KORTUC, a novel hydrogen peroxide­based radiosensitizer for the enhancement of brachytherapy in patients with unresectable recurrent uterine cervical cancer.

Kochi Oxydol Radiation Therapy for Unresectable Carcinoma (KORTUC) is a novel radiosensitizer invented by Professor Ogawa at Kochi University (Japan) in 2006. The current study aimed to report the experience of the present authors with the use of KORTUC treatment in combination with interstitial brachytherapy (ISBT), with or without external beam (EB) radiotherapy (RT), in patients with locally recurrent cervical cancer (LRCC), who were likely to have a high risk of poor prognosis. Between April 2012 and January 2020, 14 female patients (15 tumoral lesions) with LRCC underwent KORTUC with ISBT. Their previous treatments included surgery (n=4), radiation therapy (n=8) and surgery plus RT (n=3). The primary lesions were located in the vaginal stump (n=5), pelvic wall (n=3), cervix (n=3), vaginal wall (n=2) and lymph nodes (n=2). At 2 h before RT, KORTUC was injected intratumorally via direct colposcopy. The dose of KORTUC ranged from 4-12 ml, adjusted for the tumor size. For patients who underwent ISBT, KORTUC was administered before and after insertion of the applicator before irradiation. Intratumoral injection of KORTUC was completed without any technical or safety issues in all 15 patients; it was well tolerated with no adverse events observed. KORTUC also showed preferable efficacy; a clinical complete response was observed in 87% of patients and the initial response rate was 100%. The 2-year local control rate in patients who underwent ISBT + KORTUC was 79%, whereas it was 63% in the re-irradiation group which was significantly lower (P=0.02) than that in the non-irradiation group (100%). Based on this finding, KORTUC with external irradiation is considered to be an optimal treatment strategy for patients with newly diagnosed LRCC this disease. Additionally, KORTUC may be an effective radiation response enhancer in multiple cancer types in which locoregional control after RT alone remains poor.

New enzyme-targeting radiosensitizer (KORTUC II) treatment for locally advanced or recurrent breast cancer.

Kochi oxydol radiation therapy for unresectable carcinomas II (KORTUC II) is currently the most widely used radiosensitizer in Japan. This sensitizer is a solution consisting of 0.83% sodium hyaluronate and 0.5% hydrogen peroxide. The mixture is injected intratumorally just before radiation therapy (RT) several times. KORTUC II has the effect of neutralizing antioxidant enzymes, while increasing the oxygen tension into the tumor tissue, and achieves marked local effects without notable adverse events. The present report describes cases in which KORTUC II was used to treat patients with locally advanced breast cancer (LABC) or recurrent breast cancer (LRBC). The present study included 30 patients with LABC (n=9) or LRBC (n=21) aimed at local control of tumors, who were followed up for ≥3 months after treatment. The irradiation dose and extent fields were determined by the attending physicians considering various patient factors, such as a performance status, prognosis and presence or absence of adjuvant therapy. The median irradiation dose was 60.4 Gy3.5 (43.6-76.1 Gy3.5) based on the calculation of equivalents of 2 Gy fractions, and the median total number of sensitizer injections was 5 (2-7) times. The median maximum tumor shrinkage was 97.0% and 15 patients (50%) were assessed to have achieved a clinical complete response. The proportion with loco-regional control at 1, 2 and 3 years was 100, 94.7 and 75.4%, respectively, and progression free survival after RT at 1 and 2 years was 59.0 and 24.1%, respectively. KORTUC II exhibited high rates of local tumor control for LABC and LRBC. KORTUC II is expected to be an inexpensive and promising RT method because it is safe and has an excellent radio-sensitizing effect.

Urinary bladder reconstruction using autologous collagenous connective tissue membrane "Biosheet®" induced by in-body tissue architecture: A pilot study.

INTRODUCTION: In-body tissue architecture (iBTA) technology, based on cell-free tissue engineering, can produces collagenous tissues for implantation by subcutaneous embedding a designed mold. The aim of this study was to evaluate the biocompatibility of iBTA-induced "Biosheet®" collagenous sheets, as scaffold materials for bladder reconstruction. METHODS: Canine Biosheet® implants were prepared by embedding molds into subcutaneous pouches in beagles for 8 weeks. A part of canine bladder wall was excised (2 × 2 cm) and repaired by patching the same sized autologous Biosheet®. The Biosheet® implants were harvested 4 weeks (n = 1) and 12 weeks (n = 3) after the implantation and evaluated histologically. RESULTS: No disruption of the patched Biosheet® implants or urinary leakage into the peritoneal cavity was observed during the entire observation periods. There were no signs of chronic inflammation or Biosheet® rejection. The urine-contacting surface of luminal surface of the Biosheet® was covered with a multicellular layer of urothelium cells 4 weeks after implantation. α-SMA-positive muscle cells were observed at the margin of the Biosheet® implants at 12 weeks after the implantation. In addition, in the center of the Biosheet® implants, the formation of microvessels stained as α-SMA-positive was observed. CONCLUSION: Biosheet® implants have biocompatibility as a scaffold for bladder reconstruction, indicating that they may be applicable for full-thickness bladder wall substitution. Further studies are required for definitive evaluation as a scaffold for bladder reconstruction.

High-dose-rate interstitial brachytherapy with hypoxic radiosensitizer KORTUC II for unresectable pelvic sidewall recurrence of uterine cervical cancer: a case report.

In order to improve oncologic outcomes in radiotherapy treatments of patients with unresectable pelvic sidewall recurrences of uterine cervical cancer, we combined high-dose-rate interstitial brachytherapy (HDR-ISBT) with newly tested hypoxic radiosensitizer Kochi oxydol-radiation therapy for unresectable carcinomas (KORTUC II), an enzyme-targeting radiosensitization treatment involving intra-tumoral injection of sodium hyaluronate mixed with hydrogen peroxide. We report on a 63-year-old patient referred to our department with an extensive pelvic sidewall recurrence of uterine cervical cancer after initial hysterectomy. The tumor size was 55 × 25 × 80 mm, with a calculated volume of 89.7 cc. Whole pelvic irradiation of 50 Gy in 25 fractions was administered, combined with weekly cisplatin injections. KORTUC II injections were given two times: at day 21 (42 Gy) and at day 24 (48 Gy). After finishing whole pelvic irradiation, HDR-ISBT of 25 Gy in 5 fractions b.i.d. over 3 days was administered. KORTUC II was also injected at the time of implantation. Dose-volume histogram (DVH) values for clinical target volume were D90, D98, and D100 of 6.0, 5.0, and 3.5 Gy per fraction, respectively. D2cc values were 2.1, 4.1, 3.2, and 2.0 Gy per fraction for the bladder, rectum, sigmoid colon, and small bowel, respectively. No acute adverse events ≥ grade 3 were observed. Repeated grade 3 pyelonephritis occurred as a late complication at 11, 24, and 26 months after the treatment, and was successfully resolved with antibiotics. Moreover, grade 2 late toxicity was documented, including sciatic neuralgia, lower limb lymphedema, and urinary incontinence. At present, 32 months after HDR-ISBT, the patient remains free of disease, with no toxicity-related deterioration in physical condition.

Evaluation of the accuracy of urine analyzers in dogs and cats.

The accuracy of urine analyzers used for dogs and cats has remained uncertain. This study examines the agreement between results of urine analysis obtained using two devices marketed for animals and for humans and the results of quantitative biochemical analysis. The degrees of concordance for bilirubin and ketones in the same category were ~80%, but for pH these were only ~60% in dogs and cats. Degrees of concordance for protein and the UP/C ratio clearly differed between the devices for animals and humans. We found that values for bilirubin and ketones obtained using urine analyzers may be reliable, but pH is unlikely to be accurate enough to be clinically useful for dogs and cats.

A new implant device to prevent edema-associated underdosage in high-dose-rate interstitial brachytherapy of mobile tongue cancer.

PURPOSE: Tongue edema is a potential cause of treatment target underdosage in high-dose-rate interstitial brachytherapy (HDR-ISBT) of mobile tongue cancer. To prevent such edema-associated alteration of dosimetry, we developed a special silicon device. In this report we communicate our initial experience with two mobile tongue cancer patients whom we treated using this new device. MATERIAL AND METHODS: The device consists of silicone tubes with a fixed width and scalable length depending on tongue size. These tubes are lined and fixed like a palisade, allowing the device to be used also as a template. The device is placed next to the lateral border of the tongue and on the floor of the mouth. In addition, a vinyl template can be placed on the dorsal tongue surface with both devices combined for implantation guidance. Between June and August 2012, two patients with locally confined tongue cancer were treated. RESULTS: Between June and August 2012, two mobile tongue cancer patients classified as cT2N0M0 were treated with HDR-ISBT using the silicone device. They underwent ISBT as monotherapy with fractional doses of 6.0 Gy up to a total physical dose of 54.0 Gy. The D90 (CTV) values of both patients were 6.3 Gy and 6.6 Gy and the D2cc (mandible) values were 3.4 Gy and 2.6 Gy, respectively. At present, both patients remain without local disease recurrence at 60 and 56 months after ISBT, respectively. CONCLUSIONS: The described silicone device has the potential to prevent underdosage to the treatment target related to tongue edema. It has been shown to be safe and easy to implement.

Development of a postoperative occlusive thrombus at the site of an implanted inferior vena cava filter: A case report.

RATIONALE: Although an inferior vena cave (IVC) filter is placed to prevent fatal pulmonary embolism (PE), several complications associated with an IVC filter have been reported. We describe a case with symptomatic PE, of which the origin was an occlusive IVC thrombus that developed from the placement of an IVC filer after a laparoscopy-assisted total gastrectomy (LATG). PATIENT CONCERNS: A 71-year-old man underwent LATG under general anesthesia alone. He had an IVC filter implanted 13 years ago. An intravenous infusion of unfractionated heparin was substituted for the discontinuation of oral warfarin four days before the surgery. The proposed operation was performed and took a total of 404 minutes including the total duration of pneumoperitoneum that took 374 minutes. After the surgery, he experienced severe shivering reactions that required frequent bolus infusions of antihypertensive drugs. On the third postoperative day, he complained of dyspnea after taking a short walk, and subsequently lost consciousness. While he spontaneously recovered without requiring any resuscitation efforts, we performed computed tomography (CT) examination for suspected PE. DIAGNOSES: The CT showed that a massive thrombus was occupying the intravenous space from the IVC filter to the left common iliac vein with several embolic defects in the peripheral pulmonary arteries present. INTERVENTIONS: An anticoagulant therapy was established with 10 mg of oral apixaban given twice a day for the first four days, followed by a reduction to 5 mg. OUTCOMES: On the 17th postoperative day, an ultrasound vascular examination confirmed the complete disappearance of deep venous thrombus (DVT). LESSONS: As an IVC filter itself may be a potential source of DVT, we should carefully manage patients with a previously implanted IVC filter throughout the perioperative period.