Hosni K. Salem

A Prospective Randomized Study Comparing Shock Wave Lithotripsy and Semirigid Ureteroscopy for the Management of Proximal Ureteral Calculi

OBJECTIVES To conduct a prospective randomized study comparing both techniques for the management of solitary radio-opaque upper ureteral stones < 2 cm in diameter. The ideal treatment for upper ureteral stones > 1 cm size remains to be determined with shock wave lithotripsy (SWL) and ureteroscopy (URS) being acceptable options. METHODS A total of 200 patients were included in the study. They were randomized into 2 equal groups. Group A underwent in situ SWL as a primary therapy. Group B underwent URS, using semirigid URS with intracorporeal lithotripsy. Efficiency quotient (EQ), cost analysis, and predictors of failure were estimated for both techniques. RESULTS For stones of size > or = 1 cm, the initial stone-free rate for URS and SWL was 88% and 60%, respectively. The estimated EQ was 0.79 and 0.43 for both techniques respectively. For stones < 1 cm, the initial stone-free rate for URS and SWL was 100% and 80%, respectively. The estimated EQ was 0.88 and 0.70 for both techniques, respectively. The mean cumulative costs were significantly more in SWL group (P <.05). Predictors of URS failure included; male gender, failure to pass guidewire beyond the stone, and extravasation. Predictors of SWL failure included large stone size > 1 cm, calcium oxalate monohydrate stone, and higher degrees of hydronephrosis. CONCLUSIONS URS with intracorporeal lithotripsy is an acceptable treatment modality for all proximal ureteral calculi, particularly stones > 1 cm. SWL should remain the first-line therapy for proximal ureteral calculi < or = 1 cm because of the less invasive nature and lower anesthesia (i.v. sedation).

Environmental immune disruptors, inflammation and cancer risk

An emerging area in environmental toxicology is the role that chemicals and chemical mixtures have on the cells of the human immune system. This is an important area of research that has been most widely pursued in relation to autoimmune diseases and allergy/asthma as opposed to cancer causation. This is despite the well-recognized role that innate and adaptive immunity play as essential factors in tumorigenesis. Here, we review the role that the innate immune cells of inflammatory responses play in tumorigenesis. Focus is placed on the molecules and pathways that have been mechanistically linked with tumor-associated inflammation. Within the context of chemically induced disturbances in immune function as co-factors in carcinogenesis, the evidence linking environmental toxicant exposures with perturbation in the balance between pro- and anti-inflammatory responses is reviewed. Reported effects of bisphenol A, atrazine, phthalates and other common toxicants on molecular and cellular targets involved in tumor-associated inflammation (e.g. cyclooxygenase/prostaglandin E2, nuclear factor kappa B, nitric oxide synthesis, cytokines and chemokines) are presented as example chemically mediated target molecule perturbations relevant to cancer. Commentary on areas of additional research including the need for innovation and integration of systems biology approaches to the study of environmental exposures and cancer causation are presented.

Causes of genome instability: the effect of low dose chemical exposures in modern society

Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genomes integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis.

The effect of environmental chemicals on the tumor microenvironment

Potentially carcinogenic compounds may cause cancer through direct DNA damage or through indirect cellular or physiological effects. To study possible carcinogens, the fields of endocrinology, genetics, epigenetics, medicine, environmental health, toxicology, pharmacology and oncology must be considered. Disruptive chemicals may also contribute to multiple stages of tumor development through effects on the tumor microenvironment. In turn, the tumor microenvironment consists of a complex interaction among blood vessels that feed the tumor, the extracellular matrix that provides structural and biochemical support, signaling molecules that send messages and soluble factors such as cytokines. The tumor microenvironment also consists of many host cellular effectors including multipotent stromal cells/mesenchymal stem cells, fibroblasts, endothelial cell precursors, antigen-presenting cells, lymphocytes and innate immune cells. Carcinogens can influence the tumor microenvironment through effects on epithelial cells, the most common origin of cancer, as well as on stromal cells, extracellular matrix components and immune cells. Here, we review how environmental exposures can perturb the tumor microenvironment. We suggest a role for disrupting chemicals such as nickel chloride, Bisphenol A, butyltins, methylmercury and paraquat as well as more traditional carcinogens, such as radiation, and pharmaceuticals, such as diabetes medications, in the disruption of the tumor microenvironment. Further studies interrogating the role of chemicals and their mixtures in dose-dependent effects on the tumor microenvironment could have important general mechanistic implications for the etiology and prevention of tumorigenesis.

Changing Patterns (Age, Incidence, and Pathologic Types) of Schistosoma-associated Bladder Cancer in Egypt in the Past Decade

OBJECTIVE To assess the patterns of schistosomiasis-associated bladder cancer in Egypt from 2001 to 2010 in a retrospective study. Bilharzial bladder carcinoma is the most common cancer, particularly in Egyptian men. Classically, carcinoma in a bilharzial bladder is most commonly of the squamous cell type. During the past decade, certain changes have occurred in the features in Schistosomiasis-associated carcinoma in Egypt with a decline in the frequency of squamous cell carcinoma and increase in the frequency of transitional cell carcinoma. METHODS This was a retrospective study of 1932 patients treated at Kasr Al Aini Hospital, Cairo University, from 2001 to 2010. Two groups were selected: group 1 included 1002 patients from 2001 to 2005 and group 2 included 930 patients from 2006 to 2010. RESULTS The mean patient age increased from 41±11.2 years to 52±8.6 years, and the male/female ratio changed from 5.6:1 to 4.2:1. The incidence of associated bilharziasis decreased from 80% to 50%. A significant increased occurred in transitional cell carcinoma from 20% to 66%, with a significant decrease in squamous cell carcinoma from 73% to 25%. No difference was observed in the tumor stage or grade or incidence of lymph node metastases between the 2 groups. CONCLUSION The pattern of incidence of the various histologic types of bladder cancer have changed, with most cases now transitional cell carcinoma, in contrast to the findings in the earlier Egyptian series. Additional studies are encouraged to explain the factors explaining these changes.

Metabolic reprogramming and dysregulated metabolism: cause, consequence and/or enabler of environmental carcinogenesis?

Environmental contributions to cancer development are widely accepted, but only a fraction of all pertinent exposures have probably been identified. Traditional toxicological approaches to the problem have largely focused on the effects of individual agents at singular endpoints. As such, they have incompletely addressed both the pro-carcinogenic contributions of environmentally relevant low-dose chemical mixtures and the fact that exposures can influence multiple cancer-associated endpoints over varying timescales. Of these endpoints, dysregulated metabolism is one of the most common and recognizable features of cancer, but its specific roles in exposure-associated cancer development remain poorly understood. Most studies have focused on discrete aspects of cancer metabolism and have incompletely considered both its dynamic integrated nature and the complex controlling influences of substrate availability, external trophic signals and environmental conditions. Emerging high throughput approaches to environmental risk assessment also do not directly address the metabolic causes or consequences of changes in gene expression. As such, there is a compelling need to establish common or complementary frameworks for further exploration that experimentally and conceptually consider the gestalt of cancer metabolism and its causal relationships to both carcinogenesis and the development of other cancer hallmarks. A literature review to identify environmentally relevant exposures unambiguously linked to both cancer development and dysregulated metabolism suggests major gaps in our understanding of exposure-associated carcinogenesis and metabolic reprogramming. Although limited evidence exists to support primary causal roles for metabolism in carcinogenesis, the universality of altered cancer metabolism underscores its fundamental biological importance, and multiple pleiomorphic, even dichotomous, roles for metabolism in promoting, antagonizing or otherwise enabling the development and selection of cancer are suggested.

Management of high-grade renal injuries in children after blunt abdominal trauma: Experience of 40 cases

OBJECTIVE We present our experience of management of high-grade renal trauma in a pediatric population, including assessment of the long-term function and morphology of the ipsilateral kidney. PATIENTS AND METHODS From 1997 to 2005, 40 children with high-grade renal injury (III, IV, V) after blunt abdominal trauma were managed. Initial evaluation included vital signs, color of urine, hemoglobin (Hb%), hematocrit, serum creatinine and computed tomography (CT). Follow up included vital signs, urine analysis, Hb%, CT, +/-intravenous pyelogram and renogram. RESULTS One patient needed superselective embolization due to continuing hemorrhage in spite of conservative treatment. Internal stenting plus percutaneous tube drain was indicated in three cases due to progressive extravasation. Exploration was indicated in four cases, one at presentation due to hemodynamic instability which ended in nephrectomy; the other three were successfully repaired. Conservative treatment was successful in 32 cases (80%). Blood transfusion was indicated in 16 cases (40%). Length of hospital stay was 4-20 days (mean 12.1). At the last follow up (range 1-8 years, mean 3.5), scars were detected in 10 cases, while all showed normal levels of Hb% and creatinine. No patient developed hypertension. Apart from in the nephrectomy case, the ipsilateral kidney showed split function of 40-50%. CONCLUSION After exclusion of hemodynamic instability and continuing hemorrhage, conservative treatment is successful in 80% of patients. Internal stenting with or without percutaneous drainage is indicated if there is progressive urinoma. Angioembolization is successful in selected cases.

The potential for chemical mixtures from the environment to enable the cancer hallmark of sustained proliferative signalling.

The aim of this work is to review current knowledge relating the established cancer hallmark, sustained cell proliferation to the existence of chemicals present as low dose mixtures in the environment. Normal cell proliferation is under tight control, i.e. cells respond to a signal to proliferate, and although most cells continue to proliferate into adult life, the multiplication ceases once the stimulatory signal disappears or if the cells are exposed to growth inhibitory signals. Under such circumstances, normal cells remain quiescent until they are stimulated to resume further proliferation. In contrast, tumour cells are unable to halt proliferation, either when subjected to growth inhibitory signals or in the absence of growth stimulatory signals. Environmental chemicals with carcinogenic potential may cause sustained cell proliferation by interfering with some cell proliferation control mechanisms committing cells to an indefinite proliferative span.

Long‐term Follow‐up (18–35 years) of Male Patients with History of Bladder Exstrophy (BE) Repair in Childhood: Erectile Function and Fertility Potential Outcome

INTRODUCTION Bladder exstrophy is a rare condition that may lead to severe psychosexual malformation and require a lifelong follow-up. AIM We describe the long-term sexual outcome of patients with bladder exstrophy treated at our institution at early stage. METHODS Thirty patients with mean age of 26 years (range 18-35 years) were included in the study. Fifteen patients underwent staged primary reconstruction, five patients underwent complete primary repair, and 10 patients underwent primary or secondary ureterosigmoidostomy. MAIN OUTCOME MEASURES Evaluation consisted of pediatric medical records, interview questionnaire including the psychosexual history, International Index of Erectile Function (IIEF), and semen analysis. RESULTS Erectile functions were maintained in 28 patients based on IIEF domain score. In all cases, penile length was objectively less than average (mean 7.65 cm). Seven patients were not satisfied with their penile length, and four cases complained of slight curvature. Ten patients were married (33%), of whom four patients had children (after normal conception in three, and after assisted reproductive technique in one). The remaining 20 patients were not married because of the feeling of sexual inadequacy to be able to engage in sexual intercourse (six patients), afraid of the cosmetic appearance of the genitalia (10 patients), and incontinence (four patients). Retrograde ejaculation was documented in 16 cases (53.5%), low volume ejaculate in eight cases (26.5%), and anejaculation in six cases (20%). Cosmetic outcome was considered satisfactory by 50% of the patients. Sixteen patients voided per urethra, four performed clean intermittent catheterization, and 10 patients had ureterosigmoidostomy diversion. Urinary tract infection was documented in 20% of the cases, and recurrent attacks of pyelonephritis in 10% of the cases. CONCLUSION Long-term outcome of bladder exstrophy repair in male patients showed fair results with respect to sexual function with more or less stable sexual relationship. We should do our best to solve the problem of those with restricted sexual lives.

Mechanisms of environmental chemicals that enable the cancer hallmark of evasion of growth suppression

As part of the Halifax Project, this review brings attention to the potential effects of environmental chemicals on important molecular and cellular regulators of the cancer hallmark of evading growth suppression. Specifically, we review the mechanisms by which cancer cells escape the growth-inhibitory signals of p53, retinoblastoma protein, transforming growth factor-beta, gap junctions and contact inhibition. We discuss the effects of selected environmental chemicals on these mechanisms of growth inhibition and cross-reference the effects of these chemicals in other classical cancer hallmarks.