Molecular allergens in the diagnosis of latex allergy.

BACKGROUND: Molecular allergens enable the definition of sensitization profiles in allergic patients. AIM: To validate the most helpful allergens for the diagnosis of latex allergy in different clinical situations. METHODS: 130 patients suspected to be allergic to latex with positive IgE against natural rubber latex (NRL) have been studied: 97 were confirmed as latex allergic (among which 55 professionally exposed to latex and 35 with a peranaesthetic anaphylactic shock) and 33 were only sensitized to latex without clinical allergy. Each serum was tested for IgE against 9 recombinant latex allergens and bromelain using Phadia ImmunoCAP 250. RESULTS: rHev b 6.01, 6.02, 2 and 5 were the major allergens in the allergic population. An excellent correlation (94%) was observed between IgE against rHev b 6.01 and latex prick test positivities. IgE against rHev b 1, 3 and 5 were more frequent and their levels significantly higher in patients with peranaesthetic anaphylactic shock. Among the asymptomatic patients (29/33 allergic to pollen), NRL IgE positivity is explained by the presence of anti-rHev b 8 and/or anti-carbohydrate IgE. CONCLUSIONS: rHev b 6.01 and rHev b 5 specific IgE are of major interest to confirm latex allergy diagnosis. rHev b 5 is particularly useful in case of monosensitization where clinical symptoms and latex skin prick tests may be discordant, rHev b1 and rHev b 3 are interesting to document multi-operated and peranaesthetic latex allergy. Finally, rHev b 8 is a helpful marker to highlight latex/pollen cross-reactivity which improves the specificity of the serological tests.

Intraperitoneal chemohyperthermia with mitomycin C for digestive tract cancer patients with peritoneal carcinomatosis.

BACKGROUND: Most patients with peritoneal carcinomatosis of digestive tract origin die within 6 months. Intraperitoneal chemohyperthermia (IPCH) associated with surgery has been reported as a possible new therapeutic approach. METHODS: A prospective Phase II trial was carried out with 83 patients who had digestive tract cancer and peritoneal carcinomatosis to evaluate the tolerance and efficacy of IPCH with mitomycin C (MMC) associated with surgery. Eighty-six IPCH treatments with MMC were given as complementary therapy after surgery (peritoneal perfusate with a 10 mg/L dose of MMC; inflow temperature, 46-49 degrees C; use of a closed circuit; duration, 90 minutes). Primary tumors were mainly gastric (in 42 cases) or colorectal (in 27 cases). RESULTS: Mortality and morbidity occurred in 3 of 83 cases and 8 of 83 cases, respectively. For patients with resectable tumors, the median survival time was 16 months when carcinomatosis was Stage I and II (malignant granulations less than 5 mm in greatest dimension), whereas it was 6 months when carcinomatosis was Stage III and IV (malignant granulations more than 5 mm in greatest dimension). For patients with resectable gastric cancer and Stage I and II carcinomatosis, 1-, 2-, and 3-year actuarial survival rates were 80%, 61%, and 41%, respectively, whereas the rate was 10% at 1 year for patients with bulky disease (Stage III and IV). CONCLUSIONS: IPCH appears to be a promising new approach to treating patients with digestive tract cancers and peritoneal carcinomatosis with small, malignant granulations (Stage I and II).

Peritonectomy combined with intraperitoneal chemohyperthermia in abdominal cancer with peritoneal carcinomatosis: phase I-II study.

OBJECTIVE: To evaluate the feasibility and the tolerance of Peritonectomy Procedure (PP) combined with Intraperitoneal Chemohyperthermia (IPCH) in patients with peritoneal carcinomatosis, a phase I-II study has been realised from January 1997 to September 1998. METHODS: Eighteen patients were included for peritoneal carcinomatosis from colorectal cancer (13), ovarian cancer (2), gallbladder cancer (1), gastric cancer (1) and peritoneal mesothelioma (1). Peritoneal carcinomatosis were mainly advanced disease (16 stage 3 and 4, 2 stage 2). All the patients underwent surgical resection of their primary tumor with PP as described by Sugarbaker and IPCH (with Mitomycin C, Cisplatinum or both). IPCH used in this study was a "closed sterile circuit" device with inflow temperatures ranging from 46 to 48 degrees C. IPCH was performed on the same day as PP (8118) or delayed (10/18). RESULTS: Significant down-staging of peritoneal carcinomatosis was achieved for 16 patients. One patient died postoperatively, while the morbidity rate was 6/18 (long postoperative ileus, grade 3 leucopenia and anastomotic leakage). CONCLUSIONS: Combination of PP and IPCH could achieve significant tumoral volume reduction in peritoneal carcinomatosis. This aggressive treatment must be employed selectively because of its morbidity. Larger phase III studies are now needed.

Intraperitoneal chemo-hyperthermia with mitomycin C for gastric cancer patients with peritoneal carcinomatosis.

OBJECTIVE: This study evaluates the tolerance and efficacy of Intraperitoneal Chemo-hyperthermia (IPCH) with Mitomycin C (MMC) associated with surgery, in peritoneal carcinomatosis of gastric origin. BACKGROUND: Most patients with peritoneal carcinomatosis of gastric origin die within 6 months, and IPCH associated with surgery has been reported as a possible new therapeutic approach. METHODS: A prospective non randomized trial was carried out on 42 patients with gastric cancers and peritoneal carcinomatosis. Fourty-three IPCH with MMC were used as complementary treatment after surgery (peritoneal perfusate with a 10 mg/l dose of MMC, inflow temperature 46 to 49 degrees C, use of a closed circuit, duration 90 minutes). Fourteen primary tumors were unresectable ones and 12 patients had large malignant preoperative ascites. RESULTS: Mortality and morbidity rates were 2/42 and 4/42 respectively. For resectable gastric cancers with stage 1 and 2 carcinomatosis (malignant granulations less than 5 mm in diameter), one, two and three year survival rates were 80, 61 and 41% respectively. For unresectable primary tumors and for stage 3 and 4 carcinomatosis (granulations larger than 5 mm in diameter), six and twelve month survival rates were 50% and 10% respectively. CONCLUSIONS: IPCH appears as a safe new therapeutic approach in gastric cancers with peritoneal carcinomatosis with small malignant granulations (stage 1 and 2) and randomized trials are now needed to clearly evaluate its efficacy.

[Intraperitoneal chemo-hyperthermia with mitomycin C in cancer of the stomach with peritoneal carcinosis]. / Chimiohyperthermie intrapéritonéale avec mitomycine C dans les cancers de l'estomac avec carcinose péritonéale.

We report 42 cases of gastric cancer with peritoneal carcinosis treated with intraperitoneal chemohyperthermia. Intraperitoneal chemohyperthermia was achieved with a closed sterile circuit containing mitomycin C, 10 mg/l producing an input temperature varying from 46 to 49 degrees C for 90 minutes. There were three postoperative deaths: one pulmonary embolism at day 4, one multiple organ failure et day 4, and one septic shock at day 25 due to a colonic fistula. Two patients suffered complications: one opening of the duodenal stump requiring reoperation on day 5, and one prolonged postoperative ileus lasting to day 10. Of the 12 patients with ascites, resorption was achieved in 8. In patients with early-stage peritoneal carcinosis (granulations less than 5 mm) survival at 1, 2 and 3 years was 90%, 61% and 41% respectively. For those with more extensive carcinosis, survival at 1 year was 10%. Five patients survived more than 30 months, three have survived to 34, 43 and 73 months. Intraperitoneal chemohyperthermia is a new treatment for carcinosis of gastric origin. These early results must be assessed further with larger controlled.

Regional chemotherapy (with mitomycin C) and intra-operative hyperthermia for digestive cancers with peritoneal carcinomatosis.

Intraperitoneal chemo-hyperthermia with mitomycin C was used to treat 28 patients with far advanced digestive adenocarcinoma and histologically confirmed peritoneal carcinomatosis. Surgical resection of the primary tumor was possible in 17 cases. After closure of the abdominal wall, intraperitoneal chemo-hyperthermia was performed for 90 to 120 minutes under general anesthesia and 32 degrees C hypothermia, through 3 intraperitoneal drains forming a closed circuit, using 10 mg/l of mitomycin C in 6 liters of peritoneal dialysate heated to an inflow temperature of 46-49 degrees C. No mortality occurred, and there were 2 post-operative complications, with transitory biological side effects. In 9 out of 10 patients with preoperative malignant ascites, the ascites cleared after treatment. One-year survival rate was 54.2%. These encouraging preliminary results show that intraperitoneal chemohyperthermia with mitomycin C is a safe and reliable treatment for peritoneal carcinomatosis in far advanced digestive cancers.

Study of the pharmacokinetics of mitomycin C in humans during intraperitoneal chemohyperthermia with special mention of the concentration in local tissues.

The aim of this work is to estimate the 24-hour distribution and elimination of mitomycin C (MMC) during and after intraperitoneal chemohyperthermia (IPCH) in 18 patients (13 gastric adenocarcinoma, 3 pancreatic adenocarcinoma, 2 malignant mesothelioma) who received 60 mg MMC during 90-120 min in 6 liters of heating solution HS; (42 degrees C) or HS flowing at 0.4 liters/min in a closed circuit. MMC assay in the serum, urine, HS and in local biopsies were performed by high performance liquid chromatography. The amount of MMC in HS decreased by 54.1 +/- 13.6% during IPCH. The maximum MMC levels in serum reached 0.4 +/- 0.18 mg/l 45 min after the start of IPCH, then rapidly decreased. Only 1.77 +/- 0.93 mg were recovered in urine in 24 h. These data are consistent with a large and rapid absorption, mostly in local tissue, demonstrated by the level in 7 post-IPCH biopsies (8.3 +/- 7.6 mg/kg).

Cytokine production during intraperitoneal chemohyperthermia.

The aim of the present work is to investigate in vivo cytokine production during chemohyperthermia. 11 patients suffering from gastric adenocarcinoma (n = 6), ovarian adenocarcinoma (n = 4) or malignant mesothelioma (n = 1) were studied. Patients received 60 mg mitomycin or 100 mg cisplatin per square meter during 2 h in 6 liters of a heating solution (temperature 42 degrees C, flow rate 200 ml/min in a closed circuit) after previous surgical resection. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured at 0, 30, 45, 60 and 90 min, both in the blood stream and in the heating solution circulating intraperitoneally. We observed a slight increase in plasma IL-6 occurring as soon as 30 min, a dramatic rise in IL-6 in the heating solution. TNF-alpha values were only slightly augmented. In addition, the importance of various factors in the induction of IL-6 and TNF-alpha production during chemohyperthermia (temperature, mitomycin C, cisplatin) were studied using a whole blood ex vivo model.

[Cancers of the stomach and peritoneal carcinoses: will hyperthermia be a new therapeutic approach?]. / Cancers de l'estomac avec carcinoses péritonéales: l'hyperthermie sera-t-elle une nouvelle voie thérapeutique?

Overall survival rate of gastric adenocarcinoma is poor whatever the therapeutic is. Main reasons for this poor prognosis are regional failure and local recurrences. Using hyperthermia could be of interest in peritoneal carcinomatosis during gastric carcinoma: in vitro cytotoxic effect of hyperthermia is well known. Using hyperthermia in combination with intra peritoneal chemotherapy could improve local control. Preliminary results of pilot studies treating peritoneal carcinomatosis with intra peritoneal chemohyperthermia are reported.

Treatment of malignant peritoneal effusion in digestive and ovarian cancer.

Intra Peritoneal Chemo Hyperthermia (IPCH) with Mitomycin C (MMC) or Cisplatinum (CP) was used to treat 32 patients with far advanced digestive or ovarian cancers and peritoneal carcinomatosis. Surgical resection of the primary tumor has been possible in 18 cases. After closure of the abdominal wall, a 90 minutes IPCH as performed under general anaesthesia and 32 degrees C general hypothermia, through 3 intraperitoneal drainages realizing a closed circuit, using 10 mg/l of MMC or 15 to 25 mg/l of CP in 6 l of peritoneal dialysate heated at the inflow temperature of 46 to 49 degrees C. The mortality rate was 3% and the morbidity rate was 3%. In 11 out of 12 patients with preoperative malignant ascites, no more ascites could be found after IPCH. For peritoneal carcinomatosis from digestive origin, median survival was 11.2 months and 1 year survival rate was 46.9%. These encouraging preliminary results show that IPCH is a safe and reliable treatment for peritoneal carcinomatosis in far advanced digestive or ovarian cancers.