Real-time Continuous Esophageal High-resolution Manometry (HRM) During Laparoscopic Heller Myotomy and Dor Fundoplication for the Treatment of Achalasia. A Promising Novelty in Regards of Perfecting Surgical Technique: Could It Guide Surgical Technique Toward Excellent Results?

High-resolution manometry (HRM) is the gold-standard diagnostic tool for achalasia of the esophagus. Laparoscopic Heller-Dor technique is the preferred surgical approach with success rate estimated 90%. The use of intraoperative HRM provides real-time estimation of intraluminal esophageal pressures and identifies the exact points of esophageal luminal pressure during laparoscopy. Ten patients with achalasia underwent surgery. All patients preoperatively completed 1 manometric study and Quality of Life questionnaires (EORTC QLQ-C30 version 3.0) with Eckardt scores. We collected intraoperative manometry data and repeated manometric studies, EORTC QLQ-C30, and Eckardt scores postoperatively. Median Eckardt score was decreased from 7.5 to 0.5, mean resting pressure decreased from 51.4 to 11.9 mm Hg, whereas mean residual pressure diminished from 45.9 to 9.5 mm Hg postoperatively. The simultaneous use of HRM during the Heller-Dor technique may lead to an individualized management of the disease.

The effect of laparoscopic sleeve gastrectomy on the antireflux mechanism: can it be minimized?

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a promising procedure for the treatment of morbid obesity. The stomach is usually transected near the angle of His; hence, the lower esophageal sphincter (LES) may be affected with consequences on postoperative gastroesophageal reflux disease (GERD). The purpose of this study was to examine the effect of LSG on the LES and postoperative GERD. METHODS: Severely obese asymptomatic patients submitted to LSG underwent esophageal manometry and GERD evaluation preoperatively and at least 6 weeks postoperatively. Data reviewed included patient demographics, manometric measurements, GERD symptoms, and pathology. Statistical analysis was performed by SPSS software. RESULTS: Twelve male and eleven female patients participated in the study. Mean age was 38.5 ± 10.9 years, and initial body mass index was 47.9 ± 5.1 kg/m(2). At follow-up examination, mean excess body mass index loss was 32.3 ± 12.7%. The LES total and abdominal length increased significantly postoperatively, whereas the contraction amplitude in the lower esophagus decreased. There was an increase in reflux symptoms postoperatively (p < 0.009). The operating surgeon who mostly approximated the angle of His resulted in an increased abdominal LES length (p < 0.01). The presence of esophageal tissue in the specimen correlated with increased total GERD score (p < 0.05). CONCLUSIONS: LSG weakens the contraction amplitude of the lower esophagus, which may contribute to postoperative reflux deterioration. It also increases the total and the abdominal length of the LES, especially when the angle of His is mostly approximated. However, if this approximation leads to esophageal tissue excision, reflux is again aggravated. Thus, stapling too close to the angle of His should be done cautiously.

Reinforcing the staple line during laparoscopic sleeve gastrectomy: prospective randomized clinical study comparing two different techniques. Preliminary results.

BACKGROUND: Sleeve gastrectomy involves the creation of small gastric reservoir based on lesser curvature of the stomach, which is fashioned by a longitudinal gastrectomy that preserves the antrum and pylorus together with its vagal innervation. The main complications in the early postoperative course are bleeding and gastric leak. In order to reduce these complications the staple line can be reinforced in many different ways. The purpose of this study was to randomly compare two different techniques in laparoscopic sleeve gastrectomy (LSG): buttressing the staple line at the gastroesophageal junction (angle of Hiss) with Gore Seamguard and staple-line suturing with PDS 2.0. METHODS: Between July 2009 and July 2010, 90 patients were prospectively and randomly enrolled in the two different techniques of handling the staple line during LSG. Forty-eight of these patients belonged in group A (application of Gore Seamguard) and 42 in group B (application of a continuous suture). Operative and postoperative complications were recorded. RESULTS: Postoperative leak affected two patients in group A (4.2%) and bleeding occurred in one patient of group A (2%). Total complication rate was 6.2% for group A. No major surgical complication occurred in group B. The differences between the two groups did not reach statistical significance. CONCLUSIONS: No significant difference is evidenced in terms of bleeding and postoperative leak between the two techniques of enhancing the staple line in LSG. Suturing of the staple line may be more time consuming but costs are considerably less.

OCT4 spliced variant OCT4B1 is expressed in human colorectal cancer.

OCT4, a POU-domain transcription factor is considered to be a key factor in maintaining the pluripotency of stem cells. Several OCT4 isoforms are differentially expressed in human pluripotent and non-pluripotent cells. Reactivation of OCT4 expression is postulated to occur in differentiated cells that have undergone tumorigenesis. To examine OCT4 expression in colorectal cancer (CRC) tissues, and to assess the efficacy of OCT4 as a potential biomarker for CRC, in this study, we investigated its expression in CRC tissues, evaluated its relationship to various clinicopathological parameters and defined the isoform of OCT4 that was found to be expressed in CRC cases. Primary tumor tissues and matching adjacent non-cancerous tissues were obtained from 84 CRC patients. OCT4 expression and isoform determination were documented by reverse transcription-PCR and real-time PCR. OCT4, Sox-2, and NANOG localization were performed using immunohistochemistry. The isoforms expressed in the studied cases were confirmed by sequencing. Twenty biopsy specimens representing healthy tissues, retrieved from colonoscopy were studied in parallel as controls. OCT4 expression levels were higher in CRC tissues compared to matching, adjacent non-cancerous tissues, and healthy controls. Additionally, the levels of OCT4 expression in CRC tissues correlated with tumor stage. OCT4 and Sox-2 were localized in the nuclei and the cytoplasm of CRC cells. In all CRC cases, we found that the OCT4B1 isoform is expressed. Over-expression of OCT4B1 was found in poorly and moderately differentiated CRC tissues. In conclusion, the data imply that OCT4B1 isoform may represent a potential biomarker for the initiation, progression, and differentiation of CRC.

Stem cells in colon cancer. A new era in cancer theory begins.

INTRODUCTION: Despite the various therapeutic combinations and the emergence of new targeted therapies, there is still no curative treatment for all stages of colorectal cancer. Through the query for the best possible combination and solution, a new theory approaching colorectal cancer as a stem cell disease appeared, with a continuously growing body of evidence supporting this idea. The inability to directly recognize cancer stem cells has led researchers to an attempt of distinguishing those using indirect markers. DISCUSSION: This review focuses on colon cancer stem cell theory, the various findings supporting and contradicting this hypothesis, and the markers used up to now in characterizing stem cell populations in colorectal cancer. Despite the numerous unanswered questions on this new cancer hypothesis, it appears to have a justifiable role to play in colorectal cancer tumor biology, and furthermore, it may be the basis for the development of new therapeutic agents of the future. Therefore, every surgeon, oncologist, and physician who is implicated with this disease should be familiar with this novel colorectal cancer theory.

Prospective evaluation of health-related quality of life in a homogeneous Mediterranean group of colorectal cancer patients.

This study was designed to prospectively evaluate health-related quality of life in a homogeneous Mediterranean group of colorectal cancer patients. Ninety-five colorectal cancer patients were preoperatively assessed and followed-up with by skilled investigators using the Short Form-36 Health Survey questionnaire. Overall, patients showed deterioration in all domains, except for pain, when baseline values were compared with 3 and 6 months postoperatively (P = 0.0001). A significant improvement of all Short Form-36 Health Survey questionnaire domains was noted between 6 and 12 months (P = 0.0001). Scores for general health, pain, emotional well-being, and role limitations due to emotional problems at 1 year were shown better than preoperative (P < 0.001). Improved scores in role limitations due to physical health and emotional problems were found at baseline and at 1 year, when laparoscopic were compared with open resections (P < 0.05). Patients that received chemotherapy proved to be more vulnerable regarding their energy, social functioning, and role limitations at 3 months (P < 0.05), whereas older patients had diminished physical functioning at 3 and 6 and 12 months (P < 0.05) postoperatively. Greek colorectal cancer patients remain fragile up to 6 months after surgery, with significant improvements at 1 year, whereas certain aspects of health-related quality of life at 1 year may be even better than before surgery.

Morbid obesity and sleeve gastrectomy: how does it work?

Laparoscopic sleeve gastrectomy is known to be a safe and effective procedure for treating morbid obesity and is performed with increasing frequency both in Europe and the USA. Despite its broad use, many questions about the remaining gastric tube diameter, its long-term efficacy, its effects on gastric emptying, and the hormones involved still remain to be answered. In order to use such a relatively new surgical procedure wisely, it is essential for every surgeon and physician to understand how sleeve gastrectomy acts in obesity and what its potential benefits on the patients' metabolism are. This review focuses on the most important pathophysiologic questions referred to sleeve gastrectomy on the literature so far, in an attempt to evaluate the different issues still pending on the subject.

Laparoscopic sleeve gastrectomy performed with intent to treat morbid obesity: a prospective single-center study of 261 patients with a median follow-up of 1 year.

BACKGROUND: The aim of the study is to look at laparoscopic sleeve gastrectomy as a procedure with intent to cure morbid obesity. Secondary endpoints are related to the safety profile of the procedure. METHODS: This is a prospective clinical study conducted in a single university surgical clinic. RESULTS: Two hundred sixty-one patients (2.5:1 female to male ratio, median age of 37 years) underwent sleeve gastrectomy. Median preoperative body mass index (BMI) was 45.2 kg/m(2). Mortality and morbidity rates were 0.7% and 8.4%, respectively. Risk factors for postoperative complications were history of diabetes mellitus under medical treatment (OR, 4.0; p = 0.014) and prior bariatric operation on the same patient (OR, 5.7, p = 0.034). Median follow-up was 12 months (range 1-29 months). A BMI > 50 kg/m(2) is connected with greater weight loss. Analysis of the percentage of excess weight loss (%EWL) during follow-up at specific time intervals showed a rapid increase for the first 12 months followed by a more gradual rise thereafter. The median %EWL for the first year of follow-up was 65.7 (range 33.8-102.3). The median BMI for the patients that had completed at least 1 year of follow-up was 30.5 kg/m(2) (range 21.2-42.7). The overall success rate after the first year was 74.3% when accounted for %EWL > 50 and 81.7% for BMI < 35 kg/m(2). CONCLUSIONS: The actual long-term efficacy of the procedure remains to be confirmed. Morbidity rates may prove higher than expected especially during the learning curve.

Prospective evaluation of sexual function after open and laparoscopic surgery for rectal cancer.

BACKGROUND: Sexual function may be harmed after treatment for rectal cancer. This study aimed to evaluate prospectively the incidence of sexual dysfunction after rectal cancer treatment and to compare the effects of laparoscopic and traditional open approaches in terms of postoperative sexual function. METHODS: Baseline and 3-, 6-, and 12-month assessments of sexual dysfunction using the International Index of Erectile Function (IIEF) and its specific domains prospectively took place for 56 patients who underwent rectal cancer surgery (38 open vs. 18 laparoscopic procedures, 38 low anterior vs. 18 abdominoperineal resections). The preliminary results are presented. RESULTS: The average total IIEF and isolated IIEF response domain scores were significantly decreased after surgery (p < 0.01) except for the intercourse satisfaction and overall satisfaction scores at 12 months. An improvement in IIEF scores was observed between the 3- and 6-month assessment points (p < 0.01) except for the erectile function and orgasmic function scores. No significant differences were observed between the open and laparoscopic groups in the total IIEF and domain scores preoperatively and at the 3- and 6-month assessment points. The rates of sexual dysfunction did not differ significantly preoperatively or at 3 months postoperatively when open and laparoscopic procedures were compared, although there was a trend in favor of laparoscopic surgery at 6 months (p = 0.076). The baseline IIEF score and the baseline, 3-, and 6-month sexual desire scores were better (p = 0.035, 0.004, 0.017, and 0.061, respectively) in the low anterior resection group than in the abdominoperineal resection group. CONCLUSIONS: Rectal cancer resections were postoperatively associated with a significant reduction in IIEF scores and high rates of sexual dysfunction at 3 and 6 months. The IIEF and domain scores at different assessment points were comparable between the laparoscopic and open surgery groups. Extending the monitoring period and adding more patients in this ongoing prospective study will further elucidate postoperative sexual dysfunction after rectal cancer surgery.

P53 and EGFR expression in colorectal cancer: a reappraisal of 'old' tissue markers in patients with long follow-up.

BACKGROUND: Extensive research into the biology of colorectal cancer has identified a plethora of molecular markers reputed to provide prognostic information. During the last two decades conflicting results have been drawn on the role of the p53 tumour suppressor gene and of the first identified member of the type receptor tyrosine kinase family, EGFR, on colorectal cancer prognosis, p53 Mutational status has been associated with both improved and reduced survival. EGFR has been associated with reduced length of survival, increasing Dukes' stage and lymph node metastases in several reports, but as many studies have reported no association with unfavourable prognostic parameters. The aim of this study was to evaluate the p53 and EGFR expression in patients with an at least 5-year follow-up. PATIENTS AND METHODS: Paraffin-embedded material was retrospectively collected from 164 colorectal adenocarcinoma (50 rectal) patients, who had been operated on between 1994 and 2003. The median follow-up was 5 years (range: 1-14). p53 and EGFR expression were evaluated by immunohistochemistry. RESULTS: Positive p53 immunostaining and EGFR expression was observed in 63.4% and 43.9% of patients, respectively. p53 and EGFR positivity rates were significantly interrelated (p = 0.004). No significant correlation was found with the examined clinicopathological parameters except for advanced T-stage, which demonstrated significant associations with p53 expression (p = 0.004), EGFR expression (p = 0.0001) and p53/EGFR coexpression (p = 0.001). In univariate survival analysis (log rank test), stage (p = 0.0001), lymphovascular invasion (p = 0.005) and perineural infiltration (p = 0.004) were associated with the overall cancer-specific survival, while a trend existed for EGFR (p = 0.06) and p53/EGFR coexpression (p = 0.07). On multivariate analysis, only stage was associated with increased risk of cancer death (Cox regression analysis p = 0.0001, b-coefficient (SE): 1.898 (0.383). CONCLUSION: p53 and EGFR were overexpressed in this colorectal cancer patient population and were significantly associated with advanced T stage. In the context of new therapeutic strategies using EGFR-targeted therapies, although EGFR remains a controversial prognostic factor, this expression-stage association may play a crucial role in a decision to initiate an adjuvant treatment.

Hyperandrogenemia: pathophysiology and its role in ovulatory dysfunction in PCOS.

The most common hormonal disorder that infertile women suffer from is hyperandrogenemia, a disorder believed to show its first signs even from puberty. We discuss the impact of hyperandrogenemia on the normal ovary as well as its potential role and contribution to anovulation and infertility. The early diagnosis and management of hyperandrogenemia in women has been proved to be essential for their health and fertility.

Short-term effect of orlistat on dietary glycotoxins in healthy women and women with polycystic ovary syndrome.

Exogenous advanced glycation endproducts (AGEs, known atherogenic molecules) abundant in everyday precooked, rich in fat, overheated meals can possibly contribute to the increased risk for diabetes and cardiovascular disease in women with polycystic ovary syndrome (PCOS). The aim of the present study was to investigate the effect of a lipase inhibitor on absorbed food glycotoxins in healthy women and those with PCOS. A 2-day protocol was followed. In the first day, a meal rich in AGE was provided, which on the second day was followed by two 120-mg capsules of lipase inhibitor, orlistat. Serum AGE levels were evaluated at baseline (0 hours), and at 3 and 5 hours postmeal during the study. Thirty-six women were studied, 15 controls (mean age, 28.80 +/- 5.47 years; body mass index, 25.85 +/- 6.73 kg/m(2)) and 21 with PCOS (mean age, 25.29 +/- 5.06 years; body mass index, 30.40 +/- 7.51 kg/m(2)) (University Hospital, Athens, Greece, institutional practice). Serum AGE levels, on day 1, were significantly increased both in the control group and in the PCOS group as compared with basal values (control group, 14.1%; PCOS group, 6.0%; P < .001). The corresponding rise was significantly lower on day 2 when the same meal was combined with orlistat (control group, 4.1%; PCOS group, 2.0%; P < .01). A limitation of the study is that it is a nonplacebo, nonrandomized therapeutic trial where each subject is considered as its own control. In conclusion, this study demonstrated the beneficial effect of orlistat on the absorption of food glycotoxins.

Erythropoietin abuse and erythropoietin gene doping: detection strategies in the genomic era.

The administration of recombinant human erythropoietin (rhEPO) increases the maximum oxygen consumption capacity, and is therefore abused as a doping method in endurance sports. The detection of erythropoietin (EPO) abuse is based on direct pharmacological and indirect haematological approaches, both of which have several limitations. In addition, current detection methods cannot cope with the emerging doping strategies of EPO mimicry, analogues and gene doping, and thus novel detection strategies are urgently needed. Direct detection methods for EPO misuse can be either pharmacological approaches that identify exogenous substances based on their physicochemical properties, or molecular methods that recognise EPO transgenes or gene transfer vectors. Since direct detection with molecular methods requires invasive procedures, it is not appropriate for routine screening of large numbers of athletes. In contrast, novel indirect methods based on haematological and/or molecular profiling could be better suited as screening tools, and athletes who are suspect of doping would then be submitted to direct pharmacological and molecular tests. This article reviews the current state of the EPO doping field, discusses available detection methods and their shortcomings, outlines emerging pharmaceutical and genetic technologies in EPO misuse, and proposes potential directions for the development of novel detection strategies.