292 patients were enrolled, including 23 UGT1A1*28/*28 homozygous (7.9%), 137 wild type homozygous (46.9%) and 132 heterozygous (45.2%). There were no significant differences in phenotypic colonic characteristics between homozygous and heterozygous patients carrying the UGT1A1*28 allele as compared to *1/*1 homozygous. Patients treated with aspirin were significantly more common in the UGT1A1*28/*28 homozygous group than in the other groups (7/23 (30.4%) compared to 22/269 (8.2%), p = 0.001). CONCLUSION: Dinucleotide polymorphism in the promoter region of the UGT1A1 gene is not associated with a specific colonic phenotype in patients with sporadic colorectal cancer.

Diagnostic performance of contrast-enhanced CT-scan in sinusoidal obstruction syndrome induced by chemotherapy of colorectal liver metastases: Radio-pathological correlation.

PURPOSE: Sinusoidal obstruction syndrome (SOS) is a likely side effect of colorectal liver metastases (CRLM) chemotherapy. This study aimed to assess computed tomography scan (CT-scan) performance for SOS diagnosis for patients receiving neoadjuvant chemotherapy (NC) prior to CRLM surgery, comparing obtained results with pathological gold standard. METHODS: Preoperative CT-scans of 67 patients who had received a NC prior to liver resection for CRLM from 2011 to 2016 were retrospectively analysed. Positive diagnosis and severity of SOS were established after consensual review of the slides by three pathologists. Preoperative CT-scans were separately interpreted by two radiologists and evocative signs of SOS were sought, defined according to a literature review and operators experience. In order to identify SOS predictors, univariate analysis and multivariate logistic regression were used to study CT-scan signs and pathological results correlation. RESULTS: Twenty-nine patient (43%) had an SOS, 22 (33%) were low-grade and 7 (10%) were high-grade. All patient had received a median of 6 cures (3-27) containing Oxaliplatin for 53 (79%) of them. In univariate analysis, hepatic heterogeneity (p<0.001), puddle-like or micronodular appearance (p<0.001), peripheral distribution of heterogeneity (p=0.085), clover-like sign (p=0.02), splenomegaly (p=0.0026), spleen volume increase ≥30% (p=0.04) or splenic length increase ≥15% (p=0.04), as well as the subjective impression of the observer (P<0.001) were significantly associated with SOS diagnosis. In multivariate analysis, clover-like sign (OR 1.87, 95% CI 1.18-2.95, p=0.0081), increase in spleen volume ≥30% (OR 1.29, 95% CI 1.01-1.64, p=0.04), and the peripheral distribution of heterogeneity (OR 1.53, 95% CI 1.21-1.94, p<0.001) were independent SOS predictors. The area under the ROC curve was 0.804. The inter-observer agreement for SOS diagnosis was moderate (Kappa=0.546). CONCLUSION: CT-scan can detect suggestive signs of SOS in patients receiving chemotherapy for CRLM. By integrating clinical and biological information into CT-scan data, it may be fruitful to create a positive diagnostic and severity score for chemotherapy-induced SOS.

18F-FDG PET in Liver Transplantation Setting of Hepatocellular Carcinoma: Predicting Histology?

PURPOSE: The aim of this study was to evaluate the prognostic value of F-FDG PET/CT by predicting histopathological findings in the pretransplant evaluation of patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: F-FDG PET/CT findings of 34 patients with HCC who underwent liver transplantation were reviewed retrospectively. Visual and quantitative analysis (tumor standardized uptake values normalized to the background activity of the liver: SUVmax T/L) was done. PET tumor characteristics were compared with the histological analysis (differentiation and microvascular invasion). All patients were followed up (mean, 12 months). RESULTS: Ten patients showed tumoral uptake greater than background activity (PET+). Higher-grade tumor was more common in the F-FDG-avid tumor group (P < 0.05). PET+ also showed more microvascular invasion at explant pathology (P < 0.05). Only 1 patient PET+ developed HCC early recurrence (4 months) with an SUVmax T/L of 1.64. CONCLUSIONS: F-FDG uptake is predictive for microvascular invasion and tumor differentiation. This examination has a prognostic value regarding tumor recurrence after liver transplantation for HCC.

Case report: benefits of quantitative polymerase chain reaction in the clinical management of herpes simplex virus 1 infection with prominent hepatitis and unusual secondary progression.

Herpes simplex virus (HSV) infection is rarely considered in the differential diagnosis of severe acute hepatitis and disseminated infection in immunocompetent adults. A case of disseminated HSV-1 infection in an 82-year-old woman initially presenting with neurological problems, signs of meningitis and prominent hepatitis was investigated. Initial diagnosis, monitoring, and follow-up were based on the application of molecular methods to cerebrospinal fluid, serum, and liver tissue samples from this patient. Following an initial full recovery, the patient presented delayed intracerebral haemorrhage and diffuse arthralgia. This atypical case, with delayed secondary progression, highlights the wide range of clinical features of HSV infection and the benefits of monitoring viral load by quantitative real-time polymerase chain reaction (PCR) during patient management.

Thirteen-year disease-free survival after surgery for cystic duct carcinoma: a case report.

Cystic duct carcinoma is known to have a better prognosis compared to its location in other biliary ducts. Only one case with a survival over ten years has been previously published. The authors report a case of survival over 13 years without recurrence or metastasis. Preoperative diagnosis of cystic duct tumor was carried in a 66-year-old male. Under the diagnosis of carcinoma of the cystic duct, the patient underwent en bloc resection of the gallbladder, cystic duct, hepaticocholedochus and lymph node dissection. A Roux-en-Y hepaticojejunostomy was performed. Histological examination revealed a moderately differentiated adenocarcinoma of the cystic duct. Five months later the patient underwent second look surgery for benign obstruction of the hepaticojejunal anastomosis. The patient is still doing well 13 years later without any local recurrence or metastasis. To our knowledge, this is the longest disease-free survival ever published in the literature. This case sustains that better and longer survival is possible with a real chance of potential cure if radical surgery is performed.

Conservative treatment of a mesenteric lymphangiomyomatosis in an 11-year-old girl with a long follow-up period.

The authors report the case of a 11-year-old girl admitted for a mesenteric tumor discovered during an appendicectomy. The abdominal Doppler echography and computed tomography (CT) scan showed a 8 x 6 x 7-cm multinodular mass involved in the mesenterium. Biological markers and iodine 131 meta-iodobenzylguanidine (MIBG) scintigraphy results were normal. Percutaneous biopsies were performed. Pathology results showed perilymphatic proliferation of smooth muscle cells leading to cystic lesions. No sign of malignancy was seen. Laparotomy showed a multinodular fixed mass involved from the root of the mesenterium. The superior mesenteric vessels were encircled by the tumor, which could not be resected completely. Partial resection was performed. The pathology and the immunohistochemical tests confirmed the diagnosis of lymphangiomyomatosis. At 21 years of age, she remains asymptomatic. An echography and CT scan showed the mass remaining unchanged in size and echopattern. Lymphangiomyomatosis (LMA) is thought to affect exclusively women in their reproductive life, and the steroid hormones are supposed to play an essential role in the pathology and in the behavior of this condition. Infantile LMA is exceptional. The patient reported is remarkable for her young age, the location of the tumor, her long history, and her benign course. Because the tumor is supposed to be hormone dependent, the surge of oestrogen in this 21-year-old woman may initiate the extensive form of lymphangiomyomatosis with pulmonary involvement, the prognosis of which is extremely poor.