Delayed pharyngocutaneous fistula caused by molecular targeted therapy: a case report.

BACKGROUND: Molecular-targeted agents used as a treatment for cancer can cause some rare and serious adverse events such as, delayed wound healing. Depending on the anticancer drug used, temporary withdrawal may be recommended before and after surgery to avoid complications. Once a surgical incision has healed and closed completely, wounds rarely open because of the initiation of molecular targeted therapy several months to years after surgery. Here, we aimed to describe a rare complication of pharyngocutaneous fistula in two patients that was thought to be caused by molecular targeted therapy. CASE PRESENTATION: Case 1 involved a 64-year-old asian man who developed a delayed pharyngocutaneous fistula 3 months after total laryngectomy for laryngeal cancer. Ramucirumab, a vascular endothelial growth factor receptor inhibitor used for recurrent gastric cancer, was speculated to be involved. Case 2 involved a 71-year-old japanese man who developed a delayed pharyngocutaneous fistula 2 years and 1 month after total pharyngeal laryngectomy for pharyngeal cancer. It was speculated that imatinib, a platelet-derived growth factor receptor alpha inhibitor used for chronic myeloid leukemia, was involved. CONCLUSIONS: Although the incidence of late drug-induced anastomotic leakage is very low, when it occurs, it makes oral intake impossible for an extended period and interferes with the appropriate cancer treatment. In this report, we demonstrate the details of these two patients with such a rare complication, which may help accumulate essential data on this topic.

Vesicocutaneous fistula formation during treatment with sunitinib malate: Case report.

BACKGROUND: The oral multi-kinase inhibitor sunitinib malate improves the survival of patients with gastrointestinal stromal tumors (GIST) after the disease progresses or intolerance to imatinib mesylate develops. Urinary fistulae arising during treatment with sunitinib for GIST have not been described. CASE PRESENTATION: We describe a 62-year-old female patient diagnosed with unresectable GIST that involved the abdominal wall, urinary bladder wall, bowel, mesentery and peritoneum in the pelvic cavity. Intestinocutaneous fistulae developed on a surgical lesion after orally administered imatinib was supplemented by an arterial infusion of 5-flurouracil. Sunitinib was started after the patient developed resistance to imatinib. On day 4 of the fourth course of sunitinib, a widely dilated cutaneous fistula discharged large amounts of fluid accompanied by severe abdominal pain. Urinary communication was indicated based on the results of an intravenous injection of indigo carmine. Computed tomography findings suggested a small opening on the anterior urinary bladder wall and fistulous communication between the bladder and abdominal walls bridged by a subcutaneous cavity. The fistula closed and the amount of discharge decreased when sunitinib was discontinued. Therefore, sunitinib might have been associated with the development of the vesicocutaneous fistula in our patient. CONCLUSION: This is the first description of a vesicocutaneous fistula forming while under sunitinib treatment. Clinicians should be aware of the possible complication of vesicocutaneous fistula formation during treatment with molecular targeting agents in patients with extravesical invasion and peritoneal dissemination of GIST.

Vesicoenteric, vesicovaginal, vesicocutaneous fistula -an unusual complication with intravesical mitomycin.

Intravesical instillation of mitomycin C is a routine practice for treatment of superficial transitional cell carcinoma of bladder. Despite usual precautions serious side effects like fistulation can occur with diverse presentation as illustrated by this report. The pathology demonstrates a dense necrotic and massive inflammatory reaction in the peri vesical tissue following the extravasation of an intravesically administered chemotherapeutic agent. The severe inflammatory tissue response and the necrotic effect associated with the extravasated chemotherapeutic agent could potentially lead to local sepsis with a subsequent fistula formation.

"Spontaneous," delayed colon and rectal anastomotic complications associated with bevacizumab therapy.

Bevacizumab, a humanized monoclonal antibody used to treat recurrent and metastatic colorectal cancer, targets the vascular endothelial growth factor (VEGF) molecule. It is hypothesized that bevacizumab works by both depriving tumors of the neovascularity they require to grow, and by improving local delivery of chemotherapy through alterations of tumor vasculature permeability and Starling forces. Complications of bevacizumab treatment include bowel ischemia and perforation, but to date, these complications have only rarely been described as occurring at the site of presumably healed anastomoses following surgery. We report two cases of delayed, "spontaneous" low anterior colorectal anastomotic dehiscence and one right colon anastomotic colocutaneous fistula associated with bevacizumab therapy. After seeing three patients with complications arising from apparently healed low anterior colorectal or right colon anastomoses following initiation of bevacizumab therapy for treatment of metastatic colorectal cancer, we reviewed the experience of The Cancer Institute of New Jersey (CINJ) with use of bevacizumab in approximately 50 patients between April 2004 and December 2006. The three index cases had been treated surgically at CINJ but received chemotherapy elsewhere. None of the 50 patients receiving bevacizumab at CINJ who had previous colon or rectal anastomoses were identified as having this complication. The medical records of the three index cases were reviewed and analyzed. Additionally, a Medline search was performed to identify other reports documenting similar cases. Two reports of related cases were found in the literature. In two of our index cases who underwent low anterior anastomoses, the patients had received preoperative pelvic irradiation before their initial low anterior resection. In one of the two cases, the initial resection was complicated by an anastomotic leak requiring proximal diversion and then subsequent stoma takedown. In both cases, the dehiscence occurred more than 1 year after anastomosis, and became evident 1-10 months following initiation of bevacizumab treatment. In the third index case, a colocutaneous fistula arising from the anastomotic site presented 5 months following right colon resection and 3 months after starting adjuvant systemic therapy with FOLFOX (5-fluorouracil (5-FU), leucovorin, and oxaliplatin) and bevacizumab. Delayed colorectal anastomotic complications may occur in association with bevacizumab therapy. Contributing factors may include anastomotic leak at the time of the original operation and history of anastomotic irradiation. Clinicians treating patients who receive bevacizumab following colectomy for colorectal cancer should be aware of this possible life-threatening complication. These findings may also be relevant to the design of trials of the use of bevacizumab for the postoperative adjuvant treatment of patients with colorectal cancer.

Aneurysmal bone cysts in children: complications of fibrosing agent injection.

PURPOSE: To report complications of direct fibrosing agent injection in the treatment of aneurysmal bone cysts (ABCs) in children. MATERIALS AND METHODS: The authors retrospectively analyzed all cases of ABCs treated with direct fibrosing agent injection (Ethibloc; Ethnor Laboratories, Ethicon, Noderstedt, Germany) at Robert Debré Hospital since 1994. Histologic diagnosis was assigned by means of surgical biopsy findings prior to treatment. Treatment responses were categorized. Injection was administered with general anesthesia, computed tomographic guidance, and use of a 14- to 16-gauge needle. Contrast material was injected to determine presence of intracystic septa and verify absence of venous opacification. Amount of fibrosing agent injected corresponded to amount of contrast material necessary to fully opacify the cyst. Intraosseous needle track was obliterated with histoacryl injection. RESULTS: Fifteen patients were treated. Mean follow-up was 80 months; no patient was lost to follow-up. One patient experienced pulmonary embolus that necessitated a 7-day intensive care unit stay. Four patients experienced early aseptic fistulization after the first injection, which led to surgical débridement and curettage. Five patients had transient inflammatory reaction with mild 38 degrees C fever, which was controlled with analgesic and antiinflammatory drugs. Eleven patients did not require surgery, and results at latest follow-up were considered to indicate complete healing (type 1 results) in nine and incomplete healing (type 2 results) in two. For type 1 results: Six patients received one injection, two received two injections, and one received three injections. For type 2 results: one patient received one injection, and one received three injections. CONCLUSION: A high rate of major local and general complications was encountered with use of direct fibrosing agent injection; the technique has been abandoned for treatment of ABCs.

The split notochord syndrome with dorsal enteric fistula, meningomyelocele and imperforate anus.

A male infant was referred to our department because of lumbosacral meningomyelocele, dorsal enteric fistula and imperforate anus. The mother had received a parenteral drug containing estradiol benzoate and progesterone for inducing abortion in the first trimester. She also used an anal pomade containing triamcinolone and lidocaine-HCl during the pregnancy for hemorrhoids. Sigmoid end colostomy was performed after meningomyelocele repair. On abdominal exploration a wandering spleen was detected but no other anomalies. Two months later, an abdominoperineal pullthrough was performed, and the patient was discharged well after three weeks. Our case is the sixth that had split notochord syndrome associated with dorsal enteric fistula and imperforate anus. Additionally, penoscrotal transposition and wandering spleen were present in this case. To our knowledge, these associated anomalies have been extremely rare.