Riad Sarkis

Is therapy with calcium and vitamin D and parathyroid autotransplantation useful in total thyroidectomy for preventing hypocalcemia

Routine calcium and vitamin D administration and routine autotransplantation of parathyroid glands can prevent hypocalcemia after total thyroidectomy.

Existence and Anatomic Distribution of Double Parathyroid Adenoma

Background: Double parathyroid adenomas occur in 2% to 15% of primary hyperparathyroidism cases, but the very existence of double adenomas has been controversial. This study was conducted to evaluate the clinical significance and anatomic distribution of parathyroid double adenomas.

Fundoplication combined with mediogastric plication

BACKGROUND The purpose of this pilot study was to demonstrate the feasibility and procedural safety of laparoscopic fundoplication combined with mediogastric plication in patients with a body mass index of 32-35 kg/m(2). METHODS Sixteen patients underwent laparoscopic fundoplication combined with mediogastric plication. All procedures were performed with the patient under general anesthesia. The 1-year follow-up results encompassed gastroesophageal reflux disease recovery and excess weight loss. RESULTS The procedure time varied from 65 to 95 minutes. No serious procedure-related complications occurred. Gastroesophageal reflux disease-related symptoms resolved in all patients (P = .000). The excess weight loss was 10 ± 4 kg (58%) 1 year after the procedure. The 1-year follow-up excess weight was significantly less than the baseline excess weight (P = .000). The average body mass index decreased from 33.8 ± 1.9 kg/m(2) at baseline to 27.2 ± 1.7 kg/m(2) at 1 year (P = .02). Of the 16 patients, 14 had an excess weight loss of 62%, and 2 sweet-eaters had an excess weight loss of 33%. At 1 year of follow-up, the excess weight in those who smoked (n = 10) was greater than that of nonsmokers (n = 6; P = .02). However, smoking did not seem to significantly affect excess weight loss (P = .065). CONCLUSION Fundoplication combined with mediogastric plication produced a total recovery from gastroesophageal reflux disease and an excess weight loss of 62% in 87.5% of patients after 1 year of follow-up. This procedure is technically feasible, and no serious procedure-related complications occurred. The follow-up is ongoing to investigate the efficacy and long-term durability of the procedure.

Prevalence and risk factors for primary hyperparathyroidism in hyperthyroid patients.

Coexistence of hyperthyroidism and primary hyperparathyroidism may be more prevalent than previously recognized. We report 13 cases of concomitant occurrence of both diseases to estimate their combined prevalence and its factors.

Telomerase Inhibition Decreases Alpha-Fetoprotein Expression and Secretion by Hepatocellular Carcinoma Cell Lines: In Vitro and In Vivo Study

Alpha-fetoprotein (AFP) is a diagnostic marker for hepatocellular carcinoma (HCC). A direct relationship between poor prognosis and the concentration of serum AFP has been observed. Telomerase, an enzyme that stabilizes the telomere length, is expressed by 90% of HCC. The aim of this study was to investigate the effect of telomerase inhibition on AFP secretion and the involvement of the PI3K/Akt/mTOR signaling pathway. Proliferation and viability tests were performed using tetrazolium salt. Apoptosis was determined through the Annexin V assay using flow cytometry. The concentrations of AFP were measured using ELISA kits. The AFP mRNA expression was evaluated using RT-PCR, and cell migration was evaluated using a Boyden chamber assay. The in vivo effect of costunolide on AFP production was tested in NSG mice. Telomerase inhibition by costunolide and BIBR 1532 at 5 and 10 μM decreased AFP mRNA expression and protein secretion by HepG2/C3A cells. The same pattern was obtained with cells treated with hTERT siRNA. This treatment exhibited no apoptotic effect. The AFP mRNA expression and protein secretion by PLC/PRF/5 was decreased after treatment with BIBR1532 at 10 μM. In contrast, no effect was obtained for PLC/PRF/5 cells treated with costunolide at 5 or 10 μM. Inhibition of the PI3K/Akt/mTOR signaling pathway decreased the AFP concentration. In contrast, the MAPK/ERK pathway appeared to not be involved in HepG2/C3A cells, whereas ERK inhibition decreased the AFP concentration in PLC/PRF/5 cells. Modulation of the AFP concentration was also obtained after the inhibition or activation of PKC. Costunolide (30 mg/kg) significantly decreased the AFP serum concentration of NSG mice bearing HepG2/C3A cells. Both the inhibition of telomerase and the inhibition of the PI3K/Akt/mTOR signaling pathway decreased the AFP production of HepG2/C3A and PLC/PRF/5 cells, suggesting a relationship between telomerase and AFP expression through the PI3K/Akt/mTOR pathway

Does diclofenac increase the risk of cervical necrotizing fasciitis in a rat model

Non‐steroidal anti‐inflammatory drugs (NSAIDs) are known for aggravating in vitro infections and were reported in many cases of cervical necrotizing fasciitis (CNF). We developed a rat model of CNF, mimicking as closely as possible the human‐CNF, to study the effect of a NSAIDs, diclofenac, as a promoting factor. Twenty rats were injected bilaterally in the neck with peptostreptococcus and with a fresh saliva specimen for another 20 rats. Half of each group was given an intramuscular injection of 4 mg/kg diclofenac at the time of inoculation and 24 h later, and the other half saline injections; rats were killed at day 7 and clinical, bacterial and histological studies were performed to assess the infectious process and the incidence of CNF. No statistically significant difference was found between groups treated with diclofenac vs. the saline injection groups. However a significant correlation was noted between clinical observation, bacterial density and histological signs of inflammation. CNF has a high mortality rate and the use of NSAIDs in conditions potentially leading to CNF is very common. However, our rat model does not support the hypothesis of a promoting role of diclofenac which was occasionally suggested in the medical literature. This study suggests that diclofenac does not seem to increase the risk of occurrence of CNF. Nonetheless, NSAIDs can mask inflammatory signs of an already spreading CNF.

Gastrointestinal cancer cells treatment with bevacizumab activates a VEGF autoregulatory mechanism involving telomerase catalytic subunit hTERT via PI3K-AKT, HIF-1α and VEGF receptors

Background Targeting angiogenesis has been considered a promising treatment of choice for a large number of malignancies, including gastrointestinal cancers. Bevacizumab is an anti-vascular endothelial growth factor (anti-VEGF) being used for this purpose. However, treatment efficacy is largely questioned. Telomerase activity, responsible for cancer cell immortality, is detected in 85–95% of human cancers and is considered a potential regulator of VEGF. The aim of our study was to investigate the interrelationship between VEGF and hTERT in gastrointestinal cancers and to explore cell response to a combined inhibition of telomerase and VEGF. Methods AGS (gastric cancer), Caco-2 (colorectal cancer) and HepG2/C3A (hepatocellular carcinoma), were treated with telomerase inhibitors BIBR-1232 (10μM) and costunolide (10μM), with bevacizumab (Avastin® at 5 ng/ml or 100μg/ml) or with a combination of both types of inhibitors. VEGF and hTERT mRNA levels, and telomerase activity were detected by RT-PCR. VEGF levels were quantified by ELISA. Telomerase was knocked down using hTERT siRNA and hTERT was overexpressed in the telomerase negative cell line, Saos-2 (osteosarcoma), using constructs expressing either wild type hTERT (hTERT-WT) or dominant negative hTERT (hTERT-DN). Tube formation by HUVECs was assessed using ECMatrix™ (EMD Millipore). Results Our results showed that telomerase regulates VEGF expression and secretion through its catalytic subunit hTERT in AGS, Caco2, and HepG2/C3A, independent of its catalytic activity. Interestingly, VEGF inhibition with bevacizumab (100μg/ml) increased hTERT expression 42.3% in AGS, 94.1% in Caco2, and 52.5% in HepG2/C3A, and increased telomerase activity 30-fold in AGS, 10.3-fold in Caco2 and 8-fold in HepG2/C3A. A further investigation showed that VEGF upregulates hTERT expression in a mechanism that implicates the PI3K/AKT/mTOR pathway and HIF-1α. Moreover, bevacizumab treatment increased VEGFR1 and VEGFR2 expression in cancer cells and human umbilical vein endothelial cells (HUVECs) through hTERT. Thus, the combination of bevacizumab with telomerase inhibitors decreased VEGF expression and secretion by cancer cells, inhibited VEGFR1 and VEGFR2 upregulation, and reduced tube formation by HUVECs. Conclusions Taken together, our results suggest that bevacizumab treatment activates a VEGF autoregulatory mechanism involving hTERT and VEGF receptors and that an inhibition of this pathway could improve tumor cell response to anti-VEGF treatment.

Validation Study of a Portable Home Trainer Using a Pad for Laparoscopic Practice

The aim of this study was to describe and validate a homemade laparoscopic trainer. The abdominal cavity is simulated within a 3-mm-thick stainless steel model. Thirty-four participants were evaluated in a pilot study to validate our model. Participants were divided into experts (n = 19) and novices (n = 15) to perform basic and complex laparoscopic skills. The comparison between the homemade trainer (HT) and the standard laparoscopic trainer showed no significant differences for the 2 tasks performed for each group (P > .05). The experts’ performance of the 2 tasks was statistically different from the novices (P < .05) on both trainers. Both experts (84%) and novices (87%) approved the HT as an effective home trainer. Our HT seems to fulfill the conditions of performing the basic and complex laparoscopic psychomotor skills at a low cost and similar efficiency.

First Description of a Primitive Neuroectodermal Tumor Arising in the Nose

We report the case of a 12-year-old girl, who consulted us with one-year history of an 8 mm nose lesion that was painless and firm upon palpation. The lesion was resected conservatively. Immunohistochemistry was in favor of a primitive neuroectodermal tumor (PNET)/Ewings sarcoma lesion, excluding epithelial, lymphoid, and other tumors. After a second resection, our patient was referred to chemotherapy and has already undergone 9 cycles out of 14. The patient is to date with no evidence of persistent or recurrent disease. To our knowledge, this is the first description of a PNET arising in the nose.

An Unusual Case of Oral Metastasis from Rectal Adenocarcinoma Precipitated by Iatrogenicity.

Dear Editor: Colorectal cancer is the third most common cancer and is characterized with a relatively better overall survival compared to other cancers. The current therapeutic advances in this tumor are being developed with the better understanding of its pathophysiology. It is known that colorectal adenocarcinoma spreads primarily via the lymphatic route followed by the hematogenous route; the liver and lungs being the most affected organs. Oral and facial metastasis is a rare finding that is usually associated with a widespread disease and very poor prognosis. However, in the absence of particular symptoms, its diagnosis is quite challenging [1]. We report the case of previously healthy 36-years-old woman that presented to our clinic for an isolated hematochezia without other systemic symptoms. Investigations revealed locally advanced rectal adenocarcinoma that was treated with neoadjuvant chemoradiotherapy, followed by a proctectomy, and 5-FU-based chemoradiotherapy. On follow-up 2 years later, she had developed liver metastasis and received therefore a combination of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) with bevacizumab before proceeding to a partial hepatectomy. The patient was maintained on a combination of folinic acid, fluorouracil, and irinotecan (FOLFIRI) with cetuximab. Throughout the year, the patient was totally asymptomatic, with undetectable carcinoembryonic antigen levels and normal abdomino-pelvic imaging. Upon the appearance of an exophytic gingival mass over her first left premolar, the patient underwent a full examination of the oral cavity by her dentist who performed a transgingival trucut biopsy that confirmed the diagnosis of metastatic rectal adenocarcinoma. A radical resection of the mandibular mass was done without restaging imaging but she developed a 5-cm mass under her tongue 2 weeks later. She complained of dysphagia, disfigurement, and a left diplopia. Facial CT scan showed left sub-arachnoidal and facial bones metastases. The patient was started on chemoradiotherapy with FOLFIRI and bevacizumab. Unfortunately, the disease progressed and the patient died 3 months later.