• Nonadherent dressings can be applied to bleeding lesions of the skin.

• Packing can be utilized for bleeding involving the nose, vagina, and rectum.

• Various topical agents, such as absorbable gelatin or collagen, utilized to control surgical bleeding can be utilized for accessible skin or mucosal surfaces.

• Vaginal packing can be soaked with paraformaldehyde. Moh’s paste and Monsel’s solution can be applied topically to areas of vaginal bleeding [9].

• Radiation therapy has been demonstrated to decrease hemoptysis [10–20], hematuria [21–23], vaginal bleeding [24], and bleeding from the GI tract (melena, hematemesis, and hematochezia) (Table 9.1) [25].

• Radiation therapy to palliate bleeding can be effective within 24–48 hours of the delivery of the first dose. Patients must be hemodynamically stable to safely be transported to radiotherapy departments for treatment.

• Various fractionation schemes have been described in the palliative setting. These include short courses of 8–10 Gy in a single fraction, intermediate courses of 4–8 Gy in 3–5 fractions, or longer courses of 3 Gy in 10–15 fractions.

 No scheme has been determined to be better than any other in the palliation of hemorrhage. At least one randomized trial of radiation fractionation suggests fewer side effects with shorter courses of treatment [26].

 Some of these hypofractionated regimens have been used in patients that are medically frail with otherwise curable cancers. In these situations, the highest dose per fraction schemes may be less appropriate given that the longer life expectancy of these patients puts them at higher risk for the development of potential late complications of radiation therapy.

 For patients with advanced and metastatic cancers, shorter courses of radiation offer equal or better palliation with increased convenience and decreased cost [27].

• Delivery of additional radiation therapy may be difficult if the patient previously received radiation therapy to the same site. Re-irradiation can be considered if the benefits of retreatment outweigh the risks. Care must be taken to respect normal tissues constraints in most circumstances, especially of the spinal cord.

• Bronchoscopy, esophagogastroduodenoscopy (EGD), cystoscopy, and colonoscopy have been utilized to identify and treat bleeding tumors in the organs visualized through each procedure.

• Cautery, argon plasma coagulation (APC), deployment of clips, injection of epinephrine or other sclerosing agents, laser, and other adjunctive therapies have been described. Varying rates of success and rebleeding occur.

• Endoscopic interventions are most successful in the treatment of less advanced and nondiffusely bleeding tumors. The existing literature describing the utility of these procedures are not limited to patients with advanced cancer.

• Two small series describe the application of a hemostatic powder to a bleeding tumor. Hemostasis was reported in 100% of patients but rebleeding remains a problem [28,29].

• APC is a noncontact thermal cautery with a depth of penetration of 2–3 mm.

 Argon is a nonflammable gas that is ionized by a high-voltage spark.

 Immediate hemostasis has been reported to be 100% but rebleeding occurs in 30% of patients [30].

• Transcutaneous embolization of vessels has been described to embolize bleeding vessels in many organ sites and malignant processes. Various mechanical devices and materials are utilized to achieve vascular embolization [31].

 Mechanical devices, such as coils, are defined by the size of their core, diameter, and length.

 Various biodegradable or permanent sclerosing agents can be injected depending on the indication for embolization.

 Permanent agents, such as polyvinyl alcohol or microspheres, are used for embolization of malignant bleeding [32].

• Patients must be able to lie flat for the duration of the procedure.

• Limitations of vascular embolization include the ability to identify and catheterize the bleeding vessel and to selectively embolize the blood supply of the tumor and protect vessels supplying normal tissues.

 Arterial access is accomplished through one of the major arteries, e.g., the femoral, popliteal, brachial, and radial arteries.

 Care must be taken to ensure that preexisting coagulopathies are corrected and that the patient is hydrated as contrast agents are utilized to visualize the vasculature.

• Successful hemostasis occurs in 70–99% of patients [33].

• Rebleeding can occur early, usually due to incomplete embolization, or late, due to recanalization of the vessels.

• Complications include local site bruising or hematoma, bleeding, coil migration, vessel occlusion, and postembolization syndrome.

• Tumor necrosis induces pain, flu-like symptoms, nausea and vomiting which can last for several days [32,33].

• Various surgical procedures can provide relief of bleeding when the level of bleeding, the patient’s expected remaining life and lack of other good options warrant it.

• Surgical options range from ligation of vessels to resection of the tumor and/or bleeding organ.

• Laparoscopic procedures may result in less acute morbidity than open ones but may be associated with a higher cost.

• Additional considerations include the risks of anesthesia.

• Skin lesions are very visible manifestations of metastatic disease that can ooze, bleed, have a foul odor, or be painful.

• Nonadherent dressings can be applied to manage bleeding.

• Local therapies include surgical excision, radiation therapy, and other ablative therapies.

• For superficial lesions, laser or cryotherapy may be sufficient.

• Electrochemotherapy combines a cytotoxic agent with electrical impulses that increase the permeability of the cell membrane, which enhances uptake of the cytotoxic drug.

 Response rates of 77–87% have been reported with bleomycin. Local or general anesthesia is generally required to alleviate the painful muscle contractions caused by the electrical impulses [34].

• Intratumoral injection of interleukin-2 (IL-2) has been associated with response rates of 70–80%. It is delivered in doses of 3–18 MIU per session at 2–3 sessions per week. Isolated limb perfusion is usually reserved for melanoma and sarcoma [34].

• Palliative radiation can be very helpful in the management of pain and bleeding from skin metastases.

 Given that the goal of radiation is to palliate symptoms rather than completely eradicate the tumor, hypofractionated regimens such as 8–10 Gy in a single fraction or 20 Gy delivered in 5 fractions should be considered.

• Depending on the amount of hemoptysis and the wishes of the patient, it may be necessary to protect the airway by intubation.

• Single lumen tubes allow passage of a standard flexible bronchoscope, but do not permit reliable lung isolation.

• Rigid bronchoscopy is useful for large volume bleeding to airway control and rapid suctioning, but requires expertise and is challenging to perform outside the operating room.

 Temporary control of bleeding can be affected with balloon catheters via the scope.

 Blood clots can be suctioned and visualization of the airways can help determine the source of the bleeding.

 Various therapeutic interventions can be performed including balloon tamponade, iced saline lavage, Nd-YAG laser coagulation, electrocautery, or APC.

 Reported hemostasis ranges from 60% for Nd-YAG laser to 100% for APC [35].

• For lesions not amenable to bronchoscopic intervention, bronchial artery angiography with embolization may be appropriate.

 Angiographic signs of hemoptysis include tumor blush and active extravasation.

 Many studies of bronchial artery embolization are not limited to those with cancer, thus accurate response rates are difficult to determine.

 Care must be taken to visualize and avoid the spinal artery as spinal cord injury can result from bronchial artery embolization [36].

• Radiation therapy is very successful at palliating hemoptysis, with rates of hemostasis in 80–97% of patients [10,16].

 Various fractionation regimens have been employed ranging from 17 Gy in two weekly fractions of 8.5 Gy, 20 Gy in 5 fractions of 4 Gy and 30–39 Gy in 10–13 fractions of 3 Gy.

 No consistent significant differences in rates of palliation have been reported.

 Several studies, which were not powered to detect a survival benefit, and include otherwise curable patients, demonstrate conflicting results regarding survival.

– Both longer fraction courses of 30–39 Gy in 10–13 fractions of 3 Gy [14,15] and shorter course of 17 Gy in 2 fractions of 8.5 Gy [17,19] have been shown to result in improved survival.

– The increased convenience and decreased costs of the shorter courses and lack of data supporting longer courses of radiation favor their use [10,17,19].

– Radiation myelitis has been reported rarely in patients who survive for at least 9 months; [37] three-dimensional conformal radiation therapy techniques can be used to decrease the dose to the spinal cord and mitigate this small risk.

• Vaginal bleeding occurs commonly in advanced cervical and endometrial cancer and accounts for 6% of deaths from cervical cancer.

• Treatments should be tailored to the available resources and the wishes of the patient.

• Topical therapies include vaginal packing that can be soaked with paraformaldehyde or application of Moh’s paste or Monsel’s solution to areas of vaginal bleeding.

• If interventional radiology services are available, uterine or iliac artery embolization can be performed.

 As with embolization in other settings, mechanical devices, such as coils, or sclerosing agents help achieve embolization.

• When interventional radiology is not available, surgical ligation of vessels is a more invasive treatment option [9].

• When radiotherapy is available, palliative radiation therapy can be directed to the uterus and/or cervix.

 An early RTOG phase I/II investigated large (10 Gy) fraction radiation therapy for palliation of advanced pelvic malignancies, repeated at monthly intervals with misonidazole.

– Though there was approximately 40% complete or partial response rate seen, there was an unacceptably high level of gastrointestinal complications seen [38].

 Many other fractionation schemes are effective for the palliation of bleeding, including 3.7 Gy BID in 4 fractions, 20 Gy in 5 fractions, and 21 Gy in 3 fractions given over 3 weeks.

 Care must be taken when using large fraction sizes in frail patients with curable disease who may live long enough to be at risk for late complications of radiation therapy.

• Though palliative radiation therapy has been utilized to treat bleeding from various gastrointestinal tumors, there is relatively sparse data reporting outcomes.

• Hemostasis from locally advanced gastric cancer has been reported in 50–73% of patients treated with radiotherapy.

 A variety of palliative radiotherapy regimens have been employed [39].

 The wide reported range of hemostasis may stem in part from the varying definitions of success which include no further bleeding, to decreased transfusion requirements, to an increase in hemoglobin levels.

• In rectal cancer, a recent systematic review reported the combined results of 23 retrospective and four prospective series. Hemostasis was achieved in 81% of patients [40].

• Tumor invasion of the bladder often causes hematuria.

• Initial therapies may include bladder irrigation and discontinuation of any medications that may increase the bleeding risk, such as NSAIDs or anticoagulants.

• Transurethral resection of the bladder with coagulation may control the bleeding. Other surgical options include cystectomy with urinary diversion.

• Nonsurgical options include radiation therapy.

 Various palliative fractionation schemes ranging from 3 to 8 Gy per fraction have been utilized and report 50–92% hemostasis [41].

• Renal artery embolization [32] can palliate flank plan or hematuria caused by malignant kidney tumors.

• Embolization of branches of the anterior trunk of the iliac artery can provide hemostasis of bladder tumors [42].

• Intravesicular formalin instillation is no longer routinely used for the treatment of hematuria due to discomfort, the risk of renal failure, and requirement for general or spinal anesthesia [43].

• Intravesicular instillation of alum or prostaglandins have varying rates of hemostasis.

 Like formalin, it causes protein precipitation that occludes bleeding vessels.

 Bladder spasms can be induced that can generally be controlled with the use of antispasmodics [43].

 Prostaglandin treatment is generally reserved for the case of alum failure due to issues of cost, availability, and storage [42].

• Tranexamic acid has not been formally studied in advanced cancer.

 In trauma patients, it reduces mortality due to bleeding by approximately one-third.

 There have been minimal side effects associated with its administration.

 There is no dose response for its therapeutic effect, but there is an increase in neurologic complications with increasing doses of tranexamic acid.

 In elective surgery, metaanalyses have demonstrated a reduction in blood loss and transfusion requirements by approximately one-third [47,48].

 Current studies are evaluating its use in gastrointestinal bleeding.

 None of the studies to date have demonstrated an increased thrombotic risk with the use of tranexamic acid.

 Recommended dosing is 10 mg/kg per dose, with no benefit to doses above 1 g, administered intravenously every 6–8 hours [49].

• A thorough assessment of potential causative or exacerbating agents is a critical component of the assessment of patients who are bleeding. Full discourse on all of the medications that fall into this category are beyond the scope of this chapter.

• NSAIDs are often utilized in the care of patients with advanced malignancy to treat pain. These have definite antiplatelet and anticoagulant properties.

• Patients with advanced cancer are at increased risk of coagulopathies and are often anticoagulated with warfarin or enoxaparin.

• The risk of further bleeding must be weighed against the risks of additional deep venous or pulmonary thromboembolism.

• Patients with cancer who are anticoagulated suffer bleeding complications at a higher rate than those anticoagulated without malignancy [50].

• Chemotherapeutic agents and radiation therapy may add to the risk of bleeding by causing thrombocytopenia. These treatments can be held to let the bone marrow recover.