Operational classification of cutaneous squamous cell carcinomas based on unsupervised clustering of real cases by experts.

BACKGROUND: There is currently no staging system for cutaneous squamous cell carcinoma (cSCC) that is adapted to decision-making and universally used. Experts have unconscious ability to simplify the heterogeneity of clinical situations into a few relevant groups to drive their therapeutic decisions. Therefore, we have used unsupervised clustering of real cases by experts to generate an operational classification of cSCCs, an approach that was successful for basal cell carcinomas. OBJECTIVE: To generate a consensual and operational classification of cSCCs. METHOD: Unsupervised independent clustering of 248 cases of cSCCs considered difficult-to-treat. Eighteen international experts from different specialties classified these cases into what they considered homogeneous clusters useful for management, each with freedom regarding clustering criteria. Convergences and divergences between clustering were analysed using a similarity matrix, the K-mean approach and the average silhouette method. Mathematical modelling was used to look for the best consensual clustering. The operability of the derived classification was validated on 23 new practitioners. RESULTS: Despite the high heterogeneity of the clinical cases, a mathematical consensus was observed. It was best represented by a partition into five clusters, which appeared a posteriori to describe different clinical scenarios. Applicability of this classification was shown by a good concordance (94%) in the allocation of cases between the new practitioners and the 18 experts. An additional group of easy-to-treat cSCC was included, resulting in a six-group final classification: easy-to-treat/complex to treat due to tumour and/or patient characteristics/multiple/locally advanced/regional disease/visceral metastases. CONCLUSION: Given the methodology based on the convergence of unguided intuitive clustering of cases by experts, this new classification is relevant for clinical practice. It does not compete with staging systems, but they may complement each other, whether the objective is to select the best therapeutic approach in tumour boards or to design homogeneous groups for trials.

Dysfunctional coping is related to impaired skin-related quality of life and psychological distress in patients with neurofibromatosis type 1 with major skin involvement.

BACKGROUND: Low skin-related quality of life (QoL) is usually associated with low levels of self-confidence and self-esteem and with high levels of anxiety and depression symptoms. The way patients cope with a physical disease impacts significantly on their psychosocial adjustment to the disorder and on their emotional functioning. OBJECTIVES: To explore how coping strategies, skin-related QoL, psychological distress and self-esteem interact in a sample of individuals with neurofibromatosis type 1 (NF1). METHODS: Seventy-two adult patients with NF1 completed the following questionnaires: Coping Orientation to Problem Experiences (COPE), Skindex-29, Padua Skin-Related QoL questionnaire (PSRQ), State-Trait Anxiety Inventory-X2 form (STAI-X2), Depression Questionnaire (DQ) and Rosenberg Self-Esteem Scale (RSES). The k-modes algorithm was used to identify clusters of patients based on four variables: sex, NF1 severity, number and distribution of cutaneous neurofibromas. Individuals in different clusters were compared with regard to their scores; correlations between scores were analysed within each cluster. RESULTS: Two main clusters were identified: individuals in Cluster 1 had a larger number and more widespread distribution of neurofibromas compared with Cluster 2. Patients in Cluster 1 scored higher only on several PSRQ and Skindex-29 scales. Among patients in Cluster 1, the COPE 'avoidance strategies' scale was significantly correlated with the PSRQ 'physical distress and impairments' scale, the Skindex-29 'physical symptoms' and 'functioning' scales, the STAI-X2, the DQ and the RSES. CONCLUSIONS: Patients with major skin involvement have reduced skin-related QoL. Among them, current findings tentatively suggest that the higher the use of dysfunctional coping, the more impaired are QoL, psychological distress and self-esteem. What's already known about this topic? Neurofibromatosis type 1 (NF1) can affect the quality of life (QoL) in adolescent and adult patients. Low skin-related QoL is usually associated with low levels of self-confidence and self-esteem and with high levels of anxiety and depression symptoms. Questionnaires evaluating skin-related QoL, anxiety, depression, self-esteem and coping are available. What does this study add? Patients with a large number and a widespread distribution of cutaneous neurofibromas have reduced skin-related QoL compared with patients with minor skin involvement. The newly developed Padua Skin-Related QoL questionnaire allows the simultaneous evaluation of discomfort and comfort skin-related QoL dimensions in patients with NF1. Among patients with major skin involvement, the higher the use of dysfunctional coping, the more impaired are skin-related QoL, psychological distress and self-esteem. Our data suggest that patients with NF1 with major skin involvement who endorse dysfunctional beliefs about their own coping abilities might benefit from psychological counselling and coping skills treatments aiming to both improve perceived self-efficacy and learn more adaptive coping strategies.

Early diagnosis of anastomotic leakage after colorectal surgery by the Dutch leakage score, serum procalcitonin and serum C-reactive protein: study protocol of a prospective multicentre observational study by the Italian ColoRectal Anastomotic Leakage (iC.

BACKGROUND: Anastomotic leakage (AL) is a dreaded major complication after colorectal surgery. There is no uniform definition of anastomotic dehiscence and leak. Over the years many risk factors have been identified (distance of anastomosis from anal verge, gender, BMI, ASA score) but none of these allows an early diagnosis of AL. The DUtch LeaKage (DULK) score, C reactive protein (CRP) and procalcitonin (PCT) have been identified as early predictors for anastomotic leakage starting from postoperative day (POD) 2-3. The study was designed to prospectively evaluate AL rates after colorectal resections, in order to give a definite answer to the need for clear risk factors, and testing the diagnostic yeld of DULK score and of laboratory markers. Methods and analysis. A prospective enrollment for all patients undergoing elective colorectal surgery with anastomosis carried out from September 2017 to September 2018 in 19 Italian surgical centers. OUTCOME MEASURES: preoperative risk factors of anastomotic leakage; operative parameters; leukocyte count, serum CRP, serum PCT and DULK score assessment on POD 2 and 3. Primary endpoint is AL; secondary endpoints are minor and major complications according to Clavien-Dindo classification; morbidity and mortality rates; readmission and reoperation rates, length of postoperative hospital stay (Retrospectively registered at ClinicalTrials.gov Identifier: NCT03560180, on June 18, 2018). Ethics. The ethics committee of the "Comitato Etico Regionale delle Marche - C.E.R.M." reviewed and approved this study protocol on September 7, 2017 (protocol no. 2017-0244-AS). All the participating centers submitted the protocol and obtained authorization from the local Institutional Review Board.

Numerical activities of daily living in adults with neurofibromatosis type 1.

BACKGROUND: This study aimed to identify the mathematical domains affected in adults with neurofibromatosis 1 (NF1) and the impact of the numerical difficulties on the patients' activities of daily living. METHODS: We assessed 28 adult patients with NF1 and 28 healthy control participants. All participants completed the standardised battery of numerical activities of daily living along with clinical batteries of cognitive (Mini-Mental State Examination) and daily functioning (instrumental activities of daily living). The group comparisons of the performance on numerical activities of daily living were carried out using t-test correcting for multiple comparisons. RESULTS: The results showed that the NF1 group performed worse than controls in written subtractions, written multiplication, multiplication principles and digit comprehension (dot counting) tasks. Importantly, no significant differences in numerical ecological tasks were found between patients and controls, suggesting a possible use of compensatory strategies in daily living abilities in spite of calculation deficits. CONCLUSION: The findings indicate that NF1 affects calculation but not the basic comprehension or representation of numbers in adult patients. These data have important implications for designing cognitive interventions tailored to the cognitive profile of individuals with NF1.

Neurofibromatosis type 1 in two siblings due to maternal germline mosaicism.

Neurofibromatosis type 1 (NF1) is caused by loss of function mutations of the NF1 gene, which are de novo in 50% of cases. Although this gene shows one of the highest mutation rates in the human genome, germline mosaicism is very rare in this condition. We describe the molecular analysis of a family in which neurofibromatosis type 1 occurred in two out of four siblings born to unaffected parents. Molecular analysis of the NF1 gene identified in both patients the same splicing mutation c.1392+1G>A, which was absent in parental lymphocytes. Microsatellite analysis showed that the two affected siblings shared the same maternal allele, however a specific PCR-RFLP assay excluded the presence of the NF1 splicing mutation in multiple maternal tissues. Our molecular and clinical findings are consistent with a germline mosaicism for the NF1 splicing mutation. This is the first case of maternal germline mosaicism for a NF1 mutation characterized so far at the molecular level. Our data confirm that germline mosaicism is rare in neurofibromatosis 1, but it has important implications for genetic counseling.

Unbiased next generation sequencing analysis confirms the existence of autosomal dominant Alport syndrome in a relevant fraction of cases.

The mode of inheritance of Alport syndrome (ATS) has long been controversial. In 1927, the disease was hypothesized as a dominant condition in which males were more severely affected than females. In 1990, it was considered an X-linked (XL) semidominant condition, due to COL4A5 mutations. Later on, a rare autosomal recessive (AR) form due to COL4A3/COL4A4 mutations was identified. An autosomal dominant (AD) form was testified more recently by the description of some large pedigrees but the real existence of this form is still questioned by many and its exact prevalence is unknown. The introduction of next generation sequencing (NGS) allowed us to perform an unbiased simultaneous COL4A3-COL4A4-COL4A5 analysis in 87 Italian families (273 individuals) with clinical suspicion of ATS. In 48 of them (55%), a mutation in one of the three genes was identified: the inheritance was XL semidominant in 65%, recessive in 4% and most interestingly AD in 31% (15 families). The AD form must therefore be seriously taken into account in all pedigrees with affected individuals in each generation. Furthermore, a high frequency of mutations (>50%) was shown in patients with only 1 or 2 clinical criteria, suggesting NGS as first-level analysis in cases with a clinical suspicion of ATS.

Genotypic testing on HIV-1 DNA as a tool to assess HIV-1 co-receptor usage in clinical practice: results from the DIVA study group.

PURPOSE: We have developed a sequencing assay for determining the usage of the genotypic HIV-1 co-receptor using peripheral blood mononuclear cell (PBMC) DNA in virologically suppressed HIV-1 infected patients. Our specific aims were to (1) evaluate the efficiency of V3 sequences in B versus non-B subtypes, (2) compare the efficiency of V3 sequences and tropism prediction using whole blood and PBMCs for DNA extraction, (3) compare the efficiency of V3 sequences and tropism prediction using a single versus a triplicate round of amplification. RESULTS: The overall rate of successful V3 sequences ranged from 100 % in samples with >3,000 copies HIV-1 DNA/10(6) PBMCs to 60 % in samples with <100 copies total HIV-1 DNA /10(6) PBMCs. Analysis of 143 paired PBMCs and whole-blood samples showed successful V3 sequences rates of 77.6 % for PBMCs and 83.9 % for whole blood. These rates are in agreement with the tropism prediction obtained using the geno2pheno co-receptor algorithm, namely, 92.1 % with a false-positive rate (FPR) of 10 or 20 % and of 96.5 % with an FPR of 5.75 %. The agreement between tropism prediction values using single versus triplicate amplification was 98.2 % (56/57) of patients using an FPR of 20 % and 92.9 % (53/57) using an FPR of 10 or 5.75 %. For 63.0 % (36/57) of patients, the FPR obtained via the single amplification procedure was superimposable to all three FPRs obtained by triplicate amplification. CONCLUSIONS: Our results show the feasibility and consistency of genotypic testing on HIV-1 DNA tropism, supporting its possible use for selecting patients with suppressed plasma HIV-1 RNA as candidates for CCR5-antagonist treatment. The high agreement between tropism prediction by single and triple amplification does not support the use of triplicate amplification in clinical practice.

Surgical and functional outcomes of Dorsal Inlay Graft urethroplasty in revision vs primary hypospadias repair in the pediatric age.

INTRODUCTION: Over the years, Dorsal Inlay Graft (DIG) urethroplasty has gained worldwide acceptance for primary hypospadias repair. However, its safety and effectiveness for revision surgery are yet to be proven. OBJECTIVE: The aim of the study is to assess and compare complication rates and functional outcomes of DIG surgery in revision versus primary hypospadias repair. MATERIAL AND METHODS: We carried out a retrospective analysis of data collected from 53 consecutive DIG urethroplasties performed by a single surgeon at our institution. Patients were stratified in two groups - primary repair and redo-urethroplasty. For each group, we recorded standard pre-operative characteristics, surgical technicalities, complication rates and uroflowmetry parameters. RESULTS: Out of 53 DIG urethroplasties, 21 (39.6 %) where primary and 32 (60.4 %) were re-do. As expected, the two groups differed for median age at surgery: 20 months for primary and 68.5 months for revision surgery (p < 0.001). Additionally, all 21 (100 %) primary interventions were performed with a preputial graft, whereas among revision DIG urethroplasties only 2 (6.3 %) where preputial and 30 (93.8 %) were buccal (p < 0.001). Catheterization time (7 vs 8 days, p = 0.155) and postoperative complication rates (14.3 % vs 9.4 %, p = 0.581) were comparable between the primary and revision surgery group, respectively (all p > .05). Forty-two of the 53 patients underwent uroflowmetry during follow-up. Of these, 19 (63 %) patients presented with abnormal uroflowmetry and 11 (37 %) had equivocal parameters with no difference between the two groups. DISCUSSION: Dorsal Inlay Graft urethroplasty has long been known to be safe and effective for primary hypospadias repair. On the other hand, data on dorsal inlay graft urethroplasty as a salvage surgery after primary hypospadias repair failure is scarce. Surprisingly, according to our findings, surgical outcomes and complication rates are comparable between primary and revision hypospadias cases. Additionally, our results in the redo group are absolutely encouraging if compared to those reported in the literature for the same subset of patients. CONCLUSIONS: According to our findings, DIG urethroplasty is a safe and effective option to treat revision hypospadias repair.

Pregnancy outcome following maternal exposure to statins: a multicentre prospective study.

OBJECTIVE: This contribution addresses the risk associated with exposure to statins during pregnancy. DESIGN: Multicentre observational prospective controlled study. SETTING: European Network of Teratology Information Services. POPULATION: Pregnant women who contacted one of 11 participating centres, seeking advice about exposure to statins during pregnancy, or to agents known to be nonteratogenic. METHODS: Pregnancies exposed during first trimester to statins were followed up prospectively, and their outcomes were compared with a matched control group. MAIN OUTCOME MEASURES: Rates of major birth defects, live births, miscarriages, elective terminations, preterm deliveries and gestational age and birthweight at delivery. RESULTS: We collected observations from 249 exposed pregnancies and 249 controls. The difference in the rate of major birth defects between the statin-exposed and the control groups was small and statistically nonsignificant (4.1% versus 2.7% odds ratio [OR] 1.5; 95% confidence interval [95% CI] 0.5-4.5, P = 0.43). In an adjusted Cox model, the difference between miscarriage rates was also small and not significant (hazard ratio 1.36, 95% CI 0.63-2.93, P = 0.43). Premature birth was more frequent in exposed pregnancies (16.1% versus 8.5%; OR 2.1, 95% CI 1.1-3.8, P = 0.019). Nonetheless, median gestational age at birth (39 weeks, interquartile range [IQR] 37-40 versus 39 weeks, IQR 38-40, P = 0.27) and birth weight (3280 g, IQR 2835-3590 versus 3250 g, IQR 2880-3630, P = 0.95) did not differ between exposed and non-exposed pregnancies. CONCLUSIONS: This study did not detect a teratogenic effect of statins. Its statistical power remains insufficient to challenge current recommendations of treatment discontinuation during pregnancy.

SPINK3 modulates mouse sperm physiology through the reduction of nitric oxide level independently of its trypsin inhibitory activity.

Serine protease inhibitor Kazal-type (SPINK3)/P12/PSTI-II is a small secretory protein from mouse seminal vesicle which contains a KAZAL domain and shows calcium (Ca(2+))-transport inhibitory (caltrin) activity. This molecule was obtained as a recombinant protein and its effect on capacitated sperm cells was examined. SPINK3 inhibited trypsin activity in vitro while the fusion protein GST-SPINK3 had no effect on this enzyme activity. The inactive GST-SPINK3 significantly reduced the percentage of spermatozoa positively stained for nitric oxide (NO) with the specific probe DAF-FM DA and NO concentration measured by Griess method in capacitated mouse sperm; the same effect was observed when sperm were capacitated under low Ca(2+) concentration, using either intracellular (BAPTA-AM) or extracellular Ca(2+) (EDTA) chelators. The percentage of sperm showing spontaneous and progesterone-induced acrosomal reaction was significantly lower in the presence of GST-SPINK3 compared to untreated capacitated spermatozoa. Interestingly, this decrease was overcome by the exogenous addition of the NO donors, sodium nitroprusside (SNP), and S-nitrosoglutathione (GSNO). Phosphorylation of sperm proteins in tyrosine residues was partially affected by GST-SPINK3, however, only GSNO was able to reverse this effect. Sperm progressive motility was not significantly diminished by GST-SPINK3 or BAPTA-AM but enhanced by the addition of SNP. This is the first report that demonstrates that SPINK3 modulates sperm physiology through a downstream reduction of endogenous NO concentration and independently of SPINK3 trypsin inhibitory activity.

CAG repeat length in androgen receptor gene is not associated with amyotrophic lateral sclerosis.

BACKGROUND: Epidemiological and clinical studies show higher prevalence of amyotrophic lateral sclerosis (ALS) in males than in females and more severe lesions in androgen receptor (AR)-expressing tissues. The AR gene contains a polymorphic CAG trinucleotide repeat, whose expansion over a certain threshold is toxic to motor neurons, causing spinal and bulbar muscular atrophy (SBMA). PURPOSE AND METHODS: We tested the hypothesis that the AR CAG repeat linked to SBMA is a risk factor for ALS. We analyzed AR CAG expansions in 336 patients with ALS and 100 controls. RESULTS: We found a negative association of AR CAG expansions with ALS susceptibility, clinical presentation, and survival. CONCLUSIONS: Our findings do not support a role of the AR CAG repeat length in ALS.

Human papillomavirus viral load expressed as relative light units (RLU) correlates with the presence and grade of preneoplastic lesions of the uterine cervix in atypical squamous cells of undetermined significance (ASCUS) cytology.

Human papillomavirus (HPV) testing is more sensitive and has higher negative predictive value (NPV) than the Pap test for the detection of cervical intraepithelial neoplasia (CIN) in patients with atypical squamous cells of undetermined significance (ASCUS) cytology, but has low specificity, leading to high referral rates to second-level triage. Our goal was to identify the prognostic significance of HPV viral load figures. We evaluated whether a correlation between viral load, expressed as relative light units/cutoff (RLU/CO), and the severity of cervical lesions existed in 614 ASCUS cases. Hybrid Capture 2 (HC2®) RLU/CO values, categorised into five classes, were correlated to clinical outcomes and statistically analysed. A significant correlation (p < 0.0001) was observed between increasing RLU values and the prevalence of high-grade CIN (CIN2/CIN3). The mean RLU values for negative, low-grade and high-grade lesions were 68.1, 172.5 and 1,020.0 RLU/CO, respectively (p < 0.0001). CIN2/CIN3 ranged from 4% for 0 < RLU/CO values ≤ 1, to 5% for 1 < RLU/CO values ≤ 10, to 9% for 10 < RLU/CO values ≤ 100, to 23% for 100 < RLU/CO values ≤ 1,000 and to 48% when RLU/CO values were >1,000 (p < 0.05). The HPV viral load in ASCUS cases significantly correlates with the severity of cervical cancer precursors. These data may have prognostic value, as they significantly correlate with the probability of a CIN2+ .

Microarray application in prenatal diagnosis: a position statement from the cytogenetics working group of the Italian Society of Human Genetics (SIGU), November 2011.

A precise guideline establishing chromosomal microarray analysis (CMA) applications and platforms in the prenatal setting does not exist. The controversial question is whether CMA technologies can or should soon replace standard karyotyping in prenatal diagnostic practice. A review of the recent literature and survey of the knowledge and experience of all members of the Italian Society of Human Genetics (SIGU) Committee were carried out in order to propose recommendations for the use of CMA in prenatal testing. The analysis of datasets reported in the medical literature showed a considerable 6.4% incidence of pathogenic copy number variations (CNVs) in the group of pregnancies with sonographically detected fetal abnormalities and normal karyotype. The reported CNVs are likely to have a relevant role in terms of nosology for the fetus and in the assessment of reproductive risk for the couple. Estimation of the frequency of copy number variations of uncertain significance (VOUS) varied depending on the different CMA platforms used, ranging from 0-4%, obtained using targeted arrays, to 9-12%, obtained using high-resolution whole genome single nucleotide polymorphism (SNP) arrays. CMA analysis can be considered a second-tier diagnostic test to be used after standard karyotyping in selected groups of pregnancies, namely those with single (apparently isolated) or multiple ultrasound fetal abnormalities, those with chromosomal rearrangements, even if apparently balanced, and those with supernumerary marker chromosomes.

"Low-grade positivity" of HPV viral load after atypical squamous cells of undetermined significance (ASC-US) cytology identifies women at low-risk for cervical intraepithelial neoplasia grade 2 and 3.

The correlation between high-risk HPV-DNA viral load, expressed as relative light units (RLU) values obtained from the Hybrid Capture 2 (HC2) test, and the prevalence of CIN2/CIN3 was investigated and statistically analyzed in 614 ASC-US consecutive cases. Cases were categorized into three groups according to RLU values: "low-grade positivity", "intermediate positivity" and "high-grade positivity", and the prevalence of CIN2/CIN3 was evaluated in the single groups and compared among them. CIN/CIN3 rates demonstrated a significant (p < 0.001) increase with a direct correlation with increasing RLU values: 4.6% (RLU from 1.0 to 10.0), 9.1% (RLU from 11.0 to 100.0) and 32.2% (RLU > 100.0) respectively. The prevalence of CIN2/CIN3 between the group with RLU < 10.0 (4.6%) and the group with RLU > 10 (24.2%) showed statistical significance (p = 0.0002). Increasing hrHPV viral load significantly correlates with increasing prevalence of CIN2/CIN3 in ASC-US cases.

Gastric Bypass after multiple restrictive procedures: Roux-en-Y or One Anastomosis? A retrospective multicentric study.

OBJECTIVE: When restrictive surgery fails, conversion to more malabsorptive techniques is frequently proposed. The aim of this study is to evaluate the weight loss figures between Roux-en-Y Gastric Bypass (RYGB) and One Anastomosis Gastric Bypass (OAGB) in patients who have already undergone Multiple Restrictive Procedures (MRP). PATIENTS AND METHODS: All patients who underwent conversion of Laparoscopic Sleeve Gastrectomy (LSG) to RYGB or OAGB between 2010 and 2019 were retrospectively analyzed. Only patients who had conversion for Weight Regain (WR) or Insufficient Weight Loss (IWL) after both Laparoscopic Gastric Banding (LGB) and LSG entered the study population. Finally, 44 patients underwent conversion to RYGB, and 24 patients to OAGB. RESULTS: Concerning Excess Weight Loss (%EWL) at 3, 6, 12, 24 postoperative months, the results for RYGB were 33.7%, 47.95%, 61.8%, 61.8%, while for OAGB were 38.3%, 51.9%, 63.75%, 79.45%. A significant difference was recorded in favor of OAGB at 3 (p=0.03) and 24 (p=0.046) postoperative months. % EWL at 24 months in the case of IWL was 57.8% for RYGB, while for OAGB was 72.7% (p=0.047). No significant difference was found considering patients with WR (80.9% and 80.5%; p= 0.999). Patients with better results at 24 months after surgery had a significantly longer time between sleeve and bypass than those with a lower % EWL. CONCLUSIONS: The results of the present study seem to show that both techniques give good results at 24 months in patients who have undergone MRP. However, OAGB shows overall better results, particularly in patients with IWL.

Long-term results of laparoscopic gastric sleeve: the importance of follow-up adherence.

OBJECTIVE: This study was conducted to assess the long-term results of the Laparoscopic Sleeve Gastrectomy (LSG) in patients not compliant with follow-up, and in patients who completed a postoperative follow-up program. PATIENTS AND METHODS: The data concerning LSG patients operated from February 2011 to December 2013 were retrospectively reviewed basing on a single center database. The patients with complete long-term follow-up were scheduled in Group A, while patients who failed to attend controls for more than two years were scheduled in Group B. Long-term results (weight loss, comorbidity improvement and late complications) were compared between the two groups. RESULTS: The study population consisted of 285 patients. Of these, 101 had a complete follow-up with a mean duration of 71 ± 7.6 months (Group A). The remaining 184 patients (Group B) were not compliant with follow-up and, consequently, the mean duration of follow-up was 5.5 ± 7.3 months (p < 0.00001). A higher number of patients with insufficient weight loss was recorded in Group B with respect to Group A (78 vs. 23; p = 0.001). The number of patients with results below 25% EWL was significantly higher in Group B than in Group A (24 vs. 5; p = 0.04). In the long-term, the rate of patients with symptomatic reflux requiring medical treatment was two-fold higher in Group B than in Group A. CONCLUSIONS: The adherence to a long-term follow-up plan after LSG seems to decrease the number of patients experiencing insufficient weight loss and those at risk for developing a gastro-esophageal reflux disease.

Genetic control of the CD4/CD8 T-cell ratio in humans.

We studied the genetic pattern of inheritance of the ratio between circulating CD4+ and CD8+ T lymphocytes in a population of healthy donors. The distribution of the CD4/CD8 ratio in males and females was significantly different and was significantly affected by age. In 46 randomly selected families, the parental CD4/CD8 ratio significantly influenced the ratio in offspring. Complex segregation analysis of the data rejected the non-genetic hypothesis; among the genetic models tested, a major recessive gene with a polygenic component and random environmental effects was the most parsimonious model. These findings indicate that the ratio of CD4+ and CD8+ T cells is genetically controlled in humans.

The role of antral resection in sleeve gastrectomy. An observational comparative study.

OBJECTIVE: The role of antral resection (AR) in laparoscopic sleeve gastrectomy (LSG) is still a greatly debated topic in the literature. The aim of this study was to evaluate the results and complications of AR in LSG. PATIENTS AND METHODS: In this observational comparative study, 101 patients who underwent LSG were divided into two groups based on the extent of antral resection: 1 cm from the pylorus (1-DP group), or 6 cm from the pylorus (6-DP group). The %EWL (%Excess weight loss), resolution of T2D (Type 2 Diabetes Mellitus) and GLP-1 were investigated 48 hours before surgery and 3, 6 and 12 months after LSG. Postoperative complications in the first 30 days after surgery were also compared between the two groups using the Clavien-Dindo (CD) score. RESULTS: A significant difference in %EWL was observed at 3 and 6 months in favor of the 1-DP group (38.9% and 57.8%, respectively) compared to the 6-DP group (31.4% and 49.7%, respectively). No difference in T2D resolution was observed between two groups during the follow-up period, with similar changes in GLP-1. Statistically significant differences were found between 1-DP and 6-DP group for the reintervention rate (CD III, 7.7% and 1.9%, respectively; p = 0.02) and life-threatening complications requiring intensive care unit management (CD IV, 3.8% and 0%, respectively, p = 0.03). CONCLUSIONS: In LSG, sparing the antrum is associated with a significant reduction in the rate of postoperative complications, but the metabolic and weight results are comparable to those for antrum resection.

Successful laparoscopic trans-peritoneal repair of an incisional inguinal hernia, resulting from deep lymph node dissection for melanoma: A case report.

INTRODUCTION: Deep pelvic lymph node dissection for cancer may result in incisional inguinal hernias. We present a case report of successful laparoscopic trans-peritoneal repair of a large ventral inguinal hernia that developed following ileo-inguinal lymph node dissection (CLND) for melanoma. CASE PRESENTATION: A successful 3 port laparoscopic trans-peritoneal procedure was performed on a 56-year-old female for the repair of a left inguinal hernia, developed 13 months following CLND for melanoma. The large oval 18 × 14 cm inguinal defect, with superior margins bordering the conjoint tendon and inferior margins bordering the ileo-psoas muscle, femoral vessels and nerve, was not closed in order to avoid excessive tension and was repaired by fixing a 25 × 20 cm intra-peritoneal mesh to abdominal borders at superior and lateral margins with permanent fasteners and at the inferior margin by a cyanoacrylate-glued overlap to protect femoral vessels and nerves from damage. No hernia recurrence was observed 8 months following this procedure. DISCUSSION: Incisional inguinal hernias, following CLND, are rare but present a challenge to surgeons due to the difficulty in identifying both anatomical plains and safe sites for stable repair. CONCLUSIONS: We report a laparoscopic trans-peritoneal approach for the safe, reproducible and efficacious repair of incisional inguinal hernias that result from CLND. In our opinion prevention of hernia recurrence can be achieved by a intraperitoneal large mesh fixed at superior and lateral margin borders with permanent fasteners and using cyanoacrylate glue to overlap inferior margin borders in order to prevent vessels and/or nerve injury.