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Abstract Introduction Acute intoxication with drugs of abuse in children is often only the tip of the iceberg, actually hiding chronic exposure. Analysis using non-conventional matrices such as hair can provide long-term information about exposure to recreational drugs. Case presentation We report the case of a one-month-old Caucasian boy admitted to our pediatric emergency unit with respiratory distress and neurological abnormalities. A routine urine test was positive for opiates, suggesting an acute opiate ingestion. No other drugs of misuse, such as cocaine, cannabis, amphetamines or derivatives, were detected in the baby's urine. Subsequently, hair samples from the baby and the parents were collected to evaluate the possibility of chronic exposure to drug misuse by segmental analysis. Opiates and cocaine metabolites were detected in hair samples from the baby boy and his parents. Conclusions In light of these and previous results, we recommend hair analysis in babies and children from risky environments to detect exposure to heroin and other drug misuse, which could provide the basis for specific social and health interventions.

Background & Aims: Ductular reaction expansion is associated with poor prognosis in patients with advanced liver disease. However, the mechanisms promoting biliary cell proliferation are largely unknown. Here, we identify neutrophils as drivers of biliary cell proliferation and the defective wound-healing response., Methods: The intrahepatic localization of neutrophils was evaluated in patients with chronic liver disease. Neutrophil dynamics were analyzed by intravital microscopy and neutrophil-labeling assays in DDC-treated mice. Neutrophil depletion or inhibition of recruitment was achieved using a Ly6g antibody or a CXCR1/2 inhibitor, respectively. Mice deficient in PAD4 (peptidyl arginine deiminase 4) and ELANE/NE (neutrophil elastase) were used to investigate the mechanisms underlying ductular reaction expansion., Results: In this study we describe a population of ductular reaction-associated neutrophils (DRANs), which are in direct contact with biliary epithelial cells in chronic liver diseases and whose numbers increased in parallel with disease progression. We show that DRANs are immobilized at the site of ductular reaction for a prolonged period of time. In addition, liver neutrophils display a unique phenotypic and transcriptomic profile, showing a decreased phagocytic capacity and increased oxidative burst. Depletion of neutrophils or inhibition of their recruitment reduces DRANs and the expansion of ductular reaction, while mitigating liver fibrosis and angiogenesis. Mechanistically, neutrophils deficient in PAD4 and ELANE abrogate neutrophil-induced biliary cell proliferation, thus indicating the role of neutrophil extracellular traps and elastase release in ductular reaction expansion., Conclusions: Overall, our study reveals the accumulation of DRANs as a hallmark of advanced liver disease and a potential therapeutic target to mitigate ductular reaction and the maladaptive wound-healing response., Impact and Implications: Our results indicate that neutrophils are highly plastic and can have an extended lifespan. Moreover, we identify a new role of neutrophils as triggers of expansion of the biliary epithelium. Overall, the results of this study indicate that ductular reaction-associated neutrophils (or DRANs) are new players in the maladaptive tissue-healing response in chronic liver injury and may be a potential target for therapeutic interventions to reduce ductular reaction expansion and promote tissue repair in advanced liver disease., (Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Loss of hepatocyte identity is associated with impaired liver function in alcohol-related hepatitis (AH). In this context, hepatocyte dedifferentiation gives rise to cells with a hepatobiliary (HB) phenotype expressing biliary and hepatocyte markers and showing immature features. However, the mechanisms and impact of hepatocyte dedifferentiation in liver disease are poorly understood., Methods: HB cells and ductular reaction (DR) cells were quantified and microdissected from liver biopsies from patients with alcohol-related liver disease (ArLD). Hepatocyte-specific overexpression or deletion of C-X-C motif chemokine receptor 4 (CXCR4), and CXCR4 pharmacological inhibition were assessed in mouse liver injury. Patient-derived and mouse organoids were generated to assess plasticity., Results: Here, we show that HB and DR cells are increased in patients with decompensated cirrhosis and AH, but only HB cells correlate with poor liver function and patients' outcome. Transcriptomic profiling of HB cells revealed the expression of biliary-specific genes and a mild reduction of hepatocyte metabolism. Functional analysis identified pathways involved in hepatocyte reprogramming, inflammation, stemness, and cancer gene programs. The CXCR4 pathway was highly enriched in HB cells and correlated with disease severity and hepatocyte dedifferentiation. In vitro, CXCR4 was associated with a biliary phenotype and loss of hepatocyte features. Liver overexpression of CXCR4 in chronic liver injury decreased the hepatocyte-specific gene expression profile and promoted liver injury. CXCR4 deletion or its pharmacological inhibition ameliorated hepatocyte dedifferentiation and reduced DR and fibrosis progression., Conclusions: This study shows the association of hepatocyte dedifferentiation with disease progression and poor outcome in AH. Moreover, the transcriptomic profiling of HB cells revealed CXCR4 as a new driver of hepatocyte-to-biliary reprogramming and as a potential therapeutic target to halt hepatocyte dedifferentiation in AH., Impact and Implications: Here, we show that hepatocyte dedifferentiation is associated with disease severity and a reduced synthetic capacity of the liver. Moreover, we identify the CXCR4 pathway as a driver of hepatocyte dedifferentiation and as a therapeutic target in alcohol-related hepatitis. Therefore, this study reveals the importance of preserving strict control over hepatocyte plasticity in order to preserve liver function and promote tissue repair., (Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: : The accumulation of adipose tissue macrophages (ATMs) in obesity has been associated with hepatic injury. However, the contribution of ATMs to hepatic fibrosis in non-alcoholic fatty liver disease (NAFLD) remains to be elucidated. Herein, we investigate the relationship between ATMs and liver fibrosis in patients with patients with NAFLD and evaluate the impact of modulation of ATMs over hepatic fibrosis in an experimental non-alcoholic steatohepatitis (NASH) model., Methods: Adipose tissue and liver biopsies from 42 patients with NAFLD with different fibrosis stages were collected. ATMs were characterised by immunohistochemistry and flow cytometry and the correlation between ATMs and liver fibrosis stages was assessed. Selective modulation of the ATM phenotype was achieved by i.p. administration of dextran coupled with dexamethasone in diet-induced obesity and NASH murine models. Chronic administration effects were evaluated by histology and gene expression analysis in adipose tissue and liver samples. In vitro crosstalk between human ATMs and hepatic stellate cells (HSCs) and liver spheroids was performed., Results: Patients with NAFLD presented an increased accumulation of pro-inflammatory ATMs that correlated with hepatic fibrosis. Long-term modulation of ATMs significantly reduced pro-inflammatory phenotype and ameliorated adipose tissue inflammation. Moreover, ATMs modulation was associated with an improvement in steatosis and hepatic inflammation and significantly reduced fibrosis progression in an experimental NASH model. In vitro , the reduction of the pro-inflammatory phenotype of human ATMs with dextran-dexamethasone treatment reduced the secretion of inflammatory chemokines and directly attenuated the pro-fibrogenic response in HSCs and liver spheroids., Conclusions: Pro-inflammatory ATMs increase in parallel with fibrosis degree in patients with NAFLD and their modulation in an experimental NASH model improves liver fibrosis, uncovering the potential of ATMs as a therapeutic target to mitigate liver fibrosis in NAFLD., Impact and Implications: We report that human adipose tissue pro-inflammatory macrophages correlate with hepatic fibrosis in non-alcoholic fatty liver disease (NAFLD). Furthermore, the modulation of adipose tissue macrophages (ATMs) by dextran-nanocarrier conjugated with dexamethasone shifts the pro-inflammatory phenotype of ATMs to an anti-inflammatory phenotype in an experimental murine model of non-alcoholic steatohepatitis. This shift ameliorates adipose tissue inflammation, hepatic inflammation, and fibrosis. Our results highlight the relevance of adipose tissue in NAFLD pathophysiology and unveil ATMs as a potential target for NAFLD., Competing Interests: All authors declare no conflicts of interest related to this manuscript. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Authors.)

Background Current methods used to diagnose and prognosticate oropharyngeal cancer have contributed to unfavorable patient survival rates that have not significantly improved for the last several decades. Precision medicine oncology relies on molecular diagnostics and biomarkers to supplement existing methods of detecting and prognosticating cancers. This study evaluated the expression of DJ-1, an oncogene that is implicated in the pathogenesis of oral squamous cell carcinoma (OSCC), the most common type of head and neck cancer, to determine its utility as a diagnostic and prognostic biomarker. Methodology Immunohistochemistry (IHC) was performed on 13 normal oral mucosa tissue samples and 143 OSCC tissue samples of varying histopathological grades. Computer-assisted image analysis was performed using the Aperio ImageScope software from Leica Biosystems (Buffalo Grove, IL), which utilizes an algorithm of positive pixel counting for the quantification of immunoreactivity and the percentage of positive cell staining, generating a histo-score (H-score). The comparisons of the average H-scores of the different groups were made using a two-tailed T-test with P ≤ 0.05 set as the level of significance. Results The study found a significant increase in DJ-1 expression in oral squamous cell carcinoma tissue samples in comparison to the normal oral mucosa tissue samples. Additionally, the study documented a significant upregulation in DJ-1 expression in the OSCC tissue samples with high histopathological grades compared to the OSCC tissue samples with low histopathological grades. Conclusions DJ-1 expression patterns were able to reliably differentiate between oral squamous cell carcinoma and the normal counterpart tissues of the oral mucosa, thereby highlighting its role as a potential diagnostic biomarker. Moreover, DJ-1 expression significantly correlates with the OSCC histological grade, which serves as an indicator of the differentiation status and a predictor of the biological behavior of malignant neoplasms, adding to DJ-1's potential utility as a prognostic biomarker for this common type of head and neck cancer., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, De La Torre et al.)

Objective Oral cancer has a five-year survival rate of 68%, and the methods used to assess it still rely heavily on morphology. Protein biomarkers can potentially increase the predictive power of histopathological evaluation. This study aims to examine the expression of three closely linked proteins implicated in the pathogenesis of oral squamous cell carcinoma (OSCC); protein deglycase (DJ-1), an oncogene, phosphatase, and tensin homolog (PTEN), a tumor suppressor gene, and phosphorylated protein kinase B (p-Akt), the activated form of a vital serine/threonine kinase, which is involved in the oncogenesis of several human malignancies, throughout the tumor progression steps to establish their potential as prognostic biomarkers. Study design Western blot analysis was carried out using four different cell lines representing the successive steps of OSCC progression, including normal oral keratinocytes, dysplastic oral keratinocytes, locally invasive OSCC, and metastatic OSCC.  Results DJ-1 expression was found to be upregulated gradually throughout the successive steps of OSCC progression from normal to dysplastic to locally invasive to metastatic OSCC. PTEN expression showed an overall opposite trend. Interestingly, a significant downregulation of p-Akt was seen in the locally invasive OSCC cells, although it was followed by a significant increase in p-Akt expression in the metastatic OSCC cell line, which is consistent with the role of p-Akt in the motility and migration of cancer cells. Conclusion This study documented trends in expression patterns of three important signaling molecules, DJ-1, PTEN, and p-Akt, in normal, premalignant, and malignant oral keratinocytes. The oncogenic DJ-1 and tumor suppressor PTEN were expressed in a manner consistent with their respective roles in tumorigenesis, while p-Akt only showed a significant upregulation in the metastatic OSCC cells. Overall, all three proteins exhibited unique trends throughout the progressive stages of OSCC tumor progression, thereby adding to their potential utility as prognostic biomarkers for oral cancer patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Kerdjoudj et al.)

Minimally-Invasive robotic spine surgery (MARSS) has expanded the surgeons armamentarium to treat a variety of spinal disorders. In the last decade, robotic developments in spine surgery have improved the safety, accuracy and efficacy of instrumentation placement. Additionally, robotic instruments have been applied to remove tumors in difficult locations while maintaining minimally invasive access. Gross movements by the surgeon are translated into fine, precise movements by the robot. This is exemplified in this chapter with the use of the da Vinci robot to remove apical thoracic tumors. In this chapter, we will review the development, technological advancements, and cases that have been conducted using MARSS to treat spine pathology in a minimally invasive fashion., (Copyright © 2022 Pérez de la Torre, Ramanathan, Williams and Perez-Cruet.)

Fibrosis contributes to ~45% of deaths in western countries. In chronic liver disease, fibrosis is a major factor determining outcomes, but efficient antifibrotic therapies are lacking. Although platelet-derived growth factor and transforming growth factor-β constitute key fibrogenic mediators, they do not account for the well-established link between cell death and fibrosis in the liver. Here, we hypothesized that damage-associated molecular patterns (DAMPs) may link epithelial cell death to fibrogenesis in the injured liver. DAMP receptor screening identified purinergic receptor P2Y14 among several candidates as highly enriched in hepatic stellate cells (HSCs), the main fibrogenic cell type of the liver. Conversely, P2Y14 ligands uridine 5'-diphosphate (UDP)-glucose and UDP-galactose were enriched in hepatocytes and were released upon different modes of cell death. Accordingly, ligand-receptor interaction analysis that combined proteomic and single-cell RNA sequencing data revealed P2Y14 ligands and P2Y14 receptor as a link between dying cells and HSCs, respectively. Treatment with P2Y14 ligands or coculture with dying hepatocytes promoted HSC activation in a P2Y14-dependent manner. P2Y14 ligands activated extracellular signal-regulated kinase (ERK) and Yes-associated protein (YAP) signaling in HSCs, resulting in ERK-dependent HSC activation. Global and HSC-selective P2Y14 deficiency attenuated liver fibrosis in multiple mouse models of liver injury. Functional expression of P2Y14 was confirmed in healthy and diseased human liver and human HSCs. In conclusion, P2Y14 ligands and their receptor constitute a profibrogenic DAMP pathway that directly links cell death to fibrogenesis.

Hepatic stellate cells (HSCs) are nonparenchymal liver cells responsible for extracellular matrix homeostasis and are the main cells involved in the development of liver fibrosis following injury. The lack of reliable sources of HSCs has hence limited the development of complex in vitro systems to model liver diseases and toxicity. Here we describe a protocol to differentiate human induced pluripotent stem cells (iPSCs) into hepatic stellate cells (iPSC-HSCs). The protocol is based on the addition of several growth factors important for liver development sequentially over 12 d. iPSC-HSCs present phenotypic and functional characteristics of primary HSCs and can be expanded or frozen and used to perform high-throughput in vitro studies. We also describe how to coculture iPSC-HSCs with hepatocytes, which self-assemble into three-dimensional (3D) hepatic spheroids. This protocol enables the generation of HSC-like cells for in vitro modeling and drug screening studies.

Background: Limbal stem cells (LSC) are progenitor cells in the ocular surface that renew the corneal epithelium. Limbal stem cell deficiency usually induces blindness through the loss of corneal transparency, and bilateral cases do not an accurate treatment because of the lack of an autologous source of stem cells., Methods: Induced pluripotent stem cells (iPSC) are promising for use in cell therapy because of their autologous origin and the capability to differentiate into corneal epithelial cells. However, there are not standardized protocols to achieve a complete corneal epithelial differentiation. We examined the expression of several markers in a human episomal iPSC line after an induction period from embryoid bodies., Results: Progenitor LSC and corneal epithelial differentiation markers, some extracellular matrix protein adhesion molecules, and wingless signaling pathway were studied. Overall, LSC progenitor and corneal epithelium differentiation markers increased after maintaining cell culture in specific conditions for 14 days, whereas pluripotency markers decreased., Conclusions: Our approach indicated that the optimal time point to initiate iPSC differentiation into LSC and corneal phenotypes, with the use of specific medium, is from 14 days after initial embryoid bodies treatment induction., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Parkinson's disease justifies the use of deep brain stimulation (DBS) in certain patients who suffer from this condition. We present mid-term and long-term post-surgical outcomes in a cohort of 60 patients, who underwent DBS in the Hospital de Especialidades at Centro Médico Nacional Siglo XXI, in Mexico City., Methods: Patients underwent conventional stereotactic surgery with FrameLink software (Medtronics Inc). This technique consisted in the presurgical evaluation, the placement of stereotactic frame, imaging studies, preoperative planning procedure, microrecording, macrostimulation, as well as the placement of electrodes and generators in two phases. The variables were included in a data platform for Excel management. It was also included a variety of measurement instruments for data comparison. As a standard measure, it was used the Unified Parkinson Disease Rating Scale (UPDRS) before the surgery and at 3, 12, and 36 months., Results: 60 patients underwent surgery: 41 men and 19 women, with an average age of 56.5 years (39-70). There were good results in the majority of patients with preoperative UPDRS and at 3, 12 and 36 months of 79.57, 66.85, 65.29 and 58.75, respectively (p < 0.0001). There were complications in nine patients (15 %) and they were managed in a conservative manner., Conclusions: Postsurgical outcomes were from good to excellent in the majority of patients. Complications were minimal and conservatively managed. We propose the use of this procedure in a selected group of Parkinson's patients.

Renal cell cancer (RCC) incidence varies worldwide with a higher incidence in developed countries and lifestyle is likely to contribute to the development of this disease. We examined whether meat and fish consumption were related to the risk of RCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 493,179 EPIC participants, recruited between 1992 and 2000. Until December 2008, 691 RCC cases have been identified. Meat and fish consumption was assessed at baseline using country-specific dietary assessment instruments; 24-hour recalls were applied in an 8% subsample for calibration purposes. Cox proportional hazards regression was used to calculate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI). Women with a high consumption of red meat (HR = 1.36, 95% CI 1.14-1.62; calibrated, per 50 g/day) and processed meat (HR = 1.78, 95% CI 1.05-3.03; calibrated, per 50 g/day) had a higher risk of RCC, while no association existed in men. For processed meat, the association with RCC incidence was prominent in premenopausal women and was lacking in postmenopausal women (p interaction = 0.02). Neither poultry nor fish consumption were statistically significantly associated with the risk of RCC. The results show a distinct association of red and processed meat consumption with incident RCC in women but not in men. A biological explanation for these findings remains unclear., (© 2014 UICC.)

Normal renal function is essential for vitamin D metabolism, but it is unclear whether circulating vitamin D is associated with risk of renal cell carcinoma (RCC). We assessed whether 25-hydroxyvitamin D3 (25(OH)D3) was associated with risk of RCC and death after RCC diagnosis in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC recruited 385,747 participants with blood samples between 1992 and 2000. The current study included 560 RCC cases, 557 individually matched controls, and 553 additional controls. Circulating 25(OH)D3 was assessed by mass spectrometry. Conditional and unconditional logistic regression models were used to calculate odds ratios and 95% confidence intervals. Death after RCC diagnosis was assessed using Cox proportional hazards models and flexible parametric survival models. A doubling of 25(OH)D3 was associated with 28% lower odds of RCC after adjustment for season of and age at blood collection, sex, and country of recruitment (odds ratio = 0.72, 95% confidence interval: 0.60, 0.86; P = 0.0004). This estimate was attenuated somewhat after additional adjustment for smoking status at baseline, circulating cotinine, body mass index (weight (kg)/height (m)(2)), and alcohol intake (odds ratio = 0.82, 95% confidence interval: 0.68, 0.99; P = 0.038). There was also some indication that both low and high 25(OH)D3 levels were associated with higher risk of death from any cause among RCC cases., (© The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the fourth most common renal disease requiring renal replacement therapy (RRT). Still, there are few epidemiological data on the prevalence of, and survival on RRT for ADPKD., Methods: This study used data from the ERA-EDTA Registry on RRT prevalence and survival on RRT in 12 European countries with 208 million inhabitants. We studied four 5-year periods (1991-2010). Survival analysis was performed by the Kaplan-Meier method and by Cox proportional hazards regression., Results: From the first to the last study period, the prevalence of RRT for ADPKD increased from 56.8 to 91.1 per million population (pmp). The percentage of prevalent RRT patients with ADPKD remained fairly stable at 9.8%. Two-year survival of ADPKD patients on RRT (adjusted for age, sex and country) increased significantly from 89.0 to 92.8%, and was higher than for non-ADPKD subjects. Improved survival was noted for all RRT modalities: haemodialysis [adjusted hazard ratio for mortality during the last versus first time period 0.75 (95% confidence interval 0.61-0.91), peritoneal dialysis 0.55 (0.38-0.80) and transplantation 0.52 (0.32-0.74)]. Cardiovascular mortality as a proportion of total mortality on RRT decreased more in ADPKD patients (from 53 to 29%), than in non-ADPKD patients (from 44 to 35%). Of note, the incidence rate of RRT for ADPKD remained relatively stable at 7.6 versus 8.3 pmp from the first to the last study period, which will be discussed in detail in a separate study., Conclusions: In ADPKD patients on RRT, survival has improved markedly, especially due to a decrease in cardiovascular mortality. This has led to a considerable increase in the number of ADPKD patients being treated with RRT., (© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Postsurgical leaks after bariatric procedures are a significant cause of morbidity and mortality. They usually arise from anastomotic and staple line failures that are attributed to surgical technique, ischemia, and patient comorbid conditions. Timely diagnosis from subtle clinical clues is the key to appropriate management. Traditional treatment consists of adequate control of the intra-abdominal infection via surgical or percutaneous drainage maneuvers, antibiotics, and nutrition support via parenteral or feeding tube routes. Recently, endoscopically placed covered esophageal stents have been used to exclude the leak site, allowing oral nutrition and speeding healing., (Copyright © 2011. Published by Elsevier Inc.)

Introduction: Marginal ulcer perforation is a known complication of Roux-en-Y gastric bypass (RYGB), and laparoscopic repair may be a feasible option minimizing the morbidity associated with a large laparotomy incision. We present our experience with laparoscopic repair of perforated marginal ulcers in patients who have previously undergone RYGB., Methods: A retrospective chart review from August 2005 to April 2007 was performed identifying all patients who underwent laparoscopic repair of perforated marginal ulcer after RYGB at one hospital. The perforation was repaired either by laparoscopic primary suture closure followed by application of an omental patch or by laparoscopic Graham patch without primary suture repair. Operative time, duration of hospitalization, postoperative follow-up, and postoperative complications were recorded. Data are presented as mean ± standard deviation., Results: Six patients underwent laparoscopic repair of a perforated marginal ulcer. Operative time was 101.8 ± 50 minutes with a mean hospitalization of 5.3 ± 2.7 days. Follow-up was 6.2 ± 7.5 months. Postoperative complications included 2 patients with nausea and vomiting related to an exposed suture at the gastrojejunostomy, 1 patient with chronic gastritis, and 1 patient developed a stricture at the gastrojejunostomy., Conclusions: We present the largest series to date of laparoscopic repair of perforated marginal ulcers utilizing an omental patch for repair. We demonstrate that a laparoscopic repair can be completed in a reasonable operative time, with minimal postoperative hospitalization, and low associated morbidity. Patients who develop a perforated marginal ulcer after RYGB can be safely and effectively treated with laparoscopic repair with an omental patch.

Background: Failure of primary bariatric surgery is frequently due to weight recidivism, intractable gastric reflux, gastrojejunal strictures, fistulas, and malnutrition. Of these patients, 10-60% will undergo reoperative bariatric surgery, depending on the primary procedure performed. Open reoperative approaches for revision to Roux-en-Y gastric bypass (RYGB) have traditionally been advocated secondary to the perceived difficulty and safety with laparoscopic techniques. Few studies have addressed revisions after RYGB. The aim of the present study was to provide our experience regarding the safety, efficacy, and weight loss results of laparoscopic revisional surgery after previous RYGB and sleeve gastrectomy procedures., Methods: A retrospective analysis of patients who underwent laparoscopic revisional bariatric surgery for complications after previous RYGB and sleeve gastrectomy from November 2005 to May 2007 was performed. Technical revisions included isolation and transection of gastrogastric fistulas with partial gastrectomy, sleeve gastrectomy conversion to RYGB, and revision of RYGB. The data collected included the pre- and postoperative body mass index, operative time, blood loss, length of hospital stay, and intraoperative and postoperative complications., Results: A total of 26 patients underwent laparoscopic revisional surgery. The primary operations had consisted of RYGB and sleeve gastrectomy. The complications from primary operations included gastrogastric fistulas, refractory gastroesophageal reflux disease, weight recidivism, and gastric outlet obstruction. The mean prerevision body mass index was 42 ± 10 kg/m(2). The average follow-up was 240 days (range 11-476). The average body mass index during follow-up was 37 ± 8 kg/m(2). Laparoscopic revision was successful in all but 1 patient, who required conversion to laparotomy for staple line leak. The average operating room time and estimated blood loss was 131 ± 66 minutes and 70 mL, respectively. The average hospital stay was 6 days. Three patients required surgical exploration for hemorrhage, staple line leak, and an incarcerated hernia. The overall complication rate was 23%, with a major complication rate of 11.5%. No patients died., Conclusion: Laparoscopic revisional bariatric surgery after previous RYGB and sleeve gastrectomy is technically challenging but compared well in safety and efficacy with the results from open revisional procedures. Intraoperative endoscopy is a key component in performing these procedures., (Copyright © 2010 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: The evolution of single-incision laparoscopic surgery (SILS) has no doubt been impacted by the decrease or elimination of incisions seen with natural orifice transluminal endoscopic surgery (NOTES). SILS upholds the principal advantages of minimal access surgery including shortened hospital stays, the potential for decreased postoperative pain, and cosmetically acceptable scars by reducing large or multiple incisions to a relatively small, single one., Methods: As opposed to NOTES, SILS does not violate a natural orifice and so the potential for contamination is identical to that of laparoscopy. SILS also utilizes familiar technology regarding ports and instruments which make technical adaptation easier and costs remain essentially unchanged. Standard laparoscopic techniques for gastric band placement use up to six ports in various configurations to safely accomplish this procedure. We describe a 40-year-old female with a body mass index of 41 who underwent placement of a gastric band for weight reduction via a single incision. A novel liver retractor technique eliminated one of the typical incisions utilized in other described "single-incision" techniques., Results: The total number of trocars used at the sole, transumbilical incision was three. The operative time was 58 min. There were no intraoperative or postoperative complications. The patient was discharged on postoperative day 1., Conclusions: Single-incision transumbilical placement of gastric band is safe and technically feasible. Evolution of this technique with improved instrumentation will facilitate its adoption.

Background: To analyze the outcomes of a series of endoscopically placed polyester self-expanding polyflex stents (SEPSs) for the management of anastomotic leaks after Roux-en-Y bypass. Anastomotic leaks after gastric bypass cause significant morbidity and mortality. Covered polyester SEPSs might have a role in the treatment of these leaks., Methods: A retrospective chart review was performed from January 2006 to November 2006 that included all acute and chronic leaks treated with SEPSs., Results: A total of 6 patients were treated with stents, with a mean procedure time of 22 minutes. Of these 6 patients, 5 had acute postoperative leaks and 1 had a chronic fistula. Five patients started oral intake 1-6 days after their procedure. All acute leaks had complete healing at a median of 44 days. The patient with a chronic gastrocutaneous fistula required revisional surgery for fistula closure. In addition, 5 patients had stent migration, and 3 required stent replacement., Conclusion: An endoscopically placed SEPS provides a less-invasive alternative to treat acute anastomotic leaks after Roux-en-Y bypass while simultaneously allowing oral intake. The results of this case series have demonstrated this treatment to be safe and effective.

Background: Complications after bariatric surgery often require longterm parenteral nutrition to achieve healing. Recently, endoscopic treatments have become available that provide healing while allowing for oral nutrition. The purpose of this study was to present outcomes of the largest series to date treating staple line complications after bariatric surgery with endoscopic covered stents., Study Design: A retrospective evaluation was performed of all patients treated for staple line complications after bariatric surgery at a single tertiary care bariatric center. Acute postoperative leaks, chronic gastrocutaneous fistulas, and anastomotic strictures refractory to endoscopic dilation after both gastric bypass and sleeve gastrectomy were included., Results: From January 2006 to June 2007, 19 patients (11 with acute leaks, 2 with chronic fistulas, and 6 with strictures) were treated with a total of 34 endoscopic silicone covered stents (23 polyester, 11 metal). Mean followup was 3.6 months. Immediate symptomatic improvement occurred in 90% (91% of acute leaks, 100% of fistulas, and 84% of strictures). Oral feeding was started in 79% of patients immediately after stenting. Resolution of leak or stricture after stent treatment occurred in 16 of 19 patients (84%). Healing of leak, fistula, and stricture occurred at means of 33 days, 46 days, and 7 days, respectively. Three patients (1 with leak, 1 with fistula, and 1 with stricture) had unsuccessful stent treatment. Migration of the stent occurred in 58% of 34 stents placed. Most migration was minimal, but three stents were removed surgically after distal small bowel migration. There was no mortality., Conclusions: Treatment of anastomotic complications after bariatric surgery with endoscopic covered stents allows rapid healing while simultaneously allowing for oral nutrition. The primary morbidity is stent migration.

As minimally invasive surgery (MIS) has grown in scope and complexity, new challenges have been introduced along the way, including the need for endoscopic hemostatic techniques. Traditional electrical and mechanical means are still the mainstay, but new technologies for hemostasis continue to emerge. Restricted access to the operative site can limit the use of some tools, and yet multiple chemical hemostats and tamponading agents are used in MIS today. Systemic agents also have been developed and have a role in certain MIS circumstances. These products allow surgeons to continue to approach more difficult procedures using minimally invasive techniques. On the horizon are the newer, even less-invasive approaches of natural orifice endoluminal and transluminal surgery, which will increase the difficulties with reliable hemostat agents and delivery mechanisms.

Background: Previous descriptions of a laparoscopic Roux-en-Y gastric bypass, using a circular stapler to perform the gastrojejunal anastomosis, have employed the esophagus as a conduit to introduce the anvil of the stapling device into the stomach. The authors believe that the risk of injury to the esophagus, as well as the difficulty in maneuvering the anvil from the pharynx to the proximal part of the stomach, make this technique less than optimal. In other descriptions (in a porcine model) the anvil has been guided into position through a distal gastrotomy by attaching it to a Prolene suture on a straight needle and directing the needle toward a chosen site. Although the authors prefer this method because it avoids potential esophageal injury, they sought a technique that would be even more precise in anvil placement and would avoid pushing a needle across gastric mucosa., Methods: The authors have developed a method that is totally intra-abdominal and does not risk injury to the esophagus. The circular stapler is still used, thus giving a consistent, small opening through the gastrojejunal anastomosis., Results: Over a 1-year period, 49 (of 50) patients underwent laparoscopic Roux-en-Y gastric bypass with the described method. The average body mass index dropped from 42.63 to 34.12 over the first postoperative 3 months, with an average loss in excess body weight of 38.5%. The length of hospitalization following the procedure averaged 3.8 days, and the time to return to work (where applicable) was 11.9 days., Conclusion: This totally intra-abdominal laparoscopic technique is feasible and advantageous.

To obviate the need for general anesthesia or dissection of the rectus sheath, we have transferred laparoscopic herniorrhaphy back to the groin by first dissecting the suprainguinal parietoperitoneal space of Bogros via the femoral canal. Cadaver dissections demonstrated that the preperitoneal plane could be routinely fingered and distended with a digitally placed balloon introduced through a 1-cm incision immediately below the inguinal ligament. A 10-mm femoral laparoscopic port was then inserted and pressurized, allowing two standard 5-mm ports to be introduced from above, through the lower quadrant, under vision. The procedure was then carried out in the usual way, the mesh being inserted from below. Ten patients (two women), 23-73 years old, selected because general anesthesia was inadvisable, underwent uncomplicated prosthetic repair of unilateral (eight) or bilateral (two) inguinal defects. Half of the peritoneal sacs were pushed up and out of the inguinal canal; 18 months later there were no recurrences (inguinal or femoral). Preliminary experience with this new technique is promising. It may prove applicable to retroperitoneal exposure of the distal aorta and iliac vessels, allowing laparoscopic bypass for Leriche syndrome.

The use of a balloon as a dissecting tool was pioneered by Gauer and Kieturakis in the early 1990s.This newapplication of balloon dissection in surgery allows the creation of a working space in which a procedure is performed. This is combined with minimally invasive techniques that confer the advantages of shorter recovery and less pain for several different procedures.

Knowledge about mutagenic properties of plants commonly used in traditional medicine is limited. A screening for genotoxic activity was carried out in aqueous or alcoholic extracts prepared from 13 medicinal plants widely used as folk medicine in Cuba: Lepidium virginicum L. (Brassicaceae): Plantago major L. and Plantago lanceolata L. (Plantaginaceae); Ortosiphon aristatus Blume, Mentha x piperita L., Melissa officinalis L. and Plectranthus amboinicus (Lour.) Spreng. (Lamiaceae); Cymbopogon citratus (DC.) Stapf (Poaceae); Passiflora incarnata L. (Passifloraceae); Zingiber officinale Roscoe (Zingiberaceae); Piper auritum HBK. (Piperaceae); Schinus terebinthifolius Raddi (Anacardeaceae) and Momordica charantia L. (Cucurbitaceae). A plate incorporation assay with Aspergillus nidulans was employed, allowing detection of somatic segregation as a result of mitotic crossing-over, chromosome malsegregation or clastogenic effects. Aspergillus nidulans D-30, a well-marked strain carrying four recessive mutations for conidial color in heterozygosity, which permitted the direct visual detection of segregants, was used throughout this study. As a result, only in the aqueous extract of one of the plants screened (Momordica charantia) a statistical significant increase in the frequency of segregant sectors per colony was observed, and consequently, a genotoxic effect is postulated.

Tinidazole is an antiparasitic drug belonging to the 5-nitroimidazole family. It is prescribed against protozoal infestations and is widely used in Mexico as well as other underdeveloped countries where infectious diseases are the first cause of children mortality. The drug is a direct mutagen in Salmonella typhimurium TA100 strain and the presence of S9 mixture did not modify its mutagenic effect. At low doses no mutagenicity was detected with strains TA100NR, TA98 or UTH8414 (Uvr+ derivative of TA100). Urine from four patients under tinidazole treatment exhibited a mutagenic activity on strain TA100, greater than the expected from the tinidazole concentrations determined by high-performance liquid chromatography (HPLC). Components from the urine samples were separated on thin-layer chromatography (TLC) plates, and their mutagenic effects tested by direct application of the Salmonella assay onto sections of the developed chromatoplate. The Rf of one component (0.62) corresponded to the one obtained for a tinidazole standard and showed the expected mutagenicity, while a second component with an Rf=0.39, exhibited a mutagenic potency slightly greater than the observed for tinidazole; however, as in the case of the drug itself, reduction of the nitro group was necessary for a mutagenic activity.

A 22-year-old man who had previously undergone work-up for right cryptorchidism and been diagnosed as having right testicular absence was referred for repair of a right inguinal hernia. A laparoscopic approach was chosen for this patient, and at the time of laparoscopic herniorrhaphy, a small intraabdominal testicle was visualized and removed laparoscopically. Laparoscopy has served as an excellent procedure for locating intraabdominal testes and planning the most appropriate treatment for many cryptorchid patients. Until recently, atrophic testes located within the abdominal cavity through use of a laparoscope were removed via an open technique. Advances in laparoscopy now enable detection and definitive treatment for these patients without the need for large, more painful incisions. The laparoscopic approach to this patient enabled diagnosis and management of his cryptorchidism and provided a means for repair of his hernia.

Mebendazole is an anthelmintic drug widely used in Cuba and in Mexico. Its interaction with tubulin interferes with the assemblage of the mitotic apparatus in the parasite cells, thus suggesting a possible genotoxic activity leading to chromosomal malsegregation. The heterozygous diploid strain D30 of Aspergillus nidulans was used to establish the ability of mebendazole to induce mitotic recombination and/or chromosomal non-disjunction, and the haploid strain FGSC #219 of A. nidulans was used to study the ability of mebendazole to induce point mutations in the methG suppressor system. Our results show that mebendazole can induce chromosomal non-disjunction but it fails to promote point mutations.

To compare techniques of gastrostomy in elderly patients, the records of 100 patients age 70 and older who underwent gastrostomy tube placement as a primary procedure were reviewed. Two separate unmatched groups of 50 patients each were identified: those that underwent operative gastrostomy tube (OGT) placement and those that underwent percutaneous endoscopic gastrostomy tube (PEG) placement. The groups were studied for demographic similarities and for differences in morbidity, mortality, and ease of feeding. Comparison showed that PEGs had a lower mortality (0%) and morbidity (10%) than did OGTs where mortality was 4 per cent and morbidity was 22 per cent. PEGs began feeding sooner (1.0 day vs. 2.8 days) than OGTs. In addition, almost 60 per cent of the PEG patients underwent complete upper endoscopy at the time of the PEG, which revealed pathology that either altered the type of tube placed or the eventual medical management. PEG offers a less morbid, safer, and easier to use method of gastrostomy tube placement than OGT in the majority of elderly patients.

Establishment of a percutaneous endoscopic jejunostomy via direct jejunal puncture was accomplished in a 45-year-old woman five years after a partial esophagectomy with cervical esophagogastrostomy for adenocarcinoma of the esophagus. The patient had recurrence of the cancer at the anastomotic site with subsequent inability to eat, necessitating a feeding tube for prolonged enteral nutrition. Although percutaneous puncture of the jejunum has been previously described, it has been limited to patients who had undergone partial or complete gastrectomies with Bilroth II anastomoses. This case report of direct endoscopic jejunal tube placement in a patient after esophagectomy further establishes this procedure as a viable alternative to surgically placed feeding tubes in patients with altered gastric anatomy.

A 2-5-month treatment with niclosamide, a widely used drug in developing countries, has been reported to induce lymphosarcomas in toad liver and kidney. The genotoxic effects of this drug have also been evaluated in Salmonella typhimurium, in somatic and germinal cells of mice and in human lymphocytes exposed in vitro and in vivo. The present study shows that niclosamide is also capable of inducing mitotic crossing-over and non-disjunction in Aspergillus nidulans, which points to the wide potential of this drug as a genotoxic agent.