Pirfenidone targeted mechanisms for alleviating methotrexate-induced testiculopathy in Wistar rats.

Testicular injury and affected spermatogenesis are major complications of methotrexate (MTX) use. Oxidative stress is one contributing process leading to inflammation and apoptosis induction. Pirfenidone (PFD) is a well-known anti-fibrotic drug prescribed for interstitial lung fibrosis, in addition to anti-inflammatory, antioxidative, and antiapoptotic capabilities. The study aimed to explore the potential protection afforded by PFD in a rat model of MTX-induced testiculopathy. The experimental design included four groups, each containing seven adult Wistar rats: control, PFD (500 mg/kg/day, orally)-, MTX (0.5 mg/kg, intraperitoneal, twice weekly)-, and PFD/MTX-treated groups. Treatment continued for 4 weeks. Blood and testicular samples were harvested for biochemical, histological, immunohistochemical, and polymerase chain reaction (PCR) analyses. Also, the testicular damage and spermatogenic activity were graded by the testicular injury and Johnsen scoring system, respectively. PFD positively affected the serum testosterone (TST) level, reduced the testicular inflammatory mediators [tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß)], reduced the testicular oxidative burden, increased superoxide dismutase (SOD), and protected the testicular histological structure. In addition, antifibrotic effects, anti-caspase-3, and PCNA enhancement activity were recorded. PFD exhibited a protective potential and mitigated the MTX-induced testiculopathy via suppression of testicular oxidative stress, inflammation, fibrosis, and apoptosis and retaining the testicular proliferative efficacy as confirmed by histological, immunohistochemical, and biochemical methods.

Enhancement of porous asphalt mixtures modified with various fibers and ethylene-vinyl acetate polymer.

Porous asphalt mixture is conventional hot mix asphalt (HMA) with substantially decreased fines, which produces an open-graded mixture that enables the water to flow through an interconnected void space. Porous asphalt is a permeable system that has a lot of benefits. However, because of its open structure, the durability of this mixture decreases, and both its stability and resilient modulus are much lower compared to the dense conventional asphalt mixtures. Also, the high void percentage may lead to an increase in the draindown proportion. Fibers (cellulose or mineral) and polymer-modified binders are recommended for porous asphalt mixtures, especially in hot and moderate climates. The objective of this study is to improve the porous asphalt mixture's performance by using ethylene-vinyl acetate (EVA) polymer-modified bitumen. Two types of fibers (cellulose fibers and glass wool fibers) were used, separately to determine the control mixture. Four different proportions of EVA polymer were added to the bitumen (1%, 2%, 3%, and 4%) and Scanning Electron Microscopy (SEM) was used for better investigating of the bitumen microstructure, then The Marshall mix design was used to determine the optimum EVA content (OEC) for the porous asphalt mixture. Several performance tests were conducted to investigate the characteristics of the porous asphalt mixture, such as the infiltration rate, binder draindown, the wheel track and the cantabro abrasion tests. The findings of the study conclude that the addition of EVA polymer to the porous asphalt mixtures enhances the performance as it increases stability by 20.8% and the infiltration rate by 20.6%. It decreases binder draindown proportion by 33.3%, cantabro abrasion loss by 25.1% and the rut depth at 5,000 cycles and 10,000 cycles by 29.8% and 19.7%, respectively.

Lactobacillus rhamnosus GG and Tannic Acid Synergistically Promote the Gut Barrier Integrity in a Rat Model of Experimental Diarrhea via Selective Immunomodulatory Cytokine Targeting.

SCOPE: Diarrhea is a common health issue that contributes to a significant annual death rate among children and the elderly worldwide. The anti-diarrheal activity of Lactobacillus rhamnosus GG (LGG) and tannic acid (TA), alone or combined, is examined, in addition to their effect on intestinal barrier integrity. METHODS AND RESULTS: Fifty-six adult male Wistar rats are randomly assigned into seven groups: control, LGG alone, TA alone, diarrhea model, diarrhea+LGG, diarrhea+TA, and diarrhea+LGG+TA-treated groups. Diarrhea is induced by high-lactose diet (HLD) consumption. LGG (1x109 CFU/rat) and TA (100 mg Kg-1 d-1) were given orally 4 days after HLD feeding and continued for 10 days. Ileum specimens are processed for biochemical analysis of the local intestinal cytokines, polymerase chain reaction (PCR), and histological study. Also, immunohistochemistry-based identification of Proliferating Cell Nuclear Antigen (PCNA) and zonula occludens 1 (ZO-1) is performed. Compared to the diarrhea model group, both treatments maintain the intestinal mucosal structure and proliferative activity and preserve ZO-1 expression, with the combination group showing the maximal effect. However, LGG-treated diarrheic rats show a remarkable decrease in the intestinal tissue concentrations of tumor necrosis factor-alpha (TNF-α) and nuclear factor Kappa beta (NF-κB); meanwhile, TA treatment leads to a selective decrease of interferon-gamma (INF-γ) and transforming growth factor-beta (TGF-ß1). CONCLUSION: Individual LGG and TA treatments significantly alleviate diarrhea, probably through a selective immunomodulatory cytokine-dependent mechanism, while the combination of both synergistically maintains the intestinal mucosa by keeping the intestinal epithelial barrier function and regenerative capability.

Interrogating the estrogen-mediated regulation of adrenocortical Klotho expression using ovariectomized albino rat model exposed to repeated restraint stress.

Reproductive aging is associated with altered stress response and many other menopausal symptoms. Little is known about the adrenal expression of the anti-aging protein Klotho or how it is modulated by estrogen in ovariectomized stressed rats. Fifty-six Wistar female rats were assigned into seven equal groups. Sham-operated (Sham), sham stressed (Sham/STS), ovariectomized (OVR), ovariectomized stressed (OVR/STS), ovariectomized stressed rosiglitazone-treated (OVR/STS/R), ovariectomized stressed estrogen-treated (OVR/STS/E), and ovariectomized stressed estrogen/GW9662 co-treated (OVR/STS/E/GW) groups. All stressed rats were subjected daily to a one-hour restraint stress test for 19 days. At the end of the experiment, blood was collected for serum corticosterone (CORT) analysis. Adrenal tissues were obtained and prepared for polymerase chain reaction (PCR) assay, hematoxylin and eosin (H&E), immunohistochemistry-based identification of Klotho and PPAR-γ, and Oil Red O (ORO) staining. The rise in serum CORT was negligible in the OVR/STS group, in contrast to the Sham/STS group. The limited CORT response in the former group was restored by estrogen and rosiglitazone and blocked by estrogen/GW9226 co-administration. ORO-staining revealed a more evident reduction in the adrenal fat in the OVR/STS group, which was reversed by estrogen and counteracted by GW. Also, there was a comparable expression pattern of Klotho and PPAR-γ in the adrenals. The adrenal Klotho decreased in the OVR/STS group, but was reversed by estrogen treatment. GW9226/estrogen co-treatment interfered with the regulatory effect of estrogen on Klotho. The study suggested modulation of the adrenal Kotho expression by estrogen, in the ovariectomized rats subjected to a restraint stress test. This estrogen-provided adrenal protection might be mediated by PPAR-γ activation.

Modeling the Effects of Cypermethrin Toxicity on Ovalbumin-Induced Allergic Pneumonitis Rats: Macrophage Phenotype Differentiation and p38/STAT6 Signaling Are Candidate Targets of Pirfenidone Treatment.

Although the classic form of asthma is characterized by chronic pneumonitis with eosinophil infiltration and steroid responsivity, asthma has multifactorial pathogenesis and various clinical phenotypes. Previous studies strongly suggested that chemical exposure could influence the severity and course of asthma and reduce its steroid responsiveness. Cypermethrin (CYP), a common pesticide used in agriculture, was investigated for the possible aggravation of the ovalbumin (OVA)-induced allergic pneumonitis and the possible induction of steroid resistance in rats. Additionally, it was investigated whether pirfenidone (PFD) could substitute dexamethasone, as an alternative treatment option, for the induced steroid resistance. Fifty-six male Wistar albino rats were randomly divided into seven groups: control, PFD alone, allergic pneumonitis, CYP alone, allergic pneumonitis/CYP-exposed, allergic pneumonitis/CYP/dexamethasone (Dex), and allergic pneumonitis/CYP/PFD-treated groups. Allergic pneumonitis was induced by three intraperitoneal OVA injections administered once a week, followed by an intranasal OVA instillation challenge. CYP (25 mg/kg/d), Dex (1 mg/kg/d), and PFD (100 mg/kg/d) were administered orally from day 15 to the end of the experiment. Bronchoalveolar lavage fluid (BALF) was analyzed for cytokine levels. Hematoxylin and eosin (H&E) and periodic acid Schiff (PAS)-stained lung sections were prepared. Immunohistochemical identification of p38 MAPK and lung macrophages was performed. The inflammatory/oxidative status of the lung and PCR-quantification of the STAT6, p38 MAPK, MUC5AC, and IL-13 genes were carried out. The allergic pneumonitis-only group showed eosinophil-mediated inflammation (p < 0.05). Further CYP exposure aggravated lung inflammation and showed steroid-resistant changes, p38 activation, neutrophil-mediated, M1 macrophage-related inflammation (p < 0.05). All changes were reversed (p < 0.05) by PFD, meanwhile not by dexamethasone treatment. Pirfenidone could replace dexamethasone treatment in the current rat model of CYP-induced severe steroid-resistant asthma via inhibiting the M1 macrophage differentiation through modulation of the STAT6/p38 MAPK pathway.

Synthetic Graft Augmentation Is Safe and Effective for the Repair of Acute Achilles Tendon Rupture in Patients With Preexisting Tendinopathy.

Purpose: To assess the safety and report the clinical outcomes of synthetic graft augmentation using polypropylene (PP) mesh in the repair of acute Achilles tendon (AT) rupture in patients with preexisting tendinopathy. Methods: Patients who underwent open repair for acute AT rupture at our institution between April 2017 and March 2019 were retrospectively identified. The inclusion criteria were acute AT rupture in patients with preexisting tendinopathy. All patients included in the study underwent acute repair augmented by an inlay PP mesh and had 30 months' follow-up. Patient characteristics, operative details, and outcomes were analyzed. Continuous data were described by mean, standard deviation, median, and range. The Wilcoxon signed rank test was used to analyze the change in patient-reported outcome measures. The significance level was set at a P-value of .05. Results: Thirteen patients were included. There were 5 female and 8 male patients, withan average age of 52 years (range 49-56 years). No cases of rerupture or graft-related complications requiring additional treatment occurred during mean follow -up of 38 months. All patients reported good functional outcome, as shown from nonsignificant difference between the preinjury and 38-month postoperative Achilles Tendon Rupture Score (88.5 ± 2.2 vs 89.2 ± 2.2, P = .107) and the excellent postoperative American Orthopedic Foot and Ankle Society Ankle/Hindfoot Scale score (92.22 ± 2.2) at last follow-up. At the end of follow-up, all patients were able to perform single-legged heel rise as the noninvolved side. By average of 16 weeks, all patients returned to their preinjury activity level. Conclusions: The use of inlay PP mesh to augment the repair of acute AT rupture in patients with preexisting tendinopathy appears to be safe and effective, allowing early return to preinjury activity level with favorable clinical outcomes. Level of Evidence: Level IV, therapeutic case series.

Histomorphological Changes in a Rat Model of Polycystic Ovary Syndrome and the Contribution of Stevia Leaf Extract in Modulating the Ovarian Fibrosis, VEGF, and TGF-ß Immunoexpressions: Comparison with Metformin.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder of fertile females. It has been reported that stevia leaf extract (SLE) has antidiabetic and antihyperlipidemic properties. Therefore, the current study hypothesized and investigated the role and mechanistic aspects of a natural sweetener; SLE in treating a rat model of letrozole-induced PCOS and to compare it with metformin. Thirty-five female Wistar albino rats were divided into 5 groups: control, PCOS-induced group (letrozole, 1 mg/kg/d, for 21 days), SLE, metformin, and combination-treated groups (300 mg/kg/d, for the next 28 days in SLE and metformin-treated groups). Vaginal smears were done. The levels of glucose, lipid, and hormonal profiles were measured in the serum meanwhile, malonyl dialdehyde (MDA), superoxide dismutase (SOD), and tumour necrosis factor (TNF-α) were measured in the ovary. Ovarian sections were subjected to hematoxylin and eosin, Masson, and immunohistochemical identification of VEGF and TGF-ß followed by morphometric analysis. PCOS rats showed altered hormonal and lipid profiles, in addition to hyperglycemia. Also, the ovarian tissue levels of MDA and TNF-α were elevated, and SOD was decreased. Numerous cystic follicles, decrease/absence of corpora lutea, interstitial fibrosis with positive VEGF and TGF-ß immunoreactivity were evident. SLE improved all altered parameters. SLE showed potential therapeutic merits in letrozole-induced PCOS via anti-inflammatory, antioxidant, anti-fibrotic, and angiogenesis regulating mechanisms. Its effects were almost comparable to metformin, and the combination of both has no further synergistic effect.

The anti-tumour effect of induced pluripotent stem cells against submandibular gland carcinoma in rats is achieved via modulation of the apoptotic response and the expression of Sirt-1, TGF-ß, and MALAT-1 in cancer cells.

The era of induced pluripotent stem cells (iPSCs) was used as novel biotechnology to replace embryonic stem cells bypassing the ethical concerns and problems of stem cell transplant rejection. The anti-tumour potential of iPSCs against many tumours including salivary cancer was proven in previous studies. The current study aimed to investigate the contribution of the Bax, Sirt-1, TGF-ß, and MALAT genes and/or their protein expression to the pathogenesis of submandibular carcinogenesis before and after iPSCs treatment. Thirty Wistar albino rats were equally assigned into three groups: group I (control), group II (Squamous cell carcinoma (SCC)): submandibular glands were injected SCC cells, and group III (SCC/iPSCs): SCC rats were treated by 5 × 106 iPSCs. Submandibular gland sections were subjected to histological and immunohistochemical analyses to detect mucopolysaccharides, Bax, and TGF-ß expression as well as PCR quantification for TGF-ß, Sirt-1, and lncRNA MALAT-1 gene expressions. Western blotting was also used to detect Sirt-1 and TGF-ß protein expressions. SCC group revealed infiltration by sheets of malignant squamous cells with or without keratin pearls and inflammatory cells, in addition to upregulation of TGF-ß, Sirt-1, MALAT-1, and Bax, whereas SCC/iPSCs group showed an improved submandibular histoarchitecture with the maintenance of the secretory function. Bax and TGF-ß immunoexpression were significantly reduced. The upregulated TGF-ß, Sirt-1, and MALAT-1 genes were significantly decreased. iPSCs protected against the experimentally induced submandibular gland carcinoma that might be achieved via their regenerative potential and their regulatory modulation of Sirt-1, TGF-ß, and MALAT-1 gene/protein expressions and of the apoptotic response in cancer cells.

The short-term impact of COVID-19 pandemic on spine surgeons: a cross-sectional global study.

PURPOSE: The outbreak of COVID-19 erupted in December 2019 in Wuhan, China. In a few weeks, it progressed rapidly into a global pandemic which resulted in an overwhelming burden on health care systems, medical resources and staff. Spine surgeons as health care providers are no exception. In this study, we try to highlight the impact of the crisis on spine surgeons in terms of knowledge, attitude, practice and socioeconomic burden. METHODS: This was global, multicentric cross-sectional study on 781 spine surgeons that utilized an Internet-based validated questionnaire to evaluate knowledge about COVID-19, availability of personal protective equipment, future perceptions, effect of this crisis on practice and psychological distress. Univariate and multivariate ordinal logistic regression analyses were used to evaluate the predictors for the degree of COVID-19 effect on practice. RESULTS: Overall, 20.2%, 52% and 27.8% of the participants were affected minimally, intermediately and hugely by COVID-19, respectively. Older ages (ß = 0.33, 95% CI 0.11-0.56), orthopedic spine surgeons (ß = 0.30, 95% CI 0.01-0.61) and those who work in the private sector (ß = 0.05, 95% CI 0.19-0.61) were the most affected by COVID-19. Those who work in university hospitals (ß = - 0.36, 95% CI 0.00 to - 0.71) were affected the least. The availability of N95 masks (47%) and disposable eye protectors or face shields (39.4%) was significantly associated with lower psychological stress (p = 0.01). Only 6.9%, 3.7% and 5% had mild, moderate and severe mental distress, respectively. CONCLUSION: While it is important to recognize the short-term impact of COVID-19 pandemic on the practice of spine surgery, predicting where we will be standing in 6-12 months remains difficult and unknown. The COVID-19 crisis will probably have an unexpected long-term impact on lives and economies.

Insufflation in minimally invasive surgery: Is there any advantage in staying low?

AIM: Minimally invasive repair of esophageal atresia with tracheoesophageal fistula (EA/TEF) and congenital diaphragmatic hernia (CDH) is feasible and confers benefits compared to thoracotomy or laparotomy. However, carbon dioxide (CO2) insufflation can lead to hypercapnia and acidosis. We sought to determine the effect of lower insufflation pressures on patients' surrogate markers for CO2 absorption - arterial partial pressure of CO2 (PaCO2), end tidal CO2 (EtCO2) and pH. METHODS: Single center retrospective review, including neonates without major cardiac anomaly. Selected patients formed 2 groups: Historical pressure (HP) group and low pressure (LP) group. We reported on the patients' preoperative characteristics that potentially confound the degree of CO2 absorption or elimination. Outcome measures were perioperative PaCO2, EtCO2, arterial pH and anesthetic time. RESULTS: 30 patients underwent minimally invasive surgery for CDH and 24 patients for EA/TEF with similar distribution within the HP and LP group. For CDH patients as well as for EA/TEF patients, there were no significant differences in their preoperative characteristics or surgery duration comparing HP and LP groups. With a decrease in insufflation pressure in CDH patients, there were a significant decrease (p = 0.002) in peak PaCO2 and an improvement in nadir pH (p = 0.01). For the EA/TEF patients, the decrease in insufflation pressure was associated with a significant decrease (p = 0.03) in peak EtCO2. Considering all 54 patients, we found EtCO2 to be highly significantly inversely correlated with pH and positively correlated with intraoperative PaCO2 (p < 0.001). Baseline Hb was inversely correlated with mean EtCO2 (p < 0.001). CONCLUSION: With lower insufflation pressures, CDH patients had significantly improved hypercapnia and acidosis, while EA/TEF patients had significantly reduced EtCO2. EtCO2 was correlated with acidosis and hypercapnia. TYPE OF STUDY: Retrospective case control study. LEVEL OF EVIDENCE: Level III.

Correlation of Specimen/Breast Volume Ratio to Cosmetic Outcome After Breast Conserving Surgery.

Breast conserving surgery (BCS) is currently the standard of care for early breast cancer. One of the key determinants for the line of treatment in breast cancer is the size of the tumor in relation to the breast size. The aim of this study is to determine the effect of the ratio of the excised specimen to breast volume on the cosmetic outcome after conventional BCS. This is a retrospective study conducted on female patients with early stage breast cancer who underwent BCT at National Cancer Institute, Cairo University. The study included 41 patients with stage I and II breast cancer. Breast volume was calculated using mammography, and ratio of the specimen to breast volume was determined. This ratio was correlated with the cosmetic outcome using the BCCT.core software. Thirty-six out of the 41 breast cancer patients completed the study. Favorable outcome (excellent + good) was detected in 52.7% of patients, while 47.3% had unfavorable outcome (fair + poor). Breast volume, tumor site, patients' age, and weight did not seem to alter the cosmetic result. The only statistically significant factors affecting the cosmetic outcome were the specimen volume and the ratio of the specimen to the normal breast volume (p = 0.006 and 0.019 respectively). In order to obtain a satisfactory cosmetic outcome after conventional BCS, the ratio of the excised specimen to breast volume has to be seriously considered.

Stem cells and metformin synergistically promote healing in experimentally induced cutaneous wound injury in diabetic rats.

INTRODUCTION: Diabetes mellitus (DM) is a serious, chronic metabolic disorder commonly complicated by diabetic foot ulcers with delayed healing. Metformin was found to have a wound healing effect through several mechanisms. The current study investigated the effect of both bone marrow-derived mesenchymal stem cells (BM-MSCs) and metformin, considered alone or combined, on the healing of an experimentally induced cutaneous wound injury in streptozotocin-induced diabetic rats. MATERIAL AND METHODS: Forty adult male albino rats were used. Diabetes was induced by single intravenous (IV) injection of streptozotocin (STZ). Next, two circular full thickness skin wounds were created on the back of the animals, then randomly assigned into 4 groups, ten rats each. BM-MSCs were isolated from albino rats, 8 weeks of age and labeled by PKH26 before intradermal injection into rats of Group III and IV. Groups I (diabetic positive control), II (metformin-treated, 250 mg/kg/d), III (treated with 2×106 BM-MSCs), and IV (wounded rats treated both with metformin and BM-MSCs cells). Healing was assessed 3, 7, 14, and 21 days post wound induction through frequent measuring of wound diameters. Skin biopsies were obtained at the end of the experiment. RESULTS: Gross evaluation of the physical healing of the wounds was done. Skin biopsies from the wound areas were processed for hematoxylin and eosin (H&E), Masson's trichrome staining and immunohistochemical staining for CD31. The results showed better wound healing in the combined therapy group (IV) as compared to monotherapy groups. CONCLUSIONS: Although both metformin and BM-MSCs were effective in the healing of experimentally induced skin wounds in diabetic rats, the combination of both agents appears to be a better synergistic option for the treatment of diabetic wound injuries.

Hyperthermic Intraperitoneal Chemotherapy Versus Systemic Chemotherapy in Recurrent Platinum-Sensitive Ovarian Cancer NCI Case Control Study

Objectives: To assess the efficacy of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent platinum-sensitive ovarian cancer patients in comparison with standard intravenous chemotherapy in terms of progression free survival and overall survival. Methods: Retrospective case control study matching 15 cases with 20 controls with at least 24 months of follow up. Results: The two groups were comparable and well matched in all aspects. Median follow up was 36 months in cases and 38 months in controls. The PFS2 revealed a median of 6 months (range 2-14) in cases and 5 months (range 2-18) in controls. The median OS was 36 and 38 months in cases and controls respectively. No statistically significant difference between the cases and controls were observed in progression free survival (PFS2) and overall survival OS (P-value, 0.350 and 0.711 respectively). However, the PFS2 was in favor of cases and OS was in favor of controls without reaching significance. The percentage of patients who survived 5 years or more was 20% in cases and 35% in controls. The only issue in favor of HIPEC is the significant reduction in chemotherapeutic toxicity when given by the intraperitoneal way (P- value 0.003). Conclusion: According to our study, CRS and HIPEC do not seem to have impact on OS and PFS in the setting of recurrent platinum sensitive ovarian cancer. However, we recommend on going researches with much more refined selection criteria and with larger sample size.

Oncologic and Cosmetic Outcomes of Oncoplastic Breast Surgery in Locally Advanced Breast Cancer After Neoadjuvant Chemotherapy, Experience from a Developing Country.

Oncoplastic surgery (OPS) has emerged as a new approach for extending breast conserving surgery (BCS) possibilities, reducing both mastectomy and re-excision rates, while avoiding breast deformities. OPS is based upon the integration of plastic surgery techniques for immediate reshaping after wide excision for breast cancer. This is a prospective feasibility cohort study of oncoplastic breast surgery after neoadjuvant chemotherapy that was carried at the National Cancer Institute, Cairo University and included 70 patients. The primary outcome was the local recurrence rate. Secondary outcomes included survival and margins obtained as well as cosmetic outcomes. Survival analysis was performed. Oncoplastic breast surgery did not compromise oncologic safety in the patients included in the study. It even allowed wider margins of resection which could be associated with better oncologic outcomes. At the same time, it gave a better cosmetic outcome and therefore higher patient satisfaction. Oncoplastic breast surgery includes a wide spectrum of surgical techniques, ranging from the basic level I techniques in breast conserving surgery to the more complex procedures of level II which are broadly classified into volume replacement (therapeutic mammoplasty) and volume displacement procedures. We suggest that oncoplastic breast surgery techniques should be the standard of care in breast surgery. They are the basis for breast conserving surgery techniques in early breast cancer. In our experience, oncoplastic surgery is feasible in locally advanced tumours after downstaging with neoadjuvant chemotherapy without compromising the oncologic safety.

Clinical spectrum of neonates presenting with pneumoperitoneum: A retrospective study.

BACKGROUND: Neonatal pneumoperitoneum is attributed, in most of the reported cases, to necrotising enterocolitis (NEC). There are also other causes leading to free intraperitoneal air. The aim of this study is to describe the clinical spectrum, causes, management and outcome of neonates admitted with pneumoperitoneum in the paediatric surgery unit of a university hospital. SUBJECTS AND METHODS: This retrospective study included neonates having radiographic evidences of pneumoperitoneum from 2012 to the end of 2014. Patients' files were analysed regarding age at admission, birth weight, history, clinical picture, management, operative findings and subsequent outcome. RESULTS: Fifty-six out of 379 neonates (14.7%) were found to have pneumoperitoneum during the study period. There were 35 males (62.5%) and 21 females (37.5%). Cases diagnosed as NEC represented 27 neonates (48.2%). There were 29 cases (51.8%) with causes not related to NEC. Non-NEC causes were spontaneous intestinal perforation (8.9%), ano-rectal malformations (7.1%), Hirschsprung's disease (14.2%), ileal atresia (3.5%), incarcerated inguinal hernia (1.7%), gastric perforation (1.7%) and meconium ileus (1.7%). In seven patients (12.5%), those who were managed conservatively (8.9%) or whose laparotomy was negative (3.6%), no cause of pneumoperitoneum could be reached. Overall mortality was 25%, 78.5% of which was NEC-related. CONCLUSIONS: Neonatal pneumoperitoneum is an alerting finding for paediatric surgeons. Most cases imply serious causes with a significant morbidity and mortality, NEC being the most common cause. On the other hand, pneumoperitoneum is not an absolute indication for surgery. Careful assessment and tailored management can limit the morbidity of unnecessary laparotomies.

Low cost biological lung volume reduction therapy for advanced emphysema.

BACKGROUND: Bronchoscopic lung volume reduction (BLVR), using biological agents, is one of the new alternatives to lung volume reduction surgery. OBJECTIVES: To evaluate efficacy and safety of biological BLVR using low cost agents including autologous blood and fibrin glue. METHODS: Enrolled patients were divided into two groups: group A (seven patients) in which autologous blood was used and group B (eight patients) in which fibrin glue was used. The agents were injected through a triple lumen balloon catheter via fiberoptic bronchoscope. Changes in high resolution computerized tomography (HRCT) volumetry, pulmonary function tests, symptoms, and exercise capacity were evaluated at 12 weeks postprocedure as well as for complications. RESULTS: In group A, at 12 weeks postprocedure, there was significant improvement in the mean value of HRCT volumetry and residual volume/total lung capacity (% predicted) (P-value: <0.001 and 0.038, respectively). In group B, there was significant improvement in the mean value of HRCT volumetry and (residual volume/total lung capacity % predicted) (P-value: 0.005 and 0.004, respectively). All patients tolerated the procedure with no mortality. CONCLUSION: BLVR using autologous blood and locally prepared fibrin glue is a promising method for therapy of advanced emphysema in term of efficacy, safety as well as cost effectiveness.

Laparoscopic marsupialization of postrenal transplantation lymphoceles.

BACKGROUND AND PURPOSE: Clinically significant post-transplantation lymphoceles are not uncommon. Surgical marsupialization with internal peritoneal drainage is the treatment of choice. We describe the successful laparoscopic formation of a peritoneal window for post-transplantation lymphocele drainage as an effective and minimally invasive procedure. PATIENTS AND METHODS: Between August 1995 and September 2001, 135 consecutive renal transplantations were performed, and 9 patients developed clinically significant lymphoceles. Four of the nine patients were treated by laparoscopic drainage via a peritoneal window. Analysis of predisposing risk factors commonly associated with lymphoceles was performed. The surgical outcome was assessed. RESULTS: Laparoscopic drainage was successful in all patients. The average operative time was 40 minutes. The mean hospital stay was 1.5 days for patients undergoing laparoscopic drainage versus 5 days for those having open surgical drainage. Accidental division of the right native ureter occurred in one patient, which was identified intraoperatively. None of the patients had developed recurrence of lymphocele after a mean follow-up of 10.7 months (range 6-22) months. CONCLUSION: In patients with a clinically significant post-transplantation lymphocele of appropriate size and location, laparoscopic drainage is easy, safe, and effective. It decreases hospital stay and hastens convalescence.

Locally advanced rectal carcinoma: preoperative radiotherapy versus postoperative chemoradiation, 10-year follow-up results of a randomized clinical study.

PURPOSE: A prospective study was designed to randomize locally advanced rectal carcinoma patients between either preoperative radiotherapy (+/- postoperative chemotherapy) or postoperative adjuvant chemoradiation. Two end points were evaluated, local recurrence and survival, aiming at defining prognostic parameters that can help in the choice of the optimum treatment modality. PATIENTS AND METHODS: This is a prospective randomized clinical study including patients with locally advanced low rectal cancer treated at the National Cancer Institute (NCI), Cairo University, during the period from December 1994 to January 1999. Fifty patients with previously untreated rectal cancer were randomized into two groups, Group I: Subjected to surgery followed by radiation therapy (50Gy/5 weeks, 2Gy/fraction, 5 days/week) plus chemotherapy and Group II, subjected to preoperative radiotherapy (46Gy/4.5 weeks, 2Gy/ fraction, 5 days/week) followed by surgery +/- postoperative chemotherapy. Chemotherapy in the concomitant setting was given in the form of Leucovorin in a dose of 300mg/m2 as a short i.v. infusion followed by 5-FU in a dose of 350mg/m2 as a 6 hour i.v. infusion, whereas adjuvant chemotherapy consisted of 5- FU as 600mg/m2 short i.v. infusion weekly for 48 weeks, in addition to levamisole tablets. RESULTS: The long-term treatment end results obtained showed that group I patients had a slightly higher 10-year overall survival (OS) rate when compared to group II patients (63% versus 60%, p=0.698). The corresponding figures for the 10-year disease-free survival (DFS) were 65% and 66%, respectively, p=0.816. Although the 10- year local failure rate (persistent/relapsed disease) was higher for the preoperative group, it was not of statistical significance, (30% Vs. 8%, p=0.057). On the other hand, the 10-year distant metastasis free survival was higher in the preoperative group (88% Vs. 72%), yet this difference did not reach statistical significance (p=0.16). The rate of acute radiation reactions was higher in the postoperative group, with no increase in the operative complications in the preoperative group. Moreover, none of the 50 patients had grade 3 or more late radiation/surgical squealae. There were no grade 3 or 4 chemotherapy related toxicities. CONCLUSIONS: This work showed equal results for DFS and OS rates between preoperative and postoperative radiation therapy with the same acceptable acute and late radiation toxicity. High dose preoperative irradiation did not cause any significant increase in acute or late radiation induced reactions, delay in wound healing or increased postoperative morbidity when compared to postoperative adjuvant radiochemotherapy. Duke' s stage and response to preoperative irradiation proved to be of significance regarding DFS, while compliance to systemic therapy was of significance regarding both OS and DFS.

A prognostic index (bladder prognostic index) for bilharzial-related invasive bladder cancer.

PURPOSE: Bladder cancer is still the most common solid tumor among adult males in Egypt because of the prevalence of bilharzial infestation, especially in the countryside. In this prospective study, we have recorded the prognostic factors for 180 patients with invasive bladder cancer for whom standard radical cystectomy had been performed to develop a prognostic index (bladder prognostic index) that defines high risk patients who are more vulnerable to disease relapse after surgery and who may benefit from additional therapy. PATIENTS AND METHODS: The study was performed between January 1997 and December 1999, in which 180 patients with histopathologically proved invasive bladder cancer associated with bilharziasis underwent radical cystectomy or anterior pelvic exenteration. After surgery, patients were regularly followed for a minimum of 2 years. RESULTS: Our patients included 141 males and 39 females. Squamous cell carcinoma was the most common type (53.3%), and most of the tumors were grade II (61.1%). A total of 173 patients had their tumors operable, while 7 were inoperable. We had 5 (2.8%) operative related mortalities. At 5 years postoperatively, free and overall survival rates for the whole group of patients were 31.44%+/-5.9% and 32.5%+/-6.8%, respectively. Tumor pathologic stage, grade, and nodal affection were the only significant factors with impact on survival (P=0.008, 0.051, and 0.004, respectively). These 3 prognostic indexes were used to design a model to predict an individual patient's risk factor for recurrence. Patients were then assigned to one of the 4 risk groups according to the score achieved in this prognostic index (0=low risk, 1=intermediate risk, and 2 or 3=higher risk). These 4 risk groups had distinctly different rates of disease-free survival, i.e., 91.7%, 53%, 13%, and 7% for low, intermediate, and higher risk groups, respectively. CONCLUSION: Although this prognostic index appears to be of a significant clinical relevance, it needs to be more validated on a larger number of patients, and it could be a surrogate variable for biologic factors responsible for the heterogeneity of bladder cancer.

Clinico-pathological features and outcome of management of pediatric gastrointestinal lymphoma.

PURPOSE: The purpose of this study is to evaluate pediatric GIT lymphomas as regards clinico-pathological features, controversies in surgical treatment, role of chemotherapy and the prognostic features. PATIENTS AND METHODS: This study included forty three patients with pediatric GIT Non-Hodgkin's lymphoma collected over 7 years at the NCI Cairo University between January 1997 and December 2003. The data of every patient included: Age, sex, presenting symptoms and signs, preoperative investigations, extent of the disease at diagnosis and the type of resection performed, histopathological examination, details of chemotherapy and state at follow up. Overall and disease free survival were calculated and correlated with all parameters. RESULTS: The study included 30 boys and 13 girls with median age 5.00 years (range: 0.4:17). The lesions were located in the small intestine (n=15), the large intestine (n=14), the ileocecal region (n=10), stomach (n=2), and multifocally (n=2). Burkitt's lymphoma was the commonest histological type (n=24). The majority were stage IIE and IIIE (22 and 17 respectively). Exploration was done in thirty nine patients (complete resections were done in 23 cases, incomplete resections (debulking) were done in 14 cases and in 2 cases only lymph node biopsies were done). All patients received a sort of systemic chemotherapy. The median follow up duration was 44 months (range 4- 116 months). The only parameters that had significantly affected the overall survival were localized disease, complete resection, earlier stage and response to chemotherapy with p values, (0.005, 0.001, 0.005 and <0.001 respectively). As regards the disease free survival the only significant factor was localized disease (p=0.035). CONCLUSION: The extent of disease at presentation is the most important prognostic factor in pediatric GIT lymphoma. Surgery still plays an important role such as complete resection in localized disease, management of complicated disease and diagnostic biopsy. There is no value of debulking and surgery is not advised for gastric lesions. Chemotherapy represents a cornerstone in the treatment and offers an excellent chance for long term, disease free survival.