Learning curve in open inguinal hernia repair: a quality improvement multicentre study about Lichtenstein technique.

PURPOSE: Inguinal hernia repair is one of the most performed procedure all over the world with more than 20 million procedures performed each year. Due to the lack of data in literature about the learning curve of the Lichtenstein procedure, we decided to reproduce a research on learning curves with the same methodology proposed in our previous study about laparoscopic hernia repair. The aim of this multicentre study was to analyse how many cases are required to achieve the learning curve for a Lichtenstein procedure. METHODS: We performed a retrospective analysis of the first 100 Lichtenstein procedures performed by 4 trainees from three different institutions and compared them with the same number of procedures performed by 3 senior surgeons from the same institutions. The data about the achieving of learning curve were evaluated with CUSUM and KPSS test. RESULTS: No differences about biometrical features were found between the seven groups of patients. CUSUM analysis showed that the trainees achieve the learning curve after 37-42 procedures, reaching an operative time similar to that one of the senior surgeons. CONCLUSIONS: In conclusion, we have shown that the number of procedures required to reach the learning curve from the beginning of surgical residency is around 40 hernia repairs. This number, produced in a controlled environment under strict supervision, could be the minimum requirement to start the procedure of accreditation and specialization in hernia surgery and is higher and steeper than previously reported.

Pooled data analysis of primary ventral (PVH) and incisional hernia (IH) repair is no more acceptable: results of a systematic review and metanalysis of current literature.

PURPOSE: Primary (PVHs) and incisional (IHs) ventral hernias represent a common indication for surgery. Nevertheless, most of the papers presented in literature analyze both types of defect together, thus potentially introducing a bias in the results of interpretation. The purpose of this systematic review and meta-analysis is to highlight the differences between these two entities. METHODS: Methods MEDLINE, Scopus, and Web of Science databases were reviewed to identify studies evaluating the outcomes of both open and laparoscopic repair with mesh of PVHs vs IHs. Search was restricted to English language literature. Risk of bias was assessed with MINORS score. Primary outcome was recurrence, and secondary outcomes were baseline characteristics and intraoperative and postoperative data. Fixed effects model was used unless significant heterogeneity, assessed with the Higgins I square (I2), was encountered. RESULTS: The search resulted in 783 hits, after screening; 11 retrospective trials were selected including 38,727 patients. Mean MINORS of included trials was 15.2 (range 5-21). The estimated pooled proportion difference for recurrence was - 0.09 (- 0.11; - 0.07) between the two groups in favor of the PVH group. On metanalysis, PVHs were smaller in area and diameters, affected younger and less comorbid patients, and were more frequently singular; the operative time and length of stay was quicker. Other complications did not differ significantly. CONCLUSION: Our paper supports the hypothesis that PVH and IH are different conditions with the latter being more challenging to treat. Accordingly, EHS classifications should be adopted systematically as well as pooling data analysis should be no longer performed in clinical trials.

Beneficial effects of fibrin glue (Quixil) versus Lichtenstein conventional technique in inguinal hernia repair: a randomized clinical trial.

INTRODUCTION: In inguinal hernia repair, many complications are due to mesh fixation technique. Therefore, new types of atraumatic methods of fixation have been proposed. In this article, we present the results of a prospective multicentric parallel randomized controlled trial aiming to compare two mesh fixation techniques: fibrin sealant (QUIXIL(®), Omrix Biopharmaceuticals S.A., Belgium) and Lichtenstein technique. METHOD: Adult patients with primary uncomplicated inguinal hernia were randomized in two groups: fibrin sealant group (FSG) and Lichtenstein group (LTG). The two groups underwent a follow-up of 15 months. Operative time is the primary outcome. Intraoperative and postoperative outcomes were analyzed. Moreover, a differential cost analysis was performed. Patients and evaluators (with exception of the surgeon who treated the patient) were blinded. RESULTS: A total of 102 patients, 50 in FSG and 52 in LTG, were enrolled from January 2009 to June 2010, and two patients were lost to follow-up at the twelfth month. No significant differences in baseline and clinical characteristics were observed in the two groups. Operative time was longer in LTG (median/ interquartile range: 35 min/30-42.5 min vs. 31 min/28-35 min; effect size: 0.65/95% CI 0.50-0.91; p < 0.05). No differences in intraoperative complications were observed. No significant differences were observed in early complication rate (RR = 0.62; p > 0.05). Numbness rate was lower in the FSG at 1 week (RR = 0.43; p < 0.01) and at 1 month (RR = 0.17; p < 0.05). No significant differences were observed after 6 months. Postoperative pain was lower in the FSG at 1 week (0/0-1 vs. 1/0-2; p < 0.05) and at 1 month (0/0-0 vs. 0/0-1; p < 0.05). Pain disappeared in all patients after 6 months. Analgesic assumption rate was lower in the FSG (RR = 0.42; p < 0.05). Twenty per cent of FSG and 9.62% of LTG patients were discharged within 12 h; 78% of FSG and 90.38% of LTG patients were discharged within 24 h. The only one recurrence we observed was in FSG group. About costs, although fibrin sealant needed for one mesh fixation is about 10 times more costly than the needed sutures, the total costs of the two procedures did not change significantly. This was mainly due to reduction in operative time. CONCLUSIONS: The use of fibrin sealant determined a significant reduction in short-term numbness rate and postoperative pain. There was no relevant difference in total costs per patient between the two procedures.

Single access laparoscopic left hemicolectomy with or without inferior mesenteric artery preservation: our preliminary experience.

AIM: We report our preliminary experience in single access laparoscopic left hemicolectomy (SALLH) with or without inferior mesenteric artery preservation, showing the results of a selected group of patients. METHODS: This retrospective case series enclosed all patients operated between October 2009 and June 2012 of a left hemicolectomy with single laparoscopic access for benign and malignant diseases. The mean follow-up was 18 months. Intraoperative and postoperative results were recorded. RESULTS: This retrospective case series enclosed 24 patients. Mean operative time was 157.8 min. The mean final skin incision length was 3.65 cm. All operations were completed by a single access laparoscopic approach. There were no conversion or intraoperative mortality. There were no required any intraoperative blood transfusion. Only three cases of postoperative complication were registered. The mean flatus canalization was two days. The mean discharge time was seven days. At a mean 18-month follow-up there were no incisional hernia or deaths. CONCLUSION: As best of our knowledge, we report one of the largest experience gained in Italy about SALLH. We think that although SALC could be safe and feasible, it cannot be considered as a "new standard" procedure used by anyone. In contrast we retain that it is mandatory that SALC continued to be evaluated into larger multicentric RCT.

Cromoblastomicosis: a propósito de un caso / Chromoblastomycosis: case report

Varón, oriundo de Paraguay con lesiones nodulares, tumorales, verrugosas y cicatrizales en miembro inferior izquierdo de más de 20 años de evolución. Con la presunción diagnóstica de micosis profunda, los exámenes complementarios realizados conducen al diagnóstico final de cromoblastomicosis por Fonsecae pedrosoi. Aún siendo descritos los tratamientos combinados como primera línea, en este caso se describe una excelente respuesta a la monoterapia con itraconazol (AU)

A Paraguayan male patient, with nodular, tumor, warty and scarring lesions in the left leg that had evolved over a period of 20 years is reported. With the inicial diagnosis of a deep fungal infection, complementary testing confirmed the diagnosis of chromoblastomycos is caused by Fonsecae pedrosoi. While combination therapy is still being described as first line treatment, in this case we observed an excellent response to itraconazole as monotherapy (AU)

Eating disorders and diabetic ketoacidosis in a pregnant woman with type 1 diabetes: a case report.

OBJECTIVE: To describe a case of diabetic ketoacidosis (DKA) in a pregnant woman with type 1 diabetes (T1DM) and disordered eating behaviour treated with a continuous subcutaneous insulin infusion, and to discuss some aspects of the monitoring and management of DKA in pregnancy and whether a pump is the safest therapeutic choice in the presence of some eating disorders. CASE REPORT: This 26-year-old Caucasian woman affected by T1DM was hospitalised during the last weeks of her fourth pregnancy because of DKA due to disordered eating. She was treated with a fluid infusion, intravenous insulin, and her electrolyte imbalance was carefully corrected. An elective cesarean section was performed after the correction of DKA in the 34th week (+6 days) of gestation. CONCLUSIONS: We suggest that pregnancy in T1DM women with eating disorders may not be rare. The prevention, early recognition and aggressive management of DKA can minimise the possible complications, and is mandatory for the safety of the fetus and mother.

Thymoma-associated immunodeficiency: a syndrome characterized by severe alterations in NK, T and B-cells and progressive increase in naïve CD8+ T Cells.

Thymomas are rare tumours that sustain T-lymphopoiesis and trigger a variety of autoimmune diseases and immunodeficiencies, including a fatal hypogammaglobulinemia, namely Goods Syndrome (GS). Due to its rarity, GS has been poorly investigated and immunological features, as well as pathogenetic mechanisms underlying this syndrome, are unclear. We studied 30 thymoma patients by performing an immunological assessment, including immunophenotype and analysis of T cell repertoire (TCR). Development of GS was characterized by a progressive decrease in B, CD4 T and NK lymphocytes. These alterations paired with accumulation of CD8+CD45RA+ T cells that showed a polyclonal repertoire without expansions of specific clonotypes. GS is defined as hypogammaglobulinemia with thymoma. Here, we show for the first time that this syndrome is characterized by a severe loss of CD4+, NK and B cells. Furthermore, the accumulation of CD8+CD45RA+ T lymphocytes parallels these changes; this accumulation may have a role in determining the disease and can be used to monitor clinical stages of immunodeficiency in thymoma.

Preliminary results of phase II study of capecitabine and gemcitabine (CAP-GEM) in patients with metastatic pretreated thymic epithelial tumors (TETs).

BACKGROUND: No previous prospective trials have been reported with capecitabine and gemcitabine (CAP-GEM) in patients with metastatic thymic epithelial tumors (TETs). We conducted a multicenter study to determine the activity and tolerability of this regimen in pretreated TETs. PATIENTS AND METHODS: A total of 15 patients were enrolled in the first stage of phase II study. All patients received CAP-GEM every 3 weeks. The primary end point was objective response rate (RR); secondary end points were toxicity, progression-free survival (PFS) and overall survival. RESULTS: Complete responses (CR) and partial responses were observed in three (20%) and three (20%) patients for a 40% RR, respectively. Grade 1-2 neutropenia, anemia and thrombocytopenia were the most common side-effects, noted in seven (46.7%), five (33.3%) and five (33.3%) patients, respectively. The most common grade 3 toxicity was neutropenia in three patients (20%). Median PFS was 11 months (95% confidence interval 4-17). The 1- and 2-year survival rates were 80% and 67%, respectively. CONCLUSION: We have decided to publish the preliminary results because this regimen was more active than that expected. Although our results are preliminary, CAP-GEM shows activity and safety in pretreated TETs. Furthermore, multicenter trials, also in first-line setting, are necessary to confirm our results.

CD8+ T-cell alveolitis in familial pulmonary alveolar microlithiasis.

Pulmonary alveolar microlithiasis (PAM) is a rare diffuse lung disease characterised by the accumulation of calcium phosphate microliths within the alveoli. The causative mechanism of PAM has only recently been discovered, and involves a gene mutation of sodium phosphate co-transporter, which is expressed by alveolar epithelial cells. This mutation may have variable consequences on the clinical phenotype. However, pulmonary cell immune phenotyping in familial PAM has not previously been assessed. In the present article, the analysis of bronchoalveolar lavage fluid of two siblings with PAM diagnosis revealed a pattern of lymphocytic alveolitis with accumulation of CD8+ T-cells. The clonal complexity of this lymphocyte's population was assayed by spectratyping, which showed an oligoclonal accumulation of T-cells with a restricted variable beta T-cell receptor (TCR) gene usage. TCR analysis in peripheral blood lymphocytes revealed no abnormal patterns of T-lymphocytes. In the pulmonary alveolar microlithiasis familial cases reported, CD8-mediated maladaptive immune response may have taken place in the bronchoalveolar compartment. The relationship between this immune dysregulation and genetic background in pulmonary alveolar microlithiasis warrants further investigation.

Measuring, modelling and testing ozone exposure, flux and effects on vegetation in southern European conditions--what does not work? A review from Italy.

Ozone (O3) exposure at Italian background sites exceeds UN/ECE concentration-based critical levels (CLe(c)), if expressed in terms of AOT40. Yet the occurrence of adverse effects of O3 on forests and crops is controversial. Possible reasons include (i) ability of response indicators to provide an unbiased estimate of O3 effects, (ii) setting of current CLe(c) in terms of cut-off value and accumulation level, (iii) response functions adopted to infer a critical level, (iv) environmental limitation to O3 uptake and (v) inherent characteristics of Mediterranean vegetation. In particular, the two latter points suggest that critical levels based on accumulated stomatal flux (CLe(f)) can be a better predictor of O3 risk than CLe(c). While this concept is largely acknowledged, a number of factors may limit its applicability for routine monitoring. This paper reviews levels, uptake and vegetation response to O3 in Italy over recent years to discuss value, uncertainty and feasibility of different approaches to risk assessment.

Response to ambient ozone of two white clover (Trifolium repens L.cv. "Regal") clones, one resistant and one sensitive, grown in a Mediterranean environment.

Two clones of white clover (Trifolium repens L.) differing in ozone tolerance were grown in southern Italy during 1997 and 1998 to study the effects of ambient ozone exposure on yield, leaf morphology and water use. Ambient ozone levels were high in both years with values exceeding the threshold for leaf injury reported in the literature. In both years ozone injury was observed on the sensitive clone (NC-S) but not on the resistant one (NC-R), and leaf and stolon dry matter production was significantly lower in NC-S than in NC-R. However, it cannot be excluded that other factors, such as high temperature, interacted with the effect of ozone on biomass production. The clones differed in morphological characteristics. Lower total leaf area in NC-S plants was due to a smaller number of leaves per plant, but the average area per leaf was higher in NC-S. Specific leaf weight and net assimilation rate were higher in the more productive clone (NC-R). Cumulative plant water use was higher in NC-R in each growth period because of the larger leaf area; by contrast, water use per unit leaf area was higher in NC-S, indicating higher leaf conductance to water vapour. The results suggest that ozone significantly reduces the yield of sensitive white clover plants under well-watered conditions, and that the difference in ozone tolerance between clover clones is related to differences in leaf morphology and water use.

Comparative study of the survival rate of frozen-thawed embryos with perforated zonae from microsurgical fertilization and frozen-thawed embryos with intact zonae.

OBJECTIVE: To compare the survival rate of frozen-thawed embryos with perforated zonae from microsurgical fertilization (subzonal insemination) (SUZI) with that of embryos with intact zonae. DESIGN: Thirty-eight embryos resulting from microsurgical fertilization by SUZI were cryopreserved in 16 patient cycles. Within the same period, 140 zonae-intact embryos from 46 patient cycles were cryopreserved. The survival rate of the SUZI embryos was compared with the zonae-intact embryos after thawing. Clinical pregnancies were compared after the transfer of the thawed embryos. RESULTS: The total survival rates were 94.7% and 89.3% for thawed SUZI embryos and zonae-intact embryos, respectively. Within each type of embryo, total survival rates were similar irrespective of the age of the embryos at freezing. The blastomere loss per thawed embryo was the same for zonae-intact and SUZI embryos. One clinical pregnancy was obtained in patients who received thawed SUZI embryos and nine in patients who received embryos with intact zonae. CONCLUSIONS: It is concluded that SUZI embryos can be cryopreserved and thawed with the same degree of confidence as zonae-intact embryos. The low implantation rate of thawed SUZI embryos requires confirmation in a larger clinical series.

A simplified alternative to the AOAC official method for cholesterol in multicomponent foods.

An AOAC official method for quantitating cholesterol in multicomponent foods, which was first published in the 13th edition of the Official Methods of Analysis, is rarely used. The method includes so many operations and manipulations--all described in excruciating detail--that most laboratories shun it altogether. Intent on finding an alternative, laboratories have developed their own methods for specific foods. As a result, new methods have proliferated, but still no practical method has been developed for the broader categories of multicomponent foods. The aim of AOAC, which is to promote greater accuracy and uniformity of analytical results primarily through collaborative testing, has not been well served under these circumstances. A different approach guided the work reported in the present paper. This approach was directed toward updating and dramatically simplifying the existing AOAC official method. The method's chloroform-methanol-water mixed-solvent extraction is preserved; however, all the remaining steps have been streamlined, updated, or eliminated by using newer technology. Cholesterol is quantitated with highly specific capillary gas-liquid chromatography using the internal standardization technique. The lipid extract is prepared for the chromatography step by a brief saponification carried out in a culture tube. The resulting method has been validated by using Standard Reference Materials and the standard addition method. Because a simplified method is now available for quantitating cholesterol in the lipid extracts, the expectation is that more attention can be given to the development of improved and efficient extraction methods. This step remains as the central difficulty in any number of methods of analysis for lipid analytes.

Leucine kinetics and the effects of hyperinsulinemia in patients with Cushing's syndrome.

As muscle wasting and resistance to insulin-mediated glucose utilization are features of Cushing's syndrome (CS), we examined glucose and amino acid metabolism in six patients with CS and six normal subjects before and during euglycemic hyperinsulinemic clamp studies (plasma insulin concentrations, approximately 0.36, approximately 0.65, and approximately 10.05 mmol/L). The two groups had similar body mass index values. In the postabsorptive state, leucine and alpha-ketoisocaproate (KIC) rates of appearance (Ra), KIC oxidation, and nonoxidized leucine-carbon flux, an index of leucine entering protein (Leu----P), were comparable in CS patients [2.38 +/- 0.14 (+/- SE), 0.22 +/- 0.04, and 2.16 +/- 0.12 mumol/kg.min) and in normal subjects (2.73 +/- 0.25, 0.17 +/- 0.02, and 2.59 +/- 0.22 mumol/kg.min). During the euglycemic clamp studies the leucine and KIC Ra values, KIC oxidation, and Leu----P decreased to a similar extent in both groups. In contrast, insulin-mediated glucose utilization was impaired in the CS patients at each clamp step (P less than 0.05). In summary, postabsorptive whole body leucine metabolism is normal in patients with CS and is normally suppressed by hyperinsulinemia, indicating a dissociation in insulin sensitivity with respect to glucose and amino acid metabolism.

Corticotropin releasing hormone stimulation test: diagnostic aspects in Cushing's syndrome.

The effect of exogenous ovine Corticotropin-Releasing Hormone (oCRH) on plasma ACTH and cortisol levels was investigated in 10 normal volunteers and in 37 patients with Cushing's syndrome (26 with pituitary-dependent disease, 5 with an adrenal adenoma, 2 with an adrenal carcinoma and 4 with bilateral nodular hyperplasia). In all normal subjects and in patients with Cushing's disease, oCRH 100 micrograms as a bolus produced an increase in both plasma ACTH and cortisol. The peak of ACTH occurred after 15-30 min, while plasma cortisol showed highest levels between 30 and 60 min after oCRH administration. The hormonal response in Cushing's disease showed great variability with a clear hyperresponsiveness at least in 6 out of 26 patients with Cushing's disease. A slight and delayed response occurred in 3 cases of bilateral nodular adrenal hyperplasia, while a fourth case showed hyperresponsiveness similar to that found in pituitary-dependent Cushing's disease. No response was observed in patients with an adrenal tumor. Eleven patients with Cushing's disease were tested before and 1 month after pituitary microadenomectomy. After surgery basal cortisol levels were reduced in 10 and became unresponsive or less responsive to oCRH. ACTH patterns were variable with a normal response only in few cases. Although this test seems of limited value in the diagnosis of hypercortisolism, it is a useful tool to differentiate some types of Cushing's syndrome (adrenal tumor from pituitary-dependent Cushing's disease). Variable patterns of response in cases with bilateral nodular adrenal hyperplasia limit the usefulness of this test in recognizing this rare form of hypercortisolism.

Evidence for ectopic ACTH production years after bilateral adrenalectomy for Cushing's syndrome: in vivo and in vitro studies.

Three patients presented with hyperpigmentation and high plasma levels of ACTH 4-5 years after bilateral adrenalectomy for Cushing's "disease". X-rays and ct-scan of the lungs showed a small pulmonary mass in all. ACTH levels (1100-2000 pg/ml) were not suppressible by high doses hydrocortisone. A carcinoid tumor was removed in two cases and a chemodectoma in the third. Evidence for ACTH secretion by these tumors was provided by both decrease of ACTH levels after surgery and/or in vitro studies. Both carcinoid cultures showed a basal ACTH production, which was clearly increased by LVP (10(-7) M) and CRF (10(-7) M). Our findings in vitro studies suggest the presence of specific receptor sites for physiological stimuli (LVP and CRF) in tumor cell membranes.

Prolonged treatment of Cushing's disease by ketoconazole.

Ketoconazole, used in clinical practice as an antifungal medication, recently was found to be a potent inhibitor of gonadal and adrenal steroidogenesis in vitro and in vivo. The effects of prolonged treatment with this agent in Cushing's disease were investigated in five patients who had recurrent severe hypercortisolism after selective transsphenoidal surgery. The patients received the drug for at least 2 months. Urinary cortisol markedly decreased in all patients immediately after the beginning of treatment with ketoconazole (800 mg/day) and remained within low normal levels when the daily dose was lowered to 600 mg/day. Plasma cortisol also decreased. After 4-6 weeks of treatment, the clinical features of the disease regressed in all patients without signs of toxicity. These findings indicate that ketoconazole may be a valuable drug for the management of patients with Cushing's disease because of its ability to correct hypercortisolism quickly.

Effect of short and long-term administration of lisuride in Cushing's disease.

To define the role of dopaminergic drugs on pituitary ACTH secretion, we studied the effect of a dopamine-agonist, lisuride, on a group of 9 patients with pituitary dependent Cushing's syndrome. Lisuride (0.4-0.6 mg/day) was administered for two days: in only two out of eight cases the ACTH levels, sampled every 30 min for 6 h (08:00-14:00 h), showed some reduction when compared with the control day. Two of the nonresponders (R.P.; B.F.) and one untested patient (L.E.) were then treated chronically with a similar amount of lisuride per day for 20 days (L.E.) and for 4 months (B.F.; R.P.). One patient (L.E.) showed a clear decrease in urinary free cortisol without clinical improvement; while in the other two cases, followed for a longer period of time, a clinical improvement was observed together with a decrease of the hormonal parameters. In conclusion, lisuride may occasionally reduce ACTH secretion in patients with pituitary dependent Cushing's syndrome, but the acute test fails to identify the patients who would benefit from this treatment.