[Implementation of hybrid-NOTES sigmoidectomy for diverticular disease : In a center for minimally invasive surgery]. / Implementierung der Hybrid-NOTES-Sigmoidektomie bei Divertikelkrankheit : In einem Zentrum für minimalinvasive Chirurgie.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) describes surgical procedures through a natural orifice. In hybrid-NOTES small transabdominal trocars are combined with a NOTES access. OBJECTIVE: To evaluate hybrid-NOTES sigmoidectomy as a standard procedure for diverticulitis. MATERIAL AND METHODS: Elective laparoscopic sigmoidectomies performed between May 2011 and January 2016 were prospectively collated. Primary endpoint was the feasibility of hybrid-NOTES sigmoidectomy. The reasons for planning a laparoscopically-assisted sigmoidectomy (LAS), intraoperative change of treatment and reactive conversion were evaluated. Secondary endpoints were complications and operative time. RESULTS: Out of 130 laparoscopic sigmoidectomies 83% were planned for hybrid-NOTES and 8 out of 52 (15%) transvaginal (TVS) and 14 out of 56 (25%) transrectal (TRS) sigmoidectomies were intraoperatively changed to LAS. The reason for the change in 64% was that the specimen was too bulky and 80% of scheduled hybrid-NOTES procedures were carried out as planned. The operative time for TVS (146.8 ± 44.5 min) was shorter compared to LAS (173.2 ± 58.8 min, P = 0.016). The morbidities of TVS (15.3%) and TRS (14.9%) were not significantly different from LAS (23.9%, P = 0.501 and P = 0.537, respectively). CONCLUSION: Hybrid-NOTES for diverticular disease may be indicated in more than 80% of cases. In respect of intraoperative change of treatment, hybrid-NOTES is feasible in two thirds of patients. Given a high level of expertise, hybrid-NOTES can be provided as a standard procedure in sigmoidectomy for diverticular disease.

Hartmann's procedure and laparoscopic reversal versus primary anastomosis and ileostomy closure for left colonic perforation.

PURPOSE: Emergency surgical strategies for acute left-sided colonic perforation are evolving preferring primary anastomosis (PA) with ileostomy to Hartmann's procedure (HP) based on the morbidity and reversal rates. However, HP is still commonly performed. Hartmann's reversal is associated with considerable morbidity. It is of interest whether laparoscopic reversal results in a lower morbidity as retrospective data suggest. Here, we compared the combined morbidity rates for two surgical strategies: strategy A, HP followed by laparoscopic reversal, and strategy B, sigmoid resection with PA followed by ileostomy closure. METHODS: Prospectively collected data of all consecutive patients undergoing HP for benign left-sided colonic perforation between 2010 and 2014 were retrospectively compared to data of patients undergoing PA. Groups were matched for age and Charlson comorbidity index. Additionally, patients were analyzed for American Society of Anesthesiologists score, body mass index, and peritonitis stage. End points were morbidity, operation time, reversal rate, time to reversal, and length of hospital stay. RESULTS: The study included 32 patients for whom Hartmann's reversal was planned, along with 32 matched patients who underwent PA and diverting ileostomy. Median age was 75 and 72 years, Charlson score was 6 (4-9) and 6 (5-7), and patients classified by the American Society of Anesthesiologists (ASA) higher than III were 81 % in both groups. Combined major morbidity rates were 21 % for strategy A and 20 % for strategy B (p = 1.0). Combined comprehensive complication index was 16.4 ± 14.1 and 12.3 ± 19.1 (p = 0.08). HP reversal by laparoscopy was achieved in 71 %. The colostomy reversal rate was 75 % compared to ileostomy closure rate of 88 % (p = 0.34). CONCLUSIONS: Laparoscopic Hartmann's reversal is achievable in a high proportion of patients. Strategy B tends to have lower overall morbidity; meanwhile, major morbidity seems to be similar. Yet, in critically ill patients and in the absence of expertise of the surgeon on call, HP followed by elective laparoscopic reversal represents a viable alternative.

Non-Hodgkin lymphoma and benzene exposure: a systematic literature review.

Epidemiological papers that address an association between benzene exposure and non-Hodgkin lymphoma (NHL) were identified and separated by study design. Eighteen studies contained 21 study groups-11 population-based case-control study groups, 3 nested occupation-based case-control study groups and 7 occupational benzene cohort study groups. Petroleum industry studies were not included. Only two of these 21 study groups showed statistically significant associations. However, these were among workers with multiple exposures across industries. Eleven of the 21 study groups presented ratios less than one, two equaled one, and eight were greater than one. Over all, about as many cases were observed (404) as expected (390.0) for an observed to expected ratio of 1.04 (0.94-1.14). After removal of the studies with multiple chemical exposures problems, the observed was 359 cases with 373.2 cases expected, yielding an odds ratio of 0.96 (0.86-1.06). Further assessment of an association with NHL should document the benzene exposure and separate out the contribution of non-benzene exposures.

Perchlorate clinical pharmacology and human health: a review.

Potassium perchlorate has been used at various times during the last 50 years to treat hyperthyroidism. Since World War II ammonium perchlorate has been used as a propellant for rockets. In 1997, the assay sensitivity for perchlorate in water was improved from 0.4 mg/L (ppm) to 4 microg/L (ppb). As a result, public water supplies in Southern California were found to contain perchlorate ions in the range of 5 to 8 ppb, and those in Southern Nevada were found to contain 5 to 24 ppb. Research programs have been developed to assess the safety or risk from these exposures and to assist state and regulatory agencies in setting a reasonable safe level for perchlorate in drinking water. This report reviews the evidence on the human health effects of perchlorate exposure. Perchlorate is a competitive inhibitor of iodine uptake. All of its pharmacologic effects at current therapeutic levels or lower are associated with inhibition of the sodium-iodide symporter (NIS) on the thyroid follicular cell membrane. A review of the medical and occupational studies has been undertaken to identify perchlorate exposure levels at which thyroid hormone levels may be reduced or thyrotropin levels increased. This exposure level may begin in the 35 to 100 mg/d range. Volunteer studies have been designed to determine the exposure levels at which perchlorate begins to affect iodine uptake in humans. Such effects may begin at levels of approximately 1 mg/d. Environmental studies have assessed the thyroidal health of newborns and adults at current environmental exposures to perchlorate and have concluded that the present levels appear to be safe. Whereas additional studies are underway both in laboratory animals and in the field, it appears that a safe level can be established for perchlorate in water and that regulatory agencies and others are now trying to determine that level.

Prevalence of thyroid diseases in Nevada counties with respect to perchlorate in drinking water.

Perchlorate is well-known to inhibit the uptake of iodine by the thyroid and has been shown to do so at doses in the milligrams-per-day range and higher. Perchlorate has been found in the water supply of Clark County (Las Vegas), Nevada, at 4 to 24 micrograms/L (parts per billion) and may provide exposure dosages in the tens of micrograms per day. An analysis of the Medicaid database from Nevada was undertaken to determine whether an increase in the prevalence of any thyroid disease was associated with that level of perchlorate content. The prevalence of persons being seen for thyroid disease or for specific thyroid diseases (goiter, nodule, thyrotoxicosis, congenital hypothyroidism, acquired hypothyroidism, thyroiditis, and other thyroid disorders) and for thyroid cancer among the Medicaid-eligible population of each county was calculated for the 2-year period 1997 to 1998. The prevalences in Clark County were compared with those in Washoe County (i.e., Reno), the second most populous county in the state, and with those for the rest of the state. There was no evidence of an increased rate of thyroid disease (or of any specific thyroid disease) associated with perchlorate exposure. Generally, the prevalences in the metropolitan parts of the state were lower than for the rest of the state, particularly for acquired hypothyroidism. This analysis found no evidence that perchlorate-containing drinking water at the given level increased the prevalence of acquired hypothyroidism or of any other thyroid condition.

Neonatal thyroid-stimulating hormone level and perchlorate in drinking water.

BACKGROUND: The effect of perchlorate in drinking water on neonatal blood thyroid-stimulating hormone (thyrotropin; TSH) levels was examined for Las Vegas and Reno, Nevada. METHODS: The neonatal blood TSH levels in Las Vegas (with up to 15 microg/L (ppb) perchlorate in drinking water) and in Reno (with no perchlorate detected in the drinking water) from December 1998 to October 1999 were analyzed and compared. The study samples were from newborns in their first month of life (excluding the first day of life) with birth weights of 2, 500-4,500 g. A multivariate analysis of logarithmically transformed TSH levels was used to compare the mean TSH levels between Las Vegas and Reno newborns, with age and sex being controlled as potential confounders. RESULTS: This study of neonatal TSH levels in the first month of life found no effect from living in the areas with environmental perchlorate exposures of

The effect of short-term low-dose perchlorate on various aspects of thyroid function.

Perchlorate (ClO4) salts are found in rocket fuel, fireworks, and fertilizer. Because of ground water contamination, ClO4 has recently been detected in large public water supplies in several states in the 4-18 microg/L (parts per billion [ppb]) range. The potential adverse effect of chronic low level ClO4 ingestion on thyroid function is of concern to the Environmental Protection Agency (EPA). The daily ingestion of ClO4 at these levels would be magnitudes below the therapeutic effect level of hundreds of milligrams of ClO4 used in treating hyperthyroidism. Studies were carried out in nine healthy male volunteers who had normal thyroid function and negative thyroid antibodies to determine whether the ingestion of 10 mg of ClO4 daily (approximately 300 times the estimated maximum amount of ClO4 consumed from the affected water supplies) would affect any aspect of thyroid function. They ingested 10 mg of ClO4 dissolved in a liter of spring water during waking hours for 14 days. Baseline serum thyrotropin (TSH), free thyroxine index (FTI), total triiodothyronine (TT3), 4-, 8-, and 24-hour thyroid 123I uptakes (RAIU), serum and 24-hour urine ClO4, 24-hour urine iodine, complete blood count (CBC), and chemistry profile were determined. All blood and urine tests were repeated on days 7 and 14 of ClO4 administration and thyroid RAIU on day 14 of ClO4 administration. All tests were repeated 14 days after ClO4 was discontinued. No effect of ClO4 on serum thyroid hormone or TSH concentrations, urinary iodine excretion, CBC, or blood chemistry was observed. Urine and serum ClO4 levels were appropriately elevated during the course of ClO4 ingestion in all subjects, demonstrating compliance. By day 14 of ClO4 administration, the 4-, 8-, and 24-hour thyroid RAIU values decreased in all nine subjects by a mean value of 38% from baseline and rebounded above baseline values by 25% at 14 days after ClO4 withdrawal (p < 0.01 analysis of variance (ANOVA) and Tukey). It is well known that the major effect of ClO4 on the thyroid is a decrease in the thyroid iodide trap by competitive inhibition of the sodium iodide symporter (NIS). The present study demonstrates the sensitivity of the thyroid iodide trap to ClO4 because a low dose of 10 mg daily significantly decreased the thyroid RAIU without affecting circulating thyroid hormone or TSH concentrations. It is possible, however, that the daily consumption of low levels of ClO4 in drinking water over a prolonged period of time could adversely affect thyroid function but no evidence of hypothyroidism was observed at 10 mg of ClO4 daily in this 2-week study. It is now of interest to determine a no effect level for ClO4 on the inhibition of the thyroid RAIU and to carry out a long-term ClO4 exposure study.

Fibromyalgia, hypermobility, and breast implants.

OBJECTIVE: To examine possible relationships among fibromyalgia (FM, American College of Rheumatology 1990 criteria), hypermobility, and breast implants. METHODS: The medical records of 2,500 female patients (ages 25-65) who had been seen for the first time in a rheumatology practice in Atlanta, GA, during 1986-92 were abstracted and analyzed. In each analysis, patients whose records indicated that the patient met the full case criteria were compared with patients whose records had no indication of the disease. Patients whose medical records indicated the clinical onset of FM prior to breast implantation were identified. RESULTS: Univariate and multivariate regression analyses were performed, adjusting for age, income, and the presence of connective tissue disease or rheumatoid arthritis. Significant associations were found between hypermobility and FM (adjusted OR 2.20, 95% CI 1.73, 2.80) and between hypermobility and breast implantation (adjusted OR 1.80, 95% CI 1.19, 2.69). No association was found between breast implantation and subsequent FM (adjusted OR 0.74, 95% CI 0.42, 1.32). CONCLUSION: Hypermobility was found to be independently associated with both FM and with breast implantation, but FM and breast implantation were not found to be independently associated with each other.

Neonatal thyroxine level and perchlorate in drinking water.

Environmental contamination of drinking water has been observed for perchlorate, a chemical able to affect thyroid function. This study examines whether that exposure affected the thyroid function of newborns. Neonatal blood thyroxine (T4) levels for days 1 to 4 of life were compared for newborns from the city of Las Vegas, Nevada, which has perchlorate in its drinking water, and those from the city of Reno, Nevada, which does not (detection limit, 4 micrograms/L [ppb]). This study is based on blood T4 analyses from more than 23,000 newborns in these two cities during the period April 1998 through June 1999. No difference was found in the mean blood T4 levels of the newborns from these two cities. Drinking water perchlorate levels measured monthly for Las Vegas ranged during this study period from non-detectable for 8 months to levels of 9 to 15 ppb for 7 months. Temporal differences in mean T4 level were noted in both cities but were unrelated to the perchlorate exposure. This study was sufficiently sensitive to detect the effects of gender, birth weight, and the day of life on which the blood sample was taken on the neonatal T4 level, but it detected no effect from environmental exposures to perchlorate that ranged up to 15 micrograms/L (ppb).

Has perchlorate in drinking water increased the rate of congenital hypothyroidism?

Perchlorate, known to inhibit the human thyroid at doses above 200 mg/day, was detected in the drinking-water supplies of seven counties in California and Nevada at levels of 4 to 16 micrograms/L in 1997. The data from the neonatal screening programs of the state health departments in these two states were analyzed for any increased incidence of congenital hypothyroidism in those counties. County-specific, ethnicity-specific data for Nevada and California were obtained for 1996 and 1997. Within these seven counties, nearly 700,000 newborns had been screened. In all, 249 cases were identified, where 243 were expected, for an overall risk ratio of 1.0 (95% confidence interval, 0.9 to 1.2). The risk ratios for the individual counties ranged between 0.6 and 1.1. These data in this ecological analysis do not indicate an increase in the incidence of congenital hypothyroidism with the reported perchlorate levels.

Thyroid health status of ammonium perchlorate workers: a cross-sectional occupational health study.

Since pharmaceutical exposures to perchlorate are known to suppress thyroid function in patients with hyperthyroidism, a study of employees at a perchlorate manufacturing plant was conducted to assess whether occupational exposure to perchlorate suppresses thyroid function. Exposure to perchlorate was assessed by measurement of ambient air concentrations of total and respirable perchlorate particles, and systemic absorption was assessed by measurement of urinary perchlorate excretion. Airborne exposures ranged from 0.004 to 167 mg total particulate perchlorate per day. Urinary perchlorate measurements demonstrated that exposure to the airborne particulate perchlorate resulted in systemic absorption. Workers were grouped into four exposure categories with mean absorbed perchlorate dosages of 1, 4, 11 and 34 mg perchlorate per day. Thyroid function was assessed by measurement of serum thyroid-stimulating hormone, free thyroxine index, thyroxine, triiodothyronine, thyroid hormone binding ratio, thyroid peroxidase antibodies, and by clinical examination. No differences in thyroid-function parameters were found between the four groups of workers across approximately three orders of magnitude of exposure and of dose. Thus human thyroid function was not affected by these levels of absorbed perchlorate. In addition, no clinical evidence of thyroid abnormalities was found in any exposure group. The blood-cell counts were normal in all groups, indicating no evidence of hematotoxicity in this exposure range. The absence of evidence of an effect on thyroid function or blood cells from occupational airborne perchlorate exposure at a mean absorption of 34 mg/day demonstrates a no-observed-adverse-effect-level (NOAEL) that can assist in the evaluation of human health risks from environmental perchlorate contamination.

Temporal relationship modeling: DTP or DT immunizations and infantile spasms.

The time relationship between DTP immunization and infantile spasms (IS) onset was examined using three models--association, temporal shift, and no-effect--and the case/control data from the National Childhood Encephalopathy Study (NCES). Infantile spasms cases classified as being previously abnormal (e.g., tuberous sclerosis complex patients) showed a no-effect relationship, whereas those classified as previously normal suggested a fit to the temporal shift model, i.e. no increase in number of cases but a shortening of time to onset of seizure. No data fit the association model. Analyses for vaccine complications should examine for temporal changes (i.e. temporal shift) in addition to increased risks.

Poor mental development in patients with tuberous sclerosis complex: clinical risk factors.

OBJECTIVE: To identify clinical risk factors for poor mental development among patients with tuberous sclerosis complex (TSC). DESIGN: Case-control analysis of a clinic population. SETTING: Specialty clinic in a hospital. PATIENTS: One hundred six patients with TSC consecutively seen between January 1984 and December 1995 at the Child Neurology Clinic of the Children's Memorial Health Institute in Warsaw, Poland. STUDY VARIABLES: Seizure type, age at seizure onset, sex, and history of diphtheria, tetanus, and pertussis immunization. MAIN OUTCOME MEASURE: Moderate to profound developmental delays. RESULTS: Seizure type (ie, infantile spasms) was the only analyzed risk factor that showed a consistent and independent association with poor mental development (adjusted odds ratio, 3.0; 95% confidence interval, 1.1-8.4; P =.03). Age at seizure onset, which initially showed a significant association with poor mental development, was no longer significantly associated after adjustment for seizure type (adjusted odds ratio, 1.6; P = .43). Neither sex (odds ratio, 1.1; P = .96) nor history of diphtheria, tetanus, and pertussis immunization (odds ratio, 1.0; P = .80) showed evidence of being a risk factor for poor mental development among patients with TSC. CONCLUSIONS: Infantile spasms, as the type of seizure on initial examination, is a significant risk factor for poor mental development in patients with TSC. Age at time of first seizure is not an independent risk factor but reflects the early ages at which these patients are seen with infantile spasms. Neither sex nor history of diphtheria, tetanus, and pertussis immunization is a risk factor for the subsequent development of poor mental development among patients with TSC.

Cortical tuber count: a biomarker indicating neurologic severity of tuberous sclerosis complex.

The relationship between the number of cortical tubers observed by magnetic resonance imaging (MRI) and the severity of cerebral dysfunction of tuberous sclerosis patients has been examined in a meta-analysis of the published literature. The literature review has identified five independent studies for examining the association. These studies consistently reveal that the cortical tuber count detected on MRI scans is increased among those with more severe cerebral disease. Severity of the cerebral dysfunction is measured by the seizure status and its control and by the developmental status and the level of mental retardation. Meta-analysis demonstrates that within a study population, the MRI-detected cortical tuber count is six times more likely to be above the median count for tuberous sclerosis patients with severe cerebral dysfunction (poor seizure control or moderate-severe retardation or both) than more mildly affected tuberous sclerosis patients. Similarly, across studies, moderately to severely affected patients are five times more likely to have greater than seven MRI-detected cortical tubers than those more mildly affected. These associations are both statistically significant and strong. The cortical tuber count is a biomarker that reasonably predicts the severity of cerebral dysfunction of tuberous sclerosis. Cortical tubers of tuberous sclerosis form in the early gestational period. The embryologic disruption determining the clinical severity of the cortical dysfunction of tuberous sclerosis is set in the early gestational period.

Does benzene cause multiple myeloma? An analysis of the published case-control literature.

Two case series and two epidemiological studies in the 1970s and 1980s suggested that benzene exposure might be a risk factor for multiple myeloma. An analysis has now been conducted of the published population-based and hospital-based case-control studies published through mid-1995 that permit examination of the relationship between multiple myeloma and benzene exposure or surrogates for benzene exposure. No increased association was found between multiple myeloma and benzene exposure or exposure to chemical groups that included benzene. The odds ratios from these analyses approximated 1.0. Exposures to petroleum products and employment in petroleum-related occupations did not appear to be risk factors for multiple myeloma. Cigarette smoking, as a surrogate of benzene exposure, was not found to be associated with myeloma, while some studies of products of combustion described as "engine exhaust" did show a significant association with multiple myeloma. In toto, the population-based and hospital-based case-control literature indicated that benzene exposure was not a likely causal factor for multiple myeloma.

Mortality in prostate cancer.

PURPOSE: We evaluated in patients with prostate cancer whether treatment is associated with in decreased mortality and whether the association of treatment with mortality varies with calendar time. MATERIALS AND METHODS: Using the 146,979 prostate cancer patients from the 1973 to 1990 public use tape of the Surveillance, Epidemiology and End Results program, we performed survival analysis and multivariate proportional hazards modeling to estimate the relative risk of disease specific and overall mortality. RESULTS: In men with prostate cancer, advanced age, black race, high tumor stage and not having treatment were independently associated with disease specific and overall mortality. The relative risk of mortality in treated patients decreased significantly from 1973 to 1990. CONCLUSIONS: The fact that advanced age and black race are associated with disease specific mortality (even when treatment and stage are controlled) is a new observation, which suggests that tumor biology and/or response to treatment is worse in elderly and black men. Overall, the data are consistent with the hypothesis that treatment of prostate cancer is associated with lower disease specific and overall mortality rates. The decreases in relative mortality in treated patients from 1973 to 1990 indirectly support the theory that changes in patterns of care from 1973 to 1990 had a beneficial effect on mortality. This observation implies that future studies should account for calendar time when interpreting outcomes data.

Occupational health data as a basis for process engineering changes: development of a safe work environment in the sodium azide industry.

The development of an occupational health system for a plant manufacturing sodium azide has had to confront biological and hygienic difficulties related to the nature of sodium azide. Sodium azide in pellet form is used as the nitrogen generant for automobile air bags; however, it is manufactured as a very fine powder making exposure control more difficult. Sodium azide is a rapidly active, vasodilatory hypotensive agent that causes headaches and drops in blood pressure. Occupational health assessment of the plant and its employees demonstrated the need for exposure control, based on inspection, interviews, health data, process and site review. Targeted studies demonstrated the nature and magnitude of health effect problems at this plant and the relationship to azide exposure. Engineering and hygiene changes were developed in response to the evidence of worker exposure demonstrated by the targeted studies. The occupational health surveillance system provided a monitor for temporal changes. Results appear to demonstrate over the period of the development of the program, the following changes: (1) reductions in evidence of subjective symptoms from azide exposure (health incident reports of headaches and other symptoms), (2) reductions in objective signs of effects from azide exposure (drops in cross-shift mean arterial blood pressures), and (3) reductions in measured levels of azide exposure. Future studies need to validate the evidence of exposure changes and to further identify additional sources of exposure. Interventions designed to reduce exposures need to be demonstrated to be effective and need to be monitored to demonstrate continuing effectiveness.

Carcinogenic risks of inorganic arsenic in perspective.

Induction of cancer by inorganic arsenic occurs inconsistently between species and between routes of exposure, and it exhibits different dose-response relationships between different target organs. Inhaled or ingested arsenic causes cancer in humans but not in other species. Inhaled arsenic primarily induces lung cancer, whereas ingested arsenic induces cancer at multiple sites, including the skin and various other organs. Cancer potency appears to vary by route of exposure (ingestion or inhalation) and by organ site, and increases markedly at higher exposures in some instances. To understand what might explain these inconsistencies, we reviewed several hypotheses about the mechanism of cancer induction by arsenic. Arsenic disposition does not provide satisfactory explanations. Induction of cell proliferation by arsenic is a mechanism of carcinogenesis that is biologically plausible and compatible with differential effects for species or differential dose rates for organ sites. The presence of other carcinogens, or risk modifiers, at levels that correlate with arsenic in drinking water supplies, may be a factor in all three inconsistencies: interspecies specificity, organ sensitivity to route of administration, and organ sensitivity to dose rate.