Peroral endoscopic myotomy versus pneumatic dilation in treatment-naive patients with achalasia: 5-year follow-up of a randomised controlled trial.

BACKGROUND: 2-year follow-up data from our randomised controlled trial showed that peroral endoscopic myotomy is associated with a significantly higher efficacy than pneumatic dilation as initial treatment of therapy-naive patients with achalasia. Here we report therapeutic success rates in patients treated with peroral endoscopic myotomy compared with pneumatic dilation at the 5-year follow-up. METHODS: We did a multicentre, randomised controlled trial in six hospitals in the Netherlands, Germany, Italy, Hong Kong, and the USA. Adults aged 18-80 years with newly diagnosed symptomatic achalasia (based on an Eckardt score >3) were eligible for inclusion. Patients were randomly assigned (1:1) to peroral endoscopic myotomy or pneumatic dilation using web-based randomisation with a random block size of 8 and stratification according to site. Randomisation concealment for treatment type was double blind until official study enrolment. Treatment was unmasked because of the different technical approach of each procedure. Patients in the pneumatic dilation group were dilated with a single series of 30-35 mm balloons. The need for subsequent dilations in the pneumatic dilation group, and the need for dilation after initial treatment in the peroral endoscopic myotomy group, was considered treatment failure. The primary outcome was therapeutic success (Eckardt score ≤3 in the absence of severe treatment-related complications and no need for retreatment). Analysis of the primary outcome was by modified intention to treat, including all patients randomly assigned to a group, excluding those patients who did not receive treatment or were lost to follow-up. Safety was assessed in all included patients. This study is registered at the Dutch Trial Registry, NTR3593, and is completed. FINDINGS: Between Sept 21, 2012, and July 20, 2015, 182 patients were assessed for eligibility, 133 of whom were included in the study and randomly assigned to peroral endoscopic myotomy (n=67) or pneumatic dilation (n=66). 5-year follow-up data were available for 62 patients in the peroral endoscopic myotomy group and 63 patients in the pneumatic dilation group. 50 (81%) patients in the peroral endoscopic myotomy group had treatment success at 5 years, compared with 25 (40%) in the pneumatic dilation group, an adjusted absolute difference of 41% (95% CI 25-57; p<0·0001). Reasons for failure were no initial effect of treatment (one patient in the peroral endoscopic myotomy group vs 12 patients in the pneumatic dilation group) and recurrent symptoms causing treatment failure (11 patients in the peroral endoscopic myotomy group [seven patients between 2 and 5 years] vs 25 patients in the pneumatic dilation group [nine patients between 2 and 5 years]); one patient in the pneumatic dilation group had treatment failure due to an adverse event. Proton-pump inhibitor use (mostly daily) was significantly higher after peroral endoscopic myotomy than after pneumatic dilation among patients still in clinical remission (23 [46%] of 50 patients vs three [13%] of 24 patients; p=0·008). 5-year follow-up endoscopy of patients still in clinical remission showed reflux oesophagitis in 14 (33%) of 42 patients in the peroral endoscopic myotomy group (12 [29%] grade A or B, two [5%] grade C or D) and two (13%) of 16 patients in the pneumatic dilation group (two [13%] grade A or B, none grade C or D; p=0·19). No intervention-related serious adverse events occurred between 2 and 5 years after treatment. The following non-intervention-related serious adverse events occurred between 2 and 5 years: a stroke (one [2%]) in the peroral endoscopic myotomy group; and death due to a melanoma (one [2%]) and dementia (one [2%]) in the pneumatic dilation group. INTERPRETATION: Based on this study, peroral endoscopic myotomy should be proposed as an initial treatment option for patients with achalasia. Although our study has shown that peroral endoscopic myotomy has greater long-term efficacy with a low risk of major treatment-related complications, this should not lead to abandonment of pneumatic dilation from clinical practice. Ideally, all treatment options should be discussed with treatment-naive patients with achalasia and a shared decision should be made. FUNDING: Fonds NutsOhra and European Society of Gastrointestinal Endoscopy.

The Vertical Rectus Abdominis Myocutaneous Flap to Manage Vaginal Evisceration.

BACKGROUND: Pelvic organ prolapse (POP) is a significant issue requiring surgical correction in 19% of the female population by age 85 years. Complications of POP, especially in women who have undergone hysterectomy, include vaginal evisceration-a serious complication that carries high morbidity and mortality rates. Rarely, vaginal evisceration occurs after colpocleisis. CASE: A 69-year-old female with recurrent vaginal evisceration following colpocleisis underwent surgical repair using a vertical rectus abdominis myocutaneous (VRAM) flap. CONCLUSION: Recurrent cases of POP and vaginal evisceration that are refractory to conventional treatment require consideration of novel management options. To our knowledge, this is the first case using a VRAM flap for the management of vaginal evisceration.

A Phase 2/3 Prospective Multicenter Study of the Diagnostic Accuracy of Prostate Specific Membrane Antigen PET/CT with 18F-DCFPyL in Prostate Cancer Patients (OSPREY).

PURPOSE: Prostate specific membrane antigen-targeted positron emission tomography/computerized tomography has the potential to improve the detection and localization of prostate cancer. OSPREY was a prospective trial designed to determine the diagnostic performance of 18F-DCFPyL-positron emission tomography/computerized tomography for detecting sites of metastatic prostate cancer. MATERIALS AND METHODS: Two patient populations underwent 18F-DCFPyL-positron emission tomography/computerized tomography. Cohort A enrolled men with high-risk prostate cancer undergoing radical prostatectomy with pelvic lymphadenectomy. Cohort B enrolled patients with suspected recurrent/metastatic prostate cancer on conventional imaging. Three blinded central readers evaluated the 18F-DCFPyL-positron emission tomography/computerized tomography. Diagnostic performance of 18F-DCFPyL-positron emission tomography/computerized tomography was based on imaging results compared to histopathology. In cohort A, detection of pelvic nodal disease (with specificity and sensitivity as co-primary end points) and of extrapelvic metastases were evaluated. In cohort B, sensitivity and positive predictive value for prostate cancer within biopsied lesions were evaluated. RESULTS: A total of 385 patients were enrolled. In cohort A (252 evaluable patients), 18F-DCFPyL-positron emission tomography/computerized tomography had median specificity of 97.9% (95% CI: 94.5%-99.4%) and median sensitivity of 40.3% (28.1%-52.5%, not meeting prespecified end point) among 3 readers for pelvic nodal involvement; median positive predictive value and negative predictive value were 86.7% (69.7%-95.3%) and 83.2% (78.2%-88.1%), respectively. In cohort B (93 evaluable patients, median prostate specific antigen 11.3 ng/ml), median sensitivity and positive predictive value for extraprostatic lesions were 95.8% (87.8%-99.0%) and 81.9% (73.7%-90.2%), respectively. CONCLUSIONS: The primary end point for specificity was met while the primary end point for sensitivity was not. The high positive predictive value observed in both cohorts indicates that 18F-DCFPyL-positive lesions are likely to represent disease, supporting the potential utility of 18F-DCFPyL-positron emission tomography/computerized tomography to stage men with high-risk prostate cancer for nodal or distant metastases, and reliably detect sites of disease in men with suspected metastatic prostate cancer.

Diagnostic Performance of 18F-DCFPyL-PET/CT in Men with Biochemically Recurrent Prostate Cancer: Results from the CONDOR Phase III, Multicenter Study.

PURPOSE: Current FDA-approved imaging modalities are inadequate for localizing prostate cancer biochemical recurrence (BCR). 18F-DCFPyL is a highly selective, small-molecule prostate-specific membrane antigen-targeted PET radiotracer. CONDOR was a prospective study designed to determine the performance of 18F-DCFPyL-PET/CT in patients with BCR and uninformative standard imaging. EXPERIMENTAL DESIGN: Men with rising PSA ≥0.2 ng/mL after prostatectomy or ≥2 ng/mL above nadir after radiotherapy were eligible. The primary endpoint was correct localization rate (CLR), defined as positive predictive value with an additional requirement of anatomic lesion colocalization between 18F-DCFPyL-PET/CT and a composite standard of truth (SOT). The SOT consisted of, in descending priority (i) histopathology, (ii) subsequent correlative imaging findings, or (iii) post-radiation PSA response. The trial was considered a success if the lower bound of the 95% confidence interval (CI) for CLR exceeded 20% for two of three 18F-DCFPyL-PET/CT readers. Secondary endpoints included change in intended management and safety. RESULTS: A total of 208 men with a median baseline PSA of 0.8 ng/mL (range: 0.2-98.4 ng/mL) underwent 18F-DCFPyL-PET/CT. The CLR was 84.8%-87.0% (lower bound of 95% CI: 77.8-80.4). A total of 63.9% of evaluable patients had a change in intended management after 18F-DCFPyL-PET/CT. The disease detection rate was 59% to 66% (at least one lesion detected per patient by 18F-DCFPyL-PET/CT by central readers). CONCLUSIONS: Performance of 18F-DCFPyL-PET/CT achieved the study's primary endpoint, demonstrating disease localization in the setting of negative standard imaging and providing clinically meaningful and actionable information. These data further support the utility of 18F-DCFPyL-PET/CT to localize disease in men with recurrent prostate cancer.See related commentary by True and Chen, p. 3512.

Peroral endoscopic myotomy: anterior versus posterior approach: a randomized single-blinded clinical trial.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) has become the mainstay for the treatment of achalasia at many institutions around the world since its inception in 2008. POEM can be performed using either the anterior or posterior approach. The primary aim of this study was to compare the efficacy of the anterior and posterior approaches at 1 year after POEM. METHODS: This is a single-blinded, randomized, noninferiority international clinical trial. Eligible participants were adult patients with a confirmed diagnosis of achalasia via high-resolution esophageal manometry. Patients were randomly allocated with a 1:1 ratio to receive POEM with anterior or posterior approach. The primary aim was to compare the rate of clinical success (Eckardt score <3) of anterior and posterior approaches at 1 year. RESULTS: One hundred fifty patients were randomized to receive either anterior (n = 73) or posterior (n = 77) POEM. One hundred forty-eight patients received the POEM treatment, and 138 patients completed the 1-year follow-up and were included in the primary efficacy analysis. Technical success was achieved in 71 patients (97.3%) in the anterior group versus 77 patients (100%) in the posterior group (P = .23). The median (interquartile range) length of hospital stay after the procedure was 2 (1-3) days for both groups. Adverse events occurred in 15 patients (10%), 8 patients (11%) in the anterior group and 7 patients (9%) in the posterior group (P = .703). Clinical success was achieved in 90% of patients in the anterior group and 89% of patients in the posterior group. Abnormal esophageal acid exposure was detected in 29 of 59 patients (49%) and 25 of 60 patients (42%) in the anterior and posterior groups, respectively (P = .67). GERD questionnaire scores were also not significantly different between the study groups. In both groups, quality of life improved after POEM for all 36-Item Short-Form Health Survey measures and was similar between both groups. CONCLUSIONS: Posterior myotomy during POEM was not inferior to anterior myotomy in terms of efficacy and safety in the treatment of patients with achalasia. (Clinical trial registration number: NCT02454335.).

A pilot study on surgical reduction of the levator hiatus-the puborectalis sling.

INTRODUCTION AND HYPOTHESIS: Female pelvic organ prolapse recurrence has been shown to be associated with levator hiatal distensibility. Reducing hiatal size surgically may reduce recurrence risk. This study aims to demonstrate a novel surgical procedure, the puborectalis sling (PR sling), designed to reduce the levator hiatal area, and to assess the medium-term safety and efficacy of this procedure. METHODS: One hundred fifteen women undergoing prolapse repair with a pre-operative hiatal area on Valsalva of ≥ 35 cm2 were recruited into this phase 1 prospective multicentre pilot study. All underwent a PR sling procedure after completion of standard repairs. Primary outcome was levator hiatal area measured on ultrasound. RESULTS: One hundred ten patients were evaluated at least 3 months post-operatively. At 2.5 years average follow-up, there was an average of 12 cm2 (range 6-16 cm2) reduction in hiatal area from a mean pre-operative hiatal area of 43.9 (35-63) cm2. Thirty per cent (28/93) were symptomatic of prolapse, 66% (61/93) had clinical prolapse recurrence whilst 49% (46/93) had sonographic recurrence. Three patients required a return to theatre; one case of infection resulted in mesh removal, one had severe obstructed defecation requiring sling loosening and another had buttock pain with faecal impaction that resolved after manual disimpaction. There were no long-term sequelae. CONCLUSIONS: The levator hiatal area can be reduced surgically, with almost 30% reduction in area seen in this pilot study. The reduction was significant and sustained up to 2 years with no major long-term complications.

Effect of Peroral Endoscopic Myotomy vs Pneumatic Dilation on Symptom Severity and Treatment Outcomes Among Treatment-Naive Patients With Achalasia: A Randomized Clinical Trial.

Importance: Case series suggest favorable results of peroral endoscopic myotomy (POEM) for treatment of patients with achalasia. Data comparing POEM with pneumatic dilation, the standard treatment for patients with achalasia, are lacking. Objective: To compare the effects of POEM vs pneumatic dilation as initial treatment of treatment-naive patients with achalasia. Design, Setting, and Participants: This randomized multicenter clinical trial was conducted at 6 hospitals in the Netherlands, Germany, Italy, Hong Kong, and the United States. Adult patients with newly diagnosed achalasia and an Eckardt score greater than 3 who had not undergone previous treatment were included. The study was conducted between September 2012 and July 2015, the duration of follow-up was 2 years after the initial treatment, and the final date of follow-up was November 22, 2017. Interventions: Randomization to receive POEM (n = 67) or pneumatic dilation with a 30-mm and a 35-mm balloon (n = 66), with stratification according to hospital. Main Outcomes and Measures: The primary outcome was treatment success (defined as an Eckardt score ≤3 and the absence of severe complications or re-treatment) at the 2-year follow-up. A total of 14 secondary end points were examined among patients without treatment failure, including integrated relaxation pressure of the lower esophageal sphincter via high-resolution manometry, barium column height on timed barium esophagogram, and presence of reflux esophagitis. Results: Of the 133 randomized patients, 130 (mean age, 48.6 years; 73 [56%] men) underwent treatment (64 in the POEM group and 66 in the pneumatic dilation group) and 126 (95%) completed the study. The primary outcome of treatment success occurred in 58 of 63 patients (92%) in the POEM group vs 34 of 63 (54%) in the pneumatic dilation group, a difference of 38% ([95% CI, 22%-52%]; P < .001). Of the 14 prespecified secondary end points, no significant difference between groups was demonstrated in 10 end points. There was no significant between-group difference in median integrated relaxation pressure (9.9 mm Hg in the POEM group vs 12.6 mm Hg in the pneumatic dilation group; difference, 2.7 mm Hg [95% CI, -2.1 to 7.5]; P = .07) or median barium column height (2.3 cm in the POEM group vs 0 cm in the pneumatic dilation group; difference, 2.3 cm [95% CI, 1.0-3.6]; P = .05). Reflux esophagitis occurred more often in the POEM group than in the pneumatic dilation group (22 of 54 [41%] vs 2 of 29 [7%]; difference, 34% [95% CI, 12%-49%]; P = .002). Two serious adverse events, including 1 perforation, occurred after pneumatic dilation, while no serious adverse events occurred after POEM. Conclusions and Relevance: Among treatment-naive patients with achalasia, treatment with POEM compared with pneumatic dilation resulted in a significantly higher treatment success rate at 2 years. These findings support consideration of POEM as an initial treatment option for patients with achalasia. Trial Registration: Netherlands Trial Register number: NTR3593.

Per oral endoscopic tumor (POET) resection for treatment of upper gastrointestinal subepithelial tumors.

BACKGROUND: Endoscopic submucosal tunneling has evolved to allow endoscopic resection of subepithelial tumors of gastrointestinal tract without full-thickness perforation. This study aimed to investigate safety and efficacy of submucosal tunnel resection for these tumors. METHOD: Patients with subepithelial tumors (SET) located in esophagus, gastric cardia, lesser curvature, and antrum were recruited. The size of tumor was limited to < 40 mm. The procedures were performed under general anesthesia. A mucosal entrance was created 2 cm proximal to the SET after submucosal injection. Submucosal tunnel was then extended and the tumor was dissected and mobilized with intact overlying mucosa. After complete dissection, the tumors would be retrieved per orally and mucosal entrance closed by endoclips. RESULTS: From June 2012 to December 2016, 51 patients with subepithelial tumors received POET. 39 patients had SET in stomach, 11 located in esophagus, and 1 in duodenum. The mean operative time was 90.46 ± 46.49 min, while the mean size of the tumors was 20.71 ± 14.05 mm. The POET was converted to endoscopic full-thickness resection (EFTR) in three patients with gastric subepithelial tumors located at greater curvature. The overall complication rate was 4.0%, and there was no bleeding, mucosal dehiscence, or leakage. The time to resume diet was 1.7 days, while the average hospital stay was 3.2 ± 1.0 days. The mean follow-up period was 19 ± 16 months, and only 1 patient developed recurrence of leiomyoma. CONCLUSION: Per oral endoscopic tumor resection is safe and effective treatment for esophageal and gastric SET located at cardia, lesser curvature, and antrum. Currently, POET for treatment of upper GI SET is limited by the size and location of the tumor.

Efficacy and Safety of High-Specific-Activity 131I-MIBG Therapy in Patients with Advanced Pheochromocytoma or Paraganglioma.

Patients with metastatic or unresectable (advanced) pheochromocytoma and paraganglioma (PPGL) have poor prognoses and few treatment options. This multicenter, phase 2 trial evaluated the efficacy and safety of high-specific-activity 131I-meta-iodobenzylguanidine (HSA 131I-MIBG) in patients with advanced PPGL. Methods: In this open-label, single-arm study, 81 PPGL patients were screened for enrollment, and 74 received a treatment-planning dose of HSA 131I-MIBG. Of these patients, 68 received at least 1 therapeutic dose (∼18.5 GBq) of HSA 131I-MIBG intravenously. The primary endpoint was the proportion of patients with at least a 50% reduction in baseline antihypertensive medication use lasting at least 6 mo. Secondary endpoints included objective tumor response as assessed by Response Evaluation Criteria in Solid Tumors version 1.0, biochemical tumor marker response, overall survival, and safety. Results: Of the 68 patients who received at least 1 therapeutic dose of HSA 131I-MIBG, 17 (25%; 95% confidence interval, 16%-37%) had a durable reduction in baseline antihypertensive medication use. Among 64 patients with evaluable disease, 59 (92%) had a partial response or stable disease as the best objective response within 12 mo. Decreases in elevated (≥1.5 times the upper limit of normal at baseline) serum chromogranin levels were observed, with confirmed complete and partial responses 12 mo after treatment in 19 of 28 patients (68%). The median overall survival was 36.7 mo (95% confidence interval, 29.9-49.1 mo). The most common treatment-emergent adverse events were nausea, myelosuppression, and fatigue. No patients had drug-related acute hypertensive events during or after the administration of HSA 131I-MIBG. Conclusion: HSA 131I-MIBG offers multiple benefits, including sustained blood pressure control and tumor response in PPGL patients.

A descriptive study on the efficacy and complications of the Capio (Boston Scientific) suturing device for sacrospinous ligament fixation.

BACKGROUND: Sacrospinous colpopexy is an effective vaginal apical support operation. Due to morbidity associated with traditional approaches which require wide dissection, slim-line suture delivery devices have been introduced in the hope of reducing morbidity without compromise to outcomes. AIM: The aim of our series was to report outcomes and complications (particularly buttock pain and blood loss) of the sacrospinous colpopexy using the Capio suturing device and evaluate it against published results using the Miya hook. METHODS: This is a prospective, multi-centre descriptive study. The primary outcome is objective success at 12 months. Secondary outcomes include subjective success at 12 months, patient-reported outcomes at 12 months, operating time, estimated blood loss and post-operative buttock pain. RESULTS: Fifty-one consenting patients undergoing sacrospinous colpopexy were recruited at four Queensland hospitals. Objective success at 12 months was 95% (41/43) and subjective success at 12 months was 92% (44/48). Eighty-four percent of patients reported buttock pain at one week, reducing to 16% by six weeks, of which 7% required analgesia. CONCLUSIONS: At a mean of 17 months follow up, we found that the sacrospinous colpopexy using the Capio suturing device provided excellent apical support with a low requirement for blood transfusion and an average operating time of seven minutes. We found a high rate of buttock pain immediately post-operatively, but our rates became consistent with previous reports by six weeks post-operation.

Randomized controlled trial of EndoWrist-enabled robotic versus human laparoendoscopic single-site access surgery (LESS) in the porcine model.

INTRODUCTION: A robotic laparoendoscopic single-site access surgery (R-LESS) platform that incorporates the EndoWrist function of robotic instruments may provide better triangulation and retraction during LESS. The aim of the study is to assess if R-LESS is feasible with standard robotic instruments via a single incision and whether the approach could reduce the difficulty of the procedure and confer additional benefits over conventional LESS. METHODS: This was a prospective randomized controlled study investigating the workload performance, efficacy, and risks of performing R-LESS when compared with human LESS (H-LESS) in a survival porcine model for cholecystectomy and gastrojejunostomy. The primary outcome is the NASA task load index. Secondary outcomes included the difficulty of the procedures, procedural time, morbidities, and mortalities. RESULTS: Twenty-four cholecystectomies and gastrojejunostomies using the R-LESS or H-LESS approach (12:12) were performed. None of the swine suffered from procedural adverse events and none of the procedures required conversion. In both the cholecystectomy and gastrojejunostomy groups, R-LESS was associated with significantly lower NASA task load index (P < 0.001) and reduced difficulties in various steps of the procedures. No differences in the overall procedure times of the two procedures were observed (P = 0.315). CONCLUSION: The R-LESS approach significantly reduced the workload and difficulties of LESS cholecystectomies and gastrojejunostomies. A dedicated single-site platform that could reduce instrument clashing while retaining the EndoWrist function is eagerly awaited.

Phase 1 Study of High-Specific-Activity I-131 MIBG for Metastatic and/or Recurrent Pheochromocytoma or Paraganglioma.

Context: No therapies are approved for the treatment of metastatic and/or recurrent pheochromocytoma or paraganglioma (PPGL) in the United States. Objective: To determine the maximum tolerated dose (MTD) of high-specific-activity I-131 meta-iodobenzylguanidine (MIBG) for the treatment of metastatic and/or recurrent PPGL. Design: Phase 1, dose-escalating study to determine the MTD via a standard 3 + 3 design, escalating by 37 MBq/kg starting at 222 MBq/kg. Setting: Three centers. Patients: Twenty-one patients were eligible, received study drug, and were evaluable for MTD, response, and toxicity. Intervention: Open-label use of high-specific-activity I-131 MIBG therapy. Main Outcome Measures: Dose-limiting toxicities, adverse events, radiation absorbed dose estimates, radiographic tumor response, biochemical response, and survival. Results: The MTD was determined to be 296 MBq/kg on the basis of two observed dose-limiting toxicities at the next dose level. The highest mean radiation absorbed dose estimates were in the thyroid and lower large intestinal wall (each 1.2 mGy/MBq). Response was evaluated by total administered activity: four patients (19%), all of whom received >18.5 GBq of study drug, had radiographic tumor responses of partial response by Response Evaluation Criteria in Solid Tumors. Best biochemical responses (complete or partial response) for serum chromogranin A and total metanephrines were observed in 80% and 64% of patients, respectively. Overall survival was 85.7% at 1 year and 61.9% at 2 years after treatment. The majority (84%) of adverse events were considered mild or moderate in severity. Conclusions: These findings support further development of high-specific-activity I-131 MIBG for the treatment of metastatic and/or recurrent PPGL at an MTD of 296 MBq/kg.

Endoscopic Treatment of Subepithelial Lesions of the Gastrointestinal Tract.

Purpose of Review The study aimed to discuss novel endoscopic approaches to resection of submucosal lesions. Recent Findings Endoscopic resection by excavation, full-thickness resection, and submucosal tunneling are by now well-documented techniques for submucosal tumor resection. Combined approaches with laparoscopy such as several variations of laparoscopic endoscopic cooperation surgery (LECS) and non-exposed wall-inversion surgery (NEWS) are also possible now. Reports of these approaches show good results. However, lesion size is the main limitation to these approaches. Summary Endoscopic submucosal tumor resection can be effectively done endoscopically or by endoscopy combined with laparoscopy. These techniques allow localized resection of lesions at difficult locations such as in the gastroesophageal junction with limited influence on the normal anatomy. Variations in techniques are being practiced worldwide striving to achieve complete resection with minimal disturbance of function or contamination. The choice between approaches depends largely on the size and site of the lesion and expertise available.

Phase 2 Study of 99mTc-Trofolastat SPECT/CT to Identify and Localize Prostate Cancer in Intermediate- and High-Risk Patients Undergoing Radical Prostatectomy and Extended Pelvic LN Dissection.

99mTc-trofolastat (99mTc-MIP-1404), a small-molecule inhibitor of prostate-specific membrane antigen, shows high potential to detect prostate cancer (PCa) noninvasively using SPECT. We therefore wanted to assess the performance of 99mTc-trofolastat SPECT/CT in a phase 2 multicenter, multireader prospective study in patients with intermediate- and high-grade PCa, before radical prostatectomy and extended pelvic lymph node (LN) dissection, with histopathology as the gold standard. Methods: PCa patients (n = 105) with an increased risk of LN involvement (LNI) underwent pelvic 99mTc-trofolastat SPECT/CT before radical prostatectomy with extended pelvic LN dissection. The sensitivity of 99mTc-trofolastat for detection of PCa on a patient and lobe basis, using visual and semiquantitative (tumor-to-background ratio [TBR]) scores, and of LNI was evaluated as well as the correlation of uptake within the gland to Gleason scores (GS) and assessment of the predictive potential of 99mTc-trofolastat uptake for LNI. Results: PCa was detected in 98 patients (94%) with acceptable variability between readers. There was a significantly higher visual score and TBR in positive lobes compared with tumor-negative lobes. Receiver-operating characteristic analysis showed that visual scores more accurately discriminated lobes with GS ≤ 3 + 3 from ≥ 3 + 4, whereas TBRs discriminated high-grade disease from normal lobes better. Visual scores and TBRs correlated significantly with GS. 99mTc-trofolastat SPECT/CT detected LNI with a sensitivity of 50% and specificity of 87%, and TBR values significantly predicted LNI with a sensitivity of 90%. Conclusion:99mTc-trofolastat SPECT/CT detects PCa with high sensitivity in patients with intermediate- and high-risk PCa compared with histology. It has the potential to be used as a surrogate marker for GS and predict LNI.

Efficacy and Safety of Peroral Endoscopic Myotomy for Treatment of Achalasia After Failed Heller Myotomy.

BACKGROUND & AIMS: In patients with persistent symptoms after Heller myotomy (HM), treatment options include repeat HM, pneumatic dilation, or peroral endoscopic myotomy (POEM). We evaluated the efficacy and safety of POEM in patients with achalasia with prior HM vs without prior HM. METHODS: We conducted a retrospective cohort study of 180 patients with achalasia who underwent POEM at 13 tertiary centers worldwide, from December 2009 through September 2015. Patients were divided into 2 groups: those with prior HM (HM group, exposure; n = 90) and those without prior HM (non-HM group; n = 90). Clinical response was defined by a decrease in Eckardt scores to 3 or less. Adverse events were graded according to criteria set by the American Society for Gastrointestinal Endoscopy. Technical success, clinical success, and rates of adverse events were compared between groups. Patients were followed up for a median of 8.5 months. RESULTS: POEM was technically successful in 98% of patients in the HM group and in 100% of patients in the non-HM group (P = .49). A significantly lower proportion of patients in the HM group had a clinical response to POEM (81%) than in the non-HM group (94%; P = .01). There were no significant differences in rates of adverse events between the groups (8% in the HM group vs 13% in the non-HM group; P = .23). Symptomatic reflux and reflux esophagitis after POEM were comparable between groups. CONCLUSIONS: POEM is safe and effective for patients with achalasia who were not treated successfully by prior HM. Although the rate of clinical success in patients with prior HM is lower than in those without prior HM, the safety profile of POEM is comparable between groups.

Feasibility of per-oral cholecystoscopy and advanced gallbladder interventions after EUS-guided gallbladder stenting (with video).

BACKGROUND AND AIMS: The recent development of EUS-guided gallbladder drainage (EGBD) with a lumen-apposing stent has made endoscopic assessment and advanced gallbladder interventions via the stent possible. The aim of this study was to assess the feasibility and safety of per-oral cholecystoscopy and the types of gallbladder interventions that can be performed. METHODS: This was a retrospective review conducted in the Prince of Wales Hospital from June 2012 to March 2016. All patients who had acute cholecystitis with EGBD were included. Cholecystoscopy was performed 1 to 3 months after stent insertion. Patients' demographic data, technical success, types of intervention, and adverse events were recorded. RESULTS: Twenty-nine cholecystoscopies were performed in 25 patients. Twenty-seven of 29 cholecystoscopies were successful (93.1%). Magnifying endoscopy was performed in 10 patients, confocal endomicroscopy and EUS in 1 patient, and endocytoscopy in another patient. Fourteen patients (56%) had spontaneous stone passage. Eleven patients (44%) had residual gallstones on cholecystoscopy, and removed in 8. Overall stone clearance rate was 88% after a mean (standard deviation) number of 1.25 (0.46) sessions of cholecystoscopy. CONCLUSIONS: Per-oral cholecystoscopy and advanced gallbladder interventions were feasible and safe. This opens up exciting possibilities for endoscopic treatment of gallbladder pathologies.

Robotic-assisted minimally invasive esophagectomy for treatment of esophageal carcinoma.

Minimally invasive esophagectomy (MIE) is technically challenging. Da Vinci Robotic system could improve surgical dissection with additional degree of freedom from robotic arms. This study aimed to assess the feasibility and safety of performing MIE using Da Vinci Robotic system among patients with esophageal cancers. From 2009 to 2013, consecutive patients with esophageal cancers who received robotic-assisted MIE were recruited. We excluded tumors with suspected invasion to adjacent organs. Preoperative staging included EUS, CT thorax and abdomen and bronchoscopy. We perform mobilization of thoracic esophagus with two-field lymphadenectomy using robotic system, followed by laparoscopic gastric mobilization and hand-sewn cervical esophagogastric anastomosis. A total of 20 patients were recruited (16 male and 4 female) with mean age of 64.2 ± 8.8 years. All patients were successfully treated with robotic-assisted MIE with mean operative time of 499.5 ± 70 min and blood loss of 355.7 ± 329.6 mls. There was no pulmonary complication, while three patients sustained anastomotic leakage and managed conservatively. The mean hospital stay was 13 ± 6 days. Five patients had stage I tumors, five had stage II, and nine had stage III disease. One patient had complete response after neoadjuvant chemoradiotherapy. The number of lymph node dissection was 18.2 ± 13.2, and 2.8 ± 5.7 nodes involved. The follow-up period was 21 ± 9 months, and the overall survival was 75 %. Robotic-assisted MIE is feasible and safe for treatment of esophageal cancers. The surgical dissection can be enhanced by improved ergonomics from robotic arms and sense of depth from 3D images.

Long-term outcomes of per-oral endoscopic myotomy in patients with achalasia with a minimum follow-up of 2 years: an international multicenter study.

BACKGROUND AND AIMS: Per-oral endoscopic myotomy (POEM) has shown promising safety and efficacy in short-term studies. However, long-term follow-up data are very limited. The aims of this study were to assess (1) clinical outcome of patients with a minimum post-POEM follow-up of 2 years and (2) factors associated with long-term clinical failure after POEM. METHODS: A retrospective chart review was performed that included all consecutive patients with achalasia who underwent POEM with a minimum follow-up of 2 years at 10 tertiary-care centers. Clinical response was defined by a decrease in Eckardt score to 3 or lower. RESULTS: A total of 205 patients (45.8% men; mean age, 49 years) were followed for a median of 31 months (interquartile range, 26-38 months). Of these, 81 patients (39.5%) had received previous treatment for achalasia before POEM. Clinical success was achieved in 98% (185/189), 98% (142/144), and 91% (187/205) of patients with follow-up within 6 months, at 12 months, and ≥24 months, respectively. Of 185 patients with clinical response at 6 months, 11 (6%) experienced recurrent symptoms at 2 years. History of previous pneumatic dilation was associated with long-term treatment failure (odds ratio, 3.41; 95% confidence interval, 1.25-9.23). Procedure-related adverse events occurred in 8.2% of patients and only 1 patient required surgical intervention. Abnormal esophageal acid exposure and reflux esophagitis were documented in 37.5% and 18% of patients, respectively. However, these rates are simply a reference number among a very selective group of patients. CONCLUSIONS: POEM is safe and provides high initial clinical success and excellent long-term outcomes. Among patients with confirmed clinical response within 6 months, 6% had recurrent symptoms by 2 years.