Hemostatic radiotherapy in clinically significant tumor-related bleeding: excellent palliative results in a retrospective analysis of 77 patients.

BACKGROUND: Significant bleeding of tumor sites is a dreaded complication in oncological diseases and often results in clinical emergencies. Besides basic local and interventional procedures, an urgent radiotherapeutic approach can either achieve a bleeding reduction or a bleeding stop in a vast majority of patients. In spite of being used regularly in clinical practice, data reporting results to this therapy approach is still scarce. METHODS: We retrospectively analyzed 77 patients treated for significant tumor-related bleeding at our clinic between 2000 and 2021, evaluating treatment response rate, hemoglobin levels, hemoglobin transfusion necessity, administered radiotherapy dose and overall survival. RESULTS: Response rate in terms of bleeding stop was 88.3% (68/77) in all patients and 95.2% (60/63) in the subgroup, wherein radiotherapy (RT) was completed as intended. Hemoglobin transfusions decreased during treatment in a further subgroup analysis. Median overall survival (OS) was 3.3 months. Patients with primary tumors (PT) of the cervix (carcinoma of the cervix, CC) or endometrium (endometrioid carcinoma, EDC) and patients receiving the full intended RT dose showed statistically significant better OS in a multivariable cox regression model. Median administered dose was 39 Gy, treatment related acute toxicity was considerably low. CONCLUSIONS: Our data show an excellent response rate with a low toxicity profile when administering urgent radiotherapy for tumor related clinically significant bleeding complications. Nonetheless, treatment decisions should be highly individual due to the low median overall survival of this patient group.

Palliative Radiotherapy for Haemostasis in Malignancy: a Systematic Review.

AIMS: Palliative radiotherapy is commonly used to achieve haemostasis for malignancy-induced haemorrhages. Our study aimed to examine the efficacy of palliative radiotherapy in the control of haemorrhages caused by various types of malignancy. MATERIALS AND METHODS: A systematic review of the literature was conducted to determine the level of evidence for the use of palliative radiotherapy in achieving haemostasis. Searches of the Medline, Embase and Cochrane databases were completed for studies published between January 1947 and May 2017. Studies that reported either a qualitative or a quantitative effect of radiotherapy were selected for inclusion during the review process. RESULTS: In total, 836 abstracts were screened; 13 prospective and 45 retrospective studies met the criteria for inclusion in the review. Selected studies were sorted based on the underlying tumour type to provide readers the opportunity to compare dose and fractionation schedules. Significant variations in reporting of outcomes and low total patient numbers did not allow for a quantitative analysis to be carried out. A higher median dose and a hypofractionated schedule seem to provide numerically higher rates of control based on the available data. CONCLUSIONS: Palliative radiotherapy is useful in the management of bleeding related to advanced and incurable malignancies. Brachytherapy seems to be effective in haemostasis of certain malignancies, especially that of gynaecological origin. Treatment should be tailored to individual patient situations given the palliative goals of any such therapy. Further prospective studies could help to delineate optimal dose and fractionation schedules.

Effects of photobiomodulation therapy on the local experimental envenoming by Bothrops leucurus snake.

Bothrops leucurus is the major causative agent of snakebites in Brazil's Northeast. The systemic effects of its venom are effectively neutralized by antivenom therapy, preventing bitten patients' death. However, antivenom fails in neutralizing local effects that include intense pain, edema, bleeding, and myonecrosis. Such effects can lead to irreversible sequels, representing a clinically relevant issue for which there is no current effective treatment. Herein, the effects of photobiomodulation therapy (PBMT) were tested in the local actions induced by B. leucurus venom (BLV) in mice (n = 123 animals in 20 experimental groups). A continuous emission AlGaAs semiconductor diode laser was used in two wavelengths (660 or 780 nm). Mechanical nociceptive thresholds were assessed with the electronic von Frey apparatus. Local edema was determined by measuring the increase in paw thickness. Hemorrhage was quantified by digital measurement of the bleeding area. Myotoxicity was evaluated by serum creatine kinase (CK) activity and histopathological analysis. PBMT promoted anti-hypernociception in BLV-injected mice; irradiation with the 660 nm laser resulted in faster effect onset than the 780 nm laser. Both laser protocols reduced paw edema formation, whether irradiation was performed immediately or half an hour after venom injection. BLV-induced hemorrhage was not altered by PBMT. Laser irradiation delayed, but did not prevent myotoxicity caused by BLV, as shown by a late increase in CK activity and histopathological alterations. PBMT was effective in the control of some of the major local effects of BLV refractory to antivenom. It is a potential complementary therapy that could be used in bothropic envenoming, minimizing the morbidity of these snakebite accidents.

Haemostatic radiotherapy for bleeding cancers of the upper gastrointestinal tract.

Bleeding can cause significant morbidity in patients with upper gastrointestinal malignancies. Palliative radiotherapy can palliate bleeding effectively across numerous cancer sites such as the lung and rectum. The data available regarding the role in bleeding from upper gastrointestinal cancers are limited to a single meta-analysis, a phase 2 trial, eleven retrospective cohorts and two case reports, with the majority focusing on gastric cancer. From the data available radiotherapy appears to be a well-tolerated, effective haemostatic agent that should be considered in all patients with bleeding from an upper gastrointestinal malignancy. Questions remain regarding the radiobiology of haemostasis and the optimum fractionation schedule. There is no convincing evidence that protracted higher dose regimens provide additional benefit. Commonly used fractionation schedules use 1, 5 or 10 fractions. Short fractionation schedules have been used in patients with deteriorating performance status.

Radiotherapy in the control of bleeding from primary and secondary lung tumours.

This literature review clarifies the role of radiotherapy in the management of low-volume haemoptysis. Embase and Medline were interrogated, and PRISMA guidelines were then used to select relevant articles. Seventy-eight articles were considered relevant and manually reviewed. The evidence suggests that external beam radiotherapy is more effective than endobronchial brachytherapy at controlling low-volume haemoptysis. There is no evidence to recommend a combination of the two techniques. Different doses and fractionations appear equally effective, with a potential survival advantage of higher dose regimens for fitter patients. Palliative radiotherapy is effective at controlling low-volume haemoptysis. External beam radiotherapy is the first-line treatment, with endobronchial brachytherapy recommended following external beam radiotherapy failure. Choice of dose and fractionation should take into account the patient's performance status.

Haemostatic radiation therapy for a bleeding intraductal papillary neoplasm of the biliary tree.

Haemostatic radiation was effectively used as a novel rescue therapy in a 60-year-old man who presented with recurrent melaena refractory to all conventional medical and surgical measures. He needed multiple transfusions and was diagnosed to be bleeding from an intraductal papillary biliary neoplasm which was not amenable to surgical resection in view of the background liver disease. He received conventional radiation therapy (RT) of a dose of 3 Gy per fraction for 3 consecutive days after which he stabilised. After cessation of the RT, he did not require transfusion for the next 2 months. His quality of life improved and it gave us time to evaluate for other definitive measures.

[The Role of Palliative Radiotherapy in Bleeding from Locally Advanced Gastrointestinal Tumors]. / Role paliativní radioterapie pri krvácení lokálne pokrocilých nádoru gastrointestinálního traktu.

BACKGROUND: Patients with locally advanced gastrointestinal tumors present with typical symptoms including pain, obstructive problems with passage disorders and bleeding. The last of them negatively affects their quality of life and is potentially lethal. Palliative radiotherapy is used in hemostatic indication to control bleeding from locally advanced or recurrent inoperable gastrointestinal tumors for many years. PURPOSE: This review summarizes information and available literature about mechanisms, efficiency and toxicity of palliative radiotherapy used in hemostatic indication, separately for each part of the digestive system. Although most of the published studies are retrospective, all of them show fast, effective and technically safe control of bleeding with minimal risk of toxicity and show an improvement of quality of life. Hypofractionated radiotherapy, with a smaller number of high doses, seems to be the appropriate palliative fractionation schedule. The higher daily dose is associated with faster initiation of hemostatic effect, while few radiotherapy treatment sessions are comfortable for patients; both of them meet the basic principles of state-of-the-art palliative care. In addition to external beam radiotherapy, high dose rate brachytherapy represents another possibility in this indication, especially for locally advanced inoperable anal and rectal cancer. Brachytherapy is simple, practical and most importantly a one-time procedure with high local effect without significant toxicity. CONCLUSION: Radiotherapy is an important treatment possibility for palliative care of bleeding from locally advanced inoperable gastrointestinal cancers. Future prospective studies employing modern radiotherapeutic techniques and procedures are needed to provide consistent and clear evidence in order to weigh risks against benefits of palliative hemostatic radiotherapy in current daily clinical practice.Key words: locally advanced gastrointestinal tumors - bleeding - palliative radiotherapy The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 8. 5. 2017Accepted: 23. 7. 2017.

[A Case of Unresectable Advanced Gastric Cancer Treated with Palliative Radiation Therapy for Massive Bleeding].

The patient was a 77-year-old man. He was diagnosed with Stage IV gastric cancer with pancreatic invasion and pyloric stenosis. After gastrojejunostomy, S-1 monotherapy was started. Melena and fatigue appeared 2 months after chemotherapy, and Grade 3 anemia was confirmed. Palliative radiotherapy of 30 Gy in 10 Fr was administered to control bleeding from the lesion. The progression of anemia stopped and outpatient chemotherapy became possible. Palliative radiotherapy for persistent bleeding from unresectable advanced gastric cancer is considered an effective treatment option to control bleeding.

Effect of photobiomodulation on endothelial cell exposed to Bothrops jararaca venom.

Bleeding is a common feature in envenoming caused by Bothrops snake venom due to extensive damage to capillaries and venules, producing alterations in capillary endothelial cell morphology. It has been demonstrated, in vivo, that photobiomodulation (PBM) decreases hemorrhage after venom inoculation; however, the mechanism is unknown. Thus, the objective was to investigate the effects of PBM on a murine endothelial cell line (tEnd) exposed to Bothrops jararaca venom (BjV). Cells were exposed to BjV and irradiated once with either 660- or 780-nm wavelength laser light at energy densities of 4 and 5 J/cm(2), respectively, and irradiation time of 10 s. Cell integrity was analyzed by crystal violet and cell viability/mitochondrial metabolism by MTT assay. The release of lactic dehydrogenase (LDH) was quantified as a measure of cell damage. In addition, cytokine IL1-ß levels were measured in the supernatant. PBM at 660 and 780 nm wavelength was able to increase cellular viability and decrease the release of LDH and the loss of cellular integrity. In addition, the concentration of pro-inflammatory cytokine IL1-ß was reduced after PBM by both wavelengths. The data reported herein indicates that irradiation with red or near-infrared laser resulted in protection on endothelial cells after exposure to Bothrops venom and could be, at least in part, a reasonable explanation by the beneficial effects of PBM inhibiting the local effects induced by Bothrops venoms, in vivo.

Gynecologic bleeding revealing vaginal metastasis of renal cell carcinoma.

Vaginal metastases of renal cell carcinoma have been rarely described. We report a case of a 75-year old woman, who underwent radical right nephrectomy for a renal cell carcinoma. Tumour was classified pT3bN0M0 and grade III of Furhmann grading. One year later, scanner discovered mediastinal and lombo-aortic lymph nodes. She received 2 months of immunotherapy associated with bevacizumab, but stopped because of intolerance. She was readmitted in our institute for vaginal bleeding. Clinical investigations showed a vaginal mass and biopsy revealed a renal cell carcinoma metastasis. This case suggests that retrograde venous dissemination may be at the origin of vaginal metastasis of renal cell carcinoma and emphasized the preventive value of early ligature of renal vein.

Clinically significant bleeding in incurable cancer patients: effectiveness of hemostatic radiotherapy.

BACKGROUND: This study was performed to evaluate the outcome after hemostatic radiotherapy (RT) of significant bleeding in incurable cancer patients. METHODS: Patients treated by hemostatic RT between November 2006 and February 2010 were retrospectively analyzed. Bleeding was assessed according to the World Health Organization (WHO) scale (grade 0 = no bleeding, 1 = petechial bleeding, 2 = clinically significant bleeding, 3 = bleeding requiring transfusion, 4 = bleeding associated with fatality). The primary endpoint was bleeding at the end of RT. Key secondary endpoints included overall survival (OS) and acute toxicity. The bleeding score before and after RT were compared using the Wilcoxon signed rank test. Time to event endpoints were estimated using the Kaplan Meier method. RESULTS: Overall 62 patients were analyzed including 1 patient whose benign cause of bleeding was pseudomyxoma peritonei. Median age was 66 (range, 37-93) years. Before RT, bleeding was graded as 2 and 3 in 24 (39%) and 38 (61%) patients, respectively. A median dose of 20 (range, 5-45) Gy of hemostatic RT was applied to the bleeding site. At the end of RT, there was a statistically significant difference in bleeding (p < 0.001); it was graded as 0 ( n = 39), 1 ( n = 12), 2 ( n = 6), 3 ( n = 4) and 4 (n = 1). With a median follow-up of 19.3 (range, 0.3-19.3) months, the 6-month OS rate was 43%. Forty patients died (65%); 5 due to bleeding. No grade 3 or above acute toxicity was observed. CONCLUSIONS: Hemostatic RT seems to be a safe and effective treatment for clinically and statistically significantly reducing bleeding in incurable cancer patients.

[A case of squamous cell cancer of the breast in which effective hemostasis was obtained by preoperative emergency radiation].

A case was a 40-year-old woman. Her right breast was presented with massive bleeding ulcer and fixed with a pectoral muscle. Diagnosis of Stage IIIb breast cancer( T4b, N1, M0) showed a high inflammatory response and severe anemia. Palliative surgery was difficult because of hemostasis, and her general health also was in poor condition. The pathological diagnosis was squamous cell cancer. We underwent a total of 30 Gy radiation emergency hemostasisose. After radiation and chemotherapy, the lesion was undergone a radical surgery, and was reduced in size significantly. It was diagnosed as squamous cell cancer, which was more sensitive to general radiation so neoadjuvant chemoradiation therapy was effective.

Wyburn-Mason syndrome: a case report.

OBJECTIVE: Wyburn-Mason syndrome is a rare disease associated with multiple arteriovenous malformations of the brain, orbit, and face resulting from an insult occurring during embryonic development. CASE REPORT: We present the clinical and radiological features of a 47-year-old-man with Wyburn-Mason syndrome who suffered from recurrent bleeding episodes primarily at the nasal corner of the left orbit. After radiotherapy and several angioembolisations, surgical reduction with exenteration of the left orbit was performed and resulted in reduced bleeding. Two years later the patient presented with maxillary sinus empyema. Due to massive endonasal bleeding, endoscopy could not be performed and the maxillary empyema was treated via a transorbital approach. CONCLUSION: Although close observation represents the standard of care in Wyburn-Mason syndrome, patient-specific management decisions are required in the presence of symptoms or complications. In the presented case, surgical intervention proved to be successful.

Radiation therapy for intractable bleeding in extremity arteriovenous malformation: considerations on a clinical case.

Arteriovenous malformations are rare clinicopathological entities with varied distribution and a constellation of symptoms. In the extremities they are usually associated with dermatological manifestations, such as angiodermatitis with a potential risk of torrential haemorrhage. Surgical resection is a morbid procedure. Transcatheter embolization and sclerotherapy is an attractive alternative to surgical resection. However, proper case selection is a prerequisite and may not be possible in all the cases. The case reported here is a paradigm of a complex and extensive vascular malformation with torrential haemorrhage where a unique therapeutic approach of radiation therapy was used as an alternative to morbid surgery after embolization and sclerotherapy failure.

Brachytherapy for advanced prostate cancer bleeding.

Advanced prostate cancer patients frequently deal with intractable prostatic bleeding which is a difficult problem to manage. Intraurethral high-dose rate (HDR) brachytherapy may palliate this condition. Advanced prostate cancer patients with intractable prostatic bleeding were offered brachytherapy with Iridium-192 using a Micro-selectron HDR machine. During a 5-year period, analysis was performed in 23 patients with a median age and Gleason score of 78 years and 9, respectively. Following brachytherapy, haematuria resolved in 19 of the 23 patients and was recurrence free at 6 months. Intraurethral HDR brachytherapy is a potentially effective modality for treating haematuria in patients with advanced prostate cancer.

Acute progressive midbrain hemorrhage after topical ocular cyclopentolate administration.

Cyclopentolate is a synthetic anti-cholinergic agent widely used in ophthalmology clinics. It can cause cardiovascular side-effects such as hypertension, ventricular arrhythmias and tachycardias. A 55-year-old male lost his consciousness after topical cyclopentolate hydrocloride (1%) administration for routine fundoscopic examination in another center. An urgent cranial magnetic resonance imaging examination revealed a midbrain hemorrhage and he was transferred to our hospital. The Glasgow Coma Scale score was at 4 points at admission. The patient was transferred to the intensive care unit and mechanically ventilated. Despite vigorous medical treatment, spontaneous respiration and brainstem reflexes disappeared 12 h after his administration. A control cranial computerized tomography showed enlargement and opening of the hemorrhage into the ventricular system. The patient died on the 12th day of his administration. Systemic side-effects of topical ocular cyclopentolate administration and prevention methods were discussed with regard to the current literature.