A phase II study of biweekly oxaliplatin plus infusional 5-fluorouracil and folinic acid (FOLFOX-4) as first-line treatment of advanced gastric cancer patients

The aim of the study was to assess the toxicity and the clinical activity of biweekly oxaliplatin in combination with infusional 5-fluorouracil (5-FU) and folinic acid (FA) administered every 2 weeks (FOLFOX-4 regimen) in patients with advanced gastric cancer (AGC). A total of 61 previously untreated AGC patients were treated with oxaliplatin 85 mg m−2 on day 1, FA 200 mg m−2 as a 2 h infusion followed by bolus 5-FU 400 mg m−2 and a 22 h infusion of 5-FU 600 mg m−2, repeated for 2 consecutive days every 2 weeks. All patients were assessable for toxicity and response to treatment. Four (7%) complete responses and 19 partial responses were observed (overall response rate, 38%). Stable disease was observed in 22 (36%) patients, with progressive disease in the other six (10%) patients. Median time to progression (TTP) and median overall survival (OS) were 7.1 and 11.2 months, respectively. National Cancer Institute Common Toxicity Criteria grade 3 and 4 haematologic toxicities were neutropenia, anaemia and thrombocytopenia in 36, 10 and 5% of the patients, respectively. Grade 3 peripheral neuropathy was recorded in three (5%) patients. FOLFOX-4 is an active and well-tolerated chemotherapy. Response rate (RR), TTP and OS were comparable with those of other oxaliplatin-based regimens, suggesting a role for this combination in gastric cancer

Recombinant Human Endostatin Endostar Inhibits Tumor Growth and Metastasis in a Mouse Xenograft Model of Colon Cancer

To investigate the effects of recombinant human endostatin Endostar on metastasis and angiogenesis and lymphangiogenesis of colorectal cancer cells in a mouse xenograft model. Colon cancer cells SW620 were injected subcutaneously into the left hind flank of nude mice to establish mouse xenograft models. The mice were treated with normal saline or Endostar subcutaneously every other day. The growth and lymph node metastasis of tumor cells, angiogenesis and lymphangiogenesis in tumor tissue were detected. Apoptosis and cell cycle distribution were studied by flow cytometry. The expression of VEGF-A, -C, or -D in SW620 cells was determined by immunoblotting assays. Endostar inhibited tumor growth and the rate of lymph node metastasis (P < 0.01). The density of blood vessels in or around the tumor area was 12.27 ± 1.21 and 22.25 ± 2.69 per field in Endostar-treated mice and controls (P < 0.05), respectively. Endostar also decreased the density of lymphatic vessels in tumor tissues (7.84 ± 0.81 vs. 13.83 ± 1.08, P < 0.05). Endostar suppresses angiogenesis and lymphangiogenesis in the lymph nodes with metastases, simultaneously. The expression of VEGF-A, -C and -D in SW620 cells treated with Endostar was substantially lower than that of controls. Endostar inhibited growth and lymph node metastasis of colon cancer cells by inhibiting angiogenesis and lymphangiogenesis in a mouse xenograft model of colon cancer

A phase II study of mitomycin C, cisplatin and continuous infusion 5-fluorouracil (MCF) in the treatment of patients with carcinoma of unknown primary site

Carcinoma of unknown primary site remains a common clinical diagnosis, accounting for between 5 and 10% of all cancer patients. Numerous combination chemotherapy regimens have been used in the management of carcinoma of unknown primary site, resulting in response rates of 0–48%. We present the results of a single centre phase II study of the use of the combination of mitomycin C (7 mg m−2 on day 1 of cycles 1, 3 and 5) cisplatin (60 mg m−2 on day 1) and continuous infusion 5-fluorouracil (300 mg m−2 daily), MCF, delivered as a 21-day cycle, in patients with carcinoma of unknown primary site. Thirty-one patients with a diagnosis of carcinoma of unknown primary site were treated in Aberdeen Royal Infirmary between 1997 and 2001 with MCF. In total, 136 cycles of MCF were delivered (median of 5 cycles per patient). Toxicity was acceptable, with 19% grade 3 or 4 neutropenia, 16% grade 3 or 4 thrombocytopenia and 13% grade 3 or 4 nausea and vomiting. No cases of neutropenic sepsis were seen and there were no treatment-related deaths, however, six patients developed thrombotic complications. The overall response rate was 27% (CR 3%; PR 23%). Median time to progression was 3.4 months (95% CI 1.1–5.6 months) and median overall survival was 7.7 months (95% CI 5.7–9.8 months). Survival at 1 year was 28%, and at 2 years, 10%. MCF is a tolerable regimen with comparable toxicity, response rates and survival data to most platinum-based combination chemotherapy regimens in use for this devastating disease

Morbidity of thyroid surgery.

BACKGROUND: Morbidity is today\u27s concern in thyroid surgery. The purpose of this paper was to quantify risk factors\u27 contribution to morbidity rates. METHODS: During 50 months, 1,163 patients undergoing 1,192 thyroidectomies at one hospital were reviewed at follow-up of 8 to 58 months. RESULTS: There was 1 death (0.08%). Wound morbidity included 19 hematomas (1.6%), 3 chyle leaks (0.2%), and 6 abscesses (0.5%). Mean hospital stay was 4.3 days after surgery without drain and 5.3 days with drain (P \u3c 0.01). Temporary and permanent hypoparathyroidism (TH; PH) rates were 20% and 4%. Parathyroid autografting and excision rates were 19% and 9%. TH rates were higher after parathyroid autografting or accidental excision (P \u3c 0.01). There was no correlation between the severity of TH and the number of lymph nodes at neck dissection nor between postoperative serum calcium levels and the number of parathyroids identified at bilateral surgery. Temporary and permanent recurrent laryngeal nerve (RLN) palsy (TRLNP; PRLNP) rates were 2.9% and 0.5% (0.3% of 2,010 RLNs at risk). PH and TRLNP (not PRLNP) rates were higher after completion or total thyroidectomy with node dissection (P \u3c 0.01). TRLNP and PRLNP rates after RLN exposure and after nonexposure were not statistically different. Surgical volume had no bearing on hematoma, abscess, TH, PH, TRLNP, and PRLNP rates. CONCLUSIONS: High surgical volume, identifying parathyroids and RLNs, failed to reduce morbidity. Completion and total thyroidectomy with node dissection increased PH and TRLNP (not PRLNP) rates

Absorption of glycine irrigating solution during endoscopic transanal resection of rectal tumors.

PURPOSE: This study was undertaken to evaluate the potential metabolic complications of 1.5 percent glycine irrigating solution during endoscopic transanal resection (ETAR) of rectal tumors. METHODS: Thirteen consecutive frail patients (mean age, 81 (range, 57-91) years) undergoing 18 ETAR were prospectively studied from July 1993 to January 1995. Indications for ETAR included palliation of advanced rectal cancer (12 patients) and an extensive villous tumor (1 patient). A 27-French two-way Iglesias resectoscope was used. Packed cell volume, blood glucose, and serum concentrations of sodium, potassium, and creatinine were measured before, during (at 45 minutes), and after (at 6 and 24 hours) ETAR. Plasma concentration of glycine and hemoglobin levels were both measured preoperatively and at 45 minutes and 24 hours, respectively. Variables studied included resection time, volume and rate of irrigating fluid, height of irrigating fluid bag above operating table, resectate weight, occurrence of intraperitoneal and extraperitoneal perforation, blood loss, and clinical symptoms. RESULTS: Two patients were excluded. Mean operating time was 456 minutes. A mean of 192.3 liters of irrigant was infused into the rectum. Mean irrigation rate was 43,330 ml/minutes. Mean height of irrigating fluid bag was 692 cm. Extraperitoneal perforation occurred in two patients. Blood loss exceeded 200 ml in four patients, one of whom complained of nausea (operating time, 110 minutes). Mean rise in p-glycine at 45 minutes (10,028 mol/l; 387 percent of preoperative values) was significant (P = 0.006). Changes in packed cell volume, b-hemoglobin, b-glucose, s-sodium, and s-creatinine levels were not significant. There was significant correlation between p-glycine and s-creatinine levels at six hours (P = 0.033), between p-glycine levels and fall in s-sodium at 24 hours (P = 0.037), and between levels of b-hemoglobin and packed cell volume at 24 hours (P = 0.0004). There was a positive linear correlation between p-glycine and operating time (r = 0.7; P = 0.0026) and between p-glycine and volume of irrigating fluid (r = 0.5; P = 0.0386). CONCLUSIONS: Operating time best predicts increase of p-glycine in ETAR