Platelets as a prognostic factor for patients with adenocarcinoma of the gastroesophageal junction.

OBJECTIVE: The aim of this study was to investigate the prognostic role of plasma platelet count (PLT), mean platelet volume (MPV), and the combined COP-MPV score in patients with resectable adenocarcinomas of the gastroesophageal junction. BACKGROUND: Platelet activation, quantified by PLT and elevated MPV, plays an essential part in the biological process of carcinogenesis and metastasis. An increased preoperative COP-MPV is associated with poor survival in various tumor entities. METHODS: Data of 265 patients undergoing surgical resection for adenocarcinoma of the gastroesophageal junction were abstracted. COP-MPV score was defined for each patient. Utilizing univariate and multivariate Cox proportional hazard analyses, survival was determined. RESULTS: In univariate analysis, elevated PLT (HR 3.58, 95% CI 2.61-4.80, p<0.001) and increased COP-MPV (HR 0.27, 95% CI 0.17-0.42, p<0.001 and HR 0.42, 95% CI 0.29-0.60, p<0.001) significantly correlated with shorter patients' overall and disease-free survival, for all 256 patients, as well as in the subgroups of neoadjuvantly treated (p<0.001) and primarily resected patients (p<0.001). COP-MPV remained a significant prognostic factor in multivariate analysis for OS. However, PLT alone showed significant diminished OS and DFS in all subgroups (p<0.001) in univariate and multivariate analysis. CONCLUSION: PLT is a potent independent prognostic biomarker for survival in a large prospective cohort of patients with resectable adenocarcinoma of the gastroesophageal junction. Additionally, we confirm that the COP-MPV score is significantly associated with worse outcome in these patients, but has no benefit in comparison to PLT.

Effect of electrical stimulation therapy of the lower esophageal sphincter in GERD patients with ineffective esophageal motility.

BACKGROUND: Electrical stimulation therapy (EST) of the lower esophageal sphincter (LES) is a novel technique in antireflux surgery. Due to the minimal alteration at the LES during surgery, LES-EST is meant to be ideal for patients with gastroesophageal reflux disease (GERD) and ineffective esophageal motility (IEM). The aim of this prospective trial (NCT03476265) is to evaluate health-related quality of life and esophageal acid exposure after LES-EST in patients with GERD and IEM. METHODS: This is a prospective non-randomized open-label study. Patients with GERD and IEM undergoing LES-EST were included. Follow-up (FUP) at 12 months after surgery included health-related quality of life (HRQL) assessment with standardized questionnaires (GERD-HRQL) and esophageal functional testing. RESULTS: According to the study protocol, 17 patients fulfilled eligibility criteria. HRQL score for heartburn and regurgitation improved from 21 (interquartile range (IQR) 15-27) to 7.5 (1.25-19), p = 0.001 and from 17 (11-23.5) to 4 (0-12), p = 0.003, respectively. There was neither significant improvement of esophageal acid exposure nor reduction of number of reflux events in pH impedance measurement. Distal contractile integral improved from 64 (11.5-301) to 115 (IQR 10-363) mmHg s cm, p = 0.249. None of the patients showed any sign of dysphagia after LES-EST. One patient needed re-do surgery and re-implantation of the LES-EST due to breaking of the lead after one year. CONCLUSION: Although patient satisfaction improved significantly after surgery, this study fails to demonstrate normalization or significant improvement of acid exposure in the distal esophagus after LES-EST.

Modification of preoperative radiochemotherapy for esophageal cancer (CROSS protocol) is safe and efficient with no impact on surgical morbidity.

PURPOSE: Neoadjuvant radiochemotherapy (RCTH) is proven to be highly effective in the treatment of esophageal cancer (EC). We investigated oncological outcome and morbidity in patients treated with a modified CROSS protocol followed by esophagectomy at our institution. METHODS: Patients with EC receiving neoadjuvant RCTH with paclitaxel and carboplatin and concurrent radiotherapy (46 Gy) followed by esophagectomy were included in this retrospective analysis. Histopathological response, overall survival (OS) and recurrence-free interval (RFI) as well as perioperative morbidity were investigated. RESULTS: Thirty-six patients (86.1% male, mean age 61.3 years, standard deviation 11.52) received neoadjuvant RCTH before surgery. Sixteen patients (44.4%) were treated for squamous cell cancer, whereas 20 patients (55.6%) had adenocarcinoma. The majority (75%) underwent abdominothoracic esophageal resection. Major complications occurred in 7 patients (19.5%) including anastomotic leakage in 4 patients (11.1%). A R0 resection was achieved in 97.2%. A complete pathological remission was seen in 13 patients (36.1%). Major response, classified as Mandard tumor regression grade 1 and 2, was found in 26 patients (72.2%). Median OS and RFI were not reached. CONCLUSIONS: Neoadjuvant radiotherapy with 46 Gy and concomitant chemotherapy with paclitaxel and carboplatin for the treatment of locally advanced esophageal carcinoma is safe and effective. The results of this modified radiotherapy protocol are encouraging and should be considered in future patient treatment and study designs.

Electrical lower esophageal sphincter augmentation in patients with GERD and severe ineffective esophageal motility-a safety and efficacy study.

BACKGROUND: Laparoscopic fundoplication (LF), even if performed in specialized centers, can be followed by long-term side effects such as dysphagia, gas bloating or inability to belch. Patients with an ineffective esophageal motility (IEM) and concurrent GERD are prone to postoperative dysphagia after LF. The aim of this study is to evaluate the safety and efficacy of electrical lower esophageal sphincter stimulation in patients with IEM and GERD. METHODS: This is a prospective, open-label single center study. Patients with PPI-refractory GERD and ineffective esophageal motility were included for lower esophageal sphincter electrical stimulation (LES-EST). Patients underwent prospective follow-up including physical examination, interrogation of the device and were surveyed for changes in the health-related quality of life score. RESULTS: According to power analysis, 17 patients were included in this study. Median distal contractile integral (DCI) was 64 mmHg s cm (quartiles 11.5-301). Median total % pH < 4 was 8.9 (quartiles 4-21.6). Twelve patients (70.6%) underwent additional hiatal repair. At 1-month follow-up, none of the patients showed any clinical or radiological signs of dysphagia. There were no procedure related severe adverse events. Mean total HQRL improved from baseline 37.53 (SD 15.07) to 10.93 (SD 9.18) at follow-up (FUP) (mean difference 24.0 CI 15.93-32.07) p < 0.001. CONCLUSIONS: LES-EST was introduced as a potential technique to avoid side effects of LF. LES-EST significantly improved health related quality of life and does not impair swallowing in patients with GERD and ineffective esophageal motility.

Radiofrequency ablation in patients with large cervical heterotopic gastric mucosa and globus sensation: Closing the treatment gap.

BACKGROUND AND AIM: Symptomatic cervical heterotopic gastric mucosa, also known as cervical inlet patch (CIP), may present in various shapes and causes laryngopharyngeal reflux (LPR). Unfortunately, argon plasma coagulation, standard treatment of small symptomatic CIP, is limited in large CIP mainly because of concerns of stricture formation. Therefore, we aimed to investigate radiofrequency ablation (RFA), a novel minimally invasive ablation method, in the treatment of CIP focusing on large symptomatic patches. METHODS: Consecutive patients with macroscopic and histological evidence of large (≥20 mm diameter) heterotopic gastric mucosa were included in this prospective trial. Primary outcome was complete macroscopic and histological eradication rate of CIP. Secondary outcome measures were symptom improvement, quality of life, severity of LPR and adverse events. RESULTS: Ten patients (females, n = 5) underwent RFA of symptomatic CIP. Complete histological and macroscopic eradication of CIP was observed in 80% (females, n = 4) of individuals after two ablations. Globus sensations significantly improved from median visual analog scale score 8 (5-9) at baseline to 1.5 (1-7) after first ablation and 1 (1-2) after final evaluation (P < 0.001). Mental health scores significantly increased from 41.4 (± 8.5) to 54.4 (± 4.4) after RFA (P = 0.007). LPR improved significantly (P = 0.005) with absence of strictures after a mean follow up of 1.9 (± 0.5) years. CONCLUSIONS: This is the first study on RFA focusing on therapy of large symptomatic heterotopic gastric mucosa. Hereby, we demonstrate that this new technique can be successfully implemented in patients where treatment was limited so far (NCT03023280).

Electrical Stimulation of the Lower Esophageal Sphincter to Treat Gastroesophageal Reflux After POEM.

As per-oral endoscopic myotomy (POEM) is not followed by any anti-reflux procedure, a common concern is the risk of postoperative gastro-esophageal reflux disease (GERD). Electrical stimulation of the lower esophageal sphincter (LES-EST) could be an option for post-POEM GERD. A 68-year old male obese patient underwent successful POEM but developed GERD not responsive to proton pump inhibitors. Consecutively, the patient had implanted an electrical LES stimulation device, consisting of bipolar LES-electrodes connected to a subcutaneous pulse generator. POEM reduced the Eckardt score (9 vs. 0), the LES resting pressure (52.0 vs. 16.4 mmHg), and the Integrated Relaxation Pressure (62.0 vs. 10.0 mmHg). LES-EST substantially reduced post-POEM GERD symptoms. GERD-HRQL scores indicated the elimination of heartburn (26 vs. 7) and regurgitation (24 vs. 3) at three months. A reduced total number refluxes (82 vs. 14) was observed. The %-time of pH below 4 was only slightly reduced (8.6% to 6.2%).LES-EST appears to be a feasible option to symptomatically treat post-POEM GERD for patients not ideal for conventional anti-reflux surgery.

A comparative study on comprehensive, objective outcomes of laparoscopic Heller myotomy with per-oral endoscopic myotomy (POEM) for achalasia.

OBJECTIVE: To compare symptomatic and objective outcomes between HM and POEM. BACKGROUND: The surgical gold standard for achalasia is laparoscopic Heller myotomy (HM) and partial fundoplication. Per-oral endoscopic myotomy (POEM) is a less invasive flexible endoscopic alternative. We compare their safety and efficacy. METHODS: Data on consecutive HMs and POEMs for achalasia from 2007 to 2012 were collected. PRIMARY OUTCOMES: swallowing function-1 and 6 months after surgery. SECONDARY OUTCOMES: operative time, complications, postoperative gastro-esophageal reflux disease (GERD). RESULTS: There were 101 patients: 64 HMs (42% Toupet and 58% Dor fundoplications) and 37 POEMs. Presenting symptoms were comparable. Median operative time (149 vs 120 min, P < 0.001) and mean hospitalization (2.2 vs 1.1 days, P < 0.0001) were significantly higher for HMs. Postoperative morbidity was comparable. One-month Eckardt scores were significantly better for POEMs (1.8 vs 0.8, P < 0.0001). At 6 months, both groups had sustained similar improvements in their Eckardt scores (1.7 vs 1.2, P = 0.1).Both groups had significant improvements in postmyotomy lower esophageal sphincter profiles. Postmyotomy resting pressures were higher for POEMs than for HMs (16 vs 7.1 mm Hg, P = 0.006). Postmyotomy relaxation pressures and distal esophageal contraction amplitudes were not significantly different between groups. Routine postoperative 24-hour pH testing was obtained in 48% Hellers and 76% POEMs. Postoperatively, 39% of POEMs and 32% of HM had abnormal acid exposure (P = 0.7). CONCLUSIONS: POEM is an endoscopic therapy for achalasia with a shorter hospitalization than HM. Patient symptoms and esophageal physiology are improved equally with both procedures. Postoperative esophageal acid exposure is the same for both. The POEM is comparable with laparoscopic HM for safe and effective treatment of achalasia.

Intraoperative assessment of esophagogastric junction distensibility during per oral endoscopic myotomy (POEM) for esophageal motility disorders.

BACKGROUND: Per oral endoscopic myotomy (POEM) is a novel treatment for esophageal motility disorders such as achalasia. To date, the extent of the myotomy has been determined based on the subjective assessment of the endoscopist. We hypothesized that the real-time measurement of esophagogastric junction (EGJ) distensibility using a novel functional lumen-imaging probe would enable objective evaluation of POEM. METHODS: Patients diagnosed with achalasia disorders electively underwent POEM. Using impedance planimetry with a transorally inserted functional lumen-imaging probe (EndoFLIP), cross-sectional areas (CSA) and distensibilities at the EGJ were measured intraoperatively immediately before and after the transoral myotomy (n = 4). All patients completed their 6-month follow-up and two patients had repeat distensibility tests at this time. Four healthy volunteers served as a control group. RESULTS: POEM was successfully performed in all patients (4/4). Premyotomy measurements (40-ml fill mode) showed a median diameter of 6.5 mm (range = 5.2-7.9 mm) at the narrowest location of the EGJ and was 10.1 mm (7.3-13.2 mm) following POEM. CSA increased from 41.5 mm(2) (20-49 mm(2)) to 86 mm(2) (41-137 mm(2)) at a similar median intraballoon pressure (40.3 vs. 38.6 mmHg). The increased EGJ distensibility (DI, 1.0 vs. 2.4 mm(2)/mmHg) was comparable to that of healthy volunteers (2.7 mm(2)/mmHg). CONCLUSION: Functional lumen distensibility measures show that POEM can result in an immediate correction of the nonrelaxing lower esophageal sphincter, which appears similar to that of healthy controls. Intraoperative EGJ profiling may be an important tool to objectively guide the needed extent and completeness of the myotomy during POEM.

Long-term outcomes of an endoscopic myotomy for achalasia: the POEM procedure.

BACKGROUND: Esophageal achalasia is most commonly treated with laparoscopic myotomy or endoscopic dilation. Per-oral endoscopic myotomy (POEM), an incisionless selective myotomy, has been described as a less invasive surgical treatment. This study presents 6-month physiological and symptomatic outcomes after POEM for achalasia. METHODS: Data on single-institution POEMs were collected prospectively. Pre- and postoperative symptoms were quantified with Eckardt scores. Objective testing (manometry, endoscopy, timed-barium swallow) was performed preoperatively and 6 months postoperatively. At 6 months, gastroesophageal reflux was evaluated by 24-hour pH testing. Pre-/postmyotomy data were compared using paired nonparametric statistics. RESULTS: Eighteen achalasia patients underwent POEMs between October 2010 and October 2011. The mean age was 59 ± 20 years and mean body mass index was 26 ± 5 kg/m. Six patients had prior dilations or Botox injections. Myotomy length was 9 cm (7-12 cm), and the median operating time was 135 minutes (90-260). There were 3 intraoperative complications: 2 gastric mucosotomies and 1 full-thickness esophagotomy, all repaired endoscopically with no sequelae. The median hospital stay was 1 day and median return to normal activity was 3 days (3-9 days). All patients had relief of dysphagia [dysphagia score ≤ 1 ("rare")]. Only 2 patients had Eckardt scores greater than 1, due to persistent noncardiac chest pain. At a mean follow-up of 11.4 months, dysphagia relief persisted for all patients. Postoperative manometry and timed barium swallows showed significant improvements in lower esophageal relaxation characteristics and esophageal emptying, respectively. Objective evidence of gastroesophageal reflux was seen in 46% patients postoperatively. CONCLUSIONS: POEM is safe and effective. All patients had dysphagia relief, 83% having relief of noncardiac chest pain. There is significant though mild gastroesophageal reflux postoperatively in 46% of patients in 6-month pH studies. The lower esophageal sphincter shows normalized pressures and relaxation.

Video. Transanal specimen retrieval using the transanal endoscopic microsurgery (TEM) system in minimally invasive colon resection.

BACKGROUND: During laparoscopic colectomy, the specimen is retrieved through substantial incisions, which increase postoperative pain, wound infections, and incisional hernias. In the era of natural orifice transluminal endoscopic surgery (NOTES), incisionless transrectal approaches for colon resections have been investigated with promising results [4-6]. Transanal retrieval of the colonic specimen in laparoscopic colectomy has been described but not widely adopted, although it seems to be an appealing step towards NOTES colectomy. We have used the TEM rectoscope (Richard Wolf Medical Instruments Corporation, Vernon Hills, IL, USA) as a retrieval conduit, which facilitates transanal extraction of the specimen, and protects the rectal edge and anal sphincter during laparoscopic left colectomy. TECHNIQUE: After standard laparoscopic dissection and vascular control, the colon is divided distally, whereas the proximal colonic end is ligated to prevent fecal spillage. The TEM rectoscope is advanced through the rectal stump. The proximal colon is grasped and withdrawn through the rectoscope. The colon is stapled off proximally, and the specimen is removed transanally. An anvil is introduced into the pelvis through the rectoscope and inserted in the descending colon through a colotomy, which is subsequently sealed with an endo-loop. The rectoscope is withdrawn, and the rectal stump edge is stapled off. A circular stapler is introduced in the rectum, and end-to-end anastomosis is performed. DISCUSSION: The extraction incisions in laparoscopic colectomy increase invasiveness and compromise the "purity" of the laparoscopic approach. Retrieval of the specimen through natural orifices constitutes a stepping stone in the transition to future incisionless NOTES colectomy. These techniques have not been widely adopted because of technical difficulties and concerns regarding trauma. In our experience, transanal retrieval of the colonic specimen is hampered by friction between the specimen and the rectum, which requires countertraction to the edges of the open rectal stump. These manipulations are time consuming and increase the risk of injury, even when retrieval bags are used. The TEM rectoscope allows gentle dilation of the anus, provides stability during extraction, and protects the edges of the rectum, therefore decreasing the risk of rectal or anal canal injuries. It maintains pneumoperitoneum and eases retrieval of the specimen through the large-caliber metal conduit. Alternative options in the form of a rigid conduit would be the use of the transanal endoscopic operation device (Karl Storz, Tuttlingen, Germany), the plastic McCartney tube (Tyco Healthcare, Norwalk, CT, USA) used for transvaginal operations, or an anecdotally reported, "homemade" rectoscope from a customized polyvinyl chloride tube. Potential limitations of this technique include the increased cost of acquiring and using the TEM rectoscope, although this should not be significant if this reusable system is already available for transanal procedures. The 4 cm diameter of the TEM rectoscope can also be a limiting factor in the case of large, bulky, incompressible specimens or large colonic tumors. We have also avoided using this technique in patients with preexisting anal sphincter dysfunction and fecal incontinence, as well as in the presence of severe perianal disease (i.e., fistulae or fissures). Naturally, the open lumen in the peritoneal cavity raises concerns regarding bacterial contamination and potential tumor cell seeding in cases of cancer. Preliminary evidence on these issues comes from TEM and NOTES research without obvious signs of increased risk currently. We do not perform preoperative bowel preparation for our colectomies, but we do perform rectal enema with Betadine solution at the beginning of the procedure. CONCLUSIONS: Use of the TEM system facilitates transanal removal of the specimen and protects the anorectum during laparoscopic colectomy.

Quantifying mental workloads of surgeons performing natural orifice transluminal endoscopic surgery (NOTES) procedures.

BACKGROUND: During natural orifice transluminal endoscopic surgery (NOTES), surgeons often have difficulties orienting the surgical view and manipulating instruments accurately, which increases their level of mental and physical fatigue. This study quantified mental workload by measuring the spared mental resources of surgeons performing NOTES training tasks. METHODS: Assessment of mental workload was conducted in both a benchtop and a hybrid animal model. Using the benchtop model, surgeons were required to pass a ring as many times as possible in 6 min. Using the hybrid model, surgeons were required to dissect the gallbladder. While performing those primary tasks, the surgeon was required to identify true visual signals among many false signals displayed on an adjacent monitor. They were asked to repeat the trials using laparoscopy. The surgeons' performance on the primary and secondary tasks using the NOTES and laparoscopic approaches were recorded and compared. RESULTS: The nine surgeons who completed the trials in the benchtop model successfully transferred 13 ± 4 rings between targets using laparoscopy compared with a mean of 1.2 ± 1.0 rings transferred using NOTES (P < 0.001). The surgeons detected visual signals at a 74% rate using laparoscopy, which was significantly higher than the 54% detection rate with the NOTES procedure (P = 0.005). Using the hybrid model, 10 surgeons achieved a 55% accuracy rate performing the laparoscopic task. This was found to be significantly higher (P = 0.006) than when the task was performed using the NOTES platform (39%). CONCLUSION: The results showed that performance of a task using the NOTES platform increases surgeons' mental workload. Because difficulty performing NOTES is associated with flexible endoscopy, the authors expect that new operating systems providing stable platforms will help to decrease the mental workload of surgeons and enhance eye-hand coordination in performing NOTES.

Flexible endoscopic Zenkers diverticulotomy with a novel bipolar forceps: a pilot study and comparison with needleknife dissection.

BACKGROUND: Zenker's diverticulum (ZD) is the most common diverticulum of the upper gastrointestinal tract. Various flexible endoscopic techniques have been used for division of the septum. However, the learning curve associated with these techniques might be difficult to overcome given the overall rarity of this condition. This can lead either to complications or to potential recurrence of symptoms. The authors hypothesized that a flexible bipolar hemostasis forceps developed for natural orifice translumenal surgery (NOTES) procedures would facilitate precise endoscopic diverticulotomy and simultaneously enable sealing of divided tissue edges. METHODS: Because the pharyngeal diverticulum (PD) in the pig is comparable with a human ZD, this nonsurvival model was used to perform endoscopic diverticulotomy using two energy technologies. The PD septum was dissected with either a flexible and a rotating bipolar forceps (n = 5) or with standard needleknife cautery (NK; n = 3). The feasibility and safety of the two technologies were compared. RESULTS: In contrast to NK myotomy, the bipolar forceps could easily be readjusted before any tissue dissection in all (5/5) interventions, and energy was applied only on the tissue to be divided. Tissue bonding at the edges of the septum was observed in all cases. The monopolar energy in NK dissection made precise and centered division of the septum difficult to achieve and did not bond the edges of the septum. One perforation occurred with NK (1/3). CONCLUSIONS: The flexible bipolar forceps used for Zenker's diverticulotomy is appealing due to its ease of application and potential to coaptate mucomuscular tissue edges. Although further evaluation with a survival model is necessary, it also seems to be a safer approach than NK. This novel tool could facilitate performance of surgical endoscopists and may make flexible endoscopy the preferred method for Zenker's ablation.

A natural orifice transrectal approach for oncologic resection of the rectosigmoid: an experimental study and comparison with conventional laparoscopy.

BACKGROUND: A transrectal (TR) approach for natural orifice translumenal endoscopic surgery (NOTES) makes sense for colorectal surgery because the colotomy can be incorporated into subsequent anastomosis. Because cancer is a primary indication for left-sided colon resection, oncologic standards will have to be met by a NOTES procedure. This study aimed to assess whether pure TR rectosigmoidectomy can be performed with strict adherence to oncologic principles compared with a conventional laparoscopically assisted approach (LAP). METHODS: Human male cadavers were allocated to either TR (n = 4) or LAP (n = 2). A simulated sigmoid lesion was created at 25 cm. Transrectal retrograde mobilization of the rectosigmoid was performed using conventional transanal endoscopic microsurgery (TEM) instrumentation. After ligation of the superior hemorrhoidal artery and further mobilization, the specimen was delivered transanally and divided extracorporeally. Using a circular stapler, NOTES colorectal anastomosis was performed. Lymph node yield, adequate resection margins, and operative time were compared with LAP. RESULTS: Transrectal retrograde rectosigmoid dissection was achieved in all attempts (4/4) and showed numbers of lymph nodes (median, 5; range, 3-6) similar to the LAP group (median, 4.5; range, 2-7). One pure TR approach failed to resect the lesion. Three TR procedures required additional mobilization via an abdominal approach to provide adequate margins. The mean length of TR specimens was 16 ± 4 cm compared with 31 ± 9 cm achieved by LAP (p < 0.01). The TR operative time was significantly longer (247 ± 15 vs 110 ± 14 min). CONCLUSION: Lymph node yield during TR rectosigmoidectomy was similar to that achieved by the LAP approach. However, conventional TEM instrumentation alone did not permit adequate colon mobilization. This indicates a need for flexible instrumentation or other technical solutions to perform true NOTES colectomies.

Achalasia: physiology and diagnosis.

Achalasia is a rare motility disorder with incomplete relaxation of the lower esophageal sphincter and ineffective contractions of the esophageal body. It has been hypothesized that achalasia does not result from only one pathway but rather involves a combination of infectious, autoimmune, and familial etiological components. On the basis of other observations, a novel hypothesis suggests that a muscular form of eosinophilic esophagitis is involved in the pathophysiology of achalasia in some patients. This appears to progressively diminish the myenteric plexus at stage III, gradually destroy it at stage II, and finally eliminate it at stage I, the most advanced and final stage of achalasia. Although high-resolution manometry has identified these three different types of achalasia, another subset of patients with a normal-appearing sphincter relaxation has been proposed. Provocative maneuvers, such as the rapid drinking challenge, have recently been demonstrated to improve diagnosis in certain borderline patients, but have to be studied in more detail. However, whether the different types of achalasia will have a long-term impact on tailored therapies is still a matter of debate. Additionally, novel aspects of the standard timed barium swallow appear to be an important adjunct of diagnosis, as it has been shown to have a diagnostic as well as a predictive value.

Long-term anorectal and sexual function after overlapping anterior anal sphincter repair: a case-match study.

PURPOSE: The purpose of this study was to assess the impact of overlapping anal sphincter repair for fecal incontinence on overall pelvic organ function. METHODS: This study was a case-match study of 25 women undergoing overlapping anal sphincter repair from 1996 through 2003. Functional outcome was assessed using validated scoring systems. For each case, two controls matched for age and parity were assessed. RESULTS: Twenty-one patients responded to the questionnaires; mean follow-up time was 105 (SD, 33.6) months. Analyzing the Wexner incontinence score, the group median improved from 15 (range, 4-20) before the procedure to 8 (range, 2-18; P < 0.001) at follow-up.Conversely, postoperatively there was no difference in symptoms of urinary incontinence between groups. The Female Sexual Function Index of case patients was significantly lower than that of control patients (cases, 16.2 [2.3-33.6]; controls, 26.1 [3.3-36]; P = 0.004). The Short-Form-12 physical health score was similar for both groups (mean +/- standard deviation: cases, 46.1 +/- 10.8; controls, 48.6 +/- 11.4; P = 0.220), whereas the mental health score of patients was significantly lower than that of controls (cases, 39.8 +/- 10.5; controls, 47.1 +/- 8.5; P = 0.0057). CONCLUSION: Anal sphincter repair for localized sphincter defects may achieve excellent/good long-term functional results in 67 percent of patients, as judged by patients. Despite repair, continence remained significantly inferior in patients as compared with healthy control subjects. In addition, sexual function was significantly diminished in patients as compared with controls, but no correlation with the severity of fecal incontinence was found.

Pilot trial of autologous dendritic cells loaded with tumor lysate(s) from allogeneic tumor cell lines in patients with metastatic medullary thyroid carcinoma.

Immunotherapy with autologous dendritic cells (DCs) loaded with tumor lysate(s) from allogeneic tumor cell lines is a novel strategy to induce immune responses in cancer patients. We report on a pilot trial of autologous DCs pulsed with tumor cell lysate derived from allogeneic medullary thyroid carcinoma (MTC) cell lines in patients with metastatic MTC. The purpose of this study was to assess the safety, resulting immune responses and clinical activity of the DCs. DCs were injected into a groin lymph node at 3-week intervals. Monitoring included serial calcitonin tumor marker measurements, radiological imaging and immunological in vitro tests (T-cell interferon-gamma detection assay, T-cell cytotoxicity assay). Ten patients (median age 47 years, range 29-77) were enrolled. DC vaccinations were well-tolerated and safe. After a median follow-up of 11 months, (range 7-26), 3 (30%) of 10 patients had stable disease, while 7 (70%) of the patients progressed during treatment. In 2 patients with stable disease, calcitonin decreased below treatment levels, paralleled by a T-cell-mediated immune response. Notably, treatment with DCs pulsed with a combination of different tumor cell lysates was followed by a calcitonin decrease in 4 patients who had previously experienced a calcitonin increase during monotherapy with DCs pulsed with a single lysate. Allogeneic tumor cell lysate-based DC immunotherapy is well-tolerated and safe. Combined treatment with different tumor cell lysate-pulsed DCs increases the likelihood of a calcitonin tumor marker response and should therefore be preferred over monotherapy with DCs pulsed with a single lysate.

CO2 insufflation during colonoscopy decreases post-interventional pain in deeply sedated patients: a randomized controlled trial.

INTRODUCTION: Air insufflation during colonoscopy is considered the standard method in most endoscopic centers. Notably, several studies have reported reduced abdominal pain after colonoscopy with CO2 insufflation in unsedated and in lightly sedated patients. The present study was designed to assess the efficacy of CO2 insufflation after colonoscopy in moderately and deeply sedated patients. We also evaluated whether CO2 insufflation increases patients' compliance for colorectal cancer screening. PATIENTS AND METHODS: A total of 300 consecutive patients allocated to colonoscopy were randomly assigned to either CO2 or air insufflation. Propofol was titrated to a level of deep sedation and propofol combined with midazolam was used for moderate sedation. Post-interventional pain levels and satisfaction with the procedure were registered on a 10-point visual analog scale. Compliance for colorectal cancer screening was ascertained separately. RESULTS: CO2 insufflation was used during colonoscopy in 157 patients; conventional air was used in 143 patients. The two groups were comparable with regard to age, sex and body mass index. Neither major nor minor complications were observed. Pain sensation was significantly lower in the CO2 group at 15 min, 30 min and 6 h after colonoscopy (P<0.01); at 12 h no difference was observed. In contrast, levels of patient satisfaction did not show any significant difference. Voluntary colorectal cancer screening appeared not to be influenced by the type of insufflation gas used. CONCLUSIONS: CO2 insufflation in deeply and moderately sedated patients during colonoscopy has no impact on patients' satisfaction with the procedure or on their attitude to voluntary colorectal cancer screening. However, the use of CO2 insufflation significantly diminishes abdominal pain after colonoscopy.

Biomechanical properties of decellularized porcine pulmonary valve conduits.

Tissue-engineered heart valves constructed from a xenogeneic or allogeneic decellularized matrix might overcome the disadvantages of current heart valve substitutes. One major necessity besides effective decellularization is to preserve the biomechanical properties of the valve. Native and decellularized porcine pulmonary heart valve conduits (PPVCs) (with [n = 10] or without [n = 10] cryopreservation) were compared to cryopreserved human pulmonary valve conduits (n = 7). Samples of the conduit were measured for wall thickness and underwent tensile tests. Elongation measurement was performed with a video extensometer. Decellularized PPVC showed a higher failure force both in longitudinal (+73%; P < 0.01) and transverse (+66%; P < 0.001) direction compared to human homografts. Failure force of the tissue after cryopreservation was still higher in the porcine group (longitudinal: +106%, P < 0.01; transverse: +58%, P < 0.001). In comparison to human homografts, both decellularized and decellularized cryopreserved porcine conduits showed a higher extensibility in longitudinal (decellularized: +61%, P < 0.001; decellularized + cryopreserved: +51%, P < 0.01) and transverse (decellularized: +126%, P < 0.001; decellularized + cryopreserved: +118%, P < 0.001) direction. Again, cryopreservation did not influence the biomechanical properties of the decellularized porcine matrix.

Morbidity in open versus minimally invasive hybrid esophagectomy (MIOMIE): Long-term results of a randomized controlled clinical study.

BACKGROUND: The minimally invasive esophagectomy (MIE) for esophageal cancer was introduced assuming a reduction of morbidity and operation time. After implementation of MIE at our institution, a randomized controlled trial was designed. METHODS: This is a prospective randomized controlled study comparing open (OE) and laparoscopic gastric tube (MIE) formation in Ivor Lewis esophagectomy. Primary endpoints were morbidity and 30-day mortality. Secondary endpoints included the duration of intensive care unit stay, length of hospital stay, operative time as well as relapse-free and overall survival. RESULTS: Twenty patients (76.9%) were male, median age was 63 years (40-77). Median operation time was 290 (215-385) minutes in OE and 292.5 (200-450) minutes in MIE group, p = 0.421. Major complications occurred in 4 (33.3%) patients in the OE group and in 6 (35.7%) patients in the MIE group. Anastomotic leakage was seen in 2 (16.6%) and 3 (21.4%) patients, respectively (OR 1.364; CI = 0.188-9.912; p = 0.759). Due to an alarming number of consecutive anastomotic leakages, the trial was stopped after inclusion of 26 patients. Median follow-up was 41.5 (1-62.6) months. 5­year survival rate was 50%. Thirty-eight percent developed recurrence of disease in the study period. There was no significant difference in overall and relapse-free survival regarding the type of surgery. CONCLUSION: This study shows that hybrid MIE is a feasible alternative for esophageal resection. Morbidity, mortality, and oncological long-term results were equal in both groups, but the interpretation has to be done carefully due to premature termination of the trial. Interrupting a trial because of patient benefit should not be a reason to discard results but rather to improve technical aspects and strive for novel studies.

Phenotypes of Jackhammer esophagus in patients with typical symptoms of gastroesophageal reflux disease responsive to proton pump inhibitors.

This trial was designed to assess the prevalence and characteristics of Jackhammer esophagus (JE), a novel hypercontractile disorder associated with progression to achalasia and limited outcomes following anti-reflux surgery in patients with typical symptoms of GERD and responsiveness to proton pump inhibitor (PPI) therapy. Consecutive patients, who were referred for surgical therapy because of PPI responsive typical symptoms of GERD, were prospectively assessed between January 2014 and May 2017. Patients diagnosed with JE subsequently underwent rigorous clinical screening including esophagogastroduodenoscopy (EGD), ambulatory pH impedance monitoring off PPI and a PPI trial. Out of 2443 evaluated patients, 37 (1.5%) subjects with a median age of 56.3 (51.6; 65) years were diagnosed with JE and left for final analysis. Extensive testing resulted in 16 (43.2%) GERD positive patients and 5 (13.9%) participants were observed to have an acid hypersensitive esophagus. There were no clinical parameters that differentiated phenotypes of JE. The prevalence of JE in patients with typical symptoms of GERD and response to PPI therapy is low. True GERD was diagnosed in less than half of this selected cohort, indicating the need for objective testing to stratify phenotypes of JE. (NCT03347903).