CHALLENGES TO THE 10 GOLDEN RULES FOR A SAFE MINIMALLY INVASIVE SURGERY (MIS) INGUINAL HERNIA REPAIR: CAN WE IMPROVE?

BACKGROUND: Since publication of our paper "Ten Golden Rules for a Safe MIS Inguinal Hernia Repair" we have received many questions. As the authors, we feel it is important to address these topics as a follow-up to our paper. AIM: To discuss in more details the main points of controversy, review the rules and update de recommendations. METHOD: The questions and discussions came mainly over five rules, numbered 3, 5, 6, 7, 10. We analyzed all the comments about recommendations and update some technical principles. RESULTS: Rule 3 - Removing normal fat plugs from the obturator canal is unnecessary and therefore is not recommended; Rule 5 - transection of the uterine round ligament (1 cm proximal to the deep ring) facilitates adequate dissection. When performed in this way it does not appear to be associated with complications; Rule 6 - transection of huge sacs are safer than over-dissection of the cord structures. Whether dissecting completely the sac or abandon the distal part it results in less postoperative seromas is an ongoing debate; Rule 7 - any retroperitoneal structure traversing the internal ring is or play a role like a hernia. Failing to identify and remove the lipoma will ultimately result in the patient experiencing a recurrence; Rule 10 - in TAPP peritoneum should preferably be closed with suture than tackes. CONCLUSION: 10 Golden Rules emphasize the most important surgical tips and technical steps that allow the safe performance of MIS repairs of inguinal hernias, regardless the technique.

Challenges to the 10 golden rules for a safe minimally invasive surgery (mis) inguinal hernia repair: can we improve? / Desafios para as 10 regras de ouro para o reparo minimamente invasivo seguro das hérnias inguinais: podemos melhorar?

ABSTRACT Background: Since publication of our paper "Ten Golden Rules for a Safe MIS Inguinal Hernia Repair" we have received many questions. As the authors, we feel it is important to address these topics as a follow-up to our paper. Aim: To discuss in more details the main points of controversy, review the rules and update de recommendations. Method: The questions and discussions came mainly over five rules, numbered 3, 5, 6, 7, 10. We analyzed all the comments about recommendations and update some technical principles. Results: Rule 3 - Removing normal fat plugs from the obturator canal is unnecessary and therefore is not recommended; Rule 5 - transection of the uterine round ligament (1 cm proximal to the deep ring) facilitates adequate dissection. When performed in this way it does not appear to be associated with complications; Rule 6 - transection of huge sacs are safer than over-dissection of the cord structures. Whether dissecting completely the sac or abandon the distal part it results in less postoperative seromas is an ongoing debate; Rule 7 - any retroperitoneal structure traversing the internal ring is or play a role like a hernia. Failing to identify and remove the lipoma will ultimately result in the patient experiencing a recurrence; Rule 10 - in TAPP peritoneum should preferably be closed with suture than tackes. Conclusion: 10 Golden Rules emphasize the most important surgical tips and technical steps that allow the safe performance of MIS repairs of inguinal hernias, regardless the technique.

RESUMO Racional: Desde a publicação de nosso artigo "Dez Regras de Ouro para o Reparo Seguro de Hérnia Inguinal MIS", recebemos muitos questionamentos. Como autores, sentimos que é importante abordar esses tópicos como seguimento do artigo Objetivo: Discutir com mais detalhes os principais pontos de controvérsia, revisar as regras e atualizar as recomendações. Método: As dúvidas e discussões surgiram principalmente sobre cinco regras, numeradas 3, 5, 6, 7, 10. Analisamos todos os comentários sobre as recomendações e atualizamos alguns dos princípios técnicos. Resultados: Regra 3 - remoção dos plugs de gordura normais do canal obturador é desnecessária e, portanto, não é recomendada; Regra 5 - transecção do ligamento redondo do útero (1 cm proximal ao anel profundo) facilita a dissecção adequada e quando realizado dessa forma, não parece estar associada com complicações; Regra 6 - transecção de grandes sacos herniários é mais segura do que a dissecção excessiva das estruturas do cordão espermático e, se dissecar completamente o saco ou abandonar a parte distal, resulta em menos seromas pós-operatórios ainda é motivo de debate; Regra 7 - qualquer estrutura retroperitoneal que atravessa o anel interno é ou desempenha o papel como uma hérnia e deixar de identificar e remover o lipoma acabará resultando em recorrência; Regra 10 - na TAPP o peritônio deve ser fechado preferencialmente com sutura do que com tacks. Conclusão: As 10 Regras de Ouro enfatizam as dicas cirúrgicas e etapas técnicas mais importantes que permitem a realização segura de reparos MIS de hérnias inguinais, independentemente da técnica.

Medical student education in sleep and its disorders is still meagre 20 years on: A cross-sectional survey of UK undergraduate medical education.

Sleep is a pillar of health, alongside adequate nutrition and exercise. Problems with sleep are common and often treatable. Twenty years ago, UK medical school education on sleep disorders had a median teaching time of 15 min; we investigate whether education on sleep disorders has improved. This is a cross-sectional survey, including time spent on teaching sleep medicine, subtopics covered and forms of assessment. Thirty-four medical degree courses in the UK were investigated via a questionnaire. We excluded responses not concerned with general undergraduate education (i.e. optional modules). Twenty-five (74%) medical schools responded. Time spent teaching undergraduates sleep medicine was: median, 1.5 hr; mode, <1 hr; mean, 3.2 hr (SD = 2.6). Only two schools had a syllabus or core module (8%) and five (22%) were involved in sleep disorders research. Despite the above, half of the respondents thought provision was sufficient. Free-text comments had recurring themes: sleep medicine is subsumed into other specialties, obstructive sleep apnea dominates teaching, knowledge of sleep disorders is optional, and there is inertia regarding change. A substantial minority of respondents were enthusiastic about improving provision. In conclusion, little has changed over 20 years: sleep medicine is neglected despite agreement on its importance for general health. Sleep research is the exception rather than the rule. Obstacles to change include views that "sleep is not a core topic" or "the curriculum is too crowded". However, there is enthusiasm for improvement. We recommend establishment of a sleep medicine curriculum. Without better teaching, doctors will remain ill-equipped to recognize and treat these common conditions.

Ten golden rules for a safe MIS inguinal hernia repair using a new anatomical concept as a guide.

BACKGROUND: Although laparoscopic inguinal hernia repair was described about 30 years ago and advantages of the technique have been demonstrated, the utilization of this approach has not been what we would expect. Some reasons may be the need for surgeons to understand the posterior anatomy of the groin from a new vantage point, as well as to acquire advanced laparoscopic skills. Recently, however, the introduction of a robotic approach has dramatically increased the adoption of minimally invasive techniques for inguinal hernia repair. METHODS: Important recent contributions to this evolution have been the establishment of a new concept known as the critical view of the Myopectineal Orifice (MPO) and the description of a new way of understanding the posterior view of the antomy of the groin (inverted Y and the five triangles). In this paper, we describe 10 rules for a safe MIS inguinal hernia repair (TAPP, TEP, ETEP, RTAPP) that combines these two new concepts in a unique way. CONCLUSIONS: As the critical view of safety has made laparoscopic cholecystectomy safer, we feel that following our ten rules based on understanding the anatomy of the posterior groin as defined by zones and essential triangles and the technical steps to achieve the critical view of the MPO will foster the goal of safe MIS hernia repair, no matter which minimally invasive technique is employed.

Reactive Oxygen Species Generation in Human Cells by a Novel Magnetic Resonance Imaging Contrast Agent.

The novel positive-contrast magnetic resonance imaging (MRI) marker C4 consists of an aqueous solution of cobalt chloride (CoCl2) complexed with the chelator N-acetylcysteine (NAC). We evaluated whether the presence of C4 or its components would produce reactive oxygen species (ROS, including hydroxyl, peroxyl, or other reactive oxygen species) in cultured cells. Human cancer or normal cells were incubated with 1% (w/v) CoCl2·6H2O or 2% NAC or a combination of both (1% CoCl2·6H2O : 2% NAC in an aqueous solution, abbreviated as Co : NAC) in the presence or absence of H2O2. Intracellular ROS levels were measured and quantified by change in relative fluorescence units. Student's t-tests were used. In all cell lines exposed to 1000 µM H2O2, the Co : NAC led to ≥94.7% suppression of ROS at 5 minutes and completely suppressed ROS at 60 and 90 minutes; NAC suppressed ROS by ≥76.6% at 5 minutes and by ≥94.5% at 90 minutes; and CoCl2·6H2O suppressed ROS by ≥37.2% at 30 minutes and by ≥48.6% at 90 minutes. These results demonstrate that neither Co : NAC nor its components generated ROS; rather, they suppressed ROS production in cultured cells, suggesting that C4 would not enhance ROS production in clinical use.

Anticancer activity of fish oils against human lung cancer is associated with changes in formation of PGE2 and PGE3 and alteration of Akt phosphorylation.

The beneficial effects of omega-3 fatty acids are believed to be due in part to selective alteration of arachidonate metabolism that involves cyclooxygenase (COX) enzymes. Here we investigated the effect of eicosapentaenoic acid (EPA) on the proliferation of human non-small cell lung cancer A549 (COX-2 over-expressing) and H1299 (COX-2 null) cells as well as their xenograft models. While EPA inhibited 50% of proliferation of A549 cells at 6.05 µM, almost 80 µM of EPA was needed to reach similar levels of inhibition of H1299 cells. The formation of prostaglandin (PG)E3 in A549 cells was almost threefold higher than that of H1299 cells when these cells were treated with EPA (25 µM). Intriguingly, when COX-2 expression was reduced by siRNA or shRNA in A549 cells, the antiproliferative activity of EPA was reduced substantially compared to that of control siRNA or shRNA transfected A549 cells. In line with this, dietary menhaden oil significantly inhibited the growth of A549 tumors by reducing tumor weight by 58.8 ± 7.4%. In contrast, a similar diet did not suppress the development of H1299 xenograft. Interestingly, the ratio of PGE3 to PGE2 in A549 was about 0.16 versus only 0.06 in H1299 xenograft tissues. Furthermore, PGE2 up-regulated expression of pAkt, whereas PGE3 downregulated expression of pAkt in A549 cells. Taken together, the results of our study suggest that the ability of EPA to generate PGE3 through the COX-2 enzyme might be critical for EPA-mediated tumor growth inhibition which is at least partly due to down-regulation of Akt phosphorylation by PGE3.

Disruption of the gene for CYP1A2, which is expressed primarily in liver, leads to differential regulation of hepatic and pulmonary mouse CYP1A1 expression and augmented human CYP1A1 transcriptional activation in response to 3-methylcholanthrene in vivo.

The cytochrome P4501A (CYP1A) enzymes play important roles in the metabolic activation and detoxification of numerous environmental carcinogens, including polycyclic aromatic hydrocarbons (PAHs). In this study, we tested the hypothesis that hepatic CYP1A2 differentially regulates mouse hepatic and pulmonary CYP1A1 expression and suppresses transcriptional activation of human CYP1A1 (hCYP1A1) promoter in response to 3-methylcholanthrene (MC) in vivo. Administration of wild-type (WT) (C57BL/6J) or Cyp1a2-null mice with a single dose of MC (100 µmol/kg i.p.) caused significant increases in hepatic CYP1A1/1A2 activities, apoprotein content, and mRNA levels 1 day after carcinogen withdrawal compared with vehicle-treated controls. The induction persisted in the WT, but not Cyp1a2-null, animals, for up to 15 days. In the lung, MC caused persistent CYP1A1 induction for up to 8 days in both genotypes, with Cyp1a2-null mice displaying a greater extent of CYP1A1 expression. It is noteworthy that MC caused significant augmentation of human CYP1A1 promoter activation in transgenic mice expressing the hCYP1A1 and the reporter luciferase gene on a Cyp1a2-null background, compared with transgenic mice on the WT background. In contrast, the mouse endogenous hepatic, but not pulmonary, persistent CYP1A1 expression was repressed by MC in the hCYP1A1-Cyp1a2-null mice. Liquid chromatography-mass spectrometry experiments showed that CYP1A2 catalyzed the formation of 1-hydroxy-3-MC and/or 2-hydroxy-3-MC, a metabolite that may contribute to the regulation of CYP1A1 expression. In conclusion, the results suggest that CYP1A2 plays a pivotal role in the regulation of hepatic and pulmonary CYP1A1 by PAHs, a phenomenon that potentially has important implications for PAH-mediated carcinogenesis.

Persistent induction of cytochrome P4501A1 in human hepatoma cells by 3-methylcholanthrene: evidence for sustained transcriptional activation of the CYP1A1 promoter.

Cytochrome P450 (P450)1A1 plays a critical role in the metabolic activation and detoxification of polycyclic aromatic hydrocarbons (PAHs), many of which are potent human carcinogens. In this investigation, we tested the hypothesis that MC elicits persistent induction of CYP1A1 expression in human hepatoma cells (HepG2) and that this phenomenon is mediated by sustained transcriptional activation of the CYP1A1 promoter. Treatment of HepG2 cells with MC resulted in marked induction (8-20-fold) of ethoxyresorufin O-de-ethylase activities, CYP1A1 apoprotein contents, and mRNA levels, which persisted for up to 96 h. MC also caused sustained transcriptional activation of the human CYP1A1 promoter for up to 96 h, as inferred from transient transfection experiments. Experiments with deletion constructs indicated that Ah response elements located at -886, -974, and -1047, but not -491, nucleotides from the start site, contributed to the sustained transcriptional activation of the CYP1A1 promoter. Electrophoretic mobility-shift and chromatin immunoprecipitation assays suggested that prolonged CYP1A1 induction was mediated by Ah receptor (AHR)-independent mechanisms. Experiments with [3H]MC and liquid chromatography-tandem mass spectrometry demonstrated rapid elimination of MC and its metabolites from the cells by 12 to 24 h, suggesting that these compounds did not elicit sustained CYP1A1 induction via the classical AHR-mediated pathway. In conclusion, the results of this study support the hypothesis that MC causes persistent induction of CYP1A1 in human hepatoma cells by mechanisms entailing sustained transcriptional activation of the CYP1A1 promoter via AHR-independent mechanisms. These observations have important implications for human carcinogenesis mediated by PAHs.

Bile reflux after Roux-en-Y gastric bypass: an unrecognized cause of postoperative pain.

BACKGROUND: To determine, in a private practice, whether symptomatic bile reflux can occur after Roux-en-Y gastric bypass (RYGB) for morbid obesity and the outcome after laparoscopic alimentary (Roux) limb lengthening. Bile reflux as a cause of pain after laparoscopic RYGB has not been previously described. We report on a series of patients with chronic pain after RYGB as a result of bile reflux owing an abnormally short alimentary limb. METHODS: A prospective database of patients who underwent revisional surgery to treat symptomatic bile reflux at our center was retrospectively reviewed and analyzed for the onset of symptoms, interval to revision, length of alimentary limb, and outcome after revision. RESULTS: A total of 16 patients were diagnosed with bile reflux and underwent revisional surgery. The onset of symptoms occurred at 58.3 +/- 22.2 months after RYGB. All patients complained of pain, 13 (81.3%) had vomiting, and 7 (43.8%) had dysphagia. Endoscopy was performed in all patients and confirmed the presence of bile in all patients and detected marginal ulceration in 5 (31.3%) and gastritis in 8 (50.0%). At revisional surgery, the mean alimentary limb length was 37.7 +/- 12.4 cm (range 20-62 cm). At a mean follow-up of 14.9 months after revision, all patients had reported resolution of their symptoms. CONCLUSION: Although previously unreported after RYGB, bile reflux can be an important possible cause of chronic pain. Bile reflux, however, responds favorably to alimentary limb lengthening to 100 cm and was not been seen in patients with an alimentary limb length >62 cm.

Determinants of human and mouse melanoma cell sensitivities to oleandrin.

Oleandrin, a cardiac glycoside component of Nerium oleander, has been shown to induce apoptosis in malignant cells. While human tumor cells are very sensitive to growth inhibition by oleandrin, murine tumor cells are extremely resistant. Using human BRO and mouse B16 melanoma cell lines, we explored several possible determinants of cell sensitivity to oleandrin and compared with ouabain. The studies include Na+, K(+)-ATPase activity and its isoforms as well as the cellular uptake of these cardiac glycosides. Oleandrin and ouabain induced apoptosis was detected in BRO cells while no evidence of cell death was observed in B16 cells even at concentrations 1000-fold higher than that used for BRO cells. Cellular uptake of oleandrin and ouabain was 3-4 fold greater in human BRO tumor cells than murine tumor cells. Partially purified Na+, K(+)-ATPase from human BRO cells was inhibited at a concentration that was 1000-fold less than that was required to inhibit mouse B16 enzyme to the same extent. Using Western blot analyses, human BRO cells were found to express both the sensitive alpha3 isoform and the less sensitive alpha1 isoform of Na+, K(+)-ATPase while mouse B16 cells expressed only the alpha1 isoform. These data suggest that differential expressions of Na+, K(+)-ATPase activities and its isoforms in BRO and B16 cells as well as cellular drug uptake may be important determinants of tumor cell sensitivity to cardiac glycosides.

Perforated marginal ulcers after laparoscopic gastric bypass.

BACKGROUND: Perforated marginal ulcer (PMU) after laparoscopic Roux-en-Y gastric bypass (LRYGB) is a serious complication, but its incidence and etiology have rarely been investigated. Therefore, a retrospective review of all patients undergoing LRYGB at the authors' center was conducted to determine the incidence of PMU and whether any causative factors were present. METHODS: A prospectively kept database of all patients at the authors' bariatric center was retrospectively reviewed. The complete records of patients with a PMU were examined individually for accuracy and analyzed for treatment, outcome, and possible underlying causes of the marginal perforation. RESULTS: Between April 1999 and August 2007, 1% of the patients (35/3,430) undergoing laparoscopic gastric bypass experienced one or more perforated marginal ulcers 3 to 70 months (median, 18 months) after LRYGB. The patients with and without perforation were not significantly different in terms of mean age (37 vs 41 years), weight (286 vs 287 lb), body mass index (BMI) (46 vs 47), or female gender (89% vs 83%). Of the patients with perforations, 2 (6%) were taking steroids, 10 (29%) were receiving nonsteroidal antiinflammatory drugs (NSAIDs) at the time of the perforation, 18 (51%) were actively smoking, and 6 of the smokers also were taking NSAIDs. Eleven of the patients (31%) who perforated did not have at least one of these possible risk factors, but 4 (36%) of the 11 patients in this group had been treated after bypass for a marginal ulcer. Only 7 (20%) of the 35 patients who had laparoscopic bypass, or 7 (0.2%) in the entire group of 3,430 patients, perforated without any warning. There were no deaths, but three patients reperforated. CONCLUSIONS: The incidence of a marginal ulcer perforating after LRYGB was significant (>1%) and appeared to be related to smoking or the use of NSAIDs or steroids. Because only 0.2% of all patients acutely perforated without some risk factor or warning, long-term ulcer prophylaxis or treatment may be necessary for only a select group of high-risk patients.