Anastomosis

Esophageal anastomosis is still associated with a high rate of complications even though they have decreased considerably in recent years. Anastomotic leaks are more frequent in the neck than in the chest, and related mortality rate is not different. The leakage incidence does not depend on suture materials or on technical modalities used to perform the anastomosis. In fact, there is no difference between the leakage rate when comparing manual and mechanical anastomoses. The leak incidence after both mechanical and manual anastomoses is much higher in collective reviews than in reports coming from leading centers. Frequent esophageal surgeons can learn from their previous experience and therefore avoid technical errors, whereas casual esophageal surgeons do not have this opportunity. Performing an esophageal anastomosis is a technical matter, and suture healing is independent of the patient's biologic situation. Anastomotic fibrotic stricutures are frequent after both manual and mechanical anastomoses, and most can be avoided by meticulous suturing technique.

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Resumen La anastomosis esofágica todavía se asocia con una elevada incidencia de complicaciones, a pesar de que éstas han descendido en forma considerable en los últimos años. Las fugas anastomóticas son más frecuentes en el cuello que en el tórax y las tasas de mortalidad no son diferentes. La rata de fuga anastomótica no depende de los materiales de sutura o de las modalidades técnicas que se utilicen para realizar la anastomosis. De hecho no hay diferencia en cuanto a la rata de fugas entre las anastomosis manuales y las mecánicas. La incidencia de fuga, tanto en las manuales como en las mecánicas, es bastante más alta en las revisiones colectivas que en los reportes emanados de los centros médicos de mayor importancia. Los cirujanos especialistas en esófago tienen la posibilidad de aprender de sus experiencias previas y con ello evitar los errores técnicos, en tanto que aquellos cirujanos ocasionales no la poseen. La realización de una anastomosis esofágica es un asunto técnico y la cicatrización de la sutura es independiente de la condición biológica del paciente. Las estrecheces fibróticas de las anastomosis son frecuentes luego de las anastomosis manuales, al igual que luego de las anastomosis mecánicas y la mayoría puede ser evitada mediante una técnica meticulosa.

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Résumé Le taux de complications des anastomoses oesophagiennes, même s'il y en a moins ces dernières années, reste toujours élevé. La fréquence de fistules est plus grande quand l'anastomose est faite au cou par rapport au thorax, mais la mortalité n'en est pas très différente. L'incidence de fistules ne dépend ni du matériau de suture ni des modalités d'anastomoses utilisées. Il n'y a aucune différence lorsque les anastomoses manuelles sont comparées aux anastomoses méchaniques: L'incidence des fistules, que ce soit à la main ou à la machine est plus élevée dans les séries collectives par rapport à celle des centres spécialisés. Les chirurgiens qui font des anastomoses de façon régulière ont la possibilité de profiter de leur expérience et ainsi d'éviter les erreurs techniques, alors que le chirurgien occasionnel de l'oesophage n'a pas cette possibilité. L'anastomose oesophagienne est techniquement difficile et la cicatrisation est indépendante de l'état clinique et biologique du patient. Les sténoses fibreuses sont aussi fréquentes après les anastomoses manuelles qu'après les anastomoses méchaniques, mais la plupart peuvent être évitées par une technique méticuleuse.

     

Cost comparison of sevoflurane with isoflurane anesthesia in arthroscopic menisectomy surgery

PURPOSE: To determine the "real world" cost of sevoflurane compared with isoflurane in balanced general anesthesia for daycare arthroscopic menisectomy, we prospectively investigated perioperative drug requirement and expense as well as recovery time. METHODS: Following intravenous induction, 40 consenting adult patients randomly received either sevoflurane- or isoflurane-based anesthesia with a standardized gas inflow rate of 3 l x min. Recovery was assessed in the postanesthetic recovery room (PARR) in a double-blind manner at 15 min intervals using the Aldrete scoring system until patients met discharge criteria. RESULTS: Patient demographics, anesthetic duration, volatile potency and adjunct drug requirements were similar in the two groups. Total perioperative drug cost per patient was CAN$38.10+/-10.13 (mean +/- SD) for the sevoflurane group and $23.87+/-6.59 for the isoflurane group (P<0.01). Although the nonvolatile drug cost was comparable between the two groups, the volatile drug cost per patient was $19.40+/-8.80 for sevoflurane and $4.50+/-1.90 for isoflurane (P<0.01). This four-fold sevoflurane-to-isoflurane cost difference was the product of two ratios, both based on the volume of liquid anesthetic: the ratio of consumption, 2.1; and the ratio of institutional price, 2.1. Intraoperative hemodynamic response, time until discharge from the PARR and incidences of postoperative nausea and vomiting did not significantly differ between the two groups. CONCLUSIONS: When used to maintain equipotent balanced general anesthesia for daycare arthroscopic menisectomy, volatile consumption and cost were greater for sevoflurane compared with isoflurane. Nonvolatile perioperative drug cost and recovery times were similar, however, in the two groups.     

Tumor proliferative activity and response to first-line chemotherapy in advanced breast carcinoma

Summary The relationship between tumor proliferative activity and response to first-line chemotherapy and survival was investigated in 76 advanced breast cancer patients. Proliferative activity was determined by means of Ki-67 immunohistologic staining on primary tumors (55 patients) or at the relapse site (21 patients), and was classified as low ( 25% of stained cells) or high (> 25% of stained cells). The usual WHO response criteria were used. The median duration of follow-up was 18 months (range 3–58).Forty-seven patients (62%) had tumors with low, and 29 (38%) had tumors with a high rate of proliferative activity. The two groups were well balanced in terms of important variables such as disease-free survival, performance status, age, menopausal status, and the type of first-line chemotherapy (anthracycline-based regimens versus cyclophosphamide-methotrexate-5-fluorouracil). The estrogen receptor (ER) content, measured by means of immunohistochemical assay, was markedly different in the two groups, with 27/47 tumors with low proliferative activity (57%) and 6/29 with high-proliferative activity (21%) being ER positive ( 45% of stained cells) (p = 0.003). Moreover, a significant difference in the metastatic pattern was also evident, with a higher incidence of bone and a lower incidence of soft tissue metastases in the group of patients with tumors with low proliferative activity (p = 0.004). Overall, 10/47 responses (21%: PR = 7, and CR = 3) were observed in the group with a low rate of proliferative activity, versus 14/29 (48%: PR = 9, and CR = 5) in the group with highly proliferative tumors, the difference being statistically significant (p = 0.03). When a multivariate analy-sis was performed, the only factor that retained independent prognostic significance was the predominant site of disease, particularly soft tissues (p = 0.003). Despite the difference in response rate, when survival analysis was performed according to the Kaplan-Meier method, no significant difference was observed in the two groups, but when the analysis was limited to responsive patients, the median survival observed in those with a low and those with a high rate of proliferation was 35 and 19 months respectively (p = 0.02). The same results were obtained when multivariate survival analysis was carried out using Cox's regression model. These data suggest that there is a link between tumor proliferative activity and response to chemotherapy in advanced breast cancer, and may indicate the need to use more intensive treatments in selected patients with highly proliferative tumors.Presented in part at the Annual Meeting of the American Society of Clinical Oncology, May 14–17, 1994, Dallas, TX, USA     

Caustic ingestion in childhood: current treatment possibilities and their complications

In a review of 15 pediatric patients who had ingested caustic substances, the authors describe the diagnostic and therapeutic procedures to be followed as well as the complications that may occur with their use. The cases reported include 1 esophageal rupture caused by balloon dilatation and 1 recurrent stenosis treated with a silastic tutor.     

In vivo neutron dosimetry during high-energy Bremsstrahlung radiotherapy

Purpose: A new technique is presented for in vivo measurements of the dose equivalent from photoneutrons produced by high-energy radiotherapy accelerators.Methods and Materials: The dosimeters used for this purpose are vials of superheated halocarbon droplets suspended in a tissue-equivalent gel. Neutron interactions nucleate the formation of bubbles, which can be recorded through the volume of gel they displace from the detector vials into graduated pipettes. These detectors offer inherent photon discrimination, dose-equivalent response to neutrons, passive operation, and small sensitive size. An in vivo vaginal probe was fabricated containing one of these neutron detector vials and a photon-sensitive diode. Measurements were carried out in patients undergoing high-energy x-ray radiotherapy and were also repeated in-phantom, under similar irradiation geometries.Results and Conclusion: Neutron doses of 0.02 Sv were measured in correspondence to the cervix, 50 cm from the photon beam axis, following a complete treatment course of 46.5 Gy with an upper mantle field of 18-MV x-rays. This fraction of dose from neutrons is measured reliably within an intense photon background, making the technique a valid solution to challenging dosimetry problems such as the determination of fetal exposure in radiotherapy. These measurements can be easily carried out with tissue-equivalent phantoms, as our results indicate an excellent correlation between in vivo and in-phantom dosimetry.     

Formation and antitumor activity of PNU-159682, a major metabolite of nemorubicin in human liver microsomes.

PURPOSE: Nemorubicin (3'-deamino-3'-[2'(S)-methoxy-4'-morpholinyl]doxorubicin; MMDX) is an investigational drug currently in phase II/III clinical testing in hepatocellular carcinoma. A bioactivation product of MMDX, 3'-deamino-3',4'-anhydro-[2'(S)-methoxy-3'(R)-oxy-4'-morpholinyl]doxorubicin (PNU-159682), has been recently identified in an incubate of the drug with NADPH-supplemented rat liver microsomes. The aims of this study were to obtain information about MMDX biotransformation to PNU-159682 in humans, and to explore the antitumor activity of PNU-159682. EXPERIMENTAL DESIGN: Human liver microsomes (HLM) and microsomes from genetically engineered cell lines expressing individual human cytochrome P450s (CYP) were used to study MMDX biotransformation. We also examined the cytotoxicity and antitumor activity of PNU-159682 using a panel of in vitro-cultured human tumor cell lines and tumor-bearing mice, respectively. RESULTS: HLMs converted MMDX to a major metabolite, whose retention time in liquid chromatography and ion fragmentation in tandem mass spectrometry were identical to those of synthetic PNU-159682. In a bank of HLMs from 10 donors, rates of PNU-159682 formation correlated significantly with three distinct CYP3A-mediated activities. Troleandomycin and ketoconazole, both inhibitors of CYP3A, markedly reduced PNU-159682 formation by HLMs; the reaction was also concentration-dependently inhibited by a monoclonal antibody to CYP3A4/5. Of the 10 cDNA-expressed CYPs examined, only CYP3A4 formed PNU-159682. In addition, PNU-159682 was remarkably more cytotoxic than MMDX and doxorubicin in vitro, and was effective in the two in vivo tumor models tested, i.e., disseminated murine L1210 leukemia and MX-1 human mammary carcinoma xenografts. CONCLUSIONS: CYP3A4, the major CYP in human liver, converts MMDX to a more cytotoxic metabolite, PNU-159682, which retains antitumor activity in vivo.