Target fishing reveals PfPYK-1 and PfRab6 as potential targets of an antiplasmodial 4-anilino-2-trichloromethylquinazoline hit compound.

We present investigations about the mechanism of action of a previously reported 4-anilino-2-trichloromethylquinazoline antiplasmodial hit-compound (Hit A), which did not share a common mechanism of action with established commercial antimalarials and presented a stage-specific effect on the erythrocytic cycle of P. falciparum at 8 < t < 16 h. The target of Hit A was searched by immobilising the molecule on a solid support via a linker and performing affinity chromatography on a plasmodial lysate. Several anchoring positions of the linker (6,7 and 3') and PEG-type linkers were assessed, to obtain a linked-hit molecule displaying in vitro antiplasmodial activity similar to that of unmodified Hit A. This allowed us to identify the PfPYK-1 kinase and the PfRab6 GTP-ase as potential targets of Hit A.

Preventing the contamination of hospital personnel by cytotoxic agents: evaluation and training of the para-professional healthcare workers in oncology units.

This study was specifically focused on para-professional healthcare workers (PHCWs) who handle cytotoxic drugs and contaminated wastes at the Public Teaching Hospitals of Marseille (AP-HM), France. It first aimed at evaluating the knowledge and professional practice of the PHCWs who belong to a personnel category among the less informed and protected in hospitals. In a second time, this study also proposed to raise awareness, educate and train the staff on protective measures to minimise the exposure of the PHCWs to the potential toxicity of anticancer chemotherapy agents (or metabolites) when cleaning and handling both cytotoxic drugs and wastes. Among the 11 oncology units evaluated, 82% completed an assessment survey, 63% of which were PHCWs. Out of nine oncology units assessed, 89% reported limited knowledge of the general risk and of the safe handling of cytotoxic drugs, 89% reported using vinyl gloves which are the less protective ones. Forty-four per cent of the units used wet sweeping techniques for cleaning the floors, and 11% of the units did not have specific procedures for cleaning the equipments used for collecting contaminated excreta. Protective outer apparel was not always worn and chemotherapy wastes were not managed consistently between all units. Standardized procedures and guidelines to prevent occupational exposure were not used by PHCWs. More education and training are needed to improve safety.

[Late complications from abdominal wall surgery: report of three cases of mesh migration into hollow viscus]. / Complications tardives de la chirurgie pariétale abdominale: à propos de trois cas de migration de prothèse dans un organe creux.

Laparoscopic mesh repair of ventral abdominal wall hernias is routinely performed. Mesh detachment and migration within the abdominal cavity is a late complication of this procedure. Symptoms are non-specific and imaging diagnosis is difficult to achieve because this complication is rare and overlooked.

Elective (planned) colectomy in patients with colorectal obstruction after placement of a self-expanding metallic stent as a bridge to surgery: the results of a prospective study.

INTRODUCTION: Acute malignant colorectal obstruction (CRO) can be satisfactorily dealt by the placement of a self-expanding metallic stent (SEMS). The aim of this prospective study was to evaluate the rate of elective (planned) colectomy (EPC) in patients with CRO after SEMS placement as a bridge to surgery on an intention-to-treat (ITT) basis. METHOD: From 2002 to 2007, 30 SEMS were placed as a bridge to surgery in 30 CRO patients (median age 73 +/- 12 years). The obstructing lesions were located in the right (n = 1), transverse (n = 1) or left colon (n = 24) or the upper third of the rectum (n = 4). RESULTS: The SEMS was placed successfully in 25 (83%) patients. Five patients underwent Hartmann's procedure (n = 2) or a diverting colostomy (n = 3). The SEMS was functionally operational in 23 (92%) of the 25 patients. A diverting colostomy was avoided in 23 (77%) of the 30 patients (placement failure n = 5, clinical failure n = 2). There were no complications in 17 (80%) patients. On an ITT basis, 70% of the patients (21 out of 30) underwent an EPC. CONCLUSION: On an ITT basis, SEMS placement in CRO patients enabled EPC in 70% of patients.

[Longitudinal sleeve gastrectomy as a stand-alone bariatric procedure: Results of a multicenter retrospective study]. / La gastrectomie longitudinale (sleeve gastrectomy) comme unique chirurgie bariatrique : résultats d'une étude rétrospective multicentrique de 446 patients.

INTRODUCTION: Sleeve gastrectomy as an isolated procedure is a new option in bariatric surgery. The aim of this study was to evaluate its short and medium term (2 years) results in a multicenter setting. MATERIALS: This is a retrospective study including 446 patients undergoing surgery in 14 teaching, private, and public hospitals. RESULTS: The immediate post-operative course were uneventful in 83.3% of patients. Minor complications occurred in 10.9% of patients and major complications in 5.3%. Suture line leaks occurred in 4.3% of the whole series. There was no mortality and the rate of reoperation was 2%. Overall mean weight loss after two years was 32 kg and the mean excess weight loss was 62%. Weight loss was significantly greater in non super-obese patients (p=0.0003). CONCLUSIONS: This study confirms the feasibility of sleeve gastrectomy in a multicenter setting; it is efficacious at two years as an isolated bariatric procedure for non super-obese patients. It is possible that an additional second-stage procedure may be necessary for super-obese patients.

Surgical conservative treatment of recurrent bleeding duodenal ulcer.

BACKGROUND/AIMS: Endoscopic hemostasis and proton pump inhibitors (PPI) have decreased the incidence of rebleeding and reduced the need for surgery for bleeding duodenal ulcer (BDU). The gold standard surgical treatment of BDU remains vagotomy-antrectomy. Currently, no recommendation is made on the best procedure when emergency surgery is necessary. The aim of this study was to assess the results of a systematic conservative treatment (CT): under-running bleeding gastroduodenal artery (GDA) and ulcer suture through a duodenotomy with (CT+L group) or without (CT group) GDA double ligation along with continuous intravenous PPI. METHODOLOGY: From 1995 to 2006, 22 consecutive patients (11 per group) underwent emergency surgery for BDU. Mean age was 63 +/- 18 years, ASA score 2.64 +/- 0.7. Ten patients (45%) presented collapse. Mean transfusion number was 11 +/- 9, number of therapeutic endoscopies 1.7 +/- 1, and Rockall score 6 +/- 2. RESULTS: Overall, 2 patients (9%) had rebleeding and 5 patients (22%) died. No death was reported secondary to rebleeding. In the CT+L group, 9 patients (82%) had intravenous PPI, no patient had rebleeding and 2 patients died (22%). CONCLUSIONS: Surgical CT of BDU with continuous PPI is effective, with a low rate of rebleeding. The standard use of vagotomy-antrectomy is questionable.

[Inflammatory fibroid polyp, a rare tumor of the appendix]. / Le polype fibroïde inflammatoire, une tumeur rare de l'appendice.

We report the rare occurrence of an inflammatory fibroid polyp of the appendix. The lesion was diagnosed in a 33-year-old woman presenting with abdominal pain, fever and localized tenderness in right iliac fossa on abdominal palpation. CT-scan showed an 8 cm appendiceal mass and a laparoscopic appendectomy was consequently performed. On microscopic examination, the tumor consisted of spindle cells dispersed in a loose fibromyxoid stroma containing numerous blood cells and inflammatory cells with abundant eosinophils. On immunohistochemistry, the spindle tumor cells were positive for vimentin, fascin and focally for CD34 and CD35. They were negative for smooth muscle actin, desmin, CD21, CD23, CD117 and S100 protein. Inflammatory fibroid polyp is a rare benign mesenchymal tumor of the gastrointestinal tract rarely reported in the appendix. This tumor shares some common pathologic features with the myofibroblatic inflammatory tumor but they are two different entities. The pathogenesis of this tumor remains unclear but fascin and CD35 immunoreactivity of the tumor cells suggests a probable dendritic cell origin.

Colorectal carcinoma with potentially resectable metastases: factors associated with the failure of curative schedule.

BACKGROUND: The management of patients with colorectal cancer (CRC) and synchronous liver metastases (SLM) depends on the primitive tumor, resectability of the metastatic disseminations and the patient's comorbid condition(s). Considering all patients with potentially resectable primary CRC and SLM, curative resection (R0) will be possible in some patients, although in others surgery will never be performed. The purpose of our study was to identify factors of failure of the curative schedule in these patients. METHODS: We reviewed the data of patients with CRC and SLM between January 2002 and March 2007. Two groups were defined: group R0 when complete metastatic and primary tumor resection was finally achieved after one and more surgical stages and group R2 when curative resection was not possible at the end of the schedule. Clinical, pathologic and outcome data were retrospectively analyzed as well as preoperative management of SLM (chemotherapy, radiofrequency, portal vein embolization). RESULTS: Forty-five patients were included. Curative resection (group R0) was performed in 31 patients (69%) with 48% undergoing major hepatic resection. Mortality of hepatic resection was 0% although it was 9% for primitive tumor. Portal vein embolization was performed preoperatively in eight patients and radiofrequency ablation in 13. Median follow-up was 21 months. Overall survival was 86% at one year and 39% at three years. Survival in group 1 was 97 and 57% at one and three years respectively. Disease-free survival was 87 and 40% at one and three years. Tumor recurrence was noted in 61% of resected patients. At multivariate analysis, number of hepatic metastases superior than three and complicated initial presentation of primitive tumor were found to be significant and predictors of failure of hepatic resection. CONCLUSION: Aggressive management with curative resection of SLM may enable long-term survival. More than three SLM and complicated initial presentation of primitive tumor are factors predictive of failure of the curative schedule.

[Primary hepatic lymphoma of MALT-type: a tumor that can simulate a liver metastasis]. / Le lymphome primitif hépatique de type MALT: une tumeur rare pouvant simuler une métastase hépatique.

Primary hepatic lymphomas are rare tumors. We report a case of a 72 year-old woman with a past history of colonic adenocarcinoma who presented primary hepatic lymphoma of MALT-type. The patient had been operated on 3 years before for colonic adenocarcinoma, pT3N0, revealed by a bowel obstructive syndrome. She had been treated by chemotherapy for 6 months. During the follow-up, the computed tomography-scan (CT-scan) revealed the presence of a not well-demarcated mass in segment III of the liver, measuring 4 cm in diameter. The tumor was hypodense and was not enhanced on dynamic study. The mass was already present on the initial CT-scan. Left lobectomy was performed with the diagnosis of liver metastasis of the colonic adenocarcinoma. Surgical specimen showed a tumor composed of a dense infiltrate of small lymphocytes positive for B-cell markers on immunohistochemistry. The tumor contained reactive lymphoid follicles and there were numerous lympho-epithelial biliary lesions. The patient is alive and free of disease 2 years after the diagnosis. Primary hepatic lymphoma of MALT-type is a low-grade B cell lymphoma. Twenty-five cases had been reported in the literature so far. The patients were 16 females and 9 males, mean age 63.5 years. The pathogenesis is still unclear but half of the patients had a past history of chronic inflammatory liver disease (hepatitis B or C virus infection, ascaris infection, primary biliary cirrhosis) or malignant neoplasm. This tumor has a good prognosis; it is usually limited to the liver and surgical resection cures the patient in most cases.

[The Association Française de Chirurgie (AFC) colorectal index: a reliable preoperative prognostic index in colorectal surgery]. / L'index (AFC) colorectal : un index préopératoire reproductible en chirurgie colorectale.

INTRODUCTION: Evaluation of outcome after colorectal surgery is always necessary. A new index which permits to appreciate preoperatively postoperative mortality after colorectal resection in colorectal cancer (CRC) and in diverticular disease has been published (i.e., Association Française de Chirurgie, AFC colorectal index). PATIENTS AND METHODS: From November 2002 to July 2004, in-hospital mortality was analysed on 253 patients who underwent colic resection (N = 220, 87%) or rectal resection, with anastomosis (N = 175, 70%). Mortality was analysed according to emergency resection, neurological co morbidity, lost of weight more than 10% of weight, age older than 70 years. RESULTS: Mean age of patients was 63 +/- 18 years (17-92) (45% older than 70 years), 26% of patients were ASA >or= III, 35% underwent surgery in emergency, and 12% underwent laparoscopic surgery. One hundred and fifteen (45%) patients underwent surgery for CRC and 50 (20%), for diverticular disease and 11 patients underwent surgery for ischemic colitis. Overall mortality rate was 10% (N = 26), it was 19% in emergency surgery versus 5% after elective surgery. Global morbidity was 38%, percentage of anastomotic leak was 8% (N = 14/175), reoperation was necessary in 14%. The mean length of stay was 13 +/- 8 days. Ten percent of patients necessitated unplanned readmission. After surgery for CCR or diverticular disease. -i) overall mortality was 9% - ii) among patients who had 0, 1, 2, or 3 predictive risk factors of mortality; mortality was 0% , 5% 15% and 33%. After surgery for other aetiology than CCR or diverticular disease, among patients who had 0, 1, 2, or 3 predictive risk factors of mortality; mortality was 0%, 12% 36% and 25%. CONCLUSIONS: These results showed the reproducibility of the AFC colorectal index and its potential application in all aetiologies after colorectal surgery.

[Conservative management in blunt splenic trauma]. / Atitudinea conservativa in leziunile traumatice de splina.

We reviewed for analysis the charts of two groups of adults patients with blunt splenic injuries issued from two University Hospital Centers; the group 1 (G1) of 22 patients and the group 2 (G2) of 20 patients. The results of actually therapeutic procedures concerning blunt splenic injuries and subsequently the effectiveness of non operative treatment were evaluated. Splenectomy was performed in G1 for 11 patients, instead of 19 patients in G2 (p = 0.0003), whereas, the non surgical treatment was done in 9 patients and 1 patient, respectively (p = 0.02). The mean Splenic Injury Score (SIS) was 2,95 in G1 and 3.47 in G2 (p = 0.03). The spleen was preserved in G1 for 8 patients, instead 1 patient in G2 (p = 0.04). In G1, the non operative treatment was successfully accomplished in 66% of patients. It was obtained with lack of mortality, with a lower overall morbidity and a lower length of hospital stay than in splenectomized patients, but the latter group accounted higher values of Injury Severity Scores (p < 0.05). If proper selection criteria for non operative management are used, more than a third of patients with blunt splenic injury can be treated by splenic preservation at least as safely as splenectomized patients.

[Contribution of Arantius' ligament to the control of left and middle hepatic veins]. / Apport du ligament veineux (ligament d'Arantius) lors du contrôle de la veine hépatique gauche et du tronc veineux hépatique.

Control of the left hepatic vein or of the common trunk left hepatic vein-middle hepatic vein during a hepatic resection is presumed difficult. This control is facilitated by the knowledge of the Arantius' ligament anatomy. The combined manoeuvre which associates lowering the top of segment I and section-traction of the Arantius' ligament allows exposure of the inferior aspect of the left or middle hepatic veins and allows safe dissection of these veins.

[Morbi-mortality after Hartmann procedure for peritonitis complicating sigmoid diverticulitis. A retrospective analysis of 85 cases]. / Morbimortalité de l'intervention de Hartmann pour péritonite diverticulaire. Etude rétrospective multicentrique à propos de 85 patients.

INTRODUCTION: Hartmann's procedure (HP) is a simple operation, which can be performed by all the surgeons. However, it remains criticized (high morbimortality, low rate of intestinal continuity restoration). The aim of this study was to analyse natural history of HP and intestinal continuity restoration for sigmoid diverticulitis, and to assess risk factors for mortality, morbidity and absence of intestinal continuity restoration. PATIENTS AND METHODS: In three centers, from 1992 to 2002, 85 patients underwent HP. A retrospective analysis was performed on mortality, early and late morbidity of HP and intestinal continuity restoration. RESULTS: 22% of patients (mean age, 68 years) presented comorbidity, 17% of them, an altered immunity, and 3 or 4 Hinchey score for 64%. ASA score was > or =3 in 49% of the cases. Mean AFC and Mannheim scores were 2 and 21 respectively. Mortality rate was 14% and in-hospital morbidity, 50%. Main complications were: cardiorespiratory (18%), wound abcess (14%) and stomal (6%). No rectal stump fistula was noted. Mean hospital stay was 19+/-13 days. Late morbidity rate was 29%, mainly due to stomal complications (12%) and small bowel obstruction (7%). Intestinal continuity restoration was done in 77% of the cases, followed by only 1 fistula. Mortality rate for intestinal continuity restoration was 0% and morbidity was 13%. Mean hospital stay was 10+/-3 days. Age >75 years, ASA score > or =3 and comorbidity were risk factors for morbidity and mortality and for absence of intestinal continuity restoration. CONCLUSIONS: HP is associated with a high morbidity and mortality rates. Intestinal continuity restoration rate was high in this series. HP is a simple operation in high-risk patients with advanced peritonitis. This study allows to precise natural history of HP. Knowledge of this history is crucial for choosing the best operation (between HP and anastomosis) for patient with peritonitis complications sigmoid diverticuitis.

Intrapericardial fibrinolysis: a useful treatment in the management of purulent pericarditis.

Since the introduction of antibiotics into clinical practice, purulent pericarditis has become a rare disease. The major complication of the standard management for this condition is constrictive pericarditis. We report two cases of purulent pericarditis in which intrapericardial fibrinolysis was performed in order to minimize this complication. The first case was a 38-year-old man admitted to our intensive care unit (ICU) for management of constrictive pericarditis complicating purulent pericarditis diagnosed 17 days previously. The patient was treated with four intrapericardial injections of streptokinase (250,000 IU each). Fluid drainage and cardiac output were improved. No change in clotting parameters was noted. Pericardiectomy and esophagectomy were then performed for a diagnosis of esophageal neoplasm. The postoperative course was uneventful. The second case was a 16-year-old boy admitted with loss of consciousness due to cardiac tamponade. Percutaneous pericardiocentesis drained 900 ml of cloudy fluid. Two intrapericardial injections were performed (day 1 and day 5) without any complication. Pericardial drainage was withdrawn on day 13 and the patient was discharged from ICU on the same day. Six months later, there was no evidence of constrictive pericarditis. Intrapericardial fibrinolysis appears to be safe and effective when prescribed rapidly in the course of purulent pericarditis.

The use of Dacron in the repair of hernias of the groin.

Two French surgical teams particularly interested in hernia problems detail the use of Dacron (Mersilene) mesh in the treatment of groin hernias for the reinforcement or the replacement of the fascia transversalis , as by an artificial endoabdominal fascia. The article reports the experiences and techniques of the two teams, which have used Dacron for 20 years, either by the inguinal or the preperitoneal abdominal approach. The good results reported allow the statement that, without ruling out classic techniques for simpler cases, surgical repair using prostheses offers an excellent opportunity for use and for preventing the recurrence of hernias.

Bleeding cecal typhoid ulcer. Value of emergency angiography for selective surgical hemostasis.

A case of bleeding cecal typhoid ulcer in a 22-year-old patient demonstrated by superior mesenteric arteriography is described. An attempt to stop hemorrhage using intraarterial vasopressin infusion, failed. However, arteriography proved helpful in locating the bleeding site, and in permitting conservative surgery, namely cecal ulcer suture to achieve hemostasis. On the basis of this case and a review of the literature, management of complicating hemorrhage resulting from typhoid fever is discussed, with particular reference to radiological procedures.

Current surgical treatment of post-operative eventrations.

A series of 247 post-operative eventrations (POE) is reported with a study of general features, such as: patients' sex and age, size, location and etiology of POE (serial laparotomies, parietal sepsis), classic predisposing factors. Pre-operative preparation involved the use of Goni-Moreno progressive pneumo-peritoneum in 18.5% of patients. The procedures used were: parietal suturing (25%), the same plus a dacron buttress (6%), or a large reinforcing Dacron Mesh prosthesis (67%). Early sepsis was slightly more frequent after Dacron use. The incidence of predisposing factors in this field is reported. Other complications of the use of Dacron Mesh are studied (hematomas, skin necrosis). The post-operative uncomplicated course rate is 91%. Follow-up of 77% of operated patients showed satisfactory overall results in 81% of patients treated with Dacron prosthesis and in less than 50% after parietal suturing. Aseptic recurrence factors and late sepsis factors are also studied. Finally the efficiency of POE prosthetic repair is stressed and mandatory rules for the safe of Dacron Mesh are underlined.

Pyloric stenosis: organic or functional? The need for an intraoperative test in peptic ulcer surgery.

A new method to evaluate and dilate pyloric stenosis in the presence of peptic ulcer is presented. The pylorus is explored by means of a probe (26 to 38 Ch) which is inserted orogastrically. This procedure is used in association with highly selective vagotomy (HSV). Healing of the ulcer and the pyloric stenosis was observed in 12 patients.

Prosthetic repair in the treatment of groin hernias.

Prosthetic repairs are an important development in herniology because of their excellent results. Reinforcement or replacement of the fascia transversalis is performed by interposition of a synthetic mesh between muscles and peritoneum aiming at the restoration of the tightness of the abdominal wall against the intra-abdominal pressure. All synthetic materials are not equally appropriate; Marlex mesh has been used exclusively in this report. The midline preperitoneal way allows the placement of large bilateral prostheses kept in place by intra-abdominal pressure; they need not be fixed nor associated with any suturing of the hernial hole. This is a very easy operation even in multirecurrent hernias. Because of the more disagreeable septic accidents after prosthetic repair, an important question is related to its indications, which must be selective. Randomized studies, comparing diverse techniques, are unlikely to lead to an exclusive choice because hernias are polymorphous lesions and also because of the time lag-factor and suturing must be followed up for 20 years. In socioeconomic terms, a prosthesis is the most appropriate treatment for hernias liable to recur. Nowadays it is impossible to reject the remarkable possibilities offered by prostheses in hernial surgery after the developments of the past 20 years.

[Xanthogranulomatous cholecystitis. X-ray computed tomographic study of a pseudotumoral form]. / Cholécystite xanthogranulomateuse. Etude scanographique d'une forme pseudo-tumorale.

The authors report a case of xanthogranulomatous cholecystitis in a 63-year-old woman hospitalized because of a right hypochondrium mass. Ultrasonography, computed tomography, and celiac arteriogram showed a gallbladder tumour. Surgical management allowed subtotal tumour resection. Diagnosis of xanthogranulomatous cholecystitis was established by histological examination. Twenty-two months later, patient is in good health. From this observation and a world-wide literature review (90 previously reported cases), the authors analyse the clinical, pathological, and pathophysiological features of this very unusual entity.