Curative surgery for gastric cancer: Study of 166 consecutive patients

From January 1980 to December 1991 we operated on 295 patients with a gastric carcinoma. In 166 cases (56.3%) surgery was performed with curative intent. In 93 patients (56%) a subtotal gastrectomy was performed, and in 73 cases (44%) a total gastrectomy. In all the cases a D-2 type lymphadenectomy was used. The global morbidity rate was 23%, and in-hospital mortality was 3.6%. The morbidity and mortality rates of these two operations were statistically different. Global 5-year survival estimate for the whole series is 61.3%. Univariate and multivariate analysis according to T and N (TNM classification), the number of positive nodes resected, and the relation of positive per resected nodes, revealed statistically different outcomes. This kind of quantitative classification allowed identification of high risk groups irrespective of site of nodal involvement. Tumors classified as intestinal or diffuse type by the Lauren classification had similar survival curves and 5-year survival estimates (p=0.834). By univariate and multivariate analysis this classification did not reveal a prognostic value in this group of patients. In our opinion, tumor penetration and lymph node involvement are at present the most reliable prognostic factors available.

---

Resumen En el período enero 1980 a diciembre 1991 se operaron 295 pacientes con carcinoma gástrico. En 166 (56.3%), la cirugía fue realizada con intención curativa; en 93 (56%) se realizó gastrectomía subtotal y en 73 (44%) gastrectomía total. En la totalidad de los casos se realizó linfadenectomía D-2. La mortalidad global fue 23% y la mortalidad hospitalaria 3.6%. Las tasas de mortalidad y morbilidad de estas dos operaciones aparecieron significativamente diferentes. La sobrevida global a cinco años estimada para la totalidad de la serie es de 61.3%. Los análisis uni y multivariables de acuerdo con la clasificación TNM, el número de ganglios positivos resecados y la relación positivos/resecados revelaron resultados estadísticamente diferentes. Este tipo de clasificación cuantitativa permitió la identificación de Grupos de alto riesgo independientes del lugar de la invasión ganglionar. Los tumores clasificados como intestinales o difusos (clasificación de Lauren), registraron similares curvas de sobrevida y de sobrevida estimada a cinco años (P=0.834). Mediante el análisis univariable y multivariable esta clasificación no demostró tener valor pronóstico en nuestro Grupo de pacientes. En nuestra opinión, el grado de penetración del tumor y la invasión ganglionar son los factores de pronóstico más confiables.

---

Résumé Entre Janvier 1980 et Décembre 1991, nous avons opéré 295 patients ayant un cancer gastrique. Chez 166 (56.3%), l'exérèse a été jugée curative. Chez 93 (56%) des cas, il s'agissait d'une gastrectomie subtotale alors que dans 73 (44%) cas, une gastrectomie totale a été pratiquée. Dans tous les cas une lymphadénectomie du type D-2 lui a été associée. La morbidité globale a été de 23% et la mortalité hospitalière de 3.6%. La morbidité et la mortalité des deux types d'intervention différaient de façon statistiquement significative. La survie à 5 ans de la série en entier a été de 61.3%. Une analyse uni et multifactorielle a pu mettre en évidence une différence statistiquement significative en ce qui concerne la survie par rapport à la classification T-N (TNM), le nombre de ganglions réséqués et le nombre de ganglions envahis/nombre de ganglions enlevés. Cette analyse a permis d'identifier les malades à haut risque, indépendamment du site de l'envahissement lymphatique. La courbe de survie et la survie estimée à 5 ans étaient identiques selon que la tumeur a été classée intestinale ou diffuse selon Lauren. Cette classification n'a pas, pourtant, de valeur pronostique d'après les analyses uni et multifactorielle. A notre avis, la pénétration tumorale et le degré d'envahissement lymphatique sont les deux facteurs pronostiques les plus constants.

     

Characterization of a tissue kallikrein inhibitor isolated from Bauhinia bauhinioides seeds: inhibition of the hydrolysis of kininogen related substrates

Trypsin inhibitors were purified from a saline extract of Bauhinia bauhinioides seeds by ion-exchange column chromatography on DEAE-Sephadex, gel filtration on Superose 12 column, Mono Q ion-exchange chromatography or, alternatively, by affinity chromatography on trypsin-Sepharose. Both B. bauhinioides isolated inhibitors, BbTI-I and BbTI-II, inhibit trypsin being the dissociation constant 0.6 and 0.36 nM, respectively. BbTI-II only inhibits porcine pancreatic kallikrein hydrolysis of H-Pro-Phe-Arg-AMC (Ki 2.0 nM); the bradykinin-containing sequence LGMISLMKRPPGFSPFRSSRI-NH2 and the two kininogen related flanking quenched substrates Abz-MISLMKRP-EDDnp (Ki 2.0 nM) and Abz-FRSSRQ-EDDnp (Ki 2.5 nM).     

From occupational medicine to workers' health]

The evolution of the concepts and practice of occupational medicine, occupational health and workers' health is tentatively reviewed. An attempt is made to answer the following questions: what were the major characteristics of occupational medicine throughout its evolution? How and why did occupational medicine evolve into occupational health? Why has the "occupational health model" become inadequate? Within what context did workers' health arise? What are the principal characteristics of workers' health?     

Effects of the steroidal aromatase inhibitor exemestane and the nonsteroidal aromatase inhibitor letrozole on bone and lipid metabolism in ovariectomized rats.

PURPOSE: Exemestane (EXE) and letrozole (LET) are third-generation aromatase inhibitors currently prescribed for postmenopausal hormone-dependent breast cancer. The impact on end organs of estrogen depletion in menopausal women is of significant clinical importance. We studied the effects of EXE, its principal metabolite, 17-hydroexemestane (17-H-EXE), and LET on bone and lipid metabolism in ovariectomized (OVX) rats. EXPERIMENTAL DESIGN: OVX rats were treated by weekly intramuscular injection for 16 weeks with 20, 50, and 100 mg/kg EXE, 20 mg/kg 17-H-EXE, and daily oral gavage of 1 mg/kg LET. At the end of the treatment period, bone mineral density (BMD), the bone resorption marker serum pyridinoline, the bone formation marker serum osteocalcin, bone mechanical properties, histomorphometry, and serum lipid concentrations were determined. RESULTS: Lumbar vertebral and femoral BMD, bending strength of the femur, compressive strength of the fifth lumbar vertebra, and trabecular bone volume were significantly higher in OVX animals given EXE and 17-H-EXE than in OVX controls. EXE and 17-H-EXE significantly reduced an ovariectomy-induced increase in serum pyridinoline and serum osteocalcin. EXE and 17-H-EXE given to OVX rats caused significant reductions of serum cholesterol and low-density lipoprotein cholesterol. In contrast, OVX rats treated with LET had BMD, bone biomarkers, mechanical failure properties, and lipid levels similar to those of OVX controls. CONCLUSIONS: EXE and 17-H-EXE significantly prevent bone loss, enhance bone mechanical strength, and lower serum cholesterol and low-density lipoprotein levels in OVX rats. These protective effects on end-organ function are not seen with the nonsteroidal inhibitor LET.     

Tirapazamine plus carboplatin and paclitaxel in advanced malignant solid tumors: a california cancer consortium phase I and molecular correlative study.

PURPOSE: Tumor hypoxia confers chemotherapy resistance. Tirapazamine is a cytotoxin that selectively targets hypoxic cells and has supra-additive toxicity with platinums and taxanes in preclinical studies. We conducted a Phase I study of tirapazamine, carboplatin, and paclitaxel and assessed potential plasma markers of hypoxia as surrogates for response. EXPERIMENTAL DESIGN: Forty-two patients with advanced solid tumors were treated at four dose levels; parallel dose escalations were carried out in chemotherapy-naive and previously treated subjects. Pre and post-therapy plasma levels of the hypoxia-induced proteins plasminogen activator inhibitor-1 and vascular endothelial growth factor were measured. RESULTS: Three of four chemotherapy-na?ve patients developed dose-limiting toxicities at dose level 4 (grade 3 stomatitis/infection, grade 3 emesis, and grade 4 febrile neutropenia). Four of seven previously treated patients developed dose-limiting toxicities at dose level 3, including one death [grade 3 myalgia, grade 3 infection/grade 4 neutropenia, grade 3 infection/grade 4 neutropenia, and grade 5 infection (death)/grade 4 neutropenia]. Of 38 patients assessable for response, 3 had a complete response, 1 a partial response, 1 an unconfirmed partial response, and 23 had stable disease in at least one evaluation; 10 quickly progressed. One complete responder had normalization of vascular endothelial growth factor and plasminogen activator inhibitor-1 levels. CONCLUSION: Dose levels 3 (carboplatin AUC of 6, 225 mg/m(2) paclitaxel, and 330 mg/m(2) tirapazamine) and 2 (carboplatin AUC 6, 225 mg/m(2) paclitaxel, and 260 mg/m(2) tirapazamine) are the maximum tolerated doses for chemotherapy naive and patients treated previously, respectively. Dose level 3 is the experimental arm of a Phase III Southwest Oncology Group trial (S0003) in advanced non-small cell lung cancer. Potential markers of tumor hypoxia may be useful correlates in studies of hypoxic cytotoxins and are being prospectively investigated in S0003.     

Phase II trial of edatrexate plus carboplatin in metastatic non-small-cell lung cancer: a Southwest Oncology Group study

Background: Edatrexate and carboplatin are each active single agents in the treatment of non-small-cell lung cancer (NSCLC). Preclinical studies in NSCLC lines have demonstrated schedule-dependent synergy of edatrexate followed by carboplatin. In a phase I trial, we demonstrated the tolerability of this combination, the ability of ice-chip cryotherapy to ameliorate dose-limiting mucositis, and promising activity in NSCLC. This phase II trial (SWOG 9207) was undertaken to investigate the efficacy of this regimen in stage IV NSCLC. Methods: A total of 24 patients with stage IV disease were accrued to this Southwest Oncology Group (SWOG) multicenter study. Treatment consisted of edatrexate 80 mg/m² (50% dose on day 8) intravenously weekly for 5 weeks, then every other week, and carboplatin 350 mg/m² every 28 days. Results: Of the 24 patients, 23 were assessable for toxicity and response; one was ineligible for study entry. Myelosuppression was the most significant toxicity; grade 3–4 neutropenia was seen in 8/23 patients. Two patients died of neutropenic sepsis during the first cycle of therapy, in both instances associated with the presence of pleural effusions. Although mild mucositis was common, it was dose-limiting (grade 3) in only three patients. Objective response was observed in 3/23 patients (13%). The median survival time was 7 months, and 30% of patients remained alive at one year. Conclusions: This study suggests that ice-chip cryotherapy is effective in reducing the severity of mucositis typically associated with this edatrexate schedule of administration. However, unexpectedly severe myelosuppression resulted in death from neutropenic sepsis in two patients with third space fluid collections, leading to a protocol amendment to exclude such patients from study entry. Furthermore, response and median survival with this dose schedule of edatrexate and carboplatin do not appear to be improved compared to other chemotherapeutic regimens tested by SWOG in this patient population. Received: 12 August 1996 / Accepted: 8 May 1997     

The usefulness of ovarian volume, antral follicle count and age as predictors of menopausal status.

OBJECTIVE: To compare the accuracy of ovarian volume, antral follicle count and age in predicting menopausal status in healthy women. METHODS: The cross-sectional study was set in the Gynecology Division at the Leonor Mendes de Barros Maternity Hospital, S?o Paulo, Brazil. The subjects of this study were premenopausal (n = 121) and postmenopausal (n = 71) healthy women aged between 40 and 55 years. They were submitted to a medical interview and transvaginal ultrasound examination. The ovarian volume (cm3), antral follicle count and chronological age were recorded in both groups and the accuracies of these parameters in predicting menopausal status were compared. RESULTS: Premenopausal women presented larger ovaries than postmenopausal women (p < 0.01). Premenopausal women had a higher number of antral follicles than postmenopausal women (p < 0.01). The receiver operating characteristic curves showed that ovarian volume, age and antral follicle count had similar sensitivities and specificities in predicting menopausal status. The best cut-off points were observed when ovarian volume was <4 cm3, age was > or =48 years and antral follicle count was < or = two follicles. CONCLUSIONS: Ovarian volume, antral follicle count and chronological age are all individually predictive of menopausal status, with similar accuracies.     

Structural and biological characterization of three novel mastoparan peptides from the venom of the neotropical social wasp Protopolybia exigua (Saussure).

The venom of the Neotropical social wasp Protopolybia exigua(Saussure) was fractionated by RP-HPLC resulting in the elution of 20 fractions. The homogeneity of the preparations were checked out by using ESI-MS analysis and the fractions 15, 17 and 19 (eluted at the most hydrophobic conditions) were enough pure to be sequenced by Edman degradation chemistry, resulting in the following sequences: Protopolybia MPI I-N-W-L-K-L-G-K-K-V-S-A-I-L-NH2 Protopolybia-MP II I-N-W-K-A-I-I-E-A-A-K-Q-A-L-NH2 Protopolybia-MP III I-N-W-L-K-L-G-K-A-V-I-D-A-L-NH2 All the peptides were manually synthesized on-solid phase and functionally characterized. Protopolybia-MP I is a hemolytic mastoparan, probably acting on mast cells by assembling in plasma membrane, resulting in pore formation; meanwhile, the peptides Protopolybia-MP II and -MP III were characterized as a non-hemolytic mast cell degranulator toxins, which apparently act by virtue of their binding to G-protein receptor, activating the mast cell degranulation.