Background: The application of uniportal video-assisted thoracic surgery (VATS) for both minor and major thoracic procedures is gaining widespread use across the globe. Believing its advantages, both in superb surgical results and less morbidity, our center has the privilege to be one of the first centers in the Middle East to introduce this surgical technique into our standard practice. This study presents our initial experience using this technique in 192 procedures and demonstrates the results of postoperative pain level in a sample of 90 patients.Methods: In a retrospective study of prospectively collected data, 192 uniportal VATS procedures were analyzed between November 2013 and June 2016. The level of early post-operative pain (postoperative days 1-4) was analyzed in the first 90 cases between November 2013 and March 2015. Uniportal technique was used for a wide array of procedures: blebectomies, pleurectomies, wedge resections, anatomical major lung resections, mediastinal tumors, empyema drainage and decortications.Results: The mean age of patients was 49.6 years, and 72 patients were females (37%). Thirty-five (18.2%) patients underwent anatomical resections with conversion to thoracotomy in three patients (8%). Six (3%) patients had air leak > 4 days. The average chest drain duration was 3.25 days. The average length of stay was 4.2 days. Postoperative pain level was low in the first 4 days following the surgery and 30 days mortality was 0%.Conclusions: Uniportal VATS surgery is a safe and established technique with a minimal invasive thoracic surgery. Excellent results with minimal morbidity, short hospital stay and low postoperative pain are amongst its strong points. Thoracic surgeons experienced in thoracic surgical approaches can safely perform uniportal VATS.

Clostridium difficile colitis is diagnosed using an immunoassay or polymerase chain reaction (PCR) assay for toxins A/B. Since ultrasound is frequently used as a screening test for hospitalized patients suffering from different abdominal morbidities, we searched for sonographic indicators of C. difficile infection (CDI). In a prospective and blinded case-control study, abdominal ultrasound was performed on hospitalized patients for whom stool samples were sent for C. difficile toxin immunoassay. All patients with positive toxin were included as the case group and patients with negative toxin comprised the control group. Sonographic parameters of both groups were compared. Demographic variables of the 67 patients in the toxin-positive group were similar to those of the 71 patients in the toxin-negative group. The sonographic parameters which were found to be associated with CDI included colonic wall thickening, appearing in 61 (91%) patients of the toxin-positive group versus 15 (21%) patients of the toxin-negative group (p < 0.001), and also internal ring (24 versus 0%, p < 0.001), external ring (15 versus 0%, p < 0.001), ascites (24 versus 10%, p < 0.001), and diminution of large bowel content (16 versus 1%, p < 0.001). Bowel wall thickening had high positive and negative predictive values (0.80 and 0.90, respectively), while the other features had only high positive predictive values (0.7-1.0). Abdominal ultrasound may contribute to the diagnosis of C. difficile colitis in patients developing hospital-acquired diarrhea.

Gaucher disease, a lysosomal storage disorder, is a multisystem disorder with variable and unpredictable onset and severity. Disease-specific enzyme replacement therapy (ERT) has been shown to reverse or ameliorate disease-specific hepatosplenomegaly and anemia and thrombocytopenia. ERT also impacts bone manifestations, including bone crises, bone pain, and appearance of new osteonecrosis, and improves bone mineral density to varying degrees. The objective of this study was to assess achievement of predefined therapeutic goals based on international registry outcomes for Israeli patients with Gaucher disease receiving imiglucerase for four consecutive years on a low-dose regimen followed in a single center. All data were taken from patient files. The therapeutic goals were taken from standards published in the literature for disease-specific clinical parameters. Among 164 patients at baseline, values for spleen and liver volumes, hemoglobin and platelet counts, and Z-scores for lumbar spine and femoral were significantly different from the goal. After four years ERT, there was a significant improvement (P = 0.000) in each of the therapeutic goal parameters from baseline. 15.2% of these patients achieved all hematology-visceral goals. In children, there was achievement of linear growth and puberty. This survey highlights the good overall response in symptomatic patients receiving low-dose ERT with imiglucerase in Israel.

Gaucher disease, the most prevalent lysosomal storage disorder, is inherited as an autosomal recessive condition. The gold standard for diagnosis is decreased acid β-glucosidase activity in the lymphocytes or fibroblasts; molecular analysis of mutations allows for some prognostication of disease severity. Prenatal diagnosis and carrier testing for at-risk families are currently available. There is tremendous phenotypic heterogeneity in the non-neuronopathic form (type I), ranging from clinically asymptomatic to massive hepatomegaly, hypersplenism, growth retardation in children and extensive involvement of bone and lungs. Presence on one allele of the most common mutation, N370S, which is the most prevalent among Ashkenazi Jews for whom there is a predilection for Gaucher disease, is protective of neurological involvement. Some mutations, such as 84GG and IVS2+1, are associated with more severe disease manifestations when appearing as compound heterozygotes with N370S, but when occurring in the homozygous state are not compatible with life. Other mutations, such as L444P, are associated with severe non-neurological disease when occurring as compound heterozygotes with N370S, but when occurring in the homozygous state may be predictive of neurological disease of either acute (type II) or subacute (type III) forms. In the past decade, enzyme replacement therapy has become available which has resulted in a reduction in liver and spleen volume and consequently improved anemia and thrombocytopenia in most patients. It has also engendered catch-up growth in many children, induced improvement in lung involvement secondary to Gaucher disease, and to some extent ameliorated episodes of bone pain. By virtue of treatment, many children who may have been severely affected no longer need to undergo splenectomy to treat hypersplenism, and therefore they are not at risk of bone involvement consequent to the loss of the preferred reservoir for lipid-laden ‘Gaucher cells’. However, enzyme treatment is ineffective in reversing neurological signs, requires a lifelong commitment to intravenous infusions, thereby reducing quality of life, and is relatively expensive for many national health schemes. Hence, alternative forms of treatment, such as substrate balance, are being explored. Symptomatic management, including orthopedic surgery, pain relief for bone pain and even splenectomy, still has importance for patients with Gaucher disease. In addition, there is the potential for bone marrow transplantation and, in the future, gene therapy to be curative, particularly for patients with the neuronopathic forms.

Objectives: Although ultrasonography (US) may be recommended for repeat assessments of spleen and liver volumes, it is less readily used than magnetic resonance imaging and computed tomography (CT) because of concerns of accuracy and reproducibility. In monitoring spleen and liver volumes for Gaucher disease where volume changes underlie management decisions, in experienced hands, US has a place because some patients are evaluated for decades and sometimes several times annually. The purpose of this survey was to ascertain whether one can maximize the efficiency of US imaging by use of one US axis if it correlates with CT-generated volumes.Methods: A patient cohort from a large tertiary clinic dedicated to Gaucher disease was used. Thirty-seven patients with simultaneous abdominal CT and US evaluations (1992-2009), 27 (73%) at the advent of Gaucher-specific therapy, and followed both by CT and US up to 3 additional times (interval, >= 12 months) were included. Ultrasound evaluation of 3 axes, longitudinal, width, and depth, was performed by one radiologist; all organs including idiosyncratically shaped and massively enlarged organs were included.Results: There was a significant correlation between CT volume and US length axis for both spleen (0.619) and for liver (0.557) volumes (P = 0.01; 2-tailed for each).Conclusion: With some training, the use of the longitudinal axis by US assessment may suffice to approximate estimation of changes in organ volumes.

BACKGROUND:Decreased spleen and liver volumes and increased hemoglobin levels and platelet counts usually occur with enzyme replacement therapy (ERT) in symptomatic patients with Gaucher disease. Because of decreased supply of imiglucerase, an FDA-approved Early Access Program (EAP) allowed use of a new, pre-licensed ERT, velaglucerase alfa. This report provides safety and efficacy findings in patients on EAP velaglucerase alfa who completed 6, 9, or 12 months as intravenous every-other-week ERT. METHOD:EAP was approved by the Israeli Ministry of Health. All patients enrolled in the EAP were included for safety measures; only those with >6 month evaluations of hemoglobin, platelet counts, and liver and spleen volumes were included for efficacy. Descriptive statistics were employed. RESULTS:Among 71 EAP patients, there were no drug-related serious adverse events or withdrawals; one patient (1.4%) with previous hypersensitivity to a different ERT had a drug-related allergic reaction. Of 44 patients with appropriate time-period evaluations, 8 patients were treatment-naïve and responded well to velaglucerase alfa. The 36 switch-over patients remained at imiglucerase low-doses; a majority of patients showed improvements in each efficacy parameter. CONCLUSION:Switch-over from imiglucerase (10-224 months) was safe and in several patients velaglucerase alfa induced a booster-effect.

Objective. Our large tertiary clinic for patients with Gaucher disease has used sonography as the preferred modality to monitor hepatosplenomegaly in hundreds of patients for more than 18 years. With the advent of specific enzyme replacement therapy (ERT), sonographic monitoring of changes in both hepatomegaly and the echogenicity of the hepatic tissue may highlight features that are amenable to ERT. Methods. All patients (500) seen at presentation and at annual or semiannual routine visits have undergone sonographic examinations by a single senior radiologist (I.H.-H.). Results. Thirty-nine patients (7.8%) had sonographic evidence of hepatic disease (21 male and 18 female; age range, 18-90 years); 26 (66.7%) of these received ERT, and 10 (25.6%) were splenectomized. Conclusions. Liver findings are relatively rare. Among 500 patients, there was no instance of computed tomographic findings that had not been previously shown by sonography. Radiologists should be acquainted with the variable sonographic spectrum of the Gaucher liver. If hepatic lesions are small, hyperechoic, and slowly evolving, one may surmise that they are due to Gaucher cell accumulation. However, special attention should be paid to progressive deterioration and irregularities in liver texture because other metabolic processes and cancers must be ruled out.

The only prognostic markers in Gaucher disease, the most common lysosomal storage disorder, are young age at first symptom/sign and the presence of null/severe mutations, both being predictive of more severe phenotypes. Therefore, it would be helpful to know whether siblings with the same genotype can be expected to experience comparable phenotypic expression. All non-neuronopathic sibling pairs in our referral clinic (1993-2008) with the same genotype were included. For each pair, gender, date of birth, severity score index at presentation, age at diagnosis and first symptom/sign, presence of bone involvement, spleen status, and use of enzyme replacement therapy were tabulated. There were 90 pairs of siblings: two sets of identical twins; 24 pairs of brothers, 24 pairs of sisters, and 42 pairs of mixed gender. For all measures of disease severity used, only in sibling pairs with an older sister and a younger brother were phenotypes significantly different between siblings. Thus, this large cohort of sibling pairs with type 1 Gaucher disease confirmed that, in general, the phenotypic expression in the younger sibling will be similar enough to that of an older affected sibling that genetic counseling may use those findings in a prognostic way.

BACKGROUND:With regard to ethnic predilections for Gaucher disease, the most common storage disorder, Ashkenazi Jews are at risk for the non-neuronopathic form (type I), Norbottnian Swedes are at risk for the subacute neuronopathic form (type III), and perhaps Arabs are at risk for the very rare cardiac variant of the subacute neuronopathic form (type IIIc) for which there is a relatively tight genotype-phenotype correlation. Type II, the acute infantile form, being the rarest form, has not been associated with any ethnic predilection.OBJECTIVES:To examine whether Arab ethnicity influences the Gaucher phenotype.METHODS:We reviewed the records of all Arab patients in a referral clinic of 586 patients in Israel.RESULTS:There were 46 patients (7.8%) of Arab ethnicity: 23 (50%) had type I disease, 16 (34.8%) had type IIIc disease, 4 (8.7%) had type IIIb disease, and 3 (6.5%) had type II disease. Type IIIc disease was characterized by genotype-phenotype correlation with homozygosity for the D409H (1342C) mutation. All five Bedouin patients (10.9%) had the R48W (C259T) mutation on at least one allele.CONCLUSIONS:For all genotypes, disease severity among Arab patients was relatively similar to that reported among other Caucasian patients. Apparently Arab ethnicity does not impact phenotypic expression in Gaucher disease in a unique manner. The predilection for type IIIc may be a result of consanguinity.

BACKGROUND Sarcoidosis is a multisystemic disorder of unknown cause that primarily affects the lungs. The diagnosis is based on the clinical manifestations, radiological findings and histological examination. OBJECTIVES To review and illustrate the typical and atypical radiological findings of sarcoidosis in the chest. METHODS We analyzed the radiographic thoracic findings of all patients who had biopsy-proven sarcoidosis over the last 10 years. RESULTS There were 100 consecutive patients (36 men and 64 women, age 20-84 years) with an established diagnosis of sarcoidosis. Thoracic lymphadenopathy was detected in 89 patients (89%). Lung parenchyma involvement was found in 60 patients. These changes were variable and included: ground-glass attenuation (n=39), multiple small nodules (n=44) and irregular thickening of the interlobular septa (n=16). Larger nodules (1-3 cm) were identified in 12 patients and frank consolidations were seen in 12 patients. Pleural thickening with subpleural nodules was identified in 17 patients. CONCLUSIONS Sarcoidosis has a wide variety of radiological manifestations in the chest. Familiarity with the various radiographic findings is important for diagnosis and management.

Enzyme replacement therapy (ERT) with imiglucerase reduces hepatosplenomegaly and improves hematologic parameters in Gaucher disease type 1 within 6-24 months. Miglustat reduces organomegaly, improves hematologic parameters, and reverses bone marrow infiltration. This trial evaluates miglustat in patients clinically stable on ERT. Tolerability of miglustat and imiglucerase, alone and in combination, pharmacokinetic profile, organ reduction, and chitotriosidase activity were assessed. Thirty-six patients stable on imiglucerase were randomized into this phase II, open-label trial. Statistically significant changes from baseline were assessed (paired t test) on primary objectives with secondary analyses on biochemical and safety parameters. Liver and spleen volume were unchanged in switched patients. No significant differences were seen between groups regarding mean change in hemoglobin. Mean change in platelet counts was only significant between miglustat and imiglucerase groups (P = .035). Chitotriosidase activity remained stable. In trial extension, clinical endpoints were generally maintained. Miglustat was well tolerated alone or in combination. Miglustat's safety profile was consistent with previous trials; moreover, no new cases of peripheral neuropathy were observed. Gaucher disease type 1 (GD1) parameters were stable in most switched patients. Combination therapy did not show benefit. Findings suggest miglustat could be an effective maintenance therapy in stabilized patients with GD1.

Extrapelvis or retroperitoneal haemorrhage has long been appreciated as having many causes and considerable variability in subsequent morbidity; however, to date only two cases have been reported in patients with Gaucher disease, the most common lysosomal storage disorder. It had been our assumption that these cases were unique and a consequence of severe disease in patients who had not been treated with enzyme (or other disease-specific) therapy. Herein we present three more cases (as well as our first patient), which allow one to make some generalizations. Ultrasound was used in one centre and computed tomography in the second centre to make the definitive diagnosis. The trigger for the bleeding in all cases was muscle strain after activity. All patients were young with massive hepatosplenomegaly, anaemia, thrombocytopenia, and bone pain with skeletal involvement; the last was the most obvious commonality among these patients. Differential diagnosis is complicated by exquisite groin pain that is common to both Gaucher disease and extrapelvis haemorrhage, but not necessarily.

BACKGROUND:Gaucher disease (GD) is caused by deficiency of acid beta-glucocerebrosidase and is the most common lysosomal storage disease. Patients may have massive hepatosplenomegaly, severe bone disease, and, occasionally, pulmonary or neurological involvement. Although other storage diseases, such as Fabry disease, frequently affect the kidneys, reports of renal abnormalities in patients with GD are limited to case reports. Our aim was to perform a comprehensive evaluation of renal function in patients with GD.METHODS:Evaluation was performed at routine clinic visits and included blood pressure recording and renal ultrasound. Serum chemistries, urinalysis, urine electrolytes, total protein, and tubular proteinuria were assessed, and estimated glomerular filtration rate (GFR) was calculated.RESULTS:One hundred sixty-one patients underwent evaluation, including 26 children. GFR was significantly greater in patients with GD than in age- and sex-matched healthy controls (P = 0.01 in men, P < 0.001 in women, P = 0.003 in children). Subgroups of patients with markers of more severe disease had a greater GFR than other patients. No patient had decreased renal function. Significant proteinuria was found only in patients with such comorbidities as diabetes mellitus or multiple myeloma. No evidence of renal tubular abnormalities was found, and kidney sonographic appearance and size were normal.CONCLUSION:Despite the multiorgan nature of the disease, a systematic evaluation did not find renal abnormalities in patients with GD. Glomerular hyperfiltration was observed in a proportion of patients, particularly those with markers of more severe disease. This phenomenon does not seem to be associated with a subsequent decline in renal function.

OBJECTIVES:To describe a unique case of a young man with Gaucher disease who was diagnosed with Menetrier's disease.BACKGROUND:After an acute episode of severe gastritis, the patient developed hypoalbuminemia and protein-losing gastroenteropathy, and became unwell.STUDY:Endoscopy revealed an abnormal stomach, with rigid, thickened folds covered with viscous greyish exudates. Superficial biopsies revealed foveolar hyperplasia, acute and severe gastritis with massive inflammatory infiltrate of neutrophils in the lamina propria with pit abscess formation. Tissue cultures for Helicobacter pylori were negative.RESULTS:Snare deep particle biopsy revealed the typical features of Menetrier's disease. Enzyme replacement therapy for Gaucher disease was started.CONCLUSION:This case poses a dilemma because the patient improved spontaneously, and as such is dissimilar to other adults who develop Menetrier's disease because of an infection; it is hoped that he may also not be at risk of the potential malignancies that are correlated with adult Menetrier's disease. The value of enzyme treatment is considered.

PURPOSE:We reviewed cosmetic and functional outcome of masculinizing genitoplasty (MPG) in intersex patients assigned as a male performed in our service for more than 12 years. MATERIALS AND METHODS:A total of 57 patients underwent MPG in our department during a 20-year period. Of these cases MPG was performed using modern 1-stage surgical techniques from 1991 to 2003 in 39 (68%). Of the 39 children 8 (21%) had 17beta-hydroxysteroid dehydrogenase deficiency, 2 (5%) had 3beta-hydroxysteroid dehydrogenase deficiency, 8 (21%) had 5alpha-reductase deficiency, 2 (5%) had mixed gonadal dysgenesis, 1 (2.6%) was a true hermaphrodite, 1 (2.6%) had Klinefelter's syndrome, 1 (2.6%) had partially androgen insensitivity syndrome and 16 (41%) had idiopathic male pseudohermaphroditism. The presenting disease was severe proximal penoscrotal hypospadias in 30 cases (77%), perineal hypospadias in 9 (23%) and müllerian duct opening in the perineum along with the urethral meatus in 16 (28%). Median patient age at surgery was 1.8 years. MPG was performed with a transverse pedicled preputial island flap as an onlay in 29 cases (74%). The remaining 10 patients (26%) underwent tubularization of the mucosa in the perineal area and end-to-end anastomosis to a tube made from the pedicled prepuce. Scrotal transposition as well as orchiopexy was performed in some patients as an independent operation so as not to jeopardize the perineal and preputial flaps. RESULTS:In 23 (59%) of the 39 children 1 operation achieved satisfactory cosmetic and functional results in terms of good urinary stream and straight phallus during erection. Three (7%) children presented with various degrees of breakdown of the urethroplasty and required a repeat operation. In 5 patients (12.8%) a small urethral fistula developed and closure was performed. CONCLUSIONS:A 1-stage male genitoplasty for male pseudohermaphroditism is accompanied by a reasonable incidence of major complications. It should be performed in early childhood to avoid psychological and social anxiety by the child and parents.

Retrospective evaluation of our 16-year experience with children with antenatal diagnosis of pelvi-ureteric junction (PUV) obstruction to determine those who are at risk for surgery. Five hundred and seven children (395 male and 112 female) with antenatal diagnosis of hydronephrosis, which led to the postnatal diagnosis of PUJ obstruction were followed conservatively at our department over a 16-year period (1988–2003). Rt sided hydronephrosis was in 110, Lt sided in 213 and Bil obstruction in 164 children respectively. According to Society for Fetal Urology (SFU) classification 2 children had grade 0 postnatal hydronephrosis, 96 grade 1, 166 grade 2, 126 grade 3, and the remaining 107 children grade 4 of postnatal hydronephrosis. Two hundred and seventy children (53.3%) required surgical correction during conservative management. Average age at surgery was 7.1 months (range 1 month-7 years). Of those, 50% underwent surgery during first 2 years of life and the remaining patients during first 4 years of life, only 2 patients required surgery latter on. Univariate analysis revealed that child sex, side of obstruction and SFU grade of prenatal hydronephrosis are not significant predictive factors for surgery. However, SFU grade 3–4 of postnatal hydronephrosis (p < 0.0001, Odds ratio 0.01913), RRF less than 40% (p < 0.0001, Odds ratio 0.09502) were significant independent risk factors in children who underwent pyeloplasty In contradiction to previously published by others and us this data shows that more than 50% of children with antenatal diagnosis of PUJ obstruction required surgical correction while on conservative protocol. SFU grade 3–4 of postnatal hydronephrosis and RRF less than 40% are significant independent predictive factors for surgery.