Effect of single-administration of D-sorbitol pretreatment on the bitterness and continued willingness to take asenapine: a randomized, single-blind, placebo-controlled, crossover trial.

BACKGROUND: Asenapine has unique orally-related side effects, such as a bitter taste induced by sublingual administration, which often results in discontinuation of the medication. While the FDA has approved black-cherry-flavored asenapine, several countries have prescribed only unflavored versions. Specifically, Asians commonly report experiencing the bitterness of asenapine because they are more sensitive to bitter tastes than other ethnic groups. In this study, with the aim of improving adherence by reducing the bitterness of asenapine, we investigated the effects of D-sorbitol, which reduced the bitterness parameters of taste sensors in our previous basic study on the bitterness and continuity of asenapine among patients with schizophrenia. METHODS: Twenty adult patients with schizophrenia were included in this single-blind, placebo-controlled, crossover trial. Participants rinsed their mouths with single-administration of D-sorbitol or a placebo prior to each administration of asenapine. We then conducted the questionnaires and assessed changes in the bitterness of asenapine (primary end point) and willingness to continue its use (secondary end point). RESULTS: D-sorbitol significantly improved the bitterness of asenapine (p = 0.038). Although it did not significantly increase the willingness to continue asenapine (p = 0.180), it did show improvement over the placebo in enhancing willingness to continue, especially in patients who were not accustomed to its taste. CONCLUSION: Our findings indicate that single-administration of D-sorbitol significantly reduces the bitterness of asenapine. In countries where flavored asenapine is not available, this finding could benefit patients who were not accustomed to its bitter taste. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials (jRCTs041210019) on May 14, 2021.

Sensory evaluation of the bitterness of asenapine using D-sorbitol pretreatment: single-blind, placebo-controlled, crossover trial.

BACKGROUND: Antipsychotics are essential in the acute treatment of and maintenance therapy for schizophrenia, but medication adherence and long-term treatment continuity are needed to maximize their effectiveness. Each antipsychotic has various side effects, which may affect adherence. Some patients with schizophrenia are reluctant to take asenapine because of its unique oral-related side effects, such as the bitter taste caused by sublingual administration. Our previous basic research found that D-sorbitol lowered the bitterness parameters of the taste sensors. However, whether D-sorbitol has the same effect in patients remains unclear. Therefore, using a D-sorbitol solution, we aim to evaluate changes in the bitterness of asenapine among patients with schizophrenia. METHODS: In this single-blind, placebo-controlled, crossover trial, we plan to recruit 20 adult patients with schizophrenia spectrum disorder who take sublingual asenapine tablets. The participants will be divided into two groups (n = 10 each). Each group will be given a D-sorbitol or placebo solution on the first day for rinsing before taking the sublingual asenapine tablets. After a 1-day interval, the participants will rinse their mouths again with a different liquid. Questionnaires regarding changes in taste and the willingness to continue asenapine will be conducted before the start of the study and after each rinse. The primary and secondary end points will be a taste evaluation of bitterness, and the willingness to continue asenapine, respectively. Differences in questionnaire scores between the D-sorbitol and placebo solutions will be calculated and analyzed using a McNemar test. DISCUSSION: This study aims to determine the efficacy of D-sorbitol in masking the bitter taste of asenapine. To our knowledge, it is the first intervention study using D-sorbitol for bitter taste of asenapine in patients with schizophrenia. Evidence of the efficacy of D-sorbitol could result in D-sorbitol pretreatment being an easy and inexpensive means of improving adherence to asenapine. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials jRCTs041210019, on May 14, 2021. Ethics approval was obtained from the Nagoya University Clinical Research Review Board.

Long-term outcomes of percutaneous endoscopic intragastric surgery in the treatment of gastrointestinal stromal tumors at the esophagogastric junction.

BACKGROUND: The treatment options for gastrointestinal stromal tumors (GITSs) at the esophagogastric junction (EGJ) are controversial. There have been reports on enucleation for EGJ GISTs in order to avoid gastrectomy. But the number of patients is too small, or the follow-up period is too short to evaluate it. The purpose of this study was to review our experience of 59 patients with EGJ GISTs treated by enucleation by percutaneous endoscopic intragastric surgery (PEIGS) and assess the clinical outcomes. METHODS: PEIGS is performed as described below. Access ports are placed through the abdominal wall and the anterior wall of the stomach. Through the access ports, an endoscope and surgical instruments are inserted into the gastric lumen and tumor enucleation and closure of the defect are carried out. In this study, 59 patients with EGJ GISTs treated by PEIGS between 2005 and 2013 were enrolled. Their hospital records were reviewed, and follow-up data for 8 years were collected to analyze the outcomes. RESULTS: En-bloc enucleation was achieved without tumor rupture in all. Average operation time was 172.3 min. Postoperative complications occurred in 3 (one localized peritonitis, one bleeding, and one surgical site infection). Average tumor size was 35.6 mm. Pathological findings confirmed negative margin in all specimens. The maximum follow-up period was 101 months. Multiple liver metastases were detected in two patients (at 12 and 29 months). The survival rate was 100 %. The disease-free rate was 98.3 % at 12 months and 96.6 % at 29 months, respectively. CONCLUSIONS: As far as the short- and long-term outcomes of our experience are reviewed, PEIGS seems as curative as other aggressive resection methods such as proximal gastrectomy. Tumor enucleation by PEIGS, offering a chance to preserve the stomach, can be a preferable option in carefully selected patients with EGJ GISTs, when performed by a skilled surgeon.

Development of scar-less laparoscopic hernia repair (TAPP-252) facilitated by new 2mm instruments.

INTRODUCTION: To minimize the invasiveness of laparoscopic transabdominal preperitoneal hernia repair (TAPP) for the treatment of adult inguinal hernia, we developed a new operative technique with the use of only one 5 mm port and two 2 mm punctures (TAPP-252). MATERIAL AND METHODS: To facilitate TAPP-252, we developed seven kinds of new 2 mm instruments, including grasping forceps, hook shaped electrode, mesh pusher, needle driver, scissors, laparoscope and port. RESULTS: TAPP-252 was stably performed in 35 patients with minimal abdominal wall destruction and excellent cosmetic result without any recurrence or morbidity. CONCLUSIONS: The newly developed 2 mm devices showed sufficient performance and durability in TAPP-252. Further investigation is necessary to assess durability and long-term outcomes.

Needlescopic intragastric surgery facilitated by newly developed 2mm instruments.

BACKGROUND: Intragastric surgery is a percutaneous endoluminal surgery in the stomach aimed at resection of tumors located at the esophagogastric junction (EGJ). We developed needlescopic intragastric surgery performed via 2 mm, 2 mm, and 5 mm ports (PEIGS-225). MATERIAL AND METHODS: In cooperation with Niti-On Co., Ltd. we developed a series of 2 mm instruments including grasping forceps, a cannula, a laparoscope, an electrocautery, scissors, and a needle holder. OPERATIVE TECHNIQUE: Two 2 mm trocars and a 5 mm one are inserted into the gastric lumen percutaneously. Intragastric procedures are performed by the instruments brought through those three ports. The specimen is extracted via the esophageal-oral route. The defect in the gastroesophageal wall is closed by hand-suture. After the intragastric procedure, the 5 mm stab wound on the gastric wall is closed by hand-suture, while the 2 mm wounds are left untreated. PATIENTS: Between March and August 2015 PEIGS-225 was performed in five patients. RESULTS: There was no operative conversion. The mean operation time was 96 minutes. There were no perioperative complications. Pathological findings indicated that the margin was negative in all cases. CONCLUSION: Needlescopic intragasric surgery performed via the smallest access (2 mm, 2 mm, 5 mm) is enabled by the 2 mm instruments developed by us.

Transanal endoscopic microsurgery for surgical repair of rectovesical fistula following radical prostatectomy.

BACKGROUND: Rectovesical fistula is a rare complication following prostatectomy, associated with significant symptoms such as urinary drainage from anus or faecaluria. While several surgical procedures have been described to treat this condition, none of them has been accepted as the universal standard. Transanal endoscopic microsurgery (TEM) is a well-established endoluminal procedure for local excision of rectal tumors. But its application to the repair of rectovesical fistula has been almost unknown. METHODS: We performed TEM as a surgical repair for refractory rectovesical fistula developing after radical prostatectomy in 10 patients. Under the magnified three-dimensional view, through the stereoscope, the fistula and the surrounding rectal mucosa were precisely resected. The defect and the muscle layer of the rectum were closed by hand-sew technique in four layers. RESULTS: Fistula was completely closed in 7 patients, who eventually underwent enterostomy closure, while in the other 3 patients the fistula recurred. In the three recurrent cases, the fistula was associated with wide, tough scar tissue due to previous irradiation, HIFU, or repeated surgical repair attempts. CONCLUSIONS: Rectovesical fistulas associated with wide, tough scar tissue due to multi-time attempt of surgical repair or any type of energy ablation should not be indicated for repair by TEM. However, for simple fistulas without tough, fibrotic surroundings, TEM can be indicated as a minimally invasive surgical option with very low morbidity, without any incision in healthy tissue for approach.

A single surgeon's experience with transanal endoscopic microsurgery over 20 years with 153 early cancer cases.

BACKGROUND: The first author performed transanal endoscopic surgery (TEM) in 302 patients in Japan for the last 20 years, 153 of which were early rectal cancer cases. The short- and long-term outcomes of the early rectal cancer cases are herein reported. MATERIAL AND METHODS: The original technique of TEM developed by Gerhard Buess was performed in all cases. The hospital records were reviewed to assess the clinical outcomes. A questionnaire was sent to the patients to analyze the long-term outcomes. RESULTS: One-hundred and fifty-three early cancer cases included 115 T0 and 38 T1 lesions. Full-thickness resection was performed in 36 patients, while 117 underwent submucosal dissection. Conversion to laparoscopic low anterior resection occurred in one case. Mortality was nil. Major operative complication was noted in only one patient, who developed stenosis. Seven patients underwent immediate salvage surgery. Six patients died of recurrence of rectal cancer. Disease-free survival rate at year 5 was 93.7%. CONCLUSIONS: Our study, one of the largest series in the world, confirms that TEM is a preferable option in the surgical treatment of T0 and T1a rectal carcinoma. As long as early cancer cases are treated, submucosal resection seems to be sufficient. When risk of recurrence is found by pathological examination, immediate salvage operation is mandatory to improve the prognosis.

Development of a novel multichannel port (x-Gate(®)) for reduced port surgery and its initial clinical results.

BACKGROUND: In order to reduce clashing between the instruments during single-incision endoscopic surgery or reduced port surgery we have developed a new multichannel port with wider distance between the channels. MATERIAL AND METHODS: We used the newly developed multichannel port (x-Gate®) in 34 patients undergoing a variety of reduced port surgery procedures. The operation records of these patients were reviewed. RESULTS: Overall performance of x-Gate® was sufficient in the clinical experience. There have been no complications attributed to x-Gate®. We found that with the x-Gate® the conflicts among the forceps have been drastically improved compared with other multi-channel ports we had used before, which had a shorter distance between the channels.

Stabilization of Single-incision Laparoscopic Cholecystectomy by Needle Puncture and Bendable Retractor.

BACKGROUND: A recent meta-analysis and systematic review suggested that single-incision laparoscopic cholecystectomy (SILC) had a higher procedure failure rate with more blood loss and that it required a longer surgical time than conventional laparoscopic cholecystectomy. Herein, we introduce our experience with the needlescopic grasper-assisted and bendable retractor-assisted SILC technique and evaluate its safety and sustainability. METHODS: The present retrospective cohort study included 407 Japanese patients who underwent needlescopic grasper-assisted and bendable retractor-assisted SILC between January 2012 and April 2017 at our institution. RESULTS: In the present study, all patients successfully underwent needlescopic grasper-assisted and bendable retractor-assisted SILC without conversion to open surgery. Regarding surgical outcomes, mean surgical time was 58.2±23.2 minutes, and additional ports were required in 9 patients (2.2%). Postoperative morbidity developed in only 6 patients (1.4%). CONCLUSIONS: The surgical approaches defined herein were safe and sustainable with favorable surgical outcomes. Compared with conventional SILC, needlescopic grasper-assisted and bendable retractor-assisted SILC might become a mainstream procedure for minimally invasive surgery from the viewpoint of surgical difficulty.

Minimally Invasive, Organ-preserving Surgery for Large Submucosal Tumors in the Abdominal Esophagus.

BACKGROUND: Surgical resection of submucosal tumors (SMTs) in the abdominal esophagus is not standardized. Enucleation may be a minimally invasive option, whereas its oncological validity is not very clear. Moreover, how to treat the esophageal wall defect after enucleation and necessity of additional antireflux procedure are also undetermined. METHODS: In 13 patients with a SMT originating the abdominal esophagus laparoscopic enucleation was performed with preserving the integrity of submucosa. When the muscular layer defect was <4 cm it was directly closed by suturing, whereas it was left open in case the defect was larger. Fundoplication was added when the esophagus was dissected posteriorly or the myotomy was not closed. RESULTS: Tumors were resected en-bloc without rupture in all cases. In 5 patients myotomy was closed, whereas in the remaining 8 it was left open. In 11 patients fundoplication was added (Toupet in 5 and Dor in 6). The patients developed neither regurgitation nor stenosis postoperatively. The histopathologic findings revealed leiomyoma in 9 patients, whereas the other 4 were miscellaneous. The average tumor size was 5.5 cm (range, 2.8 to 8.8). Microscopically surgical margin was negative in all cases. CONCLUSIONS: Laparoscopic enucleation of SMTs in the abdominal esophagus seems to be safe, reproducible operation enabling preservation of function of the lower esophagus and esophagogastric junction. Even when the muscular defect is not approximated additional fundoplication can minimize the risk of postoperative reflux disease.

Laparoscopic Surgery for Large Gastric Submucosal Tumors.

BACKGROUND: In general, laparoscopic resection for gastric gastrointestinal stromal tumors (GISTs) >5 cm is not recommended. However, there is a lack of evidence to support this recommendation. PATIENTS AND METHODS: This study included 108 patients who underwent laparoscopic surgery for gastric GISTs. Of the 108 patients, 23 had GISTs>5 cm. The aim of this study is to evaluate the oncological safety of laparoscopic surgery for large gastric GISTs. In addition, we performed a rapid systematic review of laparoscopic surgery for large gastric GISTs. RESULTS: In our cases, all patients were performed R0 resection without capsular rupture and surgical margins were negative on pathologic examination. In all studies, en bloc resection was achieved without capsular rupture in all patients. The average positive surgical margins rate was 1.6% in total reports. CONCLUSIONS: The laparoscopic approach for large gastric GISTs>5 cm has been proposed as safe when performed by experienced surgeons.