Surgical treatment for locally advanced lower third rectal cancer after neoadjuvent chemoradiation with capecitabine: prospective phase II trial

<p>Abstract</p> <p>Introduction</p> <p>Treatment of rectal cancer requires a multidisciplinary approach with standardized surgical, pathological and radiotherapeutic procedures. Sphincter preserving surgery for cancer of the lower rectum needs a long-course of neoadjuvant treatments to reduce tumor volume, to induce down-staging that increases circumferential resection margin, and to facilitate surgery.</p> <p>Aim</p> <p>To evaluate the rate of anal sphincter preservation in low lying, resectable, locally advanced rectal cancer and the resectability rate in unresectable cases after neoadjuvent chemoradiation by oral Capecitabine.</p> <p>Patients and methods</p> <p>This trial included 43 patients with low lying (4–7 cm from anal verge) locally advanced rectal cancer, of which 33 were resectable. All patients received preoperative concurrent chemoradiation (45 Gy/25 fractions over 5 weeks with oral capecitabine 825 mg/m²twice daily on radiotherapy days), followed after 4–6 weeks by total mesorectal excision technique.</p> <p>Results</p> <p>Preoperative chemoradiation resulted in a complete pathologic response in 4 patients (9.3%; 95% CI 3–23.1) and an overall downstaging in 32 patients (74.4%; 95% CI 58.5–85). Sphincter sparing surgical procedures were done in 20 out of 43 patients (46.5%; 95% CI 31.5–62.2). The majority (75%) were of clinical T₃disease. Toxicity was moderate and required no treatment interruption. Grade II anemia occurred in 4 patients (9.3%, 95% CI 3–23.1), leucopenia in 2 patients (4.7%, 95% CI 0.8–17) and radiation dermatitis in 4 patients (9.3%, 95% CI 3–23.1) respectively.</p> <p>Conclusion</p> <p>In patients with low lying, locally advanced rectal cancer, preoperative chemoradiation using oral capecitabine 825 mg/m², twice a day on radiotherapy days, was tolerable and effective in downstaging and resulted in 46.5% anal sphincter preservation rate.</p

Preoperative gemcitabine based chemo-radiotherapy in locally advanced non metastatic pancreatic adenocarcinoma

<p>Abstract</p> <p>Introduction</p> <p>Almost 30% of patients with pancreatic cancer have locally advanced tumours in absence of distant metastasis. Surgical resection is often contraindicated. The combination of gemcitabine with concurrent radiation therapy is a promising new approach that is being investigated for treating patients' unresectable pancreatic cancer. This work aims at assessing the efficacy of preoperative gemcitabine based chemo-radiotherapy in increasing the resectability rate for patients' locally advanced pancreatic cancer.</p> <p>Patients and methods</p> <p>From March 2006 to November 2007, 25 patients with locally advanced non metastatic pancreatic cancer were treated by preoperative gemcitabine based chemo-radiotherapy. The radiation dose was 54 Gray in 30 fractions over 6 weeks prescribed to the isocenter. Gemcitabine (300 mg/m2) was given through a 30 minute intravenous infusion. This was done 30 minutes before the radiation sitting on a weekly basis throughout the radiotherapy course.</p> <p>Approximately 6 weeks after the completion of chemo radiation, an evaluation was performed regarding tumour response and resectability as well as acute toxicity. Pancreaticoduodenectomy was performed for operable patients with surgical reconstruction.</p> <p>Results</p> <p>Patients who achieved complete resection (CR) numbered 2 (8%), while those achieving partial resection (PR) totalled 11 (44%); six of these patients were considered ro be operable. Thus Pancreaticoduodenectomy was performed on 8 patients (2 with CR and 6 with PR) with surgical reconstruction. Patients who had a stable disease numbered 4 (16%), and those with progressive diseases included a group of eight (32%). The postoperative 30 day mortality occurred only in one patient (12.5%). Acute toxicity of chemoradiation occurred in the form of grade I leucopoenia and thrombocytopenia. Hepatic toxicity, nausea, and vomiting were found in 8 patients (32%), 10 patients (40%) and 4 patients (16%), respectively. The postoperative 30 day mortality occurred only in 1 patient. Also, minor biliary leakage and leakage from gastrointestinal anaestomosis both occurred in a single patient. Out of the 8 patients who underwent radical surgical resection, only one developed local recurrence and simultaneous liver metastasis during the follow up period. The median survival of all patients was 12 months.</p> <p>Conclusion</p> <p>Preoperative gemcitabine based chemoradiation might benefit patients with locally advanced non metastatic pancreatic cancer by increasing the resectability without significant acute toxicity.</p

Fetus in fetu: a case report

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Increased Susceptibility to Apoptosis and Growth Arrest of Human Breast Cancer Cells Treated by a Snake Venom-Loaded Silica Nanoparticles

Background: The development of effective treatments against metastatic cancers, including breast cancer, is among the most important challenges in current experimental and clinical cancer research. We recently demonstrated that Walterinnesia aegyptia venom (WEV), either alone or in combination with silica nanoparticles (WEV+NP), resulted in the growth arrest and apoptosis of different cancer cell lines. Aims: In the present study, we evaluated the impact of WEV alone and WEV+NP on human breast cancer cells isolated from cancer biopsies. Methods: The potential effects of WEV alone and WEV+NP on the proliferation, induction of apoptosis and generation of free radicals in breast cancer cells isolated from 80 patients clinically diagnosed with breast cancer were evaluated by flow cytometry and ELISA. Results: WEV alone and WEV+NP inhibited the proliferation, altered the cell cycle and enhanced the induction of apoptosis of the breast cancer cells by increasing the activities of caspase-3, caspase-8 and caspase-9. In addition, the combination of WEV and NP robustly sensitized the breast cancer cells to growth arrest and apoptosis by increasing the generation of free radicals, including reactive oxygen species (ROS), hydroperoxide and nitric oxide. The combination of WEV with NP significantly enhanced the anti-tumor effect of WEV in breast cancer cells. Conclusion: Our data indicate the therapeutic potential of the nanoparticle-sustained delivery of snake venom for the treatment of breast cancer

Apoptotic Versus Angiogenic Factors in Gastric and Colorectal Cancers

Objective. Gastric-colon cancer is a complex, multi-stage disease involving deregulation of different signaling cascades. This study was conducted to determine the extent of apoptosis, angiogenesis, inflammation, and oxidative stress in patients with gastric-colon cancers. Plasma levels of soluble (s) Fas, bcl-2 as antiapoptotic indices; cathepsin D (CD), calpain I and II as proteolytic, apoptotic indices; nitric oxide (NO), lipid peroxides (LPER) as oxidative stress, angiogenic indices, and tumor necrosis factor (TNF)- and #945; as apoptotic, inflammatory, angiogenic indices were measured in gastric-colon cancer patients. Methods. Thirty gastric-colon cancer patients [colorectal (n=20), gastric (n=10) cancers], 30 with benign gastrointestinal tract (GIT) masses and 30 healthy controls, were recruited. sFas, bcl-2 and TNF- and #945; were measured by immunosorbent assay kits, and CD, calpain I and II, LPER and NO by chemical methods. Results. sFas, bcl-2, CD, calpain I, calpain II, NO, and TNF- and #945; were higher in malignant and benign GIT masses than controls, and in malignant than benign masses. In gastric tumors, calpain I, calpain II, CD, LPER, and NO levels were higher than colorectal. In benign and malignant GIT masses, positive correlations were found between sFas, bcl-2, CD, calpain I, calpain II, LPER, NO and TNF- and #945;. Conclusions. Gastric-colon malignancy patients exhibited decreased apoptosis, as evident by an increase in antiapoptotic indices, i.e. sFas and bcl-2, and increased angiogenic activity, as evident by enhanced proteolytic activity of cathepsin-D and calpain I and II. These parameters were higher in gastric than colorectal cancers reflecting aggressive behavior of the earlier. Thus, decreased apoptosis and enhanced angiogenesis give growth priority in gastric-colon cancers, and the angiogenic factors and #8217; blockage may delay the tumor and #8217;s spread. [Arch Clin Exp Surg 2012; 1(2.000): 71-84