In vitro assessment of intra-operative and post-operative environment in reducing bladder cancer recurrence.

Urinary bladder cancer is a common cancer worldwide. Currently, the modality of treating and monitoring bladder cancer is wide. Nonetheless, the high recurrence rate of non-muscle-invasive bladder cancer after surgical resection is still unsatisfactory. Hereby, our study demonstrated whether the intra-operative and post-operative environments will affect bladder cancer recurrence utilizing in vitro cell line model. Bladder cancer cell lines were submerged in four different irrigating fluids for assessing their tumorigenic properties. Our results showed that sterile water performed the best in terms of the magnitude of cytotoxicity to cell lines. Besides, we also investigated cytotoxic effects of the four irrigating agents as well as mitomycin C (MMC) in normothermic and hyperthermic conditions. We observed that sterile water and MMC had an increased cytotoxic effect to bladder cancer cell lines in hyperthermic conditions. Altogether, our results could be translated into clinical practice in the future by manipulating the intra-operative and post-operative conditions in order to lower the chance of residual cancer cells reimplant onto the bladder, which in turns, reducing the recurrence rate of bladder cancers.

Starting a peritoneal carcinomatosis treatment program in a developing country: A prospective analysis.

BACKGROUND: Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) has become a valuable treatment strategy for selected patients with peritoneal carcinomatosis (PC). In Chile, it is an emerging technique. The aim of this study is to describe our protocol and report our perioperative results. METHODS: A prospectively maintained database for patients undergoing exploratory surgery for PC was reviewed. Eligible patients were selected using the peritoneal cancer index in correlation with the primary tumor. Patients underwent HIPEC using mitomycin C. Clinical data and postoperative results were analyzed. RESULTS: Seventy-six patients underwent exploratory surgery. Most patients were female (55%) with a median age of 62 years (range, 25-83). Complete CRS and HIPEC were achieved in 53 patients. The most frequent primary tumor site was colon-rectum (49%). The median number of resected organs was 4 (range, 1-13). Overall 90-day incidence of major complications was 26%. After a median follow-up of 26 months, 44 patients (83%) in the resected group were alive with no evidence of disease. CONCLUSIONS: The PC treatment program at our institution has been established in a safe manner, with acceptable morbidity comparable to high-volume centers. A comprehensive preoperative evaluation, careful patient selection, and a cohesive team are necessary for successful results.

Perioperative Systemic Therapy vs Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Alone for Resectable Colorectal Peritoneal Metastases: A Phase 2 Randomized Clinical Trial.

Importance: To date, no randomized clinical trials have investigated perioperative systemic therapy relative to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) alone for resectable colorectal peritoneal metastases (CPM). Objective: To assess the feasibility and safety of perioperative systemic therapy in patients with resectable CPM and the response of CPM to neoadjuvant treatment. Design, Setting, and Participants: An open-label, parallel-group phase 2 randomized clinical trial in all 9 Dutch tertiary centers for the surgical treatment of CPM enrolled participants between June 15, 2017, and January 9, 2019. Participants were patients with pathologically proven isolated resectable CPM who did not receive systemic therapy within 6 months before enrollment. Interventions: Randomization to perioperative systemic therapy or CRS-HIPEC alone. Perioperative systemic therapy comprised either four 3-week neoadjuvant and adjuvant cycles of CAPOX (capecitabine and oxaliplatin), six 2-week neoadjuvant and adjuvant cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin), or six 2-week neoadjuvant cycles of FOLFIRI (fluorouracil, leucovorin, and irinotecan) and either four 3-week adjuvant cycles of capecitabine or six 2-week adjuvant cycles of fluorouracil with leucovorin. Bevacizumab was added to the first 3 (CAPOX) or 4 (FOLFOX/FOLFIRI) neoadjuvant cycles. Main Outcomes and Measures: Proportions of macroscopic complete CRS-HIPEC and Clavien-Dindo grade 3 or higher postoperative morbidity. Key secondary outcomes were centrally assessed rates of objective radiologic and major pathologic response of CPM to neoadjuvant treatment. Analyses were done modified intention-to-treat in patients starting neoadjuvant treatment (experimental arm) or undergoing upfront surgery (control arm). Results: In 79 patients included in the analysis (43 [54%] men; mean [SD] age, 62 [10] years), experimental (n = 37) and control (n = 42) arms did not differ significantly regarding the proportions of macroscopic complete CRS-HIPEC (33 of 37 [89%] vs 36 of 42 [86%] patients; risk ratio, 1.04; 95% CI, 0.88-1.23; P = .74) and Clavien-Dindo grade 3 or higher postoperative morbidity (8 of 37 [22%] vs 14 of 42 [33%] patients; risk ratio, 0.65; 95% CI, 0.31-1.37; P = .25). No treatment-related deaths occurred. Objective radiologic and major pathologic response rates of CPM to neoadjuvant treatment were 28% (9 of 32 evaluable patients) and 38% (13 of 34 evaluable patients), respectively. Conclusions and Relevance: In this randomized phase 2 trial in patients diagnosed with resectable CPM, perioperative systemic therapy seemed feasible, safe, and able to induce response of CPM, justifying a phase 3 trial. Trial Registration: ClinicalTrials.gov Identifier: NCT02758951.

Hyperthermic intrathoracic chemotherapy combined to iterative cytoreductive surgery to treat a pleural carcinosis from psudomixoma peritonei. A case report.

Pseudomyxoma peritonei (PMP) is an uncommon disease with locally-invasive attitude. Intrathoracic spread is rarely reported and its management extremely challenging. A 51-year-old Caucasian female presented with left pleural carcinosis 9-months after two sequential abdominal surgical procedures combined with HIPEC for low-grade PMP. Cytoreductive surgery (pleurectomy/decortication) was followed by 60-minutes hyperthermic intrathoracic chemotherapy mitomycin-C (215 mg/m2) infusing at same temperature (42°C) and intrapleural pression (2-4 mmH2O). No intra-operative complication occurred, the post-op stay was uneventful and no sign of recurrence was observed 9-months after surgery. Cytoreductive thoracic surgery and hyperthermic chemotherapy (HITHOC) could be a feasible therapeutic option in very selected cases.

Clinical trial of high dose hyperthermic intravesical mitomycin C for intermediate and high-risk non-muscle invasive bladder cancer during BCG shortage.

PURPOSE: Intravesical Bacillus Calmette-Guérin (BCG) is the gold standard for intermediate and high-risk non-muscle invasive bladder cancer (NMIBC), but availability is limited by global shortages. We present the first North American clinical experience using intravesical hyperthermia (HIVEC) with high-dose mitomycin C (MMC) during BCG shortage. MATERIALS AND METHODS: Single arm intermediate size expanded access protocol for high dose HIVEC MMC in patients with intermediate and high-risk NMIBC during BCG shortage. Patients received 120 mg intravesical MMC using the Combat BRS to achieve 43°C HIVEC. Primary outcome was a safety assessment of adverse events, with recurrence-free survival and a descriptive analysis of hematologic impacts as secondary outcomes. RESULTS: Fourteen patients were treated from May 2019 to June 2020, 4 (29%) intermediate and 10 (71%) high risk. The cohort is heavily pretreated, only 2 (14%) BCG naïve and median 6 BCG instillations (IQR 5.25, 8.25), with median 3.5 recurrences per patient (IQR 1.00, 5.25) 67% with >1 per year. Patients underwent a median 6 instillations (IQR 3.25, 9.25) which were well tolerated in 11/14 (79%). Seven patients (50%) experienced 10 adverse events, all grades 1 or 2. Most common was MMC allergy (4/14, 29%), followed by bladder spasm (3/14, 21%). Two had recurrences at median 11 months follow up, but both discontinued HIVEC after only 2 treatments. CONCLUSIONS: High dose MMC HIVEC is a safe and well-tolerated substitute for BCG during global shortages. The higher rate of systemic effects implies increased drug delivery, which may improve efficacy.

Phase III study of nivolumab alone or combined with ipilimumab as immunotherapy versus standard of care in resectable head and neck squamous cell carcinoma.

Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) often requires postoperative chemoradiation with high risk of toxicity. Disease-free survival (DFS) after 2 years is approximately 70%. Combining nivolumab (N), a PD-1-inhibitor and ipilimumab (I), a CTLA4- inhibitor, may improve DFS due to antitumor effects of immunotherapy. The IMSTAR-HN study compares neoadjuvant N and N ± I 6 months after adjuvant therapy versus standard therapy as first-line treatment for LA-HNSCC. Eligible patients have treatment-naive LA-HNSCC, Eastern cooperative oncology group performance score (PS) ≤1 and no distant metastasis. 276 patients will be randomized into two arms. Primary endpoint is DFS and secondary endpoint includes locoregional control (LRC) and overall survival (OS). This study is one of the first in HNSCCs implementing immunotherapy in first-line treatment in a curative setting. Clinical Trial Registration: NCT03700905 (ClinicalTrials.gov).

Comparative effectiveness trial of transoral head and neck surgery followed by adjuvant radio(chemo)therapy versus primary radiochemotherapy for oropharyngeal cancer (TopROC).

BACKGROUND: For loco-regionally advanced, but transorally resectable oropharyngeal cancer (OPSCC), the current standard of care includes surgical resection and risk-adapted adjuvant (chemo) radiotherapy, or definite chemoradiation with or without salvage surgery. While transoral surgery for OPSCC has increased over the last decade for example in the United States due to transoral robotic surgery, this treatment approach has a long history in Germany. In contrast to Anglo-Saxon countries, transoral surgical approaches have been used frequently in Germany to treat patients with oro-, hypopharyngeal and laryngeal cancer. Transoral laser microsurgery (TLM) has had a long tradition since its introduction in the early 70s. To date, the different therapeutic approaches to transorally resectable OPSCC have not been directly compared to each other in a randomized trial concerning disease control and survival. The goal of this study is to compare initial transoral surgery to definitive chemoradiation for resectable OPSCC, especially with regards to local and regional control. METHODS: TopROC is a prospective, two-arm, open label, multicenter, randomized, and controlled comparative effectiveness study. Eligible patients are ≥18 years old with treatment-naïve, histologically proven OPSCC (T1, N2a-c, M0; T2, N1-2c, M0; T3, N0-2c, M0 UICC vers. 7) which are amenable to transoral resection. Two hundred eighty patients will be randomly assigned (1:1) to surgical treatment (arm A) or chemoradiation (arm B). Standard of care treatment will be performed according to daily routine practice. Arm A consists of transoral surgical resection with neck dissection followed by risk-adapted adjuvant therapy. Patients treated in arm B receive standard chemoradiation, residual tumor may be subject to salvage surgery. Follow-up visits for 3 years are planned. Primary endpoint is time to local or locoregional failure (LRF). Secondary endpoints include overall and disease free survival, toxicity, and patient reported outcomes. Approximately 20 centers will be involved in Germany. This trial is supported by the German Cancer Aid and accompanied by a scientific support program. DISCUSSION: This study will shed light on an urgently-needed randomized comparison of the strategy of primary chemoradiation vs. primary surgical approach. As a comparative effectiveness trial, it is designed to provide data based on two established regimens in daily clinical routine. TRIAL REGISTRATION: NCT03691441 Registered 1 October 2018 - Retrospectively registered.

Cytoreductive Surgery and Hyperthermic Chemotherapy for Intrathoracic Pseudomyxoma Peritonei.

Dissemination of pseudomyxoma peritonei into the thoracic cavity is rare and carries a poor prognosis. Optimal treatment has not been defined. In our institution, patients have received cytoreductive surgery with hyperthermic intrathoracic chemotherapy, which demonstrated a good prognosis. A 51-year-old woman was referred to our hospital with right intrathoracic dissemination of pseudomyxoma peritonei. We performed parietal and mediastinal pleurectomy and simple resection of all visible tumors on the diaphragm and visceral pleura, followed by hyperthermic intrathoracic chemotherapy with 20 mg mitomycin at 42°C to 43°C. The patient had no evidence of disease progression in the thoracic cavity 1 year after surgery.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in pseudomyxoma peritonei of appendiceal origin: result of a single centre study.

Pseudomyxoma peritonei (PMP) is a rare condition characterized by the intraperitoneal accumulation of mucus derived mostly by appendiceal mucinous neoplasm. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can offer a favourable overall survival. In this study, we report a single-institute outcomes following CRS and HIPEC in patients with this condition. This is a review of prospectively collected data from 32 patients (11 men and 21 women) affected by PMP of appendiceal origin who underwent CRS and HIPEC from 2008 to 2016 in our Surgical Unit of General and Esophagogastric Surgery. The median age of the patients was 53 years (range 25-77 years). After CRS, all patients underwent HIPEC (mytomicin C 3.3 mg/m2/L and cisplatin 25 mg/m2/L at 41 °C for 60 min) with closed abdomen technique. The median (range) follow-up time for surviving patients was 43 (18-119) months. The median peritoneal cancer index (PCI) was 17. Complete cytoreductive surgery (CC0) was achieved in in 22 patients (69%). The majority of patients (88%) had grade I-II complications, 3 (9%) had grade III complications, and 1 (3%) patient had a grade IV complication. There were no perioperative mortalities. The median hospital stay was 9.5 (range 9-24) days. One year and 5-year overall survival (OS) were 90% and 58%, respectively. Regardless of histotype, disease-free survival was 95% at 1 year and 46% at 5 years. CRS in combination with HIPEC is a feasible treatment strategy and can achieve a satisfactory outcome in patients with PMP of appendiceal origin.

Optimal perfusion chemotherapy: A prospective comparison of mitomycin C and oxaliplatin for hyperthermic intraperitoneal chemotherapy in metastatic colon cancer.

BACKGROUND: Peritoneal carcinomatosis of colorectal adenocarcinoma (CRC) origin is common and is the second-most frequent cause of death in colorectal cancer. There is survival benefit to surgical resection plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with metastatic CRC. However, there remains controversy between oxaliplatin (Oxali) and mitomycin C (MMC), as the agent of choice. METHODS: A review of our 285 patients prospective HIPEC database from July 2007 to May 2018 identified 48 patients who underwent cytoreductive surgery plus HIPEC with MMC or Oxali. Patients were stratified based on preoperative and postoperative peritoneal cancer indices (PCI). The primary outcomes of survival and progression-free survival were compared. RESULTS: Type of HIPEC chemotherapy was not found to be predictive of overall survival. Preoperative PCI (P = .04), preoperative response to chemotherapy (P = .0001), and postoperative PCI (P = .05) were predictive for overall survival. CONCLUSIONS: MMC or Oxali based HIPEC chemotherapy are both safe and effective for the management of peritoneal only metastatic CRC. Both perfusion therapies should be considered with all patients receiving modern induction chemotherapy.

Perioperative safety after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei from appendiceal origin: Experience on 254 patients from a single center.

OBJECTIVE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a standard treatment for pseudomyxoma peritonei (PMP) recommended by Peritoneal Surface Oncology Group International (PSOGI). The study is to analyze the incidence of perioperative serious adverse events (SAEs) of CRS + HIPEC to treat PMP patients, and identify the risk factors, for guiding the prevention of SAEs. METHODS: This is a retrospective study on the PMP database established at our center. The clinicopathological features, treatment details and SAEs information on the PMP patients are systematically established in this database. The incidence, organ system distribution and severity of perioperative SAEs are analyzed. Univariate and multivariate analyses are performed to identify the independent risk factors. RESULTS: Among the 272 CRS + HIPEC procedures for 254 PMP patients, there are 93 (34.2%) SAEs. Six systems are involved in the SAEs, including infections (9.6%), digestive system (8.1%), respiratory system (6.3%), cardiovascular system (5.5%), hematological system (2.9%), and urinary system (1.5%), in terms of frequency. In terms of severity, the majority is grade III SAEs (27.9%), followed by grade IV SAEs (4.8%) and grade V SAEs (1.5%). Univariate analysis reveals 4 risk factors for perioperative SAEs: HIPEC regimens (P = 0.020), PCI (P = 0.025), intraoperative red blood cell transfusion volume (P = 0.004), and intraoperative blood loss volume (P = 0.002). Multivariate and logistic regression model analysis identifies only one independent risk factor for perioperative SAEs: intraoperative blood loss volume (P = 0.001, OR = 0.344, 95%CI: 0.182-0.649). CONCLUSIONS: PMP patients treated by CRS + HIPEC at experienced centers could have acceptable safety. Improving the surgical techniques and developing the integrated hemostasis techniques are essential to reduce intraoperative blood loss and decrease SAEs rate.

Colorectal Peritoneal Metastases Treated by Perioperative Systemic Chemotherapy and Cytoreductive Surgery With or Without Mitomycin C-Based HIPEC: A Comparative Study Using the Peritoneal Surface Disease Severity Score (PSDSS).

BACKGROUND: The Prodige-7 trial has questioned the role of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal metastases from colorectal cancer (CRC-PM). PATIENTS AND METHODS: We compared a prospectively collected group of 48 patients undergoing oxaliplatin/irinotecan-based perioperative systemic chemotherapy (s-CT) with targeted agents, and cytoreductive surgery (CRS) (no-HIPEC group) with 48 controls undergoing the same perioperative s-CT and CRS/HIPEC (HIPEC group). Patients were matched (1:1) according to the Peritoneal Surface Disease Severity Score, completeness of cytoreduction, history of extraperitoneal disease (EPD), and Peritoneal Cancer Index. RESULTS: The groups were comparable, except for a higher number of patients in the HIPEC group with World Health Organization performance status 0, pN2 stage primary tumor, and treated with preoperative s-CT. Forty-one patients in the no-HIPEC group and 43 patients in the HIPEC group had optimal comprehensive treatment (P = 0.759), defined as complete cytoreduction of PM and margin-negative EPD resection. Median follow-up was 31.6 months in the no-HIPEC group and 39.9 months in the HIPEC group. Median overall survival was 39.3 months in the no-HIPEC group and 34.8 months in the HIPEC group (P = 0.702). In the two groups, severe morbidity occurred in 14 (29.2%) and 13 (27.1%) patients, respectively (P = 1.000), with no operative deaths. On multivariate analysis, left-sided primary and curative treatment independently correlated with better survival while HIPEC did not (hazard ratio 0.73; 95% confidence interval 0.47-1.15; P = 0.178). CONCLUSIONS: Our results confirmed that, in selected patients, perioperative s-CT and surgical treatment of CRC-PM resulted in unexpectedly high survival rates. Mitomycin C-based HIPEC did not increase morbidity but did not impact prognosis.

VITAL phase 2 study: Upfront 5-fluorouracil, mitomycin-C, panitumumab and radiotherapy treatment in nonmetastatic squamous cell carcinomas of the anal canal (GEMCAD 09-02).

AIM: VITAL, a phase II single-arm study, aimed to evaluate efficacy and safety of panitumumab addition to 5-fluorouracil (5-FU), mitomycin-C (MMC) and radiotherapy (RT) in patients with localized squamous cell carcinoma of the anal canal (SCCAC). METHODS: Adult, treatment-naïve SCCAC patients (Stage T2-T4, any N, M0) and ECOG-PS ≤2, received panitumumab (6 mg/kg, day 1 and Q2W; 8 weeks), 5-FU (1000 mg/m2 /d, days 1-4 and 29-32), MMC (10 mg/m2 , days 1 and 29) and RT 45 Gy (1.8 Gy/fraction) to the primary tumor and mesorectal, iliac and inguinal lymph nodes, plus 10-15 Gy boost dose to the primary tumor and affected lymph nodes. The primary objective was disease free survival rate (DFS) at 3-years (expected 3-year DFS rate: 73.7 ± 12%). RESULTS: Fifty-eight patients (31 women; median age: 59 years; ECOG-PS 0-1:98%; TNM II [29%] (T2 or T3/N0/M0)/IIIA (T1-T3/N1/M0 or T4/N0/M0) [21%]/IIIB (T4/N1/M0 or any T/N2 or N3/M0) [47%]/nonevaluable [4%]) were included. The median follow-up was 45 months. The 3-year DFS rate was 61.1% (95% CI: 47.1, 72.4). The 3-year overall survival rate was 78.4% (95% CI: 65.1, 87.1). Eighteen patients (31.0%) required a colostomy within 2 years posttreatment. Grade 3-4 toxicities were experienced by 53 (91%) patients. Most common grade 3-4 treatment-related events were radiation skin injury (40%) and neutropenia (24%). No toxic deaths occurred. Improved efficacy in colostomy-free survival and complete response rate was observed in human papilloma virus positive patients. CONCLUSIONS: Panitumumab addition to MMC-5FU regimen in SCCAC patients increases toxicity and does not improve patients' outcomes. RT plus MMC-5FU remains the standard of care for localized SCCAC patients.

Cytoreductive Surgery and HIPEC in an Enhanced Recovery After Surgery Program: A Feasibility Study.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have historically been associated with high morbidity given the physiologic insult of an extensive operation. Enhanced Recovery after Surgery (ERAS) pathways have been successful in improving postoperative outcomes for many procedures but have not been well studied in these cases. We examined the feasibility and effect of ERAS pathway implementation for patients undergoing CRS/HIPEC. MATERIALS AND METHODS: Patients with peritoneal carcinomatosis who underwent CRS/HIPEC between October 2015 to September 2018 were identified. Patient characteristics, disease pathology, and perioperative outcome data were obtained. Primary outcomes were hospital length of stay (LOS), 30-d readmissions, renal dysfunction, and complications. RESULTS: Of the 31 patients who were included, 11 (35.5%) patients underwent CRS/HIPEC prior to the implementation of the ERAS pathway, and 20 (64.5%) patients underwent CRS/HIPEC according to the ERAS guidelines. There were no significant differences in the baseline clinical or pathologic characteristics between groups. There was a significant decrease in LOS with ERAS pathway management from 9 d to 6 d (P = 0.002). No patients from either cohort experienced acute kidney injury. There was no significant difference in 30-d readmission rates or complications. CONCLUSIONS: In this feasibility study, ERAS pathway utilization significantly decreased postoperative LOS for patients undergoing CRS/HIPEC, without evidence of increased complications or readmissions. ERAS programs should be considered for integration into future CRS/HIPEC protocols.

Heated Intravesical Chemotherapy: Biology and Clinical Utility.

Non-muscle-invasive bladder cancer can be a challenging disease to manage. In recent years, hyperthermia therapy in conjunction with intravesical therapy has been gaining traction as a treatment option for bladder cancer, especially if Bacillus Calmette-Guerin might not be available. Trials of intravesical chemotherapy with heat are few and there has been considerable heterogeneity between studies. However, multiple new trials have accrued and high-quality data are forthcoming. In this review, we discuss the role of combined intravesical hyperthermia and chemotherapy as a novel approach for the treatment of bladder cancer.

Efficacy of Needling Revision After XEN Gel Stent Implantation: A Prospective Study.

INTRODUCTION: The XEN gel stent is currently the only minimally invasive glaucoma surgical device that targets the subconjunctival outflow pathway through an ab interno placement. It has demonstrated a significant intraocular pressure (IOP)-lowering potential and a favorable safety profile compared with traditional filtering surgery. However, despite a less invasive approach, the presence of a filtering bleb inevitably implies some risk of complications. The most commonly reported bleb-related complication, with rates as high as 45%, is bleb fibrosis associated with raised IOP. To restore filtration in those failing blebs, needling revision is considered the procedure of choice. In this study, we present the results of mitomycin C-augmented needling after XEN implantation. METHODS: This was a prospective, interventional study, conducted at a single tertiary glaucoma center. Fifty-one eyes of 51 patients with raised IOP associated with either a fibrotic or shallow bleb or increased vascularity following XEN gel stent implantation at the investigation site between January 2015 and June 2016 were enrolled in this study. Patients with other identified causes of filtration failure (stent malposition, internal ostium obstruction, retained viscoelastic) were excluded. Included patients who underwent mitomycin C-augmented needling revision, and follow-up examinations were conducted at 1 day, 1 week, and 1, 3, 6, 12, 18, and 24 months. The primary outcome was the magnitude of IOP reduction following needling revision at the last follow-up visit. Secondary outcome measures were the number of needling procedures carried out in all patients, the rate of patients requiring further filtering surgery following needling revision, and the rate of intraoperative and postoperative complications associated with needling revisions. RESULTS: The average age was 74.4±9.6 years; 66.7% (n=34) were female individuals. Primary open-angle glaucoma was the most common diagnosis (n=21, 41.2%). A total of 78 needling procedures were performed over the 24-month follow-up. Overall 20 of 51 eyes (39.2%) required >1 needling revision, and 14 eyes (24.5%) eventually required reoperation to maintain IOP within their desired target range. Before XEN implantation, mean preoperative IOP was 22.3±8.2 mm Hg and decreased to 14.1±8.0 mm Hg at day 1 postoperatively (-36.8%). The last measured IOP before the first needling revision was on average 23.6±8.9 mm Hg, which reduced to a mean 12.1±4.2 mm Hg at the first postrevision appointment (-48.7%). At the last follow-up appointment, on average 17.0±7.0 months after the first needling, the mean IOP was 14.3±4.1 mm Hg (-35.9% and -39.4% from preoperative and prerevision baselines, respectively). Complications associated with needling revisions were partial amputation of the XEN implant during needling (n=2, 3.9%), hypotony with choroidal detachment (n=1, 2%), and failure to achieve target IOP requiring subsequent surgery (n=14, 27.5%). No association was found between any of the recorded characteristics and the number of needling revisions performed or their outcomes. DISCUSSION: The present study shows that needling revision following XEN gel stent implantation is a relatively safe and efficient intervention to restore filtration in failing blebs, with a significant and durable IOP-reduction potential.

Intra-articular injection of mitomycin C prevents progression of immobilization-induced arthrogenic contracture in the remobilized rat knee.

This study tested whether cell cycle inhibitor mitomycin C (MMC) prevents arthrogenic contracture progression during remobilization by inhibiting fibroblast proliferation and fibrosis in the joint capsule. Rat knees were immobilized in a flexed position to generate flexion contracture. After three weeks, the fixation device was removed and rat knees were allowed to freely move for one week. Immediately after and three days after fixator removal, rats received intra-articular injections of MMC or saline. The passive extension range of motion (ROM) was measured before and after myotomy of the knee flexors to distinguish myogenic and arthrogenic contractures. In addition, both cellularity and fibrosis in the posterior joint capsule were assessed histologically. Joint immobilization significantly decreased ROMs both before and after myotomy compared with untreated controls. In saline-injected knees, remobilization increased ROM before myotomy, but further decreased that after myotomy compared with that of knees immediately after three weeks of immobilization. Histological analysis revealed that hypercellularity, mainly due to fibroblast proliferation, and fibrosis characterized by increases in collagen density and joint capsule thickness occurred after remobilization in saline-injected knees. Conversely, MMC injections were able to prevent the remobilization-enhanced reduction of ROM after myotomy by inhibiting both hypercellularity and joint capsule fibrosis. Our results suggest that joint capsule fibrosis accompanied by fibroblast proliferation is a potential cause of arthrogenic contracture progression during remobilization, and that inhibiting fibroblast proliferation may constitute an effective remedy.

[Safety of Hyperthermic IntraVEsical Chemotherapy (HIVEC) for BCG Unresponsive Non-Muscle Invasive Bladder Cancer Patients]. / Tolérance de la thermo-chimiothérapie par HIVEC® chez les patients réfractaires au BCG.

INTRODUCTION: There is increasing evidence that Hyperthermic Intravesical Chemotherapy is an effective treatment for non-muscle invasive bladder cancer (NMIBC). HIVEC (COMBAT BRS system) is an innovative hyperthermia delivering device. The aim of our study is to evaluate tolerance and safety of HIVEC in patients with BCG-refractory NMIBC. MATERIALS AND METHODS: In this study, we included 22 patients between January 2017 and April 2018. The treatment consisted in a weekly instillation of Hyperthermic Mitomycin for a total of 6 weeks, with a follow-up every 3 months. In order to evaluate the tolerance, patients filled a questionnaire before each instillation. We analyzed collected data to evaluate safety and efficiency of the treatment after one year. RESULTS: Among 22 patients included, no patient suffered from severe side effects. The minor side effects reported were : urinary urgency (40,1 %), urinary pain (40,1%), macroscopic hematuria (4,5%). The IPSS score didn't significantly varied before and after instillations (mean IPSS: 10.8 versus 10.1, p=0.77). The mean follow-up was 11.2 months. The recurrence rate was 27,3% with an average time to recurrence of 7.36 months. Two patients (9.1%) presented a progression to muscle-invasive disease. Four patients (18,2%) had a radical cystectomy. CONCLUSION: Hyperthermic Mitomycin using the HIVEC® device is a rather safe and well tolerated treatment. Efficiency remains partial as 27.3% of patients experienced recurrence during the first year. These data should be confirmed by prospective multicentric studies.

Intraperitoneal mitomycin C improves survival compared to cytoreductive surgery alone in an experimental model of high-grade pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is a rare cancer commonly originating from appendiceal neoplasms that presents with mucinous tumor spread in the peritoneal cavity. Patients with PMP are treated with curative intent by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The value of adding HIPEC to CRS has not been proven in randomized trials, and the objective of this study was to investigate the efficacy of intraperitoneal mitomycin C (MMC) and regional hyperthermia as components of this complex treatment. Xenograft tissue established from a patient with histologically high-grade PMP with signet ring cell differentiation was implanted intraperitoneally in 65 athymic nude male rats and the animals were stratified into three treatment groups; the cytoreductive surgery group (CRSG, CRS only), the normothermic group (NG, CRS and intraperitoneal chemotherapy perfusion (IPEC) with MMC at 35 ºC), and the hyperthermic group (HG, CRS and IPEC at 41 ºC). The main endpoints were survival and tumor weight at autopsy. Adequate imitation of the clinical setting and treatment approach was achieved. The median survival was 31 days in the CRSG, 60 days in NG and 67 days in HG. The median tumor weights at autopsy were 34 g in CRSG, 23 g NG and 20 g in HG. In conclusion, the addition of IPEC with MMC after CRS doubled the survival time and reduced tumor growth compared to CRS alone. Adding regional hyperthermia resulted in a modest improvement of treatment outcome.

Use of synthetic stomata in abdominal carcinomatosis. Case report and literature review.

BACKGROUND: The successful performance of ostomies for the treatment of different diseases has been described since 1706. We report herein the first case of successful ostomy utilizing a synthetic stoma created in a patient with peritoneal carcinomatosis. CLINICAL CASE: A 40-year-old woman presented with abdominal carcinomatosis due to psammomatous papillotubular adenocarcinoma consistent with primary ovarian carcinoma. The patient had negative estrogen and progesterone receptors and Ki-67 proliferative activity was 83%. She was initially treated with cytoreduction therapy, chemotherapy, and hyperthermic intraperitoneal chemotherapy. Because the patient presented with enteric perforations and the extensive tumor invasion and adhesions in all the intestinal segments made it impossible to create autologous decompression stomas, a synthetic stoma was constructed. CONCLUSIONS: Synthetic stomas can be a good treatment option when autologous stomas can not be created.

INTRODUCCIÓN: Desde el año 1706 se han descrito ostomías realizadas con éxito para el tratamiento de diferentes enfermedades; los autores describen el primer caso de éxito en una ostomía sintética en la carcinomatosis peritoneal. CASO CLÍNICO: Mujer de 40 años de edad con carcinomatosis abdominal por adenocarcinoma papilar tubulopapilar psamomatoso más consistente con cáncer primario de ovario, negativo a receptores de estrógenos y progesterona, con marcador Ki-67 al 83% de actividad. De modo inicial se trató con cirugía de citorreducción, quimioterapia, quimioterapia intraperitoneal hipertérmica y por último realización de estomas sintéticos debido a perforaciones entéricas e imposibilidad de realizar estomas descompresivos autólogos por la invasión tumoral extensa y adherencias de todas las asas intestinales. CONCLUSIONES: Los estomas sintéticos pueden ser una buena opción terapéutica cuando es imposible realizar estomas autólogos.