Kidney transplantation after pelvic radiotherapy: Increased morbidity?

INTRODUCTION: The impact of pelvic irradiation on kidney transplant surgery is still unclear. The main objective of our study is to evaluate the feasibility and the safety of renal transplantation following pelvic radiotherapy. METHODS: We collected characteristics and kidney transplant data from patients with a history of pelvic cancer treated with pelvic irradiation between 2005 and 2021. These data were collected via the prospective information system "Computerized Data Validated in Transplantation" (DIVAT) and medical records. We carried out a comparative study with a non-irradiated matched control group to compare the data of intraoperative surgeries, complications reported postoperatively as well as survival of the graft and the patient. Patients were matched on age, sex, side of graft implantation, and graft rank. RESULTS: Twenty-four patients were collected with an average age of 65, 18 patients were treated for prostatic adenocarcinoma, 4 for gynecological cancer and 2 testicular cancers. Twenty-one patients were treated by radiotherapy, 3 by brachytherapy. Eight patients had a target dose on the iliac lymph nodes. The comparative study showed a significant difference in operative difficulty (n=15 versus n=1, P<0.01), operative duration (190min versus 149min, P=0.005), occurrence of lymphocele (P=0.041). Urinary anastomosis surgical techniques were different, 83.3% of control patients had an uretero-vesical anastomosis against 58.3% of patients with a history of irradiation (P=0.057) and about 29% of irradiated patients had an uretero-ureteral anastomosis. There was no other significant difference in per and postoperative criteria or survival. DISCUSSION: A history of pelvic irradiation significantly increases the technical complexity of kidney transplantation without impacting safety and kidney graft survival. A history of pelvic irradiation should not be a contraindication to kidney transplant.

Dose-escalated Salvage Whole-pelvic Radiotherapy for Biochemical Recurrence After Radical Prostatectomy for High-risk Prostate Cancer.

Background/Aim: To investigate the institutional experience of dose-escalated salvage whole-pelvic radiotherapy (WPRT) with the simultaneous integrated boost (SIB) technique in patients with biochemical recurrence (BCR) after radical prostatectomy for high-risk prostate cancer. Patients and Methods: This retrospective study included 21 patients with BCR who received radical prostatectomy for high-risk prostate cancer and underwent salvage RT. Clinical target volume (CTV) of the whole pelvis (CTV56) included the prostate bed, common iliac, external iliac, internal iliac, and obturator lymph node regions. The boost CTV (CTV66) included the prostate bed. Planning target volumes (PTV) were generated by adding a margin of 6-8 mm to CTV (PTV56 and PTV66). Doses of 56.1 and 66 Gy in 33 fractions were delivered to PTV56 and PTV66, respectively. Results: The 5-year biochemical progression-free survival, overall survival, and cause-specific survival rates were 72%, 94%, and 94%, respectively. A grade 3 late genitourinary toxicity event of gross hematuria was observed in one patient (4%). Acute and late toxicities of grade ≥3, other than gross hematuria, were not observed in any patient. Conclusion: Dose-escalated salvage WPRT using the SIB technique provides appropriate tumor control without increasing the incident of significant toxicities.

Effects of bone marrow sparing radiotherapy on acute hematologic toxicity for patients with locoregionally advanced cervical cancer: a prospective phase II randomized controlled study.

OBJECTIVE: To evaluate effects of bone marrow sparing (BMS) radiotherapy on decreasing the incidence of acute hematologic toxicity (HT) for locoregionally advanced cervical cancer (LACC) patients treated by pelvic irradiation. MATERIALS AND METHODS: LACC patients were recruited prospectively from May 2021 to May 2022 at a single center and were evenly randomized into the BMS group and the control group. All patients received pelvic irradiation with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy and BM V40 < 25% in the BMS group was additionally prescribed. Acute HT was assessed weekly. Binary logistic regression model and receiver operating characteristic (ROC) curve were used for predictive value analysis. The trial was registered with Chinese clinical trial registry (ChiCTR2200066485). RESULTS: A total of 242 patients were included in the analysis. Baseline demographic, disease and treatment characteristics were balanced between the two groups. In the intention-to-treat population, BMS was associated with a lower incidence of grade ≥ 2 and grade ≥ 3 acute HT, leukopenia and neutropenia s(72.70% v 90.90%, P < 0.001*; 16.50% vs. 65.30%, P < 0.001*; 66.10% vs. 85.10%, P = 0.001*; 13.20% vs. 54.50%, P < 0.001*; 37.20% vs. 66.10%, P < 0.001*; 10.70% vs. 43.80%, P < 0.001*). BMS also resulted in decreased dose delivered to the organs at risk (OARs) including rectum, bladder and left and right femoral head. Univariate and multivariate analyses showed that BM V40 was an independent risk factor for grade ≥ 3 acute HT (odds ratio [OR] = 2.734, 95% confidence interval [CI] = 1.959-3.815, P < 0.001*). Cutoff value was 25.036% and area under the curve (AUC) was 0.786. The nomogram was constructed, which was rigorously evaluated and internally cross-validated, showing good predictive performance. CONCLUSIONS: Receiving BMS pelvic irradiation could reduce the incidence of acute HT in LACC patients, and BM V40 < 25% may be a significant factor in reducing the risks of acute HT.

Prostate cancer and elective nodal radiation therapy for cN0 and pN0-a never ending story? : Recommendations from the prostate cancer expert panel of the German Society of Radiation Oncology (DEGRO).

For prostate cancer, the role of elective nodal irradiation (ENI) for cN0 or pN0 patients has been under discussion for years. Considering the recent publications of randomized controlled trials, the prostate cancer expert panel of the German Society of Radiation Oncology (DEGRO) aimed to discuss and summarize the current literature. Modern trials have been recently published for both treatment-naïve patients (POP-RT trial) and patients after surgery (SPPORT trial). Although there are more reliable data to date, we identified several limitations currently complicating the definitions of general recommendations. For patients with cN0 (conventional or PSMA-PET staging) undergoing definitive radiotherapy, only men with high-risk factors for nodal involvement (e.g., cT3a, GS ≥ 8, PSA ≥ 20 ng/ml) seem to benefit from ENI. For biochemical relapse in the postoperative situation (pN0) and no PSMA imaging, ENI may be added to patients with risk factors according to the SPPORT trial (e.g., GS ≥ 8; PSA > 0.7 ng/ml). If PSMA-PET/CT is negative, ENI may be offered for selected men with high-risk factors as an individual treatment approach.

Radiobiological analysis of preliminary results of a phase II study of pelvic hypofractionated and accelerated radiotherapy for high-risk prostate cancer patients.

PURPOSE: Conventionally fractionated radiotherapy (CRT) is widely applied for the treatment of high-risk prostate cancer. Pelvic node irradiation improves control of the disease. Although the therapeutic guidelines support the use of hypofractionated and accelerated radiotherapy (HypoAR), this is addressed to prostate and seminal vesicles. At the same time, the safety and efficacy of HypoAR for pelvic node irradiation remain obscure. Material and Methods: In a phase II study, we evaluated the feasibility of pelvic HypoAR in 22 high-risk prostate cancer patients. The RT scheme delivers 14 consecutive fractions of 3.67 Gy (total 51.38 Gy) to the prostate, 3.5 Gy (total 49 Gy) to the seminal vesicles, and 2.7 Gy (total 37.8 Gy) to the lymph nodes, using image-guided volumetric modulated arc therapy. A comparative radiobiological analysis of dose-volume histogram is performed (HypoAR vs. hypothetical equivalent CRT regimens, without and with time correction). RESULTS: Our clinical experience shows impressively low early and short-term late toxicities, without any grade III events, within a median follow-up of 30 months. Only one biochemical relapse was recorded 30 months after irradiation. In radiobiological analysis, considering an α/ß-value of 4 Gy and a λ-value of 0.2 Gy/day for late effects, all comparisons predicted significantly lower toxicity for the HypoAR regimen (p < 0.05). For early toxicities (α/ß = 10 Gy), a λ-value lower than 0.4 Gy/day favors the HypoAR regimen, which is along with the clinical results. CONCLUSION: Radiobiological analysis favors HypoAR as a safe and effective regimen for high-risk prostate cancer patients, which is confirmed in the current phase II clinical study.

Study on Appropriate Rectal Volume for External Irradiation in Patients With Cervical Cancer.

Objective: To investigate the appropriate rectal volume for external irradiation of cervical cancer. Methods: A retrospective study of 143 patients with cervical cancer who underwent external radiotherapy from January 2017 to September 2020 was conducted. Average rectum volumes and the cumulative dose (V30, V40, V50, D2cc) to organs at risk (bladder, rectum, and small bowel) during radiotherapy were evaluated using the treatment planning system. Rates of radiation cystitis and radiation proctitis were assessed. Results: The median follow-up was 48 months, and the included patients had a median age of 53 years. Patients were divided into 3 groups based on their average rectum volume: Group A: <40 ml; Group B: 40-70 ml; and Group C: ≥70 ml. V30 and V40 in the rectum bladder and small bowel were highest in Group A (mean ± SD standard deviation), but V50 and D2cc in the rectum and bladder were highest in Group C (mean ± SD). Patients in Group B had the lower incidence of both radiation cystitis and radiation proctitis. (p<0.05). Conclusions: For external irradiation in patients with cervical cancer, a rectum volume of 40-70 ml seems most appropriate, whereas >70 ml increases the risk of severe radiation cystitis and radiation proctitis, and <40 ml increases the risk of mild radiation cystitis and mild radiation proctitis.

Radiation-induced toxicity in rectal epithelial stem cell contributes to acute radiation injury in rectum.

BACKGROUND: Radiation-induced rectal epithelial damage is a very common side effect of pelvic radiotherapy and often compromise the life quality and treatment outcome in patients with pelvic malignancies. Unlike small bowel and colon, effect of radiation in rectal stem cells has not been explored extensively. Here we demonstrate that Lgr5-positive rectal stem cells are radiosensitive and organoid-based transplantation of rectal stem cells mitigates radiation damage in rectum. METHODS: C57Bl6 male mice (JAX) at 24 h were exposed to pelvic irradiation (PIR) to determine the radiation effect in pelvic epithelium. Effect of PIR on Lgr5-positive rectal stem cells (RSCs) was determined in Lgr5-EGFP-Cre-ERT2 mice exposed to PIR. Effect of PIR or clinically relevant fractionated PIR on regenerative response of Lgr5-positive RSCs was examined by lineage tracing assay using Lgr5-eGFP-IRES-CreERT2; Rosa26-CAG-tdTomato mice with tamoxifen administration to activate Cre recombinase and thereby marking the ISC and their respective progeny. Ex vivo three-dimensional organoid cultures were developed from Lgr5-EGFP-Cre-ERT2 mice. Organoid growth was determined by quantifying the budding crypt/total crypt ratio. Organoids from Lgr5-EGFP-ires-CreERT2-TdT mice were transplanted in C57Bl6 male mice exposed to PIR. Engraftment and repopulation of Lgr5-positive RSCs were determined after tamoxifen administration to activate Cre recombinase in recipient mice. Statistical analysis was performed using Log-rank (Mantel-Cox) test and paired two-tail t test. RESULT: Exposure to pelvic irradiation significantly damaged rectal epithelium with the loss of Lgr5+ve rectal stem cells. Radiosensitivity of rectal epithelium was also observed with exposure to clinically relevant fractionated pelvic irradiation. Regenerative capacity of Lgr5+ve rectal stem cells was compromised in response to fractionated pelvic irradiation. Ex vivo organoid study demonstrated that Lgr5+ve rectal stem cells are sensitive to both single and fractionated radiation. Organoid-based transplantation of Lgr5+ve rectal stem cells promotes repair and regeneration of rectal epithelium. CONCLUSION: Lgr5-positive rectal stem cells are radiosensitive and contribute to radiation-induced rectal epithelial toxicity. Transplantation of Lgr5-positive rectal stem cells mitigates radiation-induced rectal injury and promotes repair and regeneration process in rectum.

Haute Couture or Ready-to-Wear? Tailored Pelvic Radiotherapy for Prostate Cancer Based on Individualized Sentinel Lymph Node Detection.

Prostate cancer (PCa) pelvic radiotherapy fields are defined by guidelines that do not consider individual variations in lymphatic drainage. We examined the feasibility of personalized sentinel lymph node (SLN)-based pelvic irradiation in PCa. Among a SLN study of 202 patients, we retrospectively selected 57 patients with a high risk of lymph node involvement. Each single SLN clinical target volume (CTV) was individually segmented and pelvic CTVs were contoured according to Radiation Therapy Oncology Group (RTOG) guidelines. We simulated a radiotherapy plan delivering 46 Gy and calculated the dose received by each SLN. Among a total of 332 abdominal SLNs, 305 pelvic SLNs (beyond the aortic bifurcation) were contoured (mean 5.4/patient). Based on standard guidelines, CTV missed 67 SLNs (22%), mostly at the common iliac level (40 SLNs). The mean distance between iliac vessels and the SLN was 11mm, and despite a 15mm margin around the iliac vessels, 9% of SLNs were not encompassed by the CTV. Moreover, 42 SLNs (63%) did not receive 95% of the prescribed dose. Despite a consensus on contouring guidelines, a significant proportion of SLNs were not included in the pelvic CTV and did not receive the prescribed dose. A tailored approach based on individual SLN detection would avoid underdosing pelvic lymph nodes that potentially contain tumor cells.

Fertility preservation with successful pregnancy outcome in a patient with transplanted heart and non-Hodgkin's lymphoma - a case report.

BACKGROUND: Fertility preservation must be discussed with reproductive age women before cancer treatment. Heart transplantation raises complex issues in pregnancy. Pregnancy in a heart transplant woman after pelvic irradiation involves close multidisciplinary follow-up to avoid complications in the mother and the foetus. We report the first live birth in a heart transplant woman after pelvic irradiation, chemotherapy and fertility preservation. CASE PRESENTATION: A 36-year-old heart transplant woman with pelvic non-Hodgkin lymphoma spared her fertility, with cryopreservation of oocytes and embryos, before chemotherapy and pelvic irradiation. After multidisciplinary discussion and pre-conception evaluation, pregnancy was achieved. A close follow-up by a multidisciplinary team allowed a normal pregnancy without maternal or foetal complications and the delivery of a healthy infant. CONCLUSIONS: Achieving pregnancy in heart transplant women with iatrogenic ovarian failure after oncologic treatment including pelvic irradiation is possible and can be successful. Careful and close surveillance by a multidisciplinary team is mandatory due to increased risk of maternal and foetal complications.

Autologous Platelet-Released Growth Factor and Sexual Dysfunction Amendment: A Pilot Clinical Trial of Successful Improvement Sexual Dysfunction after Pelvic Irradiation

Sexual dysfunction (SDF) is a common sequel to cancer treatment which affects the quality of life in women treated with pelvic radiotherapy. The aim of this study was to evaluate the safety, symptom resolution and objective improvement the injection of autologous platelet released growth factor (APRGF) for treatment of SDF in cited patients. This prospective pilot study enrolled 10 cancer-free patients with SDF who underwent pelvic radiotherapy at least 5 years ago, randomly. Each patient was received 1-2 cc APRGF within four weeks and all patients were re-evaluated at eight weeks and six months. CD34 immuno histochemistry and Masson's trichrome staining were performed on vaginal biopsy section for angiogenesis and fibrosis assay respectively. Sexual satisfaction after the injection of APRFG was clinically difference and the entire patient had sexual satisfaction. In the patient's follow-up, none of them needs to repeat the treatment. Our results declared that APRGF injection was effective and symptoms were disappeared in the entire patients. Significant objective improvements in vaginal diameter (mean before injection, 6.5 cm vs 7.1 cm after injection) (p-value = 0.001) and vaginal flexibility (mean before treatment, 0.72 cm vs 1.85 cm after injection) (P-value = 0.026) were observed. Characteristics of discharge before the injection in 60% of patients were included dry vagina and 40% had mild discharge but after injection 40% of patients had moderate and also 60% had mild and sufficient discharge (P-value= 0.190). Overally, our patients reported better sexual function and showed better vaginal function indexes, after APRFG injection.

Inferior vena cava syndrome caused by retroperitoneal fibrosis after pelvic irradiation: A case report.

In this case report, we share our experience of a case with inferior vena cava (IVC) syndrome caused by secondary retroperitoneal fibrosis related to prior pelvic irradiation. A 60 year-old-female who has history of pelvic irradiation developed severe leg edema. Radiological examination revealed obstruction of IVC. Soon after recanalization of IVC with metallic stent placement, her symptom relieved.

Tetramodal therapy using balloon-occluded arterial infusion of anticancer agents, the Azuma regimen, for lymph node-involved bladder cancer.

Overall, >900 patients have been treated at Osaka Medical College (Takatsuki, Osaka, Japan) using the novel approach of balloon-occluded arterial infusion (BOAI) to deliver an extremely high concentration of the anticancer agents cisplatin (CDDP)/gemcitabine to the pelvis (referred to as the OMC-regimen), together with pelvic irradiation. In a previous study, overall survival (OS) rate was significantly higher in this treatment group compared with that in a control group receiving total cystectomy (79.6 vs. 49.6%, respectively, at 10 years). It was speculated that intensive treatment of the pelvic area may aid in preventing metastasis, and thus the present study focused on the effect of this therapy in patients with lymph node metastasis (LN+). A total of 102 patients with advanced LN+ bladder cancer received tetramodal therapy (termed the Azuma regimen), comprising radical transurethral resection of the bladder tumor, systemic chemotherapy, BOAI and pelvic irradiation. Patients who failed to achieve a complete response (CR) underwent secondary BOAI with an increased amount of CDDP and/or gemcitabine with/without hemodialysis. A CR was achieved in 57.8% (59/102) of patients in total, and in 78.8% (41/52) of patients with N1 and Tis-3 disease. Among the complete responders, 81.4% (48/59) of patients retained their bladders with no evidence of recurrence or metastasis within a mean follow-up period of 121 weeks. Stages N2-3 and T4 were determined as significant risk factors for treatment failure in addition to survival. Notably, the 10-year overall survival rates in N1, Tis-3, and N1 and Tis-3 were 67.6% (vs. 33.6% in N2-3; P=0.0003), 61.5% (vs. 37.9% in T4; P=0.0485) and 75.1% (vs. 35.5% in N2-3 or T4; P=0.0002), respectively. No patients suffered from grade IV toxicities. In conclusion, the Azuma regimen may be a feasible option for patients with LN+ disease. The use of intensive treatment in the pelvic area may serve an important role in outcome improvement, and the prevention of metastasis may be its mechanism.

Concurrent Chemoradiation Affects the Clinical Outcome of Small Bowel Complications Following Pelvic Irradiation: Prospective Observational Study from a Regional Cancer Center.

Background To appraise the spectrum of small bowel complications following pelvic irradiation and to assess the clinical outcome and factors associated with adverse clinical outcome in these patients. Methods This descriptive clinical study was done for three years in a tertiary care center in South India. Patients managed for post-irradiation small bowel complications, irrespective of the indication for radiotherapy, were studied. Patients with associated non-gastrointestinal radiation toxicity, radiation proctitis, and radiation colitis were excluded. The parameters assessed were the range of small bowel complications, a comparison of operative and non-operative management, morbidity and mortality, the severity of complications in relation to the dose of radiotherapy, and various factors influencing the clinical outcome. Results A total of 50 patients were studied. Stricture and perforation peritonitis were the most common presentation (n=25; 50%). A majority of the patients (n=37; 74%) presented after six months following radiotherapy. Post-operative mortality was 16% (n=5). Age, body mass index (BMI), previous surgery, operative intervention, primary or adjuvant radiotherapy, concurrent chemoradiotherapy (CCRT), and various radiation protocols were not associated with adverse clinical outcomes with respect to overall mortality, the requirement of surgery, and operative mortality. However patients who were operated and those who received CCRT had a significantly longer mean intensive care unit (ICU) stay (3.51 days vs. 0.68 days; p = 0.0001) as well as overall mean hospital stay (14.87 days vs. 5.58 days; p = 0.001) and an insignificant mortality rate (16% vs. 15%; p = 0.4085). Conclusion The present study observed that the patients who were operated and those who received CCRT had significantly longer hospitalization and relatively higher mortality. Considering the fact that many of the patients who develop post-irradiation complications may not report back to the same center, the incidence of small bowel complications could be higher in reality, which ascertains the necessity for more precision in the radiation technique and operative care in developing countries.

Prognostic impact of nodal relapse in definitive prostate-only irradiation.

BACKGROUND: Whole pelvic irradiation in prostate cancer patients might prevent metastatic spread of cancer cells through lymphatic drainages in patients eligible for definitive radiotherapy, but its use has declined in the last decades in favor of prostate-only irradiation (POI). The aim of our study is to assess the incidence of pelvic lymph nodal relapse and outcome in prostate cancer patients receiving POI. MATERIALS AND METHODS: Data from 207 consecutive patients were collected. Clinical and treatment variables were collected. Biochemical relapse-free survival (BRFS), pelvic nodal relapse-free survival (PNRFS), distant metastasis-free survival (DMFS), disease-specific survival (DSS) and overall survival (OS) were calculated; analysis of prognostic variables was performed. RESULTS: Five-year BRFS, PNRFS, DMFS, DSS and OS were, respectively, 90, 98, 96, 97 and 91%. On multivariate analysis, independent negative predictors of BRFS were Gleason score ≥ 7 (HR: 3.25) and PSA nadir ≥ 0.08 (HR: 4.86). Pelvic nodal relapse was not correlated to impaired outcome. CONCLUSIONS: Lymph nodal pelvic relapse occurs in 2% of patients at 5 years and does not correlate with impaired outcome, suggesting the lack of theoretical benefit of a prophylactic nodal irradiation. Tumor biology and response to treatment are the main determinants of outcome.

Management of radiation induced, bilateral Primary THA loosening with an aseptic Paprosky Type IIB acetabular defect and a contralateral septic Type IIIB acetabular defect: A case report and review of literature.

INTRODUCTION: Primary THA in an irradiated hip poses risk for early loosening and inadequate ingrowth.Adverse effects such as decreased vascularity and increased infection risk pose a threat. CASE PRESENTATION: Our patient was a case of post-irradiation (for cervical cancer) bilateral THA loosening causing aseptic acetabular loosening on one side and catastrophic septic loosening with a Paprosky type IIIB acetabular defect with pelvic discontinuity on the contralateral side. DISCUSSION: There have been various studies documenting deleterious effects of irradiation on osseointegration and provide a challenge for long-term implant stability in THA patients. CONCLUSION: A meticulous treatment protocol with contemporary implant technology and staged bilateral stepwise management can lead to satisfactory clinical outcomes.This case report highlights on such specific nuances and principles.

Nationwide multi-institutional retrospective analysis of high-dose-rate brachytherapy combined with external beam radiotherapy for localized prostate cancer: An Asian Prostate HDR-BT Consortium.

PURPOSE: To report outcomes and risk factors of high-dose-rate (HDR) brachytherapy combined with external beam radiotherapy with or without androgen deprivation therapy (ADT) in prostate cancer patients. MATERIALS AND METHODS: This multi-institutional retrospective analysis comprised 3424 patients with localized prostate cancer at 16 Asian hospitals. One-thirds (27.7%) of patients received only neoadjuvant ADT, whereas almost half (49.5%) of patients received both neoadjuvant and adjuvant ADT. Mean duration of neoadjuvant and adjuvant ADT were 8.6 months and 27.9 months, respectively. Biochemical failure was defined by Phoenix ASTRO consensus. Biochemical control rate, clinical disease-free survival (cDFS), cause-specific survival, and overall survival (OS) were calculated. RESULTS: Median followup was 66 months. Ten-year biochemical control, cDFS, cause-specific survival, and OS rate were 81.4%, 81.0%, 97.2%, and 85.6%, respectively. Receiving both neoadjuvant and adjuvant ADT was detected as a favorable factor for biochemical control, cDFS, and OS, but pelvic irradiation was detected as an adverse factor for cause-specific survival, and OS. Ten-year cumulative rates of late Grade ≥2 genitourinary and gastrointestinal toxicities were 26.8% and 4.1%, respectively; receiving both neoadjuvant and adjuvant ADT was detected as a favorable factor for preventing both toxicities. CONCLUSIONS: HDR combined with external beam radiotherapy was an effective and safe treatment for localized prostate cancer. Combination of long-term ADT was suggested to be necessary, even for HDR brachytherapy, and was useful in suppressing late toxicities. Meanwhile, pelvic irradiation was suggested to have an adverse effect on OS of our study population.

The effect of interferon gamma on conventional fractionated radiation-induced damage and fibrosis in the pelvic tissue of rabbits.

We aim to investigate the effect of interferon gamma (IFN-γ) on conventional fractionated radiation-induced damage and fibrosis in ureter and colorectal mucosa. Fifty-two rabbits were randomly divided into three groups comprising a conventional radiation group, an IFN-γ group, and a control group. X-rays were used to irradiate the pelvic tissues of the rabbits in the IFN-γ and conventional radiation groups. Five days after radiation exposure, the rabbits in the IFN-γ group were administered 250,000 U/kg IFN-γ intramuscularly once a week for 5 weeks. The rabbits in the conventional radiation group received 5.0 mL/kg saline. The rabbits were sacrificed at 4, 8, 12, and 16 weeks postradiation, and the rectal and ureteral tissues within the radiation areas were collected. The results showed that the morphology of rectal and ureteral tissues was changed by X-ray radiation. The degree of damage at 4, 8, and 12 weeks, but not at 16 weeks, postradiation was significantly different between the IFN-γ and conventional radiation groups. The expression of transforming growth factor beta 1 mRNA in the ureter and colorectal mucosa of the IFN-γ group was significantly lower than that in the conventional radiation group at 4, 8, 12, and 16 weeks postradiation, but it was still higher than that in the control group. There were significant differences in the expression of collagen III among the three groups. IFN-γ can inhibit the radiation-induced upregulation of transforming growth factor beta 1 mRNA and collagen III protein in the ureter and colorectal mucosa and attenuate radiation-induced damage and fibrosis.

The safety of robot-assisted cystectomy in patients with previous history of pelvic irradiation.

OBJECTIVE: To determine the safety of robot-assisted cystectomy (RAC) in patients with an irradiated pelvis, by comparing perioperative complication outcomes after RAC in patients with and without a history of pelvic irradiation. PATIENTS AND METHODS: In all, 252 consecutive patients underwent RAC at a tertiary referral centre from 2002 to 2013. Of all patients, 46 (18%) had a history of pelvic irradiation. Complications occurring at ≤30 days and ≤90 days of RAC were graded using the modified Clavien-Dindo classification system and additionally categorised by organ system. Baseline variables and outcomes of irradiated and non-irradiated patients were compared using descriptive statistics. Multivariable logistic regression models were generated to test the effect of previous pelvic irradiation on complications. RESULTS: The indications for RAC in patients with a history of pelvic irradiation were: bladder cancer (30 patients, 65%), prostate cancer (two, 4%), fistulae (five, 11%), and intractable symptoms from radiation cystitis (nine, 20%). In all, 25 (54%) irradiated and 112 (54%) non-irradiated patients had complications at ≤90 days (P > 0.9), of which 11 (24%) and 43 (21%) respectively had major complications (P = 0.7). One (2%) patient with and two (1%) patients without a history of irradiation died from surgical complications (P = 0.5). Infectious, bleeding, and gastrointestinal complications were the most common events in both groups. In multivariable analyses, a history of pelvic irradiation was not associated with a higher risk of complications. CONCLUSION: RAC performed by an experienced surgeon is a reasonable option in selected patients with a history of pelvic irradiation, as complication rates do not significantly differ compared with non-irradiated patients.

Robotic repair of a vesicovaginal fistula in an irradiated field using a dehydrated amniotic allograft as an interposition patch.

We report the case of a 66 year old female with a supratrigonal vesicovaginal fistula (VVF) that developed after undergoing radical hysterectomy, chemotherapy and pelvic radiation therapy for advanced cervical cancer. VVF repairs in an irradiated field are known to be complicated procedures with significant morbidity and a high rate of failure due to the effect of radiation. Amniotic membranes have been demonstrated to improve healing rates in difficult to heal wounds. To decrease morbidity a minimally invasive robotic procedure was performed and a dehydrated amniotic allograft patch was used to augment tissue healing. The VVF was repaired using the da Vinci Surgical System and the amniotic membrane was used as an interposition patch over the repair. There were no operative or postoperative complications and the patient was discharged home on postoperative day one. A cystogram performed 3 weeks postoperatively demonstrated a healed fistula. Follow-up at 5 months revealed no incontinence. This is the first reported case of a robotic VVF repair performed in an irradiated pelvis and the first use of an amniotic membrane allograft in the repair a VVF.

Could machine learning improve the prediction of pelvic nodal status of prostate cancer patients? Preliminary results of a pilot study.

We tested and compared performances of Roach formula, Partin tables and of three Machine Learning (ML) based algorithms based on decision trees in identifying N+ prostate cancer (PC). 1,555 cN0 and 50 cN+ PC were analyzed. Results were also verified on an independent population of 204 operated cN0 patients, with a known pN status (187 pN0, 17 pN1 patients). ML performed better, also when tested on the surgical population, with accuracy, specificity, and sensitivity ranging between 48-86%, 35-91%, and 17-79%, respectively. ML potentially allows better prediction of the nodal status of PC, potentially allowing a better tailoring of pelvic irradiation.