The 2022 PSOGI International Consensus on HIPEC Regimens for Peritoneal Malignancies: Pseudomyxoma Peritonei.

BACKGROUND: The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) constitutes the established standard of care for pseudomyxoma peritonei patients. However, the role of HIPEC lacks validation through randomized trials, leading to diverse proposed treatment protocols. This consensus seeks to standardize HIPEC regimens and identify research priorities for enhanced clarity. METHODS: The steering committee applied the patient, intervention, comparator, and outcome method to formulate crucial clinical questions. Evaluation of evidence followed the Grading of Recommendations, Assessment, Development, and Evaluation system. Consensus on HIPEC regimens and research priorities was sought through a two-round Delphi process involving international experts. RESULTS: Out of 90 eligible panelists, 71 (79%) participated in both Delphi rounds, resulting in a consensus on six out of seven questions related to HIPEC regimens. An overwhelming 84% positive consensus favored combining HIPEC with CRS, while a 70% weak positive consensus supported HIPEC after incomplete CRS. Specific HIPEC regimens also gained consensus, with 53% supporting Oxaliplatin 200 mg/m2 and 51% favoring the combination of cisplatin (CDDP) associated with mitomycin-C (MMC). High-dose MMC regimens received an 89% positive recommendation. In terms of research priorities, 61% of panelists highlighted the importance of studies comparing HIPEC regimens post CRS. The preferred regimens for such studies were the combination of CDDP/MMC and high-dose MMC. CONCLUSIONS: The consensus recommends the application of HIPEC following CRS based on the available evidence. The combination of CDDP/MMC and high-dose MMC regimens are endorsed for both current clinical practice and future research efforts.

Initial Experience Using Laparoscopic HIPEC for Gastric Cancer with Peritoneal Metastasis: Safety and Outcomes.

BACKGROUND: Peritoneal metastases (PM) develop in approximately 20% of patients with gastric cancer (GC). For selected patients, treatment of PM with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results. This report aims to describe the safety and perioperative outcomes of laparoscopic HIPEC for GC/PM. METHODS: This retrospective cohort study evaluated patients who had GC and PM treated with laparoscopic HIPEC (2018-2022). The HIPEC involved cisplatin and mitomycin C (MMC) or MMC alone. The primary end point was perioperative safety. RESULTS: The 22 patients in this study underwent 27 procedures. The mean age was 58 ± 13 years. All the patients were Eastern Cooperative Oncology Group (ECOG) 0 or 1 (55 and 45%, respectively). Five patients underwent a second laparoscopic HIPEC, with a median of 126 days (interquartile range [IQR], 117-166 days) between procedures. The median peritoneal carcinomatosis index (PCI) was 4 (IQR, 2-9), and the median hospital stay was 2 days (IQR, 1-3 days). No 30-day readmissions or complications occurred. Eight patients (36%) underwent gastrectomy (CRS ± HIPEC). After an average follow-up period of 11 months, 7 (32%) of the 22 patients were alive. The median overall survival was 11 months (IQR, 195-739 days) from the initial procedure and 19.3 months (IQR, 431-1204 days) from the diagnosis. CONCLUSIONS: Laparoscopic HIPEC appears to be safe with minimal perioperative complications. Approximately one third of the patients undergoing initial laparoscopic HIPEC ultimately proceeded to cytoreduction and gastrectomy. Preliminary survival data from this highly selected cohort suggest that the addition of laparoscopic HIPEC to systemic chemotherapy does not compromise other treatment options. These initial results suggest that laparoscopic HIPEC may offer benefit to patients with GC and PM and aid in the selection of patients who may benefit from curative-intent resection.

Enhancing the Efficacy of HIPEC Through Bromelain: A Preclinical Investigation in Appendiceal Cancer.

INTRODUCTION: Appendiceal cancer (AC) excessive mucin production is a barrier to heated intraperitoneal chemotherapy (HIPEC) drug delivery. Bromelain is a pineapple stem extract with mucolytic properties. We explored bromelain treatment effects against mucinous AC in a patient-derived tumor organoid (PTO) model and an AC cell line. PATIENTS AND METHODS: PTOs were fabricated from tumor specimens obtained from patients with AC undergoing cytoreductive surgery with HIPEC. PTOs underwent HIPEC treatment with bromelain, cisplatin, and mitomycin C (MMC) at 37 °C and 42 °C with and without bromelain pretreatment. RESULTS: From October 2020 to May 2023, 16 specimens were collected from 13 patients with low-grade (12/16, 75%) and high-grade AC (4/16, 25%). The mucin-depleting effects of bromelain were most significant in combination with N-acetylcysteine (NAC) compared with bromelain (47% versus 10%, p = 0.0009) or NAC alone (47% versus 12.8%, p = 0.0027). Bromelain demonstrated > 31% organoid viability reduction at 60 min (p < 0.001) and > 66% in 48 h (p < 0.0001). Pretreatment with bromelain increased cytotoxicity of both cisplatin and MMC HIPEC conditions by 31.6% (p = 0.0001) and 35.5% (p = 0.0001), respectively. Ki67, CK20, and MUC2 expression decreased after bromelain treatment; while increased caspase 3/7 activity and decreased Bcl-2 (p = 0.009) and Bcl-xL (p = 0.01) suggest induction of apoptosis pathways. Furthermore, autophagy proteins LC3A/B I (p < 0.03) and II (p < 0.031) were increased; while ATG7 (p < 0.01), ATG 12 (p < 0.04), and Becline 1(p < 0.03), expression decreased in bromelain-treated PTOs. CONCLUSIONS: Bromelain demonstrates cytotoxicity and mucolytic activity against appendiceal cancer organoids. As a pretreatment agent, it potentiates the cytotoxicity of multiple HIPEC regimens, potentially mediated through programmed cell death and autophagy.

Visual Field Outcomes in the Primary Tube Versus Trabeculectomy Study.

PURPOSE: To describe visual field outcomes in the Primary Tube Versus Trabeculectomy (PTVT) Study. DESIGN: Cohort analysis. PARTICIPANTS: A total of 155 eyes (155 subjects) randomly assigned to treatment with tube shunt surgery (n = 84) or trabeculectomy with mitomycin C (n = 71). METHODS: The PTVT Study was a multicenter randomized clinical trial comparing the safety and efficacy of trabeculectomy and tube shunt surgery in eyes without previous intraocular surgery. Subjects underwent standard automated perimetry (SAP) at baseline and annually for 5 years. Standard automated perimetry tests were deemed reliable if the false-positive rate was ≤ 15%. Tests were excluded if visual acuity was ≤ 20/400 or loss of ≥ 2 Snellen lines from baseline because of a nonglaucomatous etiology. Linear mixed-effects models were used to compare rates of change in SAP mean deviation (MD) between the 2 groups. Intraocular pressure (IOP) control was assessed by percentage of visits with IOP < 18 mmHg and mean IOP. MAIN OUTCOME MEASURES: Rate of change in SAP MD during follow-up. RESULTS: A total of 730 SAP tests were evaluated (average of 4.7 tests per eye). The average SAP MD at baseline was -12.8 ± 8.3 decibels (dB) in the tube group and -12.0 ± 8.4 dB in the trabeculectomy group (P = 0.57). The mean rate of change in SAP MD was -0.32 ± 0.39 dB/year in the trabeculectomy group and -0.47 ± 0.43 dB/year in the tube group (P = 0.23). Eyes with mean IOP 14 to 17.5 mmHg had significantly faster rates of SAP MD loss compared with eyes with mean IOP < 14 mmHg (-0.59 ± 0.13 vs. -0.27 ± 0.08 dB/year; P = 0.012), and eyes with only 50% to 75% of visits with IOP < 18 mmHg had faster rates than those with 100% of visits with IOP < 18 mmHg (-0.90 ± 0.16 vs. -0.29 ± 0.08 dB/year; P < 0.001). Multivariable analysis identified older age and worse IOP control as risk factors for faster progression in both treatment groups. CONCLUSIONS: No statistically significant difference in mean rates of visual field change was observed between trabeculectomy and tube shunt surgery in the PTVT Study. Worse IOP control was significantly associated with faster rates of SAP MD loss during follow-up. Older patients were also at risk for faster progression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Evaluating Primary Treatment for People with Advanced Glaucoma: Five-Year Results of the Treatment of Advanced Glaucoma Study.

PURPOSE: To determine whether primary trabeculectomy or medical treatment produces better outcomes in terms of quality of life (QoL), clinical effectiveness, and safety in patients with advanced glaucoma. DESIGN: Multicenter randomized controlled trial. PARTICIPANTS: Between June 3, 2014, and May 31, 2017, 453 adults with newly diagnosed advanced open-angle glaucoma in at least 1 eye (Hodapp classification) were recruited from 27 secondary care glaucoma departments in the United Kingdom. Two hundred twenty-seven were allocated to trabeculectomy, and 226 were allocated medical management. METHODS: Participants were randomized on a 1:1 basis to have either mitomycin C-augmented trabeculectomy or escalating medical management with intraocular pressure (IOP)-reducing drops as the primary intervention and were followed up for 5 years. MAIN OUTCOME MEASURES: The primary outcome was vision-specific QoL measured with the 25-item Visual Function Questionnaire (VFQ-25) at 5 years. Secondary outcomes were general health status, glaucoma-related QoL, clinical effectiveness (IOP, visual field, and visual acuity), and safety. RESULTS: At 5 years, the mean ± standard deviation VFQ-25 scores in the trabeculectomy and medication arms were 83.3 ± 15.5 and 81.3 ± 17.5, respectively, and the mean difference was 1.01 (95% confidence interval [CI], -1.99 to 4.00; P = 0.51). The mean IOPs were 12.07 ± 5.18 mmHg and 14.76 ± 4.14 mmHg, respectively, and the mean difference was -2.56 (95% CI, -3.80 to -1.32; P < 0.001). Glaucoma severity measured with visual field mean deviation were -14.30 ± 7.14 dB and -16.74 ± 6.78 dB, respectively, with a mean difference of 1.87 (95% CI, 0.87-2.87 dB; P < 0.001). Safety events occurred in 115 (52.2%) of patients in the trabeculectomy arm and 124 (57.9%) of patients in the medication arm (relative risk, 0.92; 95% CI, 0.72-1.19; P = 0.54). Serious adverse events were rare. CONCLUSIONS: At 5 years, the Treatment of Advanced Glaucoma Study demonstrated that primary trabeculectomy surgery is more effective in lowering IOP and preventing disease progression than primary medical treatment in patients with advanced disease and has a similar safety profile. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Inhalation of hydrogen gas protects against mitomycin-induced pulmonary veno-occlusive disease.

BACKGROUND: As a subtype of pulmonary hypertension (PH), pulmonary veno-occlusive disease (PVOD) is devastating and life-threatening disease without effective therapy. Hydrogen has been reported to exhibits antioxidant and anti-inflammatory effects in a rat model induced by monocrotaline of PH. In this study, we investigated the effects of inhaled hydrogen gas on the prevention and treatment of PVOD induced by mitomycin C (MMC) in rats. METHODS: PVOD was induced in female Sprague-Dawley rats through intraperitoneal injection of MMC at a concentration of 3 mg·kg- 1·wk- 1 for 2 weeks. Inhalation of hydrogen gas (H2) was administered through a designed rat cage concurrently or two weeks after MMC administration. The severity of PVOD was assessed by using hemodynamic measurements and histological analysis. The expression levels of general control nonderepressible 2 (GCN2), nuclear factor erythroid 2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1) and endothelial-to-mesenchymal transition (EndoMT) related proteins in lung tissue were measured. Levels of lipid peroxidation pro-inflammatory cytokines in serum were determined. RESULTS: Inhaled H2 improved hemodynamics and right heart function, reversed right ventricular hypertrophy, and prevented pulmonary vessel reconstitution in both prevention and treatment approaches. It decreased malondialdehyde (MDA) levels in the serum and the expression of NADPH oxidase 1 (NOX-1) in lung tissue. It regulated Nrf2/HO-1 signaling pathway and anti-inflammatory factor GCN2 in lung tissue, accompanied by a decrease in macrophages and pro-inflammatory cytokines. Our data suggested that H2 inhalation effectively countered EndoMT induced by MMC, as evidenced by the detection of endothelial markers (e.g., VE-cadherin and CD31) and mesenchymal markers (e.g., vimentin and fibronectin). Further research revealed that H2 preserved p-Smad3 and induced p-Smad1/5/9. CONCLUSION: Inhalation of H2 effectively inhibits the pathogenesis of PVOD induced by MMC in rats. This inhibitory effect may be attributed to the antioxidant and anti-inflammatory properties of H2.

Adjuvant intravesical therapy in intermediate-risk non-muscle-invasive bladder cancer.

OBJECTIVE: To evaluate the impact of adjuvant therapy on oncological outcomes in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC), as due to the poorly-defined and overlapping diagnostic criteria optimal decision-making remains challenging in these patients. PATIENTS AND METHODS: In this multicentre study, patients treated with transurethral resection of bladder tumour for Ta disease were retrospectively analysed. All patients with low- or high-risk NMIBC were excluded from the analysis. Associations between adjuvant therapy administration with recurrence-free survival (RFS) and progression-free survival (PFS) rates were assessed in Cox regression models. RESULTS: A total of 2206 patients with intermediate-risk NMIBC were included in the analysis. Among them, 1427 patients underwent adjuvant therapy, such as bacille Calmette-Guérin (n = 168), or chemotherapeutic agents, such as mitomycin C or epirubicin (n = 1259), in different regimens up to 1 year. The median (interquartile range) follow-up was 73.3 (38.4-106.9) months. The RFS at 1 and 5 years in patients treated with adjuvant therapy and those without were 72.6% vs 69.5% and 50.8% vs 41.3%, respectively. Adjuvant therapy was associated with better RFS (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.70-0.89, P < 0.001), but not with PFS (P = 0.09). In the subgroup of patients aged ≤70 years with primary, single Ta Grade 2 <3 cm tumours (n = 328), adjuvant therapy was not associated with RFS (HR 0.71, 95% CI 0.50-1.02, P = 0.06). While in the subgroup of patients with at least one risk factor including patient age >70 years, tumour multiplicity, recurrent tumour and tumour size ≥3 cm (n = 1878), adjuvant intravesical therapy was associated with improved RFS (HR 0.78, 95% CI 0.68-0.88, P < 0.001). CONCLUSION: In our study, patients with intermediate-risk NMIBC benefit from adjuvant intravesical therapy in terms of RFS. However, in patients without risk factors, adjuvant intravesical therapy did not result in a clear reduction in the recurrence rate.

Clinical outcomes and prognostic factors of concurrent chemoradiotherapy for anal squamous cell carcinoma in Japan.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locoregional anal squamous cell carcinoma (ASCC) in western countries. However, there have been few reports on the clinical outcomes of CCRT in Japan. This study aimed to evaluate the clinical outcomes of CCRT, prognostic factors, and the clinical impact of programmed cell death-ligand 1 (PD-L1) expression of ASCC in Japan. METHODS: Patients with locoregional ASCC were enrolled between 2007 and 2017. All patients received CCRT consisting of ≥ 45 Gy of radiation, 5-fluorouracil, and mitomycin C. Disease-free survival (DFS), overall survival (OS), and adverse events (AEs) were estimated. Expression of p16 and PD-L1 were assessed by immunohistochemical staining (IHC). RESULTS: This study included 36 patients, of whom 30 (83.3%) were female. Among the participants, 32 (88.9%) achieved complete clinical remission, while six (16.7%) experienced recurrence. The five-year DFS and five-year OS were 72.2% and 84.7%, respectively. Grades ≥ 3 serious AEs included neutropenia in 10 (27.7%) and perianal dermatitis in eight (22.2%). In a univariate analysis, male sex, lymph node metastasis, and large tumor size were significantly associated with worse outcome. In a multivariate analysis, tumor size was an independent factor associated with short DFS. Of the 30 patients whose biopsy specimens were available for IHC, 29 (96.7%) were positive for p16, and 13 (43.3%) were positive for PD-L1. However, PD-L1 expression did not show any clinical impact. CONCLUSIONS: The comparative etiology, clinical outcomes, and prognostic factors of CCRT observed in Japanese patients with locoregional ASCC were consistent with western data.

Evaluation of Macular Thickness in Glaucoma Patients Using Prostaglandin Analog Eye Drops Undergoing Trabeculectomy with Mitomycin C: Prospective, Comparative, Randomized, Masked Examiner Study.

INTRODUCTION: The aim of the study was to evaluate the macular thickness of glaucomatous patients undergoing trabeculectomy (TREC) with mitomycin C (MMC) with or without the use of prostaglandin analog (PA) eye drops. METHODS: In this prospective, comparative clinical trial, patients with glaucoma and indications for TREC with MMC using PA and without previous macular changes were randomized into 2 groups: the study group (SG) and the control group (CG). In the CG, PA was suspended between 30 and 60 days after the preoperative exams. The subjects were evaluated, including optical coherence tomography (OCT) with the Cirrus 4000 macular protocol preoperatively and in the postoperative period on 3 occasions: 1-3 days ("PO1"), 6-9 days ("PO7"), and 27-30 days ("PO30") after surgery. The results were compared between groups. RESULTS: Thirty-five eyes of 35 patients were included (17 in the CG and 18 in the SG). There was no statistically significant difference in age (p = 0.2), the preoperative visual field mean deviation (p = 0.08), or the preoperative intraocular pressure (SG: 24.8 ± 7.8 mm Hg vs. CG: 22.8 ± 6.0 mm Hg, p = 0.4). The preoperative macular OCT parameters were equivalent between the groups (p > 0.05). When comparing the variation of parameters between the groups between preop and PO30 there was equivalence in all of the comparisons evaluated. The presence (or absence) of the lens did not affect the results. CONCLUSION: PA eye drops did not affect macular thickness after TREC with MMC in glaucomatous patients.

Local adjuncts to minimally invasive endoscopic interventions for benign laryngotracheal stenosis: a meta-analysis.

BACKGROUND: Benign laryngotracheal stenosis is widely managed with minimally invasive endoscopic interventions, such as laser incision or excision scar, and dilation. However, various endoscopic treatments are significantly associated with a high recurrence rate. Local auxiliary measures, including inhalation of steroids, injection of steroids, and local topical application of mitomycin C, have been studied in order to increase the success rate. PURPOSE: To compare the efficacy of endoscopic treatments with and without local adjuncts in patients with benign laryngotracheal stenosis, and analyze their clinical outcomes, recurrence, and complications. METHODS: In the meta-analysis, databases including PubMed, EMBASE, OVID, and Web of Science were searched for papers comparing the outcomes of adjunct therapy with non-adjunct therapy in patients with laryngotracheal stenosis. The duplicate publications, reviews, comments or letters, conference abstracts, and case reports were excluded. The random effect model was used for assessing the pooled risk estimates. RESULTS: Eight studies (1204 cases) referring to two prospective randomized controlled studies, two prospective cohort studies, and four retrospective cohort studies were ultimately included in the meta-analysis. Three delivery modes of adjuncts were identified, including intralesion steroid injection (n = 2), inhaled steroid (n = 2), and topical application of mitomycin C (n = 4). The decreased risk estimates of recurrence rate were detected in patients receiving endoscopic treatments with steroid injection or inhaled steroid, compared with endoscopic interventions alone (P < 0.05). Additionally, patients undergoing adjunct therapies had lower risk estimates of recurrence, compared to those receiving endoscopic procedures alone (P < 0.05), based on the subgroup of prospective cohort studies, subglottis, Mayer-Cotton scale of I-II degree, and stenosis length of < 3 cm. The high heterogeneity of the pooling risk estimates perhaps was due to factors of auxiliary drug, clinical characteristics of patients, and methodology. No discernible difference in the incidence of complication was identified. CONCLUSIONS: Local application of steroids to minimally invasive interventions appear to reduce the recurrence rate of laryngotracheal stenosis. Various adjuncts available, including steroids and mitomycin C, appear to be safe and associated with a low risk estimate of adjuncts-specific complication rate. High quality multi-center randomized controlled studies are needed, with sufficient periods for follow-up and subjective and objective outcome indicators, to properly evaluate the efficacy, safety, and cost-effectiveness of adjuvant drugs.

Pigtail with self-retaining bicanalicular intubation combined with Mitomycin C for the treatment of acquired lower punctal stenosis.

BACKGROUND: The pigtail was used to create an opening at the lower punctal site in grade 0 stenosis with insertion of self-retaining tube and Mitomycin C (MMC). METHODS: The patients with acquired lower punctal stenosis (grade 0) were divided randomly into equal groups, Group A: were treated with pigtail and MMC 0.02% and Group B: were treated with pigtail alone. The pigtail was inserted through the upper punctum until its tip reached the occluded punctum, this site was incised with a scalpel (No. 11). A self-retaining bicanalicular tube was then placed. RESULTS: Results of 36 eyes from 26 patients were included. No differences were observed between both groups regarding epiphora score, FDD test and punctal size preoperatively. The postoperative epiphora score, there were significant differences at 1 month (P = 0.035), 3 months (P = 0.005), and 6 months after removal (P < 0.001). The FDD test, there were significant differences at 6 months (P = 0.045), 1 month (P = 0.021), 3 months (P = 0.012), and 6 months post tube removal (P = 0.005). The punctal size, both groups differed at 1 month (P = 0.045), 3 months (P = 0.03), and 6 months post tube removal (P = 0.005). Only one case (5.5%) at each group showed extrusion of the tube. CONCLUSION: The pigtail probe, bicanalicular stent and MMC can be an effective method in treatment of severe punctal stenosis.

Efficacy and safety of intraoperative injection of mitomycin C during trabeculectomy: a systematic review and meta-analysis.

PURPOSE: Trabeculectomy, a primary surgical treatment for glaucoma, often employs mitomycin C (MMC) to reduce scar formation and improve surgical outcomes. However, the optimal application method of MMC, whether by injection or sponge, remains a subject of debate. This meta-analysis aims to compare injectable and sponge-based MMC application in terms of efficacy and safety, focusing on various clinical outcomes in glaucoma patients. METHODS: A comprehensive literature search of Scopus, MEDLINE, EMBASE, Ovid, Chinese biomedical literature database, China National Knowledge Infrastructure, and Cochrane Library was done for eligible studies that report data of glaucoma patients who were administered MMC by injection or sponge application during trabeculectomy. Outcomes of interest included intraocular pressure (IOP) reduction, bleb appearance grading (height, extent, vascularity), use of anti-glaucoma medications, and rates of complete success, qualified success, and failure. Data were reported as weighted mean differences (WMD) or odds ratios (OR) with confidence intervals (CI). The random-effects inverse-variance model with DerSimonian-Laird estimate of tau2 was employed, with continuity correction applied where necessary. RESULTS: A total of 15 studies with 1276 participants were included. The meta-analysis revealed no significant difference in IOP reduction between patients treated by MMC injection and sponge application (WMD = - 0.434). Significant differences were observed in bleb appearance grading scores for height (WMD = - 0.170) and extent (WMD = 0.174), with substantial heterogeneity. The use of anti-glaucoma medications was significantly lower in the injection group (WMD = - 0.274). However, there were no significant differences in the rates of complete success, qualified success, and failure. The study demonstrated moderate to high heterogeneity across various outcomes. CONCLUSION: This meta-analysis indicated that while both injection and sponge methods of MMC application during trabeculectomy were equally effective for IOP reduction, they differ in their impact on bleb morphology and postoperative medication requirement. The findings highlight the need for individualized treatment approaches in glaucoma surgery, taking into account the specific needs and characteristics of each patient.

The effect of adjuvant Mitomycin C during vitrectomy on functional and anatomical outcomes in patients with severe diabetic tractional retinal detachment.

PURPOSE: To evaluate the effect of adjuvant Mitomycin C (MMC) use on the anatomical and functional success of vitreoretinal surgery (VRS) in severe diabetic tractional retinal detachment (dTRD) patients. METHODS: A retrospective analysis of consecutive patients undergoing VRS due to severe dTRD was conducted. Patients were categorized into those who received 20 µg/0.1 mL MMC via MMC sandwich method (Group 1) and those who did not (Group 2). Demographics, surgical characteristics, visual outcomes, and complications that may related to MMC were analyzed. RESULTS: A total of 25 eyes were included, 13 in Group 1 and 12 in Group 2. No statistical difference was observed in baseline characteristics between the groups. The mean best-corrected visual acuity was 1.90 ± 0.43 logMAR and 1.93 ± 0.41 logMAR preoperatively and 1.60 ± 0.78 logMAR and 1.56 ± 0.78 logMAR postoperatively in Groups 1 and 2, respectively (p = 0.154). The postoperative mean intraocular pressure was 16.23 ± 2.55 mmHg and 13.08 ± 4.94 mmHg in Groups 1 and 2, respectively (p = 0.225). The rate of re-surgery was significantly lower in Group 1 (0% vs. 41.7% in Group 2, p = 0.015). Retina was attached in all patients at the last visit. No MMC-related complication was recorded. CONCLUSION: Intraoperative adjuvant MMC application for severe dTRD significantly reduces re-surgery rates with good anatomical and functional outcomes safely.

Durability of Response to Primary Chemoablation of Low-Grade Upper Tract Urothelial Carcinoma Using UGN-101, a Mitomycin-Containing Reverse Thermal Gel: OLYMPUS Trial Final Report.

PURPOSE: Our goal was to evaluate long-term safety and durability of response to UGN-101, a mitomycin-containing reverse thermal gel, as primary chemoablative treatment for low-grade upper tract urothelial carcinoma. MATERIALS AND METHODS: In this open-label, single-arm, multicenter, phase 3 trial (NCT02793128), patients ≥18 years of age with primary or recurrent biopsy-proven low-grade upper tract urothelial carcinoma received 6 once-weekly instillations of UGN-101 via retrograde catheter to the renal pelvis and calyces. Those with complete response (defined as negative ureteroscopic evaluation, negative cytology and negative for-cause biopsy) 4-6 weeks after the last instillation were eligible for up to 11 monthly maintenance instillations and were followed for ≥12 months with quarterly evaluation of response durability. Durability of complete response was determined by ureteroscopic evaluation; duration of response was estimated by the Kaplan-Meier method. Treatment-emergent adverse events (TEAEs) were monitored. RESULTS: Of 71 patients who initiated treatment, 41 (58%) had complete response to induction therapy and consented to long-term followup; 23/41 patients (56%) remained in complete response after 12 months (95% CI 40, 72), comprising 6/12 (50%) who did not receive any maintenance instillations and 17/29 (59%) who received ≥1 maintenance instillation. Kaplan-Meier analysis of durability was estimated as 82% (95% CI 66, 91) at 12 months. Ureteric stenosis was the most frequently reported TEAE (31/71, 44%); an increasing number of instillations appeared to be associated with increased incidence of urinary TEAEs. CONCLUSIONS: Durability of response to UGN-101 with or without maintenance treatment is clinically meaningful, offering a kidney-sparing therapeutic alternative for patients with low-grade disease.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases: A Systematic Review.

BACKGROUND: Combined treatment modality of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is emerging as an alternative option for colorectal peritoneal metastases, but there is ambiguity regarding patient selection, treatment protocols, and efficacy. OBJECTIVE: To elaborate on the patient characteristics, hyperthermic intraperitoneal chemotherapy protocol and health outcomes in colorectal peritoneal metastases patients undergoing a combination of hyperthermic intraperitoneal chemotherapy and cytoreductive surgery and provide guidance for future studies. DATA SOURCES: A Medline search for English language studies published between 2004 and 2019. STUDY SELECTION: Medical subject headings and key terms, including: hyperthermic intraperitoneal chemotherapy, colorectal peritoneal metastases, colorectal cancer and combinations thereof as per guidelines. MAIN OUTCOME MEASURES: Overall survival, disease-free survival, and morbidity and mortality rates. RESULTS: Of the 26 included studies, 42% were published between 2016 and 2019. More than half of the studies were retrospective in nature and conducted in tertiary specialized centers outside of the United States. The median age range was 44 to 62 years. Mitomycin C-based therapy was seen in 50% of studies. Mean weighted median disease-free survival for 11 studies was 15 months (9 to 36 months). Median OS ranged from 12 to 63 months, with an average of 33.6 months among 20 studies. Overall morbidity varied from 11% to 56%, with a weighted mean of 29% in 18 studies. Mortality ranged from 0 to 34%, with a weighted mean of 4% in 15 studies. LIMITATIONS: Despite careful study selection, variability in methodology of the included studies can limit review findings. CONCLUSION: Due to study heterogeneity, and a recent large, randomized trial showing no overall benefit, use of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in colorectal peritoneal metastases patients is highly controversial. Further standardized controlled studies can help uniformly define and build consensus among the medical community on patient eligibility and the optimal hyperthermic intraperitoneal chemotherapy techniques. PROSPERO: Registered on March 3, 2020, CRD42020146942.

Ab-Externo MicroShunt versus Trabeculectomy in Primary Open-Angle Glaucoma: One-Year Results from a 2-Year Randomized, Multicenter Study.

PURPOSE: To compare the effectiveness and safety of the MicroShunt versus trabeculectomy in patients with primary open-angle glaucoma (POAG). DESIGN: One-year results from a 2-year, prospective, randomized, multicenter, noninferiority study (NCT01881425) conducted in the United States and Europe. PARTICIPANTS: Eligible patients were aged 40-85 years with intraocular pressure (IOP) ≥15 and ≤40 mmHg and mild-to-severe POAG inadequately controlled on maximum tolerated medical therapy. METHODS: Patients were randomized 3:1 to undergo stand-alone MicroShunt implantation or trabeculectomy, both performed with adjunctive mitomycin C (0.2 mg/ml for 2 minutes). MAIN OUTCOME MEASURES: The primary effectiveness end point was surgical success, defined as ≥20% reduction in mean diurnal IOP from baseline (no medication washout) at year 1 without increasing the number of glaucoma medications. Secondary effectiveness end points at year 1 were the mean IOP change from baseline and requirement for postoperative intervention. Additional end points included glaucoma medication use and adverse events. RESULTS: Overall, 395 (MicroShunt) and 132 (trabeculectomy) patients were randomized (mean Humphrey visual field mean deviation, -12.34 decibels [dB]). At year 1, probability of success was lower in the MicroShunt group compared with the trabeculectomy group (53.9% vs. 72.7%, respectively; P < 0.01). In the MicroShunt group, mean IOP ± standard deviation decreased from 21.1 ± 4.9 mmHg at baseline to 14.3 ± 4.3 mmHg (-29.1%; P < 0.01) at year 1, with a mean of 0.6 ± 1.1 glaucoma medications (baseline 3.1 ± 1.0; P < 0.01). In the trabeculectomy group, mean IOP decreased from 21.1 ± 5.0 mmHg to 11.1 ± 4.3 mmHg (-45.4%; P < 0.01), with a mean of 0.3 ± 0.9 glaucoma medications (baseline 3.0 ± 0.9; P < 0.01). Postoperative interventions, including laser suture lysis, were reported in 40.8% (MicroShunt) versus 67.4% (trabeculectomy) of patients (P < 0.01). Reported incidence of transient hypotony was higher in the trabeculectomy group versus the MicroShunt group (49.6% vs. 28.9%; P < 0.01). Vision-threatening complications were uncommon and reported in 1.0% of MicroShunt versus 0.8% of trabeculectomy patients. CONCLUSIONS: Probability of success was lower with MicroShunt compared with trabeculectomy. Although reductions in IOP and glaucoma medications over 1 year were observed in both groups, the trabeculectomy group had a lower mean IOP on fewer medications.

Impact of intra-operative factors upon peri-operative outcomes in women undergoing hyperthermic intraperitoneal chemotherapy for gynecologic cancer.

OBJECTIVES: To evaluate the incidence of intra-operative metabolic and electrolyte abnormalities and subsequent impact on peri-operative outcomes in women with gynecologic cancer undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). METHODS: An IRB-approved single institution retrospective cohort study was performed in women with gynecologic cancer who underwent CRS + HIPEC. Patient demographics, intra-operative electrolyte and metabolic values and peri-operative outcomes were recorded. To assess the association of pH and lactate upon post-operative outcomes, patients were divided in four quartiles for both variables and univariate analysis was performed. RESULTS: 100 consecutive women who underwent CRS + HIPEC from 2017 to 2020 were identified. Intra-operative blood transfusion and pressor support were required in 40% and 86%, respectively. The rate of ICU admission was 17%. Longer operative time (7.0 vs. 5.3 h, p = 0.002), increased blood loss (400.0 vs. 200.0 mL, p = 0.02) and transfusion (70.6% vs. 34.1%, p = 0.005) were associated with ICU admission. Compared to patients in the highest quartile of pH, lower median pH, (7.211 vs. 7.349, p < 0.001) was associated with increased rates of ICU admission, prolonged intubation (36.0% vs. 0.0%, p < 0.05, respectively) and any post-operative complication (72.0% vs. 28.0%, p = 0.01). Similarly, need for prolonged intubation (40% vs. 0%, p = 0.04) and VTE (13.0% vs. 0%, p = 0.01) were increased in women with the highest quartile of lactate levels compared to the lowest (4.7 vs 1.9, p < 0.001). CONCLUSIONS: Intra-operative acidosis is associated with higher incidence of ICU admission and peri-operative complications following CRS + HIPEC in women with gynecologic cancer. These data support the importance of adequate intra-operative resuscitation and timely correction of hemodynamic and metabolic abnormalities.

Pancytopenia after administration of hyperthermic intraperitoneal chemotherapy with mitomycin-C: local therapy and systemic toxicity.

Cytoreductive surgery (CRS) coupled with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the standard of treatment for many cancers with peritoneal metastasis. Mitomycin-C (MMC), the most common chemotherapy utilized with HIPEC, is associated with neutropenia but the degree of hematologic toxicity is unclear when splenectomy is included as part of CRS with MMC. We present an interesting case of pancytopenia following treatment with HIPEC using MMC and comment on the possible role of splenectomy in exacerbating its cytotoxic effects. Our unique case highlights potential hematologic toxicity following MMC-HIPEC and splenectomy. It suggests that spleen removal may enhance toxicity profiles of chemotherapy such as MMC. Because MMC is the preferred agent of choice used in CRS-HIPEC, future studies should investigate optimal MMC dosing and patient selection when splenectomy is performed to balance survival benefit with hematologic toxicities.

The HELENA study: Hexvix®-TURB vs. white-light TURB followed by intravesical adjuvant chemotherapy-a prospective randomized controlled open-label multicenter non-inferiority study.

PURPOSE: Photodynamic diagnosis and white-light TURB with adjuvant intravesical chemotherapy (ICT) is widely used in treatment of bladder cancer. This non-inferiority trial is designed to demonstrate non-inferiority regarding recurrence-free survival (RFS) of Hexvix® TURB followed by immediate instillation compared to white-light TURB with immediate instillation followed by maintenance ICT. METHODS: Between 07/2010 and 12/2016, 129 patients with EORTC intermediate risk non-muscle invasive bladder cancer treated with TURB were included in this multicentre phase III study. Patients were randomized and received either white-light TURB with immediate ICT followed by maintenance ICT (n = 62, 20 mg Mitomycin weekly for 6 weeks as induction phase, afterwards 20 mg/month for 6 months) or Hexvix® TURB with immediate ICT only (n = 67, 40 mg Mitomycin). Primary study endpoint was RFS after 12 months. Hexvix® TURB was counted as non-inferior to white light alone if the upper limit of the one-sided 95% confidence interval of hazard ratio was lower than 1.676. Due to the non-inferiority design, the per-protocol population was used as the primary analysis population (n = 113) RESULTS: Median follow-up was 1.81 years. Hexvix® group showed more events (recurrence or death) than white-light group (19 vs. 10) resulting in a HR of 1.29 (upper limit of one-sided 95%-CI = 2.45; pnon-inferiority = 0.249). The ITT population yielded similar results (HR = 1.67); 3.18], pnon-inferiority = 0.493). There was no significant difference in overall survival between both groups (p = 0.257). CONCLUSION: Non-inferiority of Hexvix® TURB relative to white-light TURB with maintenance Mitomycin instillation in intermediate risk urothelial carcinoma of the bladder was not proven. Hence a higher effect of maintenance ICT is to assume compared to a Hexvix®-improved TURB only, confirming its important role in patient treatment.

Anal Squamous Cell Carcinoma in Ulcerative Colitis: Can Pouches Withstand Traditional Treatment Protocols?

BACKGROUND: Anal squamous cell carcinoma has rarely been reported in the setting of ulcerative colitis. OBJECTIVE: This study aimed to understand the prognosis of anal squamous cell carcinoma in the setting of ulcerative colitis. DESIGN: This is a retrospective review. SETTING: This study was conducted at a referral center. PATIENTS: Adult patients with both ulcerative colitis (556.9/K51.9) and anal squamous cell carcinoma (154.3/C44.520) between January 1, 2000 and August 1, 2019 were included. MAIN OUTCOMES MEASURES: The primary outcomes measured are treatment and survival of anal squamous cell carcinoma. RESULTS: Of the 13,499 patients with ulcerative colitis treated, 17 adult patients with ulcerative colitis and anal dysplasia and/or anal squamous cell carcinoma were included in the study: 6 had a diagnosis of anal squamous cell carcinoma, 8 had high-grade squamous intraepithelial lesions, and 3 had low-grade squamous intraepithelial lesions. There were 4 men (23%) and a median age of 55 years (range, 32-69) years. At diagnosis, 6 had an IPAA, of which 5 had active pouchitis, 1 had an ileorectal anastomosis with active proctitis, 1 had a Hartmann stump with disuse proctitis, 5 had pancolitis, and 4 had left-sided colitis. Of the 6 with anal squamous cell carcinoma, all received 5-fluorouracil and mitomycin C with external beam radiation therapy. Four patients had an IPAA, all of whom required intestinal diversion or pouch excision because of treatment intolerance. At a median follow-up of 60 months, 3 patients died: one at 0 months (treatment-related myocardial infarction), one at 60 months (metastatic anal squamous cell carcinoma), and one at 129 months (malignant peripheral nerve sheath tumor); the remaining patients had no residual disease. LIMITATIONS: This study was limited because of its retrospective nature and small number of patients. CONCLUSION: Anal squamous cell carcinoma in the setting of ulcerative colitis is extremely rare. In the setting of IPAA, diversion may be necessary to prevent radiation intolerance. Careful examination of the perianal region should be performed at the time of surveillance endoscopy. See Video Abstract at http://links.lww.com/DCR/B582. CARCINOMA ANAL DE CLULAS ESCAMOSAS EN COLITIS ULCEROSA PUEDE EL POUCH MODIFICAR LOS RESULTADOS DE LOS PROTOCOLOS DE TRATAMIENTO TRADICIONAL: ANTECEDENTES:La incidencia de cáncer anal de células escamosas es muy baja en pacientes con colitis ulcerosa.OBJETIVO:Comprender el pronóstico del cáncer anal de células escamosas en el contexto de la colitis ulcerosa.DISEÑO:Revisión retrospectiva.AJUSTE:Centro de referencia.PACIENTES:Pacientes adultos con colitis ulcerosa (556.9 / K51.9) y cáncer anal de células escamosas (154.3 / C44.520) entre el 1 de enero de 2000 y el 1 de agosto de 2019.RESULTADOS PRINCIPALES:Tratamiento y sobrevida del cáncer anal de células escamosas.RESULTADOS:De 13.499 pacientes en tratamiento por colitis ulcerosa, diecisiete presentaron displasia y/o cáncer de células escamosas: 6 con cáncer, 8 con lesiones intraepiteliales escamosas con displasia de alto grado y 3 con displasia de bajo grado.Cuatro son hombres (23 %) con una mediana de 55 años (rango 32-69). Al realizar el diagnóstico 6 tenían pouch, 5 con pouchitis activa; 1 con ileorecto anastomosis con proctitis activa y 1 con operación de Hartman y muñón con colitis por desuso; además 5 tenían pancolitis y 4 tenían colitis izquierdaTodos los casos con cáncer anal de células escamosas (6 pacientes), fueron tratados con 5-FU mas Mitomicina y radioterapia externa. Cuatro pacientes tenían pouch, todos requirieron derivación intestinal o escisión del pouch por intolerancia al tratamiento.En la mediana de seguimiento de 60 meses, tres pacientes fallecieron: uno a los 0 meses (infarto de miocardio relacionado con el tratamiento), uno a los 60 meses (cáncer de células escamosas metastásico) y uno a los 129 meses (tumor maligno de la vaina del nervio periférico); el resto no presentaba enfermedad residual.LIMITACIONES:Revisión retrospectiva, número pequeño de pacientes.CONCLUSIÓN:El cáncer anal de células escamosas en el contexto de la colitis ulcerosa es extremadamente raro. En el contexto de IPAA, la derivación puede ser necesaria para prevenir la intolerancia a la radiación. Se debe realizar un examen cuidadoso de la región perianal en el momento de la endoscopia de control. Consulte Video Resumen en http://links.lww.com/DCR/B582.