Radiotherapy For Pelvic Malignancies Research Articles

Management of Ureteral Stricture Disease After Radiation Therapy for Pelvic Malignancies: A Retrospective, Multi-Institutional Analysis

Objectives. A radiation-induced ureteral stricture (RIUS) is a challenging condition in urologic surgery, and the optimal surgical strategy is still a matter of debate. The aim of this study was to report post-operative outcomes of minimally invasive management of this condition from a multi-institutional cohort. Methods. Data of patients with diagnoses of RIUS at five referral robotic centers between January 2017 and December 2022 were retrospectively analyzed. Pre-, intra- and post-operative variables were collected. Recurrence was defined as the presence of flank pain combined with imaging findings for obstruction, and requiring further management. Univariate and multivariate logistic regression models were built to identify predictors of ureteral stricture recurrence. Results. Fifty-three patients with a diagnosis of an RIUS were included. Primary pelvic malignancy was mostly cervical (42%). In 72% of cases (mostly mid-proximal and short strictures) endourological management was attempted, which was deemed successful in 74% of patients at stent removal. The endourology success rate at a median follow-up of 12 months was 59%. Twenty-five patients (47%) were scheduled for robotic surgery. The reconstructive techniques most often performed were end-to-end anastomosis (44%) and ureteral reimplantation (52%). Three low-grade Clavien-Dindo post-operative complications (12%) occurred. Robotic surgery was successful in all cases except one. Considering the entire cohort, eight patients (15%) developed recurrence at a median follow-up of 5 months. All patients with recurrence were managed by permanent drainage. A statistically significant improvement in eGFR with respect to baseline was found at a median follow-up of 12 months (p = 0.007). The univariate logistic regression model identified ureteral stricture length >2 cm (OR 6.4, 95% C.I. 1.1–36.9, p = 0.04) and concomitant chemotherapy (OR 8.9, 95% C.I. 1.6–49.9, p = 0.01) as predictors of recurrence. At multivariate analysis concomitant chemotherapy was confirmed as an independent predictor of recurrence (OR 7.8, 95% C.I. 1.3–49.0, p = 0.03). Conclusions. Endourological management of an RIUS is reasonable for short and mid-proximal ureteral strictures, while robotics is required in almost all the remaining cases. Up to 15% of recurrence develops within 6 months. Re-do reconstructive surgery is rarely performed, even in referral centers.

A phase II study of oral chlorophyllin in haemorrhagic cystitis secondary to radiation therapy for pelvic malignancies (CLARITY).

48 Background: Chronic hemorrhagic cystitis (cHC) is seen in 5-15% of patients undergoing pelvic radiotherapy (pRT), often after a long cancer free survival. Hyperbaric oxygen therapy, the only modality with benefit proven in a randomized trial has limited utilization due of lack of availability, need of multiple sessions & cost. In this phase II study, we aimed to evaluate the efficacy & safety of Sodium-copper-chlorophyllin (CHL), a semi-synthetic mixture of sodium & copper salts of chlorophyll, in pRT-induced cHC. This study was based on our preclinical findings where CHL offered radioprotection & significantly reduced mortality & morbidity in mice exposed to lethal doses of whole-body radiation.A subsequent phase 1 trial in adult healthy volunteers established the recommended phase 2 dose. Methods: This was a prospective, single centre, single arm, interventional phase II clinical trial (NCT05348239). Adult patients with grades II-IV hematuria (CTCAE v5.0) following pRT received at least 3 months prior were eligible. All patients received oral CHL 750 mg OD for a maximum of 3 months. A Simon two-stage minimax design with a type 1 error of 2.5% & 80% power led to a sample size of 24 patients. The primary objective was the objective response rate (ORR), defined as the proportion of patients with complete response (CR) [resolution of gross hematuria] or partial response (PR) [decrease by at least one CTCAE grade of hematuria, but not complete resolution] from day 30-90 of starting the drug. At least seven objective responses were required to consider the drug for further development. Results: Thirty two patients were screened of whom 24 were enrolled, with median age of 63 (43-86) years. Indications for pRT included cervical (15), rectal (5) & prostate cancer (4). The median time from RT to cHC was 45 (4-216) months. At enrolment, 6 (25%), 17 (70.8%) & 1 (4.1%) patients had CTCAE grades 2, 3 & 4 hematuria respectively, majority being refractory. An objective response occurred in 20 patients (83.3%; 95% CI, 62-95%), (Stable=1, PR=10, & CR=10 as the best response).11 unrelated SAEs were observed in 8 patients. No treatment-related grade 4/5 adverse events were reported.No patient required angioembolisation, vesical artery ligation, or cystectomy.Proteomics studies indicated modulation of coagulation pathways and improved stem cell mediated regeneration and wound healing following chlorophyllin treatment. Conclusions: In this phase II study,oral CHL has shown objective & sustained response in cHC related grade II-IV hematuria following pRT. A randomized, placebo-controlled, phase III trial assessing the efficacy of oral CHL is now planned. Clinical trial information: NCT05348239 .

Previous external beam radiation therapy for pelvic malignancy increases complications of total hip arthroplasty.

External beam radiation therapy (EBRT) has known effects on bone health. No large database studies have looked at the effects of pelvic EBRT on total hip arthroplasty (THA) outcomes. The purpose of this study was to evaluate 90-day and long-term (>2 years) complication rates following THA in patients with a history of pelvic malignancy and EBRT. Patients were retrospectively identified using a national insurance claims database. Subjects who underwent THA for osteoarthritis or avascular necrosis were included if they had at least 2-year follow-up and were stratified into 3 cohorts: (1) prior pelvic malignancy diagnosis (prostate, cervical, uterine, ovarian, or rectal) and EBRT (Group A); (2) prior malignancy diagnosis but no EBRT (Group B); and (3) neither prior malignancy diagnosis nor EBRT (Group C). Univariate and multivariate analyses were conducted to evaluate for an association between prior EBRT and the incidence of 90-day and 2-year complication rates using chi-square, student t-tests, and logistic regression analyses where appropriate. 671,554 patients met the inclusion criteria. Group A had higher odds of all-cause revision, septic revision, and loosening with revision after 2 years when compared to Group C and Group B (p < 0.001). Group A subjects had higher rates of 90-day deep vein thrombosis, sepsis, and stroke (p < 0.001) than groups B and C. Prior EBRT for pelvic malignancy was associated with significantly increased rates of all-cause revision, septic revision, and loosening as well as 90-day medical complications.

Pelvic exenteration for late complications of radiation-induced pelvic injury: a preliminary study

Objective: To investigate the safety and efficacy of total pelvic exenteration (TPE) for treating late complications of radiation-induced pelvic injury. Methods: This was a descriptive case series study. The inclusion criteria were as follows: (1) confirmed radiation-induced pelvic injury after radiotherapy for pelvic malignancies; (2) late complications of radiation-induced pelvic injury, such as bleeding, perforation, fistula, and obstruction, involving multiple pelvic organs; (3) TPE recommended by a multidisciplinary team; (4) patient in good preoperative condition and considered fit enough to tolerate TPE; and (5) patient extremely willing to undergo the procedure and accept the associated risks. The exclusion criteria were as follows: (1) preoperative or intraoperative diagnosis of tumor recurrence or metastasis; (2) had only undergone diversion or bypass surgery after laparoscopic exploration; and (3) incomplete medical records. Clinical and follow-up data of patients who had undergone TPE for late complications of radiation-induced pelvic injury between March 2020 and September 2022 at the Sixth Affiliated Hospital of Sun Yat-sen University were analyzed. Perioperative recovery, postoperative complications, perioperative deaths, and quality of life 1 year postoperatively were recorded. Results: The study cohort comprised 14 women, nine of whom had recto-vagino-vesical fistulas, two vesicovaginal fistulas, one ileo-vesical fistula and rectal necrosis, one ileo-vesical and rectovaginal fistulas, and one rectal ulcer and bilateral ureteral stenosis. The mean duration of surgery was 592.1±167.6 minutes and the median blood loss 550 (100-6000) mL. Ten patients underwent intestinal reconstruction, and four the Hartmann procedure. Ten patients underwent urinary reconstruction using Bricker's procedure and 7 underwent pelvic floor reconstruction. The mean postoperative hospital stay was 23.6±14.9 days. Seven patients (7/14) had serious postoperative complications (Clavien-Dindo IIIa to IVb), including surgical site infections in eight, abdominopelvic abscesses in five, pulmonary infections in five, intestinal obstruction in four, and urinary leakage in two. Empty pelvis syndrome (EPS) was diagnosed in five patients, none of whom had undergone pelvic floor reconstruction. Five of the seven patients who had not undergone pelvic floor reconstruction developed EPS, compared with none of those who had undergone pelvic floor reconstruction. One patient with EPS underwent reoperation because of a pelvic abscess, pelvic hemorrhage, and intestinal obstruction. There were no perioperative deaths. During 18.9±10.1 months of follow-up, three patients died, two of renal failure, which was a preoperative comorbidity, and one of COVID-19. The remaining patients had gradual and significant relief of symptoms during follow-up. QLQ-C30 assessment of postoperative quality of life showed gradual improvement in all functional domains and general health at 1, 3, and 6 months postoperatively (all P<0.05). Conclusions: TPE is a feasible procedure for treating late complications of radiation-induced pelvic injury combined with complex pelvic fistulas. TPE is effective in alleviating symptoms and improving quality of life. However, the indications for this procedure should be strictly controlled and the surgery carried out only by experienced surgeons.

Diode Laser Therapy for Radiation-Induced Vascular Ectasia: Long-Term Results and Cost Analysis.

Collateral damage to surrounding healthy tissues has been reported in patients who undergo radiation therapy for pelvic malignancies. This study aimed to evaluate the safety, efficacy and cost efficiency of endoscopic diode laser therapy in patients diagnosed with chronic radiation proctitis (CRP). The data of 24 patients (median age 78, range 67-90 years) who presented rectal bleeding and were diagnosed with CRP after undergoing high-dose radiotherapy for prostatic cancer and underwent diode laser therapy were evaluated retrospectively. Non-contact fibers were used in the patients who underwent the procedure without sedation in an outpatient setting. The patients underwent a median of two sessions; overall, a mean of 1591 J of laser energy per session was used. No complications were noted during or after the procedures. Bleeding was completely resolved in 21/24 (88%) patients, and two patients showed improvement (96%). It was not necessary to suspend antiplatelet (six patients) or anticoagulant (four patients) therapy during the treatment course. The mean cost per session was EUR 473.4. The study findings demonstrated that endoscopic non-contact diode laser treatment in CRP patients is safe, effective and cost efficient. For this procedure, antiplatelet and anticoagulant therapy suspension, intraprocedural sedation and hospital admission are not required.

Laparoscopic Proximally Extended Colorectal Resection With Two-Stage Turnbull-Cutait Pull-Through Coloanal Anastomosis for Late Complications of Chronic Radiation Proctopathy.

BackgroundChronic radiation proctopathy (CRP) is a common complication after radiation therapy for pelvic malignancies. Compared with diversion surgery, resection surgery removes the damaged tissue completely to avoid the risks of recurrence and improve patients' outcome. Hence, resection surgery could be an optimal surgical approach when CRP is complicated by late complications. This study aimed to describe a modified surgical procedure of resection surgery and report its preliminary efficacy and safety in treating patients with CRP with late complications.MethodsWe retrospectively reviewed the patients who were diagnosed with CRP with late complications and underwent the modified surgical procedure of laparoscopic proximally extended colorectal resection with two-Stage Turnbull-Cutait pull-through coloanal anastomosis (PE-Bacon) between November 2019 and October 2020 in the Sixth Affiliated Hospital of Sun Yat-sen University.ResultsA total of 15 patients were performed the modified laparoscopic procedure of PE-Bacon, of which 1 patient underwent conversion from laparoscopic to open operation for intraoperative massive hemorrhage. Overall, the major (Clavien-Dindo III-V) postoperative complications occurred in 1 patient, anastomotic leakage was observed in 2 (13.3%) patients, and anastomotic stricture was observed in 4 (26.7%) patients. No patient had to be reoperated and died. Up to now, at the average follow-up of (524.40 ± 108.39) days, the preoperative symptoms of 93.3% (14/15) patients were relieved, with nine patients achieved complete remission, five patients only suffered minor symptoms. Because of the progression of radiation uropathy, one patient still had a vesicovaginal fistula as pre-operative complication. Colostomy reversal has been performed on 8 (53.3%) patients at an average postoperative duration of 299.5 ± 92.68 days, among whom only 2 patients suffered from major Low Anterior Resection Syndrome (LARS) until now.ConclusionsLaparoscopic PE-Bacon surgery is a safe and feasible surgical procedure for late complications of CRP with low morbidity and high symptom remission rate.

Peripheral Lymphocyte Counts and Lymphocyte-Related Inflammation Indicators During Radiotherapy for Pelvic Malignancies: Temporal Characterization and Dosimetric Predictors.

Purpose: To identify the dosimetric predictors of lymphocytopenia and retrospectively analyze the changing trend of peripheral lymphocyte counts and lymphocyte-related inflammatory indicators in patients with simple pelvic radiotherapy. Methods and Materials: We retrospectively reviewed the clinical data of 188 patients with pelvic malignancies undergoing pelvic radiotherapy. The absolute count of neutrophils, lymphocytes, monocytes, and platelets at each time point was collected, and lymphocyte-related inflammation indicators were obtained, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII). The total pelvic bone (TPB) and the body within the 5 Gy coverage were retrospectively delineated for each patient. Dose-volume histograms corresponding to the delivered volumetric arc therapy plan were used to assess the dose volumes received by the TPB and body. A paired-samples t-test or Wilcoxon signed-rank test for matched pairs was applied for pairwise comparisons. We also established a stepwise multiple linear regression model for the peripheral lymphocyte count (PLC) value at the end of radiotherapy. Results: The PLC and lymphocyte-related inflammatory indicators changed significantly after the start of radiotherapy and persisted for 3-6 months after radiotherapy. The nadirs of PLC occurred at RT-End, and the PLC was still significantly lower than the baseline value at RT-3 months and RT-6 months. NLR, PLR, and SII at RT-End are about 3.5 times the value at RT-Baseline, while LMR is one-fourth of the basal value. In a further multiple stepwise linear regression analysis, the basal PLC (β = 0.156, p ≤ .001), gender (β = 0.096, p = .005), and TPB-V5 (β = −0.016, p ≤ .001) turned out to be the predictor of the absolute value of lymphocytes at the end of radiotherapy. Conclusions: The impact of pelvic radiotherapy on PLC and lymphocyte-related inflammatory indicators is considerable and long-lasting. Minimizing pelvic bone radiation exposure dose (5 Gy) may help to avoid severe cases of lymphocytopenia.

Management of Urosymphyseal Fistula and Pelvic Osteomyelitis: A Comprehensive Institutional Experience and Improvements in Pain Control

BackgroundUrosymphyseal fistula (USF) is an uncommon but painful and devastating condition typically occurring after radiotherapy for pelvic malignancy, with a delayed diagnosis and a risk of opioid dependence. ObjectiveTo characterize our institutional experience and determine the impact of intervention for USF on pain control and opioid use. Design, setting, and participantsWe evaluated data for 33 adult patients diagnosed with USF and managed at a quaternary institution between 2009 and 2021. Outcome measurements and statistical analysisWe assessed chronic opioid use, pain scores, prior therapy for pelvic malignancy, prior endoscopic procedures, microbiology and histology congruence, and postoperative complications. For comparative analyses we used a χ2 test or Fisher’s exact test for categorical variables and a Wilcoxon signed-rank test for continuous variables. Results and limitationsNearly 94% of the patients had received prior pelvic radiotherapy and >80% occurred in 2016–2021 but were not diagnosed until a median of 10 mo (interquartile range [IQR] 3.5–19.5) following endoscopic procedure(s). Osteomyelitis was suspected in 78.8% of imaging reports and nearly 70% had a positive preoperative urine culture. Over 90% of patients underwent cystectomy, pubic bone debridement or resection, and a soft-tissue pedicle flap. Preoperative urine cultures were concordant with 60% of intraoperative tissue/bone cultures. Histologic osteomyelitis was identified in 85% and concordant with 80% of preoperative imaging. Clavien-Dindo grade ≥3 complications occurred in 15.6%. The median pain score decreased from 4 (IQR 0–8) preoperatively to 0 (IQR 0) postoperatively (p < 0.001). Chronic opioid use decreased from 39.4% to 21.2% (p = 0.02). ConclusionsPelvic osteomyelitis may complicate USF and commonly manifests with severe, persistent pain. USF incidence may be increasing or at least increasingly recognized, but diagnosis is delayed. Definitive management results in significant improvements in pain perception and a decrease in chronic opioid use. Patient summaryWe examined features of urinary fistulas, which are abnormal openings or connections between part of the urinary tract and another structure. Patients with a urinary fistula involving the pelvic bones can present with severe pain, but diagnosis of the condition is often delayed. Removal of some pelvic bone with bladder removal or repair can result in a decrease in long-term pain and in the use of opioid drugs for pain relief.

AUTHOR REPLY

We appreciate the insightful comments regarding our publication. The successful treatment of this actinic complication significantly impacts the quality of life of patients treated with radiotherapy for pelvic malignancies (especially prostate cancer) and is an area of great interest for both urologists and radiation oncologists.

PDGFC signaling is a potential therapeutic target for radiation proctopathy.

e24105 Background: Radiation proctopathy(RP), with acute or chronic rectal dysbiosis, arises as one of the most crucial complications of radiation therapy for pelvic malignancies. Common symptoms of RP patients include rectal breeding, incontinence and so on. However, its efficacy is disappointing due to lack of specific therapeutic drugs. Moreover, limitied scientific studies have been carried out to elucidate the mechanism of RP progression. Herein, we aim to study the underlying mechanism of RP with mouse model and clinical samples, and dig out its potential therapy. Methods: Firstly, chronic radiation proctopathy(CRP) mouse model is established by administering 25 Gy γ-irradiation in the pelvic region shielding the rest of bodies with lead blocks. Eight weeks later, the mice are harvested, and their colorectal tissues are used for RT-qPCR, western blot, immunostaining and transcriptome sequence analysis. Secondly, the outcomes of irradiated Pdgfc+/+ and Pdgfc−/− mice are compared and gene set enrichment analysis(GSEA) is used to further clarify the differences between these two groups. Lastly, crenolanib, a selective inhibitor of PDGFR, is subjected to mice before or after γ-irradiation to study its potential role in RP prevention and treatment. Results: In our RP mouse model, pdgfc and fibrosis markers are shown to highly express in the distal colorectal tissues after irradiation, Similarily, accumulation of PDGFC and fibrosis-related proteins is observed in RP patients’ tissues and serum. Besides, pdgfc appears in the list of cytokine and cytokine receptor interaction gene set which is the most enriched one in the radiation group. Furthermore, pdgfc knockout significantly alleviates radiation induced colorectal injuries in vivo, including mucosal lesions, submucosal thickening, and hyperplasia and edema of muscular layer. Moreover, GSEA reveals that pdgfc knockout may suppress RP progression through repression of pro-inflammatory cytokines and chemokines. Finally, crenolanib overcomes irradiation-induced injuries in the colorectal region of mice. Conclusions: PDGFC is an important regulator of RP progression, which may serve as a potentially therapeutic target for RP treatment.

Standardized treatment of chronic radiation-induced bowel injury

Radiation-induced bowel injury is a common complication of radiation therapy for pelvic malignancy. Given the huge number of patients diagnosed with pelvic malignancy, the number of patients diagnosed with radiation-induced bowel injury increased year by year, which put a great burden on the clinical diagnosis and treatment of radiation-induced bowel injury. In particular, chronic radiation-induced bowel injury, which is manifested in the process of prolonged, repeated and progressive aggravation, seriously affects the physical and mental health of patients and makes clinical diagnosis and treatment difficult. However, due to insufficient attention and understanding from doctors and patients, standardized diagnosis and treatment of radiation-induced bowel injury still have a long way to go. Radiation-induced bowel injury is self-limited but irreversible. During diagnosis, we should pay attention to overall evaluation of the stage of disease based on clinical symptoms, endoscopic examination, imaging examination, pathology and nutritional risk. The treatment methods include health education, drug therapy, enema therapy, formalin local treatment, endoscopic treatment and surgical treatment, etc. The treatment decision-making should be based on clinical symptoms, endoscopic or imaging findings to alleviate the clinical symptoms of patients as the primary goal and to improve the long-term quality of life of patients as the ultimate goal.

An evaluation of the effect of bortezomib on radiation-induced urinary bladder dysfunction.

The urinary bladder is one major organ at risk in radiotherapy of pelvic malignancies. The radiation response manifests in early and chronic changes in bladder function. These are based on inflammatory effects and changes in urothelial cell function and proliferation. This study evaluates the effect of bortezomib as an anti-proliferative and anti-inflammatory compound in an established mouse bladder model. The early radiation-induced bladder dysfunction in the mouse occurs in two phases during the first month after irradiation (phaseI: day0-15, phaseII: days16-30). Daily bortezomib injections (0.02 mg/ml, subcutaneously) were administered between days0-15 or 15-30 in separate groups. Single graded radiation doseswere administered in five dose groups. Cystometry was carried out before (individual control) and during the first month after irradiation. When bladder capacity was decreased by ≥50%, mice were considered as responders.Statistical analysis was performed by the SPSS software version24. Daily bortezomib injections between days0-15 resulted in asignificant decrease in responders for phaseI. There was no significant effect with daily bortezomib injections between days16-30. Two separate waves of acute radiation-induced urinary bladder dysfunction have distinct mechanisms that need further biological studies.

Dosimetric Comparison of Pelvic Bone Marrow Preservation between Volumetric-Modulated Arc Therapy and Intensity-Modulated Radiotherapy in Radical Radiotherapy of High-Risk Prostate Cancer

Background: Pelvic bone marrow (PBM) preservation is one of the factors that should be taken into consideration while choosing a technique for radiotherapy of pelvic malignancies. Aim: To dosimetrically compare between volumetric-modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) in PBM preservation in radical treatment of high-risk prostate cancer. Methods: In 26 patients with high-risk prostatic carcinoma, dual arc VMAT and 7 fields IMRT plans were generated. In every patient, two targets were defined, clinical target volume (CTV) including the prostate and seminal vesicles (CTV-PSV) and CTV including pelvic lymph nodes (CTV-LN). The organs at risk delineated were the rectum, urinary bladder, small intestine, bulb of the penis, femoral heads bilaterally and PBM. The dose prescribed to the CTV-PSV was 76 Gy in 38 fractions given over 7.5 weeks and the dose to CTV-LN was 54 Gy in 38 fractions given over 7.5 weeks. Planning target volume (PTV) was created from the CTV with a margin of 5 mm in all direction. For assessment of PBM dose, V10, V20, V30, V40, V50 and mean dose were calculated. The dose volume histogram of PTV and PBM for both techniques was compared. Results: The mean dose of PTV 54 Gy was achieved in both techniques adequately with better sparing of organs at risk with the VAMT technique. The mean dose for PBM in the VMAT technique was significantly less than that in the IMRT (21.7 Gy vs. 25.8 Gy, respectively; p < 0.001). The significant differences in PBM doses were in the range of 20 Gy to 40 Gy. Conclusion: In radical treatment of prostate cancer, VMAT technique can offer comparable conformality to IMRT with better PBM preservation. Awareness of PBM delineation and reduction of its doses using VMAT can help to decrease the hematological toxicity.

Evaluation of radiation cystitis treatment efficacy with glycosaminoglycan replenishment therapy

Background. Radiation cystitis is a severe late consequence of radiation therapy of pelvic malignancies. Destruction of glycosaminoglycan’s protective barrier (GAG-layer) plays key role in pathogenesis of radiation cystitis. Hence, GAG-replenishment therapy could be a promised method of treatment the radiation cystitis.The objective is to evaluate the effectiveness of glycosaminoglycan replacement therapy of chronic radiation cystitis using bladder instillation. Materials and methods. 23 female patients with radiation cystitis participated in the retrospective study. They have been randomized divided on two groups. Patients of the 1st group have been treated with intravesical administration of 0,08 % sodium hyaluronate alone, 2nd group – with intravesical sodium hyaluronate in combination with oral sodium hyaluronate and chondroitin sulfate.Results. Patients of both groups demonstrated less frequency and pain after treatment as well as increased bladder volume. Intravesical administration of glycosaminoglycans in combination with oral administration was more effective than intravesical therapy alone.Conclusions. GAG-replenishment therapy is a promised treatment options of radiation cystitis. Oral and intravesical GAG-replenishment therapy is more effective in comparison with only intravesical therapy.

Роль структурных изменений внеклеточного матрикса мочевого пузыря в возникновении побочных эффектов лучевой терапии разной степени тяжести

To investigate the role of structural changes of the urinary bladder extracellular matrix in the occurrence of different grades of adverse events after radiation therapy. The connective tissue matrix was studied using 126 images obtained from the histological sections of the bladder biopsy specimens of 12 patients classified according to the clinical presentation and the grades of late bladder toxicity according to RTOG/EORTC Late Radiation Morbidity Scoring Scheme. Control images of the normal bladder (n=23) were collected from the autopsy samples. We used nonlinear microscopy imaging method capturing the second harmonic generation (SHG) signal and two-photon excitation auto-fluorescence (TPEA). The findings of nonlinear microscopy of urinary bladder histological sections showed that the structural changes in the connective tissue differed depending on the grade of adverse events: grade II adverse events were associated with the preservation of the structure of collagen fibers and their compression, grade III adverse events caused pronounced disorganization of collagen fibers, blurring without a definite fiber direction. At the same time, in a normal bladder, the structure of collagen fibers was visualized; they had a spiral shape and in some areas were collected in bundles. Collagen fibers and bundles were loosely arranged and accompanied by elastic fibers. The findings suggest that the grade of urinary bladder radiation injury correlates with the data detected by nonlinear microscopy. The mosaic structure of radiation-induced alterations of the bladder tissue, even in the areas most affected by radiation (posterior bladder wall, bladder trigone, and bladder neck) indicates that patients with radiation-induced high-grade toxicity need comprehensive care designed to preserve the bladder functional reserves and capacity. The prevention of radiation-related adverse events before radiation therapy should be based on urologic care aimed to detect and treat chronic inflammatory diseases of the bladder and preserve its functional reserves. Another way to improve outcomes is to optimize the management of adverse events. The examination of bladder tissue specimens taken from different parts of the bladder carried out using nonlinear microscopy in the SHG and TPEA modes revealed that the degree of structural changes in the connective tissue matrix in the post-radiation period varies and correlates with the grades of the radiation bladder toxicity. The results of this study can be used to substantiate measures to prevent the onset of high-grade toxicity after radiation therapy of pelvic malignancies.

Positioning of port films for radiation: variability is present.

Pelvic radiation treatment demands precision and consistency in patient setup for efficacy of therapy and to limit radiation dosage to normal tissue. Despite the use of immobilization devices and positioning techniques, there is still concern for variation in daily setup. The purpose of this retrospective study was to determine the presence and degree of variation in sacral slope in 20 subjects receiving radiation therapy for pelvic malignancies. Each of the 20 subjects received between 20 and 25 fractions of external beam radiation treatment to the pelvis. The sacral slope was measured on each of the daily port films taken prior to treatment and compared to the sacral slope angle measured on the initial treatment planning simulation digitally reconstructed radiographic imaging. Compared to this initial imaging, the average sacral slope variation across all 20 subjects was 2.27° (± 1.43°), and the average variation among patients ranged from 1.22° to 5.09°. Variation in sacral slope across all 20 subjects from one treatment day to the next was 2.05° (± 1.47°), and ranged from 0.97° to 3.21°. This study demonstrates that despite the rigorous use of immobilization devices, there still exists day-to-day variation in sacral slope angle between treatment days and compared to initial baseline imaging off which the treatment plan is developed. There is an on-going study at our institution with an attempt to reduce this variation by offering exercises prior to radiation.

Acute radiation impacts contractility of guinea-pig bladder strips affecting mucosal-detrusor interactions.

Radiation-induced bladder toxicity is associated with radiation therapy for pelvic malignancies, arising from unavoidable irradiation of neighbouring normal bladder tissue. This study aimed to investigate the acute impact of ionizing radiation on the contractility of bladder strips and identify the radiation-sensitivity of the mucosa vs the detrusor. Guinea-pig bladder strips (intact or mucosa-free) received ex vivo sham or 20Gy irradiation and were studied with in vitro myography, electrical field stimulation and Ca2+-fluorescence imaging. Frequency-dependent, neurogenic contractions in intact strips were reduced by irradiation across the force-frequency graph. The radiation-difference persisted in atropine (1μM); subsequent addition of PPADs (100μM) blocked the radiation effect at higher stimulation frequencies and decreased the force-frequency plot. Conversely, neurogenic contractions in mucosa-free strips were radiation-insensitive. Radiation did not affect agonist-evoked contractions (1μM carbachol, 5mM ATP) in intact or mucosa-free strips. Interestingly, agonist-evoked contractions were larger in irradiated mucosa-free strips vs irradiated intact strips suggesting that radiation may have unmasked an inhibitory mucosal element. Spontaneous activity was larger in control intact vs mucosa-free preparations; this difference was absent in irradiated strips. Spontaneous Ca2+-transients in smooth muscle cells within tissue preparations were reduced by radiation. Radiation affected neurogenic and agonist-evoked bladder contractions and also reduced Ca2+-signalling events in smooth muscle cells when the mucosal layer was present. Radiation eliminated a positive modulatory effect on spontaneous activity by the mucosa layer. Overall, the findings suggest that radiation impairs contractility via mucosal regulatory mechanisms independent of the development of radiation cystitis.

10-year series studies of chronic radiation proctopathy from The Sixth Affiliated Hospital of Sun Yat-sen University

Chronic radiation proctopathy (CRP) is the delayed adverse effect after radiotherapy for pelvic malignancies. It is characterized as progressive fibrosis in pathology. The symptoms are usually unspecific which include rectal bleeding, perianal pain, tenesmus, stool frequencies and so on. The course of CRP can present from months to years after radiation. Severe complications can occur in the late stage and will greatly affect the quality of life. Currently, there is no standard guides for diagnosis and treatment of CRP. For advancing the knowledge and proposing new treatment modalities of CRP, this article summarizes our 10-year experience as follows: (1) Except the existence of vessel damage, interstitial fibrosis, mucous ulcer, edema and inflammatory cell infiltration in the radiation-injury area, the capillary count was obviously reduced in mucous substratum and angiostatin expression up-regulated remarkably in above area, resulting in the continuous development of compensatory capillary expansion and interstitial fibrosis in mucous layer. (2) Rectal ultrasound examination was used the first time to diagnose CRP. According to thickness change of rectal wall layer and increase of blood signal, severity of CRP activity was evaluated with good diagnostic value. (3) For slight-moderate rectal bleeding, moderate-heavy bleeding and heavy bleeding, application of retention enema with compound preparation based on mucoprotective agents, regional perfusion hemostasis with formaldehyde and proximal colostomy gained satisfactory efficacy. (4) Improved Parks operation should be recommended for CRP patients with advanced complications. (5) For rectal cancer patients receiving neoadjuvant chemoradiotherapy, "proximal extended excision" should be performed innovatively to decrease the risk of anastomotic complications (Tianhe Procedure).

Role of Angiogenesis in Chronic Radiation Proctitis: New Evidence Favoring Inhibition of Angiogenesis Ex Vivo.

Chronic radiation proctitis (CRP), a common complication after radiotherapy for pelvic malignancies, compromises patient quality of life. Vascular damage and aberrant angiogenesis in the mucosal layer are essential histological features, but changes to the submucosal layer are unclear. Thus, we evaluated the histological characteristics and distribution changes of key angiogenic factors in full-layered human CRP samples. Thirty paraffin-embedded CRP and twenty-nine non-CRP tissues were used to evaluate histopathological changes. Immunohistochemistry with anti-CD34 antibody was performed to calculate microvascular density (MVD). Frozen tissues from eight CRP patients and five non-CRP controls were collected and analyzed by antibody array, which contained sixty human angiogenesis-related factors. Quality controls with positive and negative controls were performed during antibody array analysis. Two differentially expressed factors were confirmed by ELISA. CRP lesions showed vasculopathy, fibrosis, mucosal ulceration, edema, and inflammatory cell infiltration. Human angiogenesis antibody array and ELISA confirmed the increased angiostatin in CRP lesions. Immunohistochemical staining showed dispersed distribution of angiostatin throughout the mucosal and submucosal layers in CRP lesions, while angiostatin accumulated within the vessel lumens in non-CRP tissues. MVD significantly decreased in the submucosal layer of CRP, suggesting a potential association with increased angiostatin. Angiostatin increased and had a distinct distribution in CRP lesions. Compensatory telangiectasia in the mucosa, vessel stenosis, and reduced MVD might attenuate blood flow in the submucosa and contribute to CRP progression. Restoration of vascular functionality by promoting angiogenesis in the submucosal layer may help alleviate CRP in clinical practice.

The Pharmacologic Management of Voiding Dysfunction, Stress Incontinence and the Overactive Bladder in Men and Women Who Have Had Prior Treatment for Pelvic Malignancies With Surgery or Radiation Therapy

Purpose of Review This review seeks to enlighten the reader on the pharmacologic management of stress urinary incontinence and overactive bladder after surgery or radiation therapy for pelvic malignancy.