BackgroundIntraperitoneal (i.p.) epinephrine was shown to increase the accumulation of i.p. cisplatin in tumours, and thus its antitumour effect in a model of peritoneal carcinomatosis in rats. MethodsTo determine the tolerance to i.p. epinephrine with cisplatin, 18 patients with recurrent ovarian carcinoma were intraoperatively treated in this phase 1 study. After maximal cytoreductive surgery, the peritoneal cavity was filled twice for 1 h with 30 mg/l of cisplatin and increasing concentrations of epinephrine (0, 1, 2, 3 mg/l) in 3 l of saline solution at 37°C. ResultsNo deaths occurred. Three patients were treated at each of the 0, 1 and 2 mg/l epinephrine levels without adverse events. Two of the three patients who received 3 mg/l epinephrine experienced cardiac intolerance. Six additional patients received 2 mg/l of epinephrine without toxicity. A relationship between the serum concentration of epinephrine and occurrence of cardiac toxicity was established. A 60% decrease in serum area under the curve of platinum was calculated in patients receiving i.p. epinephrine compared with i.p. cisplatin alone. Renal toxicity from cisplatin was not increased by epinephrine. No haematological or neurological toxicity was recorded. The other grade 3–4 adverse events [thromboembolism (5), peritonitis (1), abdominal bleeding (1), bowel fistula (1)] occurred as often as usually reported for this heavy surgical procedure. ConclusionThe combination of i.p. epinephrine with cisplatin as intraoperative chemotherapy after optimal cytoreductive surgery is feasible. The recommended concentration for further studies is 2 mg/l for i.p. epinephrine.

In this paper, the performance of a quasi-optical phonon-cooled NbN superconducting hot electron bolometer (HEB) mixer is thoroughly investigated. The variation of the receiver noise temperature and the conversion gain around 600 GHz with respect to DC bias voltage and LO pumping level has been measured. The lowest receiver noise temperature is 750 K and reduced to about 250 K after correcting the quasi-optical losses before the HEB mixer. We compared the measured results with the predictions according to one dimensional distributed hot spot model. A reasonable match between theoretical model and experiment is observed. In addition, the direct response of the HEB mixer (integrated with a log-periodic spiral antenna) is measured by using Fourier Transform Spectrometer (FTS). The stability of the receiver is also investigated by means of Allan variance time measurements performed with an intermediate frequency (IF) bandwidth of 40 MHz.

BACKGROUND:The trunk of a car occupant can be injured by a frontal or lateral impact. Lesions can be either intrusion injuries or due to the effects of deceleration alone. The aim of this study conducted with human cadavers was to explore the effects of deceleration on the liver during frontal or lateral deceleration.METHODS:Trunks previously instrumented with accelerometers in three sites, the left and right lobes of the liver and the retrohepatic inferior vena cava, were subjected to substantial deceleration in three orientations: frontal, left, and right lateral. The anatomic consequences and deceleration data were measured. A deceleration ratio was defined as a peak deceleration measured in the liver divided by peak deceleration imposed on the trunk.RESULTS:Peak deceleration imposed on the trunks was up to 60 g, which caused peak deceleration up to 26 g in the liver. No anatomic injury was observed. For each orientation, deceleration ratios were not significantly different among the three sites (p = 0.64) or between left and right lateral decelerations (p = 0.12). Deceleration ratios were significantly different (p = 0.001) between frontal (3 sites combined) and lateral (3 sites of left and right lateral orientations combined) decelerations: 39.4% (+/-6) versus 48.4% (+/-11).CONCLUSIONS:In conclusion, at tested decelerations, under the hepatic injury threshold, cadaveric liver seemed to be subjected to higher deceleration when the trunk was decelerated in lateral than in frontal direction, without terminal impact.

Desmoid tumors may occur sporadically or as part of the extraintestinal manifestations of familial adenomatous polyposis. Different phenotypes have been described and some genotype-phenotype correlations have been raised, associated with different sites of germline mutations in the adenomatous polyposis coli (APC) gene. We report on a 42-year-old woman ascertained for a large desmoid tumor of the anterior chest wall with pleural involvement, which persistently recurred despite a decade of treatment including hormone therapy, chemotherapy, and surgery. Spontaneous disappearance of the tumor was later noted after 1 year without any treatment and confirmed after 4 years of regular follow-up. Repeated colonoscopies were normal in the proband and DNA sequencing showed a frameshift mutation due to a single adenosine deletion at position 5772 (codon 1924). This mutation, located in the exon 15 at the 3' end of the APC gene, leads to an unusual and late onset phenotype. The pedigree revealed other isolated or familial adenomatous polyposis-associated cases of desmoid tumors. This family report shows that a molecular analysis of the APC gene should be performed in familial desmoid tumors for accurate genetic counseling and follow-up.

BACKGROUND:Few population-based studies investigate obstructing colorectal cancers. This study was designed to describe trends in their frequency and management.METHODS:Data were obtained for 13,331 colorectal cancers registered by the population-based cancer registry of Burgundy, France, between the years 1976 and 2000.RESULTS:Obstructing cancers represented 8.3 percent of all colorectal cancers. This proportion was stable throughout the study. Resection for cure increased from 54.9 percent (1976-1980) to 71.4 percent (1996-2000; P=0.011). Using multivariate analysis, site of cancer and period of diagnosis were the only factors significantly associated to a curative resection. Postoperative mortality for obstructing colorectal cancers decreased from 32.6 percent (1976-80) to 15.2 percent (1996-2000; P < 0.001). The presence of obstruction was significantly associated with a higher postoperative mortality, independent of age and tumor stage (odds ratio=2.55; 95 percent confidence interval=2.13-3.5).CONCLUSION:The frequency of obstructing colorectal cancers has remained unchanged for 25 years. Operative mortality is still high, although some improvements have occurred. Efforts must be made to diagnose colorectal cancers before obstruction occurs. Mass screening represents a promising approach.

BACKGROUND:Exposure of the surgical team to toxic drugs during hyperthermic intraperitoneal chemotherapy (HIPEC) remains a matter of great concern. During closed-abdomen HIPEC, operating room staff are not exposed to drugs, but the distribution of the heated liquid within the abdomen is not optimal. With open-abdomen HIPEC, the opposite is true. Although the open-abdomen method is potentially more effective, it has not become a standard procedure because of the risk of exposure of members of the team to drugs.METHODS:We present a new technique (closed HIPEC with open abdomen) which ensures protection against potentially contaminating exposure to liquids, vapours and aerosols, and allows permanent access to the whole abdominal cavity. Its principle is to extend the abdominal surgical wound upwards with a sort of "glove-box". The cutaneous edges of the laparotomy are stapled to a latex "wall expander". The expander is draped over a special L-section metal frame placed above the abdomen. A transparent cover containing a "hand-access" port, like those used in laparoscopic surgery, is fixed inside the frame.RESULTS:In 10 patients, this device proved to be hermetic for both liquids and vapours. Intra-abdominal temperature was maintained between 42 and 43 degrees C during most of the procedure. The whole abdominal cavity was accessible to the surgeon, allowing optimal exposure of all peritoneal surfaces.CONCLUSION:This technique allows optimal HIPEC, while limiting the potential toxic effects for the surgical, medical and paramedical teams.

AIM OF THE STUDY:To analyze our experience with biliary injuries during cholecystectomy in order to determine associated risk factors, morbidity, and results after reconstruction.PATIENTS AND METHODS:Review of the series of patients referred to our department for biliary injury during cholecystectomy over a 9-year period. Items regarding the type of lesion, risk factors, management, morbidity, and late results were recorded.RESULTS:Fifteen patients were referred to our department for bile duct injury during cholecystectomy between 1997 and 2005 (14 by laparoscopy and four by laparotomy; nine women and nine men). The main surgical indication was biliary colic (n=8). Three patients were operated on in an emergency setting (for acute cholecystitis). In nine patients the gallbladder wall was inflammatory. Intraoperative cholangiography was performed in nine patients, but revealed just one injury. Lateral injury to the bile duct was the most frequent type of lesion. In nine patients, the injury was detected intraoperatively and a biliary drainage was left in place; five of them had a synchronic repair and three required later reconstruction. Nine patients had a delayed identification of biliary injury; six of them required a biliodigestive anastomosis. Two patients died, three had several episodes of acute cholangitis after reconstruction and two presented incisional hernia.CONCLUSION:An inflammatory environment is the main risk factor for biliary injury during cholecystectomy. Bile duct injury is more frequent with laparoscopic cholecystectomy but can also occur with an open approach. Intraoperative cholangiography does not prevent biliary injuries nor detect them accurately. Biliary drainage can reduce morbidity for intraoperatively detected injuries and may be a sensitive approach for the surgeon with no hepatobiliary experience. Morbidity is increased in patients with delayed identification of the injury.

We present the case of large desmoid tumor of the anterior chest wall with pleural involvement, which persistently progressed despite hormonotherapy, chemotherapy and surgery. After many years of therapeutic failures, given the tumor size and its hemodynamic repercussions, the patient was presumed to be incurable and only supportive measures were given. One year later, the desmoid tumor had completely disappeared. Even though wide surgical excision is an essential element in the treatment of desmoid tumors, spontaneous regression may occur in very advanced disease.

This study evaluated by immunohistochemistry (IHC) immune cell response during neoadjuvant primary systemic therapy (PST) with trastuzumab in patients with HER2-positive primary breast cancer. In all, 23 patients with IHC 3+ primary breast cancer were treated with trastuzumab plus docetaxel. Pathological complete and partial responses were documented for nine (39%) and 14 (61%) patients, respectively. Case-matched controls comprised patients treated with docetaxel-based PST without trastuzumab (D; n = 23 ) or PST without docetaxel or trastuzumab (non-taxane, non-trastuzumab, NT–NT; n = 23 ). All surgical specimens were blind-analysed by two independent pathologists, with immunohistochemical evaluation of B and T lymphocytes, macrophages, dendritic cells and natural killer (NK) cells. Potential cytolytic cells were stained for Granzyme B and TiA1. HER2 expression was also evaluated in residual tumour cells. Trastuzumab treatment was associated with significantly increased numbers of tumour-associated NK cells and increased lymphocyte expression of Granzyme B and TiA1 compared with controls. This study supports an in vivo role for immune (particularly NK cell) responses in the mechanism of trastuzumab action in breast cancer. These results suggest that trastuzumab plus taxanes lead to enhanced NK cell activity, which may partially account for the synergistic activity of trastuzumab and docetaxel in breast cancer.

The analysis of self-excited combustion instabilies encountered in a laboratory-scale, swirl-stabilized combustion system is presented. The instability is successfully captured by reactive large-eddy simulation (LES) and analyzed by using a global acoustic energy equation. This energy equation shows how the source term due to combustion (equivalent to the Rayleigh criterion) is balanced by the acoustic fluxes at the boundaries when reaching the limit cycle. Additionally, an Helmholtz-equation solver including flame-acoustics interaction modeling is used to predict the stability characteristics of the system. Feeding the flame-transfer function from the LES into this solver allows to predict an amplification rate for each mode. The unstable mode encountered in the LES compares well with the mode of the highest amplification factor in the Helmholtz-equation solver, in terms of mode shape as well as in frequency.

OBJECTIVE:To investigate the role of increased intra-abdominal pressure (IAP) on the intratumoral accumulation and the antitumor effect of intraperitoneal cisplatin in rats with advanced peritoneal carcinomatosis. To evaluate the tolerance of IAP in pigs, as it is a large animal with a body size equivalent to humans. SUMMARY BACKGROUND DATA:To investigate if an active convection, driven by a positive IAP, increases cisplatin penetration and antitumor effectiveness in a model of advanced peritoneal carcinomatosis in rats. EXPERIMENTAL DESIGN:BDIX rats with macroscopic peritoneal tumors received cisplatin administered as intravenous injection (IV), conventional intraperitoneal injection (IP), or sustained intraperitoneal injection of cisplatin given in a large volume of solvent for maintaining IAP for 1 hour. Platinum tissue concentration was measured by atomic absorption spectroscopy (AAS), and platinum distribution into the tumor nodules was assessed by the particular-induced x-ray emission (PIXE) method. The antitumor effect was assessed in a survival experiment. The hemodynamic, local, and systemic tolerance of IAP, with or without cisplatin, was evaluated in Large White pigs. RESULTS:The maximum tolerated IAP was 22 mm Hg for 1 hour in nonventilated rats. IAP, in comparison with IV or conventional IP injections, resulted in the increased concentration and depth of diffusion of platinum into diaphragm and peritoneal tumor nodules. Consequently, IAP treatment induced an extended survival of rats treated at an advanced stage of carcinomatosis. In 7 50- to 70-kg ventilated pigs, a 40-mm Hg IAP was well tolerated when maintained stable for 2 hours. Renal failure occurred in pigs receiving a total dose of 200 and 400 mg of cisplatin with IAP, but a dose of 100 mg was well tolerated. CONCLUSIONS:Intraperitoneal chemotherapy with increased IAP, in comparison with conventional IP or IV chemotherapy, improved the tumor accumulation and the antitumor effect of cisplatin in rats bearing advanced peritoneal carcinomatosis. In preclinical conditions, the tolerance of sustained IAP was manageable in ventilated pigs.

We present the case of large desmoid tumor of the anterior chest wall with pleural involvement, which persistently progressed despite hormonotherapy, chemotherapy and surgery. After many years of therapeutic failures, given the tumor size and its hemodynamic repercussions, the patient was presumed to be incurable and only supportive measures were given. One year later, the desmoid tumor had completely disappeared. Even though wide surgical excision is an essential element in the treatment of desmoid tumors, spontaneous regression may occur in very advanced disease. (c) 2006 Elsevier SAS. Tous droits reserves.

Background: Mechanisms of hepatic injury remain poorly understood. Surgical literature reports some speculative theories that have never been proved. The aim of this study was to examine the behavior of the liver during brutal frontal deceleration. Methods: Six trunks, removed from human cadavers, underwent free falls at 4, 6, and 8 meters per second (mps). Accelerometers were positioned in the two lobes of the liver, in front of the vertebra L2, and in the retro hepatic inferior vena cava. Relative motions of the lobes of the liver and of the two other anatomic marks were observed. In parallel, numerical simulations of this experiment have been performed using a finite element model. Results: In the direction of impact, the vertebra L2 had no considerable displacement with the inferior vena cava. There was a noteworthy displacement between the two hepatic lobes. The left hepatic lobe had a large relative displacement with the vertebra L2 and the inferior vena cava. The right hepatic lobe was more stable with the vertebra L2 and the inferior vena cava. Numerical simulation of the same protocol underlined a rotation effect of the liver to the left around the axis of the inferior vena cava. Conclusions: These results support the surgical data. They highlight a crucial zone and explain how dramatic lacerations between the two lobes of the liver can occur.

La prise en charge non opératoire des traumatismes abdominaux fermés est devenue un standard chez le patient hémodynamiquement stable en absence de signes péritonéaux. Ce choix thérapeutique impose la disponibilité d’une imagerie médicale diagnostique et/ou thérapeutique pour guider la prise de décisions.

Aims: Malignant transformation in extra-ovarian endometriosis is a rare but known complication. This distinct pathological entity is reviewed with a specific focus on aetiology and treatment.Methods: Studies were identified by searching the English language literature in the MEDLINE database and by an extensive review of bibliographies from articles found through that search.Findings: Up to 1% of women with endometriosis will develop endometriosis-associated neoplasm. Almost a quarter of the reported cases of malignancy in endometriosis have involved extra-ovarian tissues. In many cases, hormonal factors may play a role in its pathogenesis. Estrogen monotherapy in obese patients significantly increase the risk of malignant extra-gonadal endometric transformation. Genetic anomalies have also been reported such as loss of heterozygosity on chromosome 5q.For patients with disease confined to the site of origin, a 82-100% 5-year survival has been noted for endometrioid cell type; disseminated intraperitoneal disease, however, has a very poor associated prognosis, with a 0-12% 5-year survival overall.Conclusions: Women with endometriosis-associated cancers most likely represent a different class of patients than traditional ovarian cancer patients and may require different therapeutic options. (c) 2005 Elsevier Ltd. All rights reserved.

There is a marked trend toward nonoperative management of abdominal trauma. This has been possible thanks to the advances in imaging and interventional techniques. Computed tomography (CT), angiography, and endoscopic retrograde cholangiopancreatography (ERCP) can guide the nonoperative management of abdominal trauma.

Intraperitoneal epinephrine above 1 mg/l concentration has been shown to enhance the intratumoral accumulation and antitumor activity of intraperitoneal cisplatin in rats with advanced peritoneal carcinomatosis. The aim of this study was to determine the tolerance of intraperitoneal epinephrine combined with intraperitoneal cisplatin in patients with advanced peritoneal carcinomatosis (17 ovarian cancers, one peritoneal mesothelioma). Intraperitoneal epinephrine (1-5 mg/l) and cisplatin (50 mg/l; 100 mg total dose) were infused in 2l of saline solution over 2 h. The maximal tolerated concentration of intraperitoneal epinephrine was not reached at 5 mg/l. Cardiovascular symptoms were infrequent and not strictly related to the epinephrine concentration. Tumor responses were obtained in some patients with disease resistant to intravenous platinum compounds. This work demonstrates for the first time that intraperitoneal epinephrine at sufficient concentration enhances the cisplatin effect and can be safely infused into the peritoneal cavity of patients with peritoneal carcinomatosis. The greatest limitation was abdominal pain and limited intraperitoneal distribution of the peritoneal fluid in this closed-abdomen procedure. Anti-Cancer Drugs 17:1211-1217 (c) 2006 Lippincott Williams & Wilkins.