Identification of molecular pathways involved in oxaliplatin-associated sinusoidal dilatation.

BACKGROUND & AIMS: Oxaliplatin-based chemotherapy for colorectal liver metastases (CRLM) can result in vascular liver lesions such as sinusoidal dilatations. Physiopathology remains unclear and variability between patients suggests that there is individual susceptibility. A better understanding of the molecular mechanisms of oxaliplatin liver toxicity may allow the identification of biomarkers and adaptation of chemotherapy delivery. METHODS: Between 1998 and 2009, 83 non-tumor frozen liver samples were obtained from patients operated on for CRLM after an exclusive oxaliplatin-based chemotherapy. Gene-expression profiles were first analyzed by microarray on a selected population of 19 patients: 9 patients with severe sinusoidal dilatation after a short period of chemotherapy and 10 patients without any sinusoidal dilatation after a long period of chemotherapy. These were compared with a control group of 5 patients without any chemotherapy and lesions. Twenty-two differentially-expressed (at least 1.5-fold difference in expression) genes were selected. These were validated using microfluidic quantitative RT-PCR in an independent set of 58 patients (28 with sinusoidal dilatation and 30 without sinusoidal dilatation). RESULTS: Among the 22 selected genes, 12 were validated as being up-regulated in samples from patients with sinusoidal dilatation compared to patients without sinusoidal dilatation. Genes involved in angiogenesis (VEGFD, THY-1, GPNMB) and cellular adhesion (VWF, CDH13, THBS2), and extracellular matrix components (COL1A1, COL4A1, SLCO1A2) were over-represented in patients with sinusoidal dilatation. CONCLUSIONS: This molecular signature confirms the involvement of angiogenesis and coagulation in sinusoidal injuries induced by oxaliplatin and reinforces a potential protective role of bevacizumab and aspirin, as suggested in retrospective clinical studies.

Laparoscopic Sleeve Gastrectomy in Kidney Transplant Candidates: a Case Series.

BACKGROUND: Patients with a body mass index (BMI) >35 kg/m2 who need kidney transplant present with increased postoperative mortality and reduced kidney graft survival compared to patients with a lower BMI. For this reason, obese patients are often excluded from the transplantation waiting list. The aim of this study was to evaluate the feasibility and the results of laparoscopic sleeve gastrectomy (LSG) for obese patients awaiting a kidney transplant. METHODS: This was a retrospective study on patients with dialysis-dependent renal failure (DDRF) operated on at two first-level bariatric centers in Paris (France). All the patients were contraindicated for kidney transplantation due to the presence of morbid obesity. RESULTS: Nine DDFR patients with a mean BMI of 45.9 kg/m2 underwent LSG for the treatment of obesity. Furthermore, all patients presented with hypertension and sleep apnea and six out nine were diabetics. In the immediate postoperative period, all patients were transferred to the intensive care unit (mean stay of 2.1 days). The only major adverse event was a delayed weaning from mechanical ventilation in one patient. The mean hospital stay was 5.5 days (3-12). The total weight loss (TWL) was 27.1, 33.6, and 39.5 kg at 6, 12, and 18 months, respectively. One patient underwent renal transplantation 18 months after LSG, and the other five patients were actively listed for kidney transplantation. CONCLUSIONS: According to the results of this small sample series, LSG seems to be an effective and safe procedure in DDRF patients with concomitant obesity and can increase access to transplantation.

The incidence of papillary thyroid carcinoma and outcomes in operative patients according to their body mass indices.

BACKGROUND: The connection between high body mass index (BMI), risk of papillary thyroid carcinoma (PTC), and the aggressiveness of PTC is still debated. We aimed to establish the relationship between excess BMI and the risk of PTC in an operative population, and the impact of obesity on histopathologic aggressiveness of PTC and on the outcome of patients. METHODS: All consecutive patients who underwent thyroid operation from June 2002 to December 2009 were reviewed in this retrospective study. BMI groupings were based on standardized categories: normal-weight, overweight, and obesity. We performed a total thyroidectomy with lymph node dissection in patients with preoperative or operative diagnosis of PTC. Radioiodine ablation was performed in every N1 patient, in case of tumor size greater than 10 mm, and if there was extrathyroidal invasion. During a median follow-up of 6.2 years, patients who were retreated by operation or (131)I were considered to have a persistent (<18 months of the initial operative treatment) or recurrent (≥ 18 months) disease. RESULTS: Of 6,684 patients who had a thyroid gland resection, we identified 1,216 (18.2%) patients with PTC. Patients who were overweight or obese were not at greater risk of PTC than normal-weight subjects. Indications for operation or radioiodine therapy were similar in the three BMI groups. During follow-up, 86 patients (7.1%) experienced persistent (4.5%) or recurrent (2.5%) disease. When excluding micro-PTCs (≤ 10 mm), we found an association between recurrent or residual locoregional thyroid cancer and BMI: 18.7% in obese patients versus 8.5% if BMI <25 kg/m(2) and 9.8% if 25 ≥ BMI < 30 kg/m(2) (P = .03). This difference was clearly marked for persistence. When adjusted for other cofounder factors, we observed that BMI was an independent factor associated with the risk of postoperative locoregional event (odds ratio 3.8, 95% confidence interval 1.6-8.8), with sex, age, lymph node metastasis, and tumor bilaterality. CONCLUSION: In macro-PTC, obese patients had an increased risk of developing a locoregional event during the follow-up, specifically a persistence of the disease. According to these results, overweight and obese patients with macro-PTC should be monitored more carefully for early detection of cancer persistence.

Laparoscopic division of a portosystemic shunt to treat chronic hepatic encephalopathy.

In the event of liver cirrhosis with severe portal hypertension, voluminous portosystemic shunt may lead to refractory encephalopathy. Obliteration of the shunt has been described as a satisfactory therapeutic solution, and reported procedures are mainly endovascular embolization and surgical shunt ligation through laparotomy. The former procedure is less invasive and seems to be as efficient. Laparoscopy, which is widely recognized to minimize mortality and morbidity in cirrhotic patients undergoing surgery, has never been used for such a procedure. Shunt division can therefore be considered using this modern approach to good effect and reduced morbidity. In support of this view, we report a case of severe chronic encephalopathy cured by laparoscopic surgical division of a large shunt after failure of the percutaneous technique.