Volume 75 - 2012 - Fasc.1 - Original articles
A phase II randomized study of Combined Infusional Leucovorin Sodium and 5- FU versus the Leucovorin Calcium followed by 5-FU both in combination with Irinotecan or Oxaliplatin in patients with metastatic colorectal cancer
Background : Leucovorin Sodium (LV/Na) has a high solubility, and is stable when given with continuous infusion of 5-FU. It could maintain significant plasma concentration of 5, 10-meTHF during the whole 5-FU perfusion with the potential of increasing 5-FU cytotoxicity. We conducted a randomized phase II clinical trial on leucovorin calcium (LV/Ca) and LV/Na in metastatic colorectal cancer patients (mCRC). Main objectives were to assess efficacy and safety.
Patients and methods : Fifty seven patients with mCRC and no previous chemotherapy for metastatic disease were randomized to receive LV/Na or LV/Ca with irinotecan or oxaliplatine combined with infusional 5-FU. LV/Na was defined as warranting further evaluation in phase III if true overall response rate (ORR) > 35% (a=5%, ss=10% in case of true ORR >55%, 51 evaluable patients planned/arm).
Results : Results for LV/Ca and LV/Na arm respectively were : observed ORR, 55% (significantly higher than 35%, p = 0.02) and 61% (p = 0.004). Median overall survival durations were 11.9 months and 22.9 months (p = 0.02) and PFS 8.0 vs. 11.5 months (ns). Grade = 3 events were 64% and 46% (p = 0.28).
Conclusion : Both LV/Na and LV/Ca disclosed an ORR > 35% with comparable safety. (Acta gastroenterol. belg., 2012, 75, 14-21).
Prognostic value of miR-93 overexpression in resectable gastric adenocarcinomas
Background and study aims : MicroRNAs (miRNAs) have been shown to be aberrantly expressed in many human carcinomas. Emerging evidence indicates that miR-93 plays important onco- genic roles in human carcinogenesis and is often up-regulated. However, its relationship with the clinicopathological features and prognosis of human gastric cancer (GC) has yet to be addressed. In this study, we investigate the expression and clinical significance of miR-93 in human gastric cancer.
Patients and methods : 158 patients with gastric adenocarcinoma who had undergone gastrectomy were enrolled. Specimens includ- ing the tumor and non-neoplastic were detected for the expression of miR-93 by Real-Time reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, the correlation of miR-93 levels with clinicopathologic variables and prognosis was analyzed.
Results : miR-93 was significantly up-regulated in 128 cases (81%) of the 158 gastric cancer (P < 0.05). Furthermore, the elevat- ed expression of miR-93 was significantly associated with advanced disease stage (P < 0.001), deep invasion level (P < 0.001) and the presence of nodal metastases (P < 0.001). Moreover, gastric cancer patients with high miR-93 expression levels had shorter overall survival (P = 0.001) and disease-free survival (P = 0.006) than that with low miR-93 expression levels.
Conclusions : miR-93 is highly elevated in gastric cancer, espe- cially in advanced and metastasized gastric cancer, suggesting miR-93 may play critical roles in carcinogenesis of gastric cancer. Overexpression of miR-93 can serve as a novel prognostic marker for gastric cancer. (Acta gastroenterol. belg., 2012, 75, 22-27).
Acute-phase response in pigs undergoing laparoscopic, transgastric or trans- colonic notes peritoneoscopy with us or eus exploration
Background : Laparoscopic surgery is associated with reduced surgical trauma, therefore with acute-phase response of lower magnitude as compared with open surgery. We hypothesized that NOTES might induce reduced immune response as compared with laparoscopy.
Objective : To compare acute-phase reactants in a controlled trial of laparoscopic peritoneoscopy and ultrasonography versus transgastric or transcolonic NOTES peritoneoscopy and intraperi- toneal endoscopic US.
Methods : Eighteen pigs were divided in 3 groups : laparoscopy, transgastric and transcolonic NOTES. Serum levels of IL-6 and TNF-a were determined preoperatively and at day 2. Serum levels of haptoglobin and IL-6 mRNA levels from isolated white blood cells were measured by RT-PCR at days 0, 1, 2 and 7. Necropsy was performed at sacrifice, with peritoneal fluid microbiological analy- sis, macroscopic and microscopic examinations on gastrotomy/ colotomy or abdominal wall closure sites, liver and parietal peri- toneum biopsy sites and any area suggestive of infection.
Results : The groups were similar with regards to perito- neoscopy completeness, ultrasonographic examination and biop- sies. The duration of NOTES procedures was significantly longer than laparoscopic procedures. Minor complications were observed in most animals by macroscopic and microscopic examination, but NOTES procedures were associated with severe complications in 3 pigs (fistula, abscess, mortality). No significant differences in acute-phase reactants levels were found between groups.
Conclusions : No significant difference in the acute-phase reac- tants could be demonstrated between surgical and NOTES proce- dures. NOTES was however associated with more severe septic complications. Optimal closure remains a challenge and better devices are needed to avoid them. (Acta gastroenterol. belg., 2012, 75, 28-34).
HBV infection in Belgium : Results of the BASL observatory of 1,456 HBsAg carriers
Introduction : Nationwide studies are mandatory to assess changes in the epidemiology of HBV infection in Europe.
Aim : To describe epidemiological characteristics of HBsAg- positive patients, especially inactive carriers, and to evaluate how practitioners manage HBV patients in real life.
Methods : Belgian physicians were asked to report all chronical- ly infected HBV patients during a one-year period.
Results : Among 1,456 patients included, 1,035 (71%) were classified into one of four phases of chronic infection : immune tolerance (n=10), HBeAg-positive hepatitis (n=248), HBeAg- negative hepatitis (n=420) and inactive carrier state (n=357 HBeAg-negative patients with ALT < upper limit of normal (ULN) and HBV DNA < 2,000 IU/mL). Using less restrictive criteria for ALT (1-2 ULN) or HBV DNA (2,000-20,000 IU/mL), 93 unclassified patients were added to the group of inactive carriers. These 93 additional inactive carriers were younger, more frequently males, with similar risk factors for HBV infection and histological fea- tures compared to inactive carriers according to recent guidelines. Recent guidelines on management of HBV patients were generally followed, but systematic HBV DNA measurements and HDV co- infection screening should be reinforced.
Conclusion : In Belgium, an inactive carrier state was a common form of chronic HBV infection. Using less restrictive criteria for classification of inactive carriers did not modify their main charac- teristics and seemed better adapted to clinical practice. Recent guidelines on management of HBV patients should be reinforced. (Acta gastroenterol. belg., 2012, 75, 35-41).