Cefazolin tissue concentrations with a prophylactic dose administered before sleeve gastrectomy in obese patients: a single centre study in 116 patients.

BACKGROUND: In obese patients undergoing sleeve gastrectomy, the blood and fatty-tissue concentrations of cefazolin required for adequate antibiotic prophylaxis are uncertain. METHODS: This was a single centre prospective study in obese (Group A: 40≤ BMI ≤50 kg m-2) and severely obese (Group B: 50< BMI ≤65 kg m-2) patients undergoing bariatric surgery. Blood and fatty-tissue samples were collected after a cefazolin 4 g i.v. injection. The primary aim was to compare cefazolin concentrations in subcutaneous fatty tissue with a targeted tissue concentration of 4 µg g-1 according to Staphylococcus aureus resistance breakpoint. RESULTS: One hundred and sixteen patients were included: 79 in Group A and 37 in Group B. At the beginning of the surgery, cefazolin concentration in subcutaneous fatty tissue was 12.2 (5.4) µg g-1 in Group A and 12 (6.1) µg g-1 in Group B (P=0.7). At the end, cefazolin concentrations in subcutaneous fatty tissue were 9.0 (4.9) and 7.8 (4.2) µg g-1 in Groups A and B, respectively (P=0.2). The plasma concentration of free cefazolin during surgery was higher in Group A than in Group B (P<0.0001). Fatty-tissue concentrations of 95% and 83% patients in Groups A and B, respectively, were above S. aureus resistance breakpoint. CONCLUSIONS: After a 4 g dose, the concentrations of cefazolin in fatty tissue were above the 4 µg g-1 tissue concentration target, providing adequate antibiotic tissue concentrations during bariatric surgery. As cefazolin concentration in fatty tissue is a surrogate endpoint, the results should be considered in conjunction with the results on free cefazolin concentrations in subcutaneous tissue. CLINICAL TRIAL REGISTRATION: NCT01537380.

Roux-en-Y gastric bypass, but not sleeve gastrectomy, decreases plasma PCSK9 levels in morbidly obese patients.

AIM: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a master regulator of low-density lipoprotein cholesterol (LDL-C) metabolism, acting as an endogenous inhibitor of the LDL receptor. While it has been shown that bariatric surgery differentially affects plasma LDL-C levels, little is known of its effects on plasma PCSK9 concentrations. Therefore, the present study aimed to: (i) investigate the effect of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on plasma PCSK9 concentrations; and (ii) correlate baseline or postoperative plasma PCSK9 concentration variations with anthropometric and metabolic parameters. METHODS: Fasting plasma PCSK9 levels were measured by ELISA in morbidly obese patients before and 6 months after bariatric surgery. Patients were recruited from three prospective cohorts (in Nantes and Colombes in France, and Antwerp in Belgium). RESULTS: A total of 156 patients (34SG, 122RYGB) were included. Plasma PCSK9, LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) levels were significantly reduced after RYGB (-19.6%, -16.6% and -19.5%, respectively; P<0.0001), but not after SG. In all patients, postoperative PCSK9 change was positively correlated with fasting plasma glucose (FPG; r=0.22, P=0.007), HOMA-IR (r=0.24, P=0.005), total cholesterol (r=0.17, P=0.037) and non-HDL-C (r=0.17, P=0.038) variations, but not LDL-C. In contrast to what was observed for glucose parameters (FPG, HOMA-IR), correlation between PCSK9 and non-HDL-C changes after RYGB was independent of total weight loss. CONCLUSION: RYGB, but not SG, promotes a significant reduction in plasma PCSK9 levels, and such changes in circulating PCSK9 levels after RYGB appear to be more associated with glucose improvement than with lipid homoeostasis parameters.

[Venous leiomyosarcoma mimicking deep venous thrombosis: contribution of positron emission tomography]. / Léiomyosarcome veineux mimant une thrombose veineuse profonde : intérêts de la tomographie par émission de positrons.

Leiomyosarcomas are rare malignant mesenchymal tumors. We report the case of a 55-year-old man with a lung metastasis from an iliofemoral leiomyosarcoma mimicking a deep venous thrombosis (DVT). Vascular leiomyosarcoma occurs in the wall of large vessels, and usually presents as unexplained DVT. To date, few cases of peripheral leiomyosarcomas have been described in the literature. This observation demonstrates the usefulness of Positron Emission Tomography (PET), beyond oncologic staging, in such indications as the workup of an unexplained DVT. In this report, PET prevented a misdiagnosis of DVT by showing a peculiar cockade appearance of the vessel. Compared with conventional imaging, PET can provide complementary information. The specificity of such information still needs to be assessed.

Enrichment in tumor-reactive CD8+ T-lymphocytes by positive selection from the blood and lymph nodes of patients with head and neck cancer.

To study antitumor functions of T-lymphocyte subpopulations in the blood [peripheral blood lymphocytes (PBLs)] and tumor-draining lymph nodes (LNs) of patients (n = 26) with squamous cell carcinoma of the head and neck (SCCHN), antibody-coated devices were used to positively select CD8+ or CD4+ cells. The mean percentage of CD8+ cells captured on antibody-coated flasks from PBLs was 92% and that captured from lymph node lymphocytes (LNLs) was 98%. The initial enrichment in CD4+ T-cells was comparable. CD8+ T-lymphocytes captured from PBLs proliferated as well as unseparated lymphocytes in both patients with SCCHN and normal donors, while captured CD4+ PBLs of the patients showed significantly lower expansion than those of normal volunteers. Unseparated LNLs proliferated as well as PBLs, but captured CD4+ or CD8+ LNLs failed to proliferate in the presence of interleukin 2 (100 units/ml) and phytohemagglutinin (5 micrograms/ml). The addition to captured LNL cultures of irradiated autologous or allogeneic feeder cells significantly improved expansion of CD8+ LNLs but not CD4+ LNLs. During 15-day culture of captured CD8+ PBLs or CD8+ LNLs in the presence of feeder cells, a significant (P less than 0.05) enrichment in CD8+ T-cells was maintained [94 +/- 5% (mean +/- SEM) or 99.5 +/- 0.1%, respectively, on day 15]. Capture of CD8+ LNLs and their expansion resulted in the outgrowth of CD8+CD11b- effectors which had no or little cytotoxicity against Daudi, low cytotoxicity against K562, and very high levels of cytotoxicity against 4 different natural killer cell-resistant SCCHN targets, as measured in 4-h 51Cr release assays. Such significant enrichment in SCCHN-restricted cytotoxicity could be obtained with LNLs from tumor-uninvolved LNs but not from tumor-involved LNs. Captured and cultured CD4+ LNLs had no preferential anti-SCCHN cytotoxicity. The addition of irradiated autologous tumor cells to captured CD8+ PBLs did not result in improved proliferation or antitumor function of the effector cells. Positive selection on antibody-coated flasks of CD8+ T-lymphocytes from tumor-uninvolved LNs of patients with SCCHN led to the enrichment in SCCHN-restricted but the major histocompatibility complex-unrestricted effector cells in 15-day cultures. Thus, CD8+ lymphocytes separated from tumor-draining LNs in patients with head and neck cancer contained cytolytic T-cell precursors capable of developing into effectors with preferential activity against SCCHN targets.

Evidence for local and systemic activation of immune cells by peritumoral injections of interleukin 2 in patients with advanced squamous cell carcinoma of the head and neck.

Interleukin 2 (IL2) was injected peritumorally and intranodally in 36 patients with unresectable squamous cell carcinoma of the head and neck enrolled in an Eastern Cooperative Oncology Group-sponsored phase Ib trial (EST P-Z388). Groups of 6 patients received escalating doses(200, 2 x 10(3), 2 x 10(4), 2 x 10(5), 2 x 10(6), and 4 x 10(6) units) of IL2 daily 5 times/week for 2 weeks. Tumor biopsies were obtained before and after IL2 therapy. Tumor tissue was provided for histology, and the remaining fresh tissue was divided for snap-freezing in -75 degrees C and for separation of tumor-infiltrating lymphocytes (TIL) and tumor cells. Immunophenotyping of TIL performed on cryostat sections of paired pre- and post-IL2 biopsy tissues showed increases after IL2 therapy in the number of T-cells (P = 0.005), natural killer (NK; CD16+) cells (P = 0.0001), CD25+ cells (P = 0.004), and HLA-DR+ cells (P = 0.001) accumulating in the tumor stroma. In the tumor parenchyma, NK cells (P = 0.0001) and HLA-DR+ cells (P = 0.003) were increased after IL2 therapy. The T:NK cell ratios in the tumor stroma and parenchyma were decreased after therapy, suggesting selective accumulation of NK cells. By flow cytometry, TIL recovered from post-IL2 biopsy tissues were enriched (P < 0.05) in CD3-CD56+ (NK) cells. In situ hybridization with [35S] cDNA probes for cytokines and IL2 receptors indicated that the numbers of cells expressing mRNA for IL2, tumor necrosis factor alpha, IL1-beta, gamma-interferon, transforming growth factor beta, and IL2 receptor p55 or p70 were increased in post-IL2 biopsy tissues as compared to pre-IL2 tissues. Cytolytic activity of TIL isolated from post-IL2 tissues was also increased, as determined in 4-h 51Cr release assays against K562 targets (12 +/- 3 mean lytic units/10(7) cells +/- SEM pre-IL2 versus 46 +/- 13 post-IL2; n = 16) and against autologous tumor (13 +/- 8 versus 68 +/- 26; n = 9). Fresh TIL of one clinical responder showed relatively high levels (195 lytic units) of autotumor cytotoxicity after IL2 therapy versus no activity prior to therapy. In the blood, NK and lymphokine-activated killer cell activity, and percentages of CD3-CD56+ NK cells and of activated (CD25+) T-lymphocytes were increased for all doses of IL2.(ABSTRACT TRUNCATED AT 400 WORDS)

Indicators of iron status are correlated with adiponectin expression in adipose tissue of patients with morbid obesity.

AIM: The aim of this study was to assess interactions between glucose and iron homoeostasis in the adipose tissue (AT) of obese subjects. METHODS: A total of 46 obese patients eligible for bariatric surgery were recruited into the study. Anthropometric and biochemical characteristics were assessed, and biopsies of subcutaneous (SCAT) and visceral adipose tissue (VAT) performed. The mRNA levels of genes involved in iron and glucose homoeostasis were measured in their AT and compared with a pool of control samples. RESULTS: Gene expression of hepcidin (HAMP) was significantly increased in the SCAT and VAT of obese patients, while transferrin receptor (TFRC) expression was reduced, compared with non-obese controls, suggesting a higher iron load in obese patients. Also, mRNA levels of adiponectin (ADIPOQ) were decreased in both SCAT and VAT in obese patients, and correlated negatively with hepcidin expression, while adiponectin expression was positively correlated with TFRC expression in both SCAT and VAT. Interestingly, TFRC expression in VAT correlated negatively with several metabolic parameters, such as fasting blood glucose and LDL cholesterol. CONCLUSION: Iron content appears to be increased in the SCAT and VAT of obese patients, and negatively correlated with adiponectin expression, which could be contributing to insulin resistance and the metabolic complications of obesity.

Immunologic effector cells in head and neck cancer.

Freshly isolated tumor-infiltrating lymphocytes (TIL) and lymph node lymphocytes (LNL) in patients with head and neck cancer (HNC) often have low or undetectable functional responses. Because impaired ability of these cells to produce cytokines could be responsible for their functional incompetence, spontaneous and in vitro-induced production of interleukin-2 (IL2), interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interferon gamma (IFN-gamma) by TIL, LNL from tumor-free as well as tumor-involved lymph nodes (LN), and peripheral blood lymphocytes (PBL) were measured. Although TIL or PBL of patients with HNC produced IL-1 beta and TNF-alpha spontaneously or after in vitro activation, LNL did not produce measurable levels of these cytokines. LNL also produced lower levels of IFN-gamma than PBL. In situ hybridization for cytokine mRNA performed with tumor tissues, and LN of patients with HNC showed that TIL as well as LNL localized in the immediate proximity of the tumor were activated, as evidenced by the expression of mRNA for IL2, IFN-gamma, IL-1 beta, TNF-alpha, and both alpha- and beta-chains of the IL2 receptor. In addition, many LNL located next to the tumor expressed mRNA for transforming growth factor-beta (TGF-beta). In contrast, LNL not adjacent to the tumor in involved LN, as well as those in tumor-uninvolved LN, did not express mRNA for cytokines or IL2 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Study of survival and prognostic factors in patients undergoing resection for gastric linitis plastica: a review of 86 cases.

A retrospective study was conducted in a series of 86 patients (51 men and 35 women; mean age 63.4 years) treated from 1979 to 1995 for linitis plastica of the stomach (LP). The mean interval between the first manifestations and surgery was 3.5 months. The most frequent clinical sign was epigastric pain which occurred in 80.4% of cases. Biopsies were positive in 75.6% of cases. Typical features of LP were found in only 46% of esogastric barium enemas and 11.8% of upper gastrofiberscopic examinations. Seventy-four patients had surgical excision (51 total and 23 partial gastrectomies). There were 6 (7%) postoperative deaths and 10 (11.6%) surgical complications. Node involvement was found in 54 (72.9%) patients. Overall actuarial survival (n = 86) was 50% at 12 months, 40% at 18 months and 7.5% at 84 months. Survival did not depend on the delay in diagnosis, histological analysis of the extremities of the excised piece, associated tissue differentiation, node involvement or the type of surgical excision. The prognosis differed according to tumor height (P<0.01) and involvement of the deep stomach wall (P<0.001). No independent prognostic factor was found in multivariate analysis. Surgery remains the sole possibility for curative therapy in these patients.

[Leiomyosarcomas of the rectum. Amputation of the rectum or local resection?]. / Les léiomyosarcomes du rectum. Amputation du rectum ou exérèse locale?

Two cases of high grade leiomyosarcoma of the rectum treated by local excision are reported. The first patient presented a local recurrence associated with liver and pulmonary metastases and eventually died, respectively 11 and 22 months after resection. The second patient's tumor recurred 3 months after excision and was treated with pelvic exenteration and CYVADIC regimen as chemotherapy and died 3 years later from local recurrence. A review of the literature indicates that local surgical excision in comparison to a more radical surgical approach, such as abdominoperineal resection, is as effective in improving survival. Lesions less than 2.5 cm in diameter, confined to the bowel can be treated by local surgical excision. To date no adjuvant therapy is effective in terms of survival or local control.

[Stomach leiomyoblastoma: contribution of cytology. Apropos of a case]. / Léiomyoblastome gastrique: apport de la cytologie. A propos d'un cas.

The authors report the case of a 51-year-old man with gastric leiomyoblastoma, presenting with a history of gastrointestinal bleeding and hemoperitoneum. CAT scan showed a mass measuring 10 x 10 cm arising from the stomach. At laparotomy the mass extended into the gastrosplenic omentum. A splenopancreatectomy was performed and the mass was excised for biopsy. The cytologic findings suggested a mesenchymal tumor; histology demonstrated the diagnosis of leiomyoblastoma. The postoperative course was uneventful. In the literature there is no evidence that intraperitoneal bledding from these tumors worsens survival. The cytopathologic features of leiomyoblastoma are discussed.

[Accessory cystic duct discovered by intraoperative cholangiography during cholecystectomy]. / Canal cystique accessoire découvert par cholangiographie peropératoire au cours d'une cholécystectomie.

The study aim was to report a rare biliary variation detected with an intraoperative cholangiography during a laparoscopic cholecystectomy. After the ligation of the cystic duct, the gallbladder was opacified via an accessory cystic duct flowing into a branch of the right hepatic duct. This accessory cystic duct was clipped and the postoperative course was uneventful.

[Intraluminal polyp of the common bile duct corresponding to a metastasis of cancer of the kidney]. / Polype intraluminal de la voie biliaire principale correspondant à une métastase de cancer du rein.

The authors report the second case to date of metastatic carcinoma of the common bile-duct from renal cell cancer presenting as an intraluminal polypoid mass. Obstructive jaundice developed in a 55-year old woman 14 years after nephrectomy for renal cell carcinoma. The diagnosis of polypoid tumor of the common bile-duct was established by sonography, endoscopic retrograde cholangiopancreatography and CT-scan. Palliative resection was performed. Postoperative histological examination revealed the resected tumor to be identical to the clear cell type of renal cell carcinoma. The postoperative course was marked by the development of distant metastases 6 months later. Diagnosis and therapeutic features of metastatic malignant biliary obstruction are discussed.

[Signet-ring cell adenocarcinoma involving the bladder and the rectum. Apropos of two cases]. / Adénocarcinome à cellules isolées envahissant la vessie et le rectum. Rapport de deux cas.

Two cases of primary signet-ring cell carcinoma involving the urinary bladder, with invasion of the rectum, are presented. Pelvic exenterations were performed, followed by a rapidly fatal outcome (6 and 7.5 months). These cases of signet-ring cell carcinoma of the bladder were reviewed with 33 previously reported cases in the literature. The clinical characteristics, histologic findings, pathogenesis, and effectiveness of aggressive treatment of this rare bladder malignancy are discussed.

[An unusual secondary localization of bronchial adenocarcinoma]. / Une localisation secondaire inhabituelle d'un adénocarcinome bronchique.

The authors report a rare case of metastatic carcinoma of the large bowel, secondary to a primary bronchogenic adenocarcinoma. Abdominal pain developed in a 44-year old man 5 months after lobectomy for lung adenocarcinoma. The diagnosis of a large caecal extraluminal mass was established by means of sonography, scanner and laparoscopy. Palliative resection (brain metastases) was performed. Postoperative histological examination revealed the resected tumor to be identical to the lung adenocarcinoma. The patient eventually died 4 months after resection (complication of intracranial hypertension). Diagnosis and therapeutic features of metastatic extra-thoracic lung carcinoma are discussed.

[Complicated colonic diverticulosis. Results of surgical treatment between 1981 and 1998 in 370 patients]. / Les diverticuloses coliques compliquées. Résultats du traitement chirurgical entre 1981 et 1998 chez 370 patients.

AIM OF THE STUDY: The aim of this retrospective study was to analyze case reports of all the patients with complicated diverticular disease of the colon admitted in the same surgical center during an 18-year period and to report the postoperative results in patients operated on in emergency and in patients operated on electively. PATIENTS AND METHOD: From 1981 to 1998, 501 patients were admitted for complicated diverticular disease. There were 233 men and 268 women. Mean age was 66 years (range: 27-96). One hundred and thirty-one patients were only treated medically and 370 patients were operated on, either as an emergency (n = 211) or electively (n = 159). The complicated diverticular disease was located on the left colon in 362 cases and in the right colon in 8 cases. RESULTS: In the emergency group, 103 patients were operated on for pelvic (n = 24) and generalized purulent (n = 67) or stercoral (n = 12) peritonitis, mainly with Hartmann procedure (n = 80) with 14 postoperative deaths; 67 were operated on for pericolic abscess with 6 deaths, 19 for colonic obstruction with two deaths and 22 for profuse hemorrhage with 4 deaths. The overall postoperative mortality rate was 12.3%, and morbidity rate 38.7%. Intestinal continuity was restored in 74% and eventrations were present in 10%. In the elective group, there were two postoperative deaths in patients with a colic fistula (n = 30), no mortality and a 10.8% morbidity rate in the other patients (n = 129). CONCLUSION: This series of an 18-year duration emphasizes the severity of surgery for acute complications in diverticular disease of the colon and the advantages of elective surgery. Large progress in the management of peritonitis and pericolic abscesses has made possible the improvement of their prognosis.

[Severe pancreaticoduodenal trauma: review of a series of 30 patients]. / Traumatismes fermés duodéno-pancréatiques sévères. A propos d'une série de 30 patients.

Retrospective study of a series of 30 patients (mean age: 25.5 years), including 8 children with severe duodenopancreatic trauma, treated over a period of 15 years. This series consisted of 14 cases of duodenal perforation, 3 cases of duodenal haematoma, 11 cases of isolated pancreatic lesions (including 5 isthmic ruptures) and 2 cases of associated duodenal and pancreatic lesions. Injuries were due to road accidents in 60% of cases. Eight patients were considered to have multiple injuries. Twelve patients required emergency surgery. Eighteen were observed in a surgical unit. Two duodenal haematomas were operated. Duodenal perforations were operated urgently in 8 cases and electively in 6 cases. The surgical procedure consisted of simple suture (n = 3), suture combined with diversion (n = 7), or resection-anastomosis (n = 4). Five patients with pancreatic contusion were operated, in a context of acute pancreatitis in four cases and for associated lesions in one case. Isthmic ruptures were treated by left pancreatic resection. This was a rare lesion (1.8 to 9% of organ lesions). Duodenal haematomas justify first-line medical treatment, while duodenal perforations must be operated. The presence of a lesion of the pancreatic duct frequently justifies pancreatic resection.

[Techniques, indications and early results of splenic preservation during left pancreatectomy]. / Techniques, indications et résultats précoces de la conservation splénique dans les exérèses pancréatiques gauches.

STUDY AIM: Splenic preservation is rarely performed during left pancreatectomy. We compared retrospectively the early results of left pancreatectomy with and without splenic preservation to define the place of this procedure. PATIENTS AND METHODS: From 1979 to 1997, among 54 left pancreatectomies for another indication than adenocarcinoma, 13 were performed with and 41 without splenic preservation. The technique used for splenic preservation was prograde dissection of the left pancreas with (n = 4) and without (n = 9) preservation of both splenic artery and vein. The preoperative characteristics of the patients, peroperative data, postoperative morbidity and length of stay were compared. RESULTS: Mean operative time was longer with splenic preservation (262 +/- 67 min versus 215.6 +/- 59 min, p < 0.05), particularly in case of splenic vessels preservation (295 +/- 38 min, p < 0.02) whereas no difference was noted with splenic vessels ligation (240 +/- 76 min, p > 0.05). No mortality occurred. Prevalence of preoperative or postoperative haemorrhage, morbidity, or length of stay (intensive care unit and whole hospitalisation) did not differ with or without splenic preservation. Five patients developed pancreatic fistula without influence of splenic preservation: 1/13 (7.7%) versus 4/41 (9.7%); conversely, surgery following acute pancreatitis was associated with an higher risk of pancreatic fistula: 3/5 versus 2/49 (p < 0.005). No splenic necrosis occurred after splenic preservation. CONCLUSION: During left pancreatectomy, splenic preservation increases the operative duration (only in case of preservation of splenic vessels) but does not increase morbidity. This technique should be used whenever possible to allow long term immunological benefits of splenic preservation.

[Meckel's diverticulum Diagnosed by CT-Enteroclysis]. / Diagnostic d'un diverticule de Meckel hémorragique par entéroscanner.

The authors report the case of a 24 year old woman presenting with acute lower GI hemorrhage caused by a Meckel's diverticulum. Diagnosis was made by CT-enteroclysis and confirmed at surgery. This new imaging technique will be briefly described and compared to the other more traditional small bowel imaging techniques. The authors will then present the CT-enteroclysis imaging features of this congenital anomaly.

[Transanal excision of villous tumors. Value of the Endo-GIA 30 Multifire clamp]. / Exérèse transanale des tumeurs villeuses. Intérêt de la pince Endo-GIA 30 Multifire.

The authors describe a new surgical procedure applied to the treatment of villous adenoma of the rectum. The mechanical device called Endo-GIA 30 Multifire (Merlin Médical, F69672 Bron), an automatic suture clamp regularly used in laparoscopic surgery, facilitates complete excision of villous adenomas if the tumour is located less than 10 cm from the anal margin.

[Postoperative hypoglycemia after excision of pheochromocytoma. A case]. / Hypoglycémie postopératoire après ablation d'un phéochromocytome. Une observation.

A case of hypoglycaemia consecutive to excision of a bilateral phaeochromocytoma in a 33-year old patient with Sipple's syndrome is reported. The severity of the hypoglycaemia (1.3 mmol/l) accounted for the brain lesions which ultimately resulted in the patient's death. Eight cases of hypoglycaemia occurring in similar circumstances have been published. The condition is due to the massive release of insulin during the hours that follow removal of the tumour. This results in the persistence of the peri-operative hyperglycaemic stimulation and in the suppression of the previous inhibition of insulin secretion due to alpha-adrenergic stimulation of catecholamines in the beta-cells of Langerhans' islets.