Rectovaginal fistula during treatment with axitinib in a patient with renal cell carcinoma: a case report and review of the literature.

Renal cell carcinoma (RCC) is one of the most frequent malignancies of the adults. Its incidence has been increasing steadily by 2-4% each year. Up to 30% of patients present with metastases at diagnosis. It is a highly vascularized cancer because of the hypoxia-induced factor stabilization as a consequence of von Hippel-Lindau inactivation. Hypoxia-induced factor accumulation leads to transactivation of molecules involved in angiogenesis including vascular endothelial growth factor (VEGF) and platelet-derived growth factor. Sunitinib is an oral tyrosine kinase inhibitor that interacts with several angiogenesis receptors including platelet-derived growth factor receptors and VEGF receptors, and is approved for the first-line treatment in metastatic RCC. In terms of tolerability, patients treated with sunitinib showed a higher incidence of diarrhea, vomiting, hypertension, hand-foot syndrome, and neutropenia, a safety profile consistent with what had been observed in earlier phase studies. Axitnib is a potent and selective tyrosine kinase inhibitor of VEGF receptors 1, 2, and 3, and is approved in the second-line setting for patients with metastatic RCC. The tolerability profile of axitinib is favorable. The most commonly reported treatment-related adverse events are diarrhea, hypertension, fatigue, nausea, and dysphonia. Bowel toxicity, especially pneumatosis intestinalis and bowel perforation, is very uncommon. In particular, the incidence of intestinal perforation or fistulae is not well known for sunitinib or axitinib. Here, for the first time, we report the incidence of rectovaginal fistula in a 57-year-old White woman, with RCC, following treatment with sunitinib and axitinib.

[Spontaneous enterocutaneous and rectovaginal fistula: potential complications during therapy with anti-angiogenic drugs in renal cancer]. / Fistula rectovaginal y enterocutánea espontáneas: potenciales complicaciones durante la terapia con fármacos antiangiogénicos en cancer renal.

We present two cases of enterovaginal and enterocutaneous fistulae associated to treatment with pazopanib, which is an angiogenesis inhibitor for the treatment of metastatic renal cancer. The times from drug administration and the first appearance of a fistula were 6 and 16 months, respectively. None of the cases had a history of surgery or radiotherapy in the area where the complication was observed. Enterovaginal and enterocutaneous fistula represent less than 1% of all published complications caused by the use of antiangiogenic drugs. However, they must be taken into account as the reported mortality rate is close to 30%. Given its low incidence, we believe that sharing this data is a great way to help specialists who have to treat these patients to take the necessary precautions and decide on an adequate approach.

Bevacizumab plus microtubule targeting agents in heavily pre-treated ovarian cancer patients: a retrospective study.

OBJECTIVES. As vascular endothelial growth factor (VEGF) is expressed in ovarian cancer, we assessed the efficacy and safety of bevacizumab (a monoclonal antibody targeting VEGF) plus microtubule targeting agents for heavily pre-treated ovarian carcinoma patients. METHODS. We retrospectively reviewed 43 patients with recurrent epithelial ovarian carcinoma. Combined treatment included bevacizumab with paclitaxel in 32 (74%), docetaxel in 10 (23%), and vinorelbine in one (2.3%) patients, respectively. RESULTS. The median number of combined treatment was six cycles (range 1-29). On RECIST criteria, the objective response rate (ORR) was 40% (16% CR and 24% PR). Clinical benefit (complete response [CR] plus partial response [PR] and stable disease [SD] lasting ≥ 3 months) was 74% (CI95%: 46.7-77%). Median duration of treatment and overall survival were 3.9 months (range 0.2-14.4 months) and 20.1 months (CI95%: 13.8-20.1) respectively. No toxic death was reported. Grade 3-4 toxicity occurred in 30% of patients. Gastrointestinal perforations and fistula occurred in 3 (7%) and 6 (14%) patients, respectively. CONCLUSION. Although being active in terms of ORR, bevacizumab plus microtubule targeting agents - mainly taxanes - leads to a high rate of gastro-intestinal perforations and fistula in heavily pre-treated ovarian carcinoma patients.

Nicorandil-induced rectovaginal fistula.

An 82-year-old woman was admitted with feculent vaginal discharge and bleeding per vagina. Investigations revealed the presence of a rectovaginal fistula with no obvious etiology. Due to the surgical team's previous experience with nicorandil-induced ulceration, the drug was stopped. The rectovaginal fistula healed completely within 6 months.

Diverticular fistulation is associated with nicorandil usage.

INTRODUCTION: We observed that a number of patients presenting to our clinic with diverticular fistulation were taking nicorandil for angina. Recognised side effects of nicorandil include gastrointestinal and genital ulceration. The aim of our study was to determine whether nicorandil is an aetiological agent in diverticular fistulation. PATIENTS AND METHODS: We conducted a case-control study of patients with diverticular disease related enteric fistulae. Two patient groups were identified: a study group of patients with diverticular fistulae, and a control group with uncomplicated diverticular disease. The proportion of patients who had ever used nicorandil was compared between the two groups. RESULTS: A total of 153 case notes were analysed, 69 patients with fistulae and 84 control patients with uncomplicated diverticular disease. Female to male ratio in both groups was 2:1. The mean age was 71 years in the fistula group and 69 years in the control diverticular disease group (P = ns). Of those with colonic fistulae, 16% were taking nicorandil compared with 2% of the control group (odds ratio 7.8; 95% confidence interval 1.5-39.1; P = 0.008). There was no significant difference in rates of ischaemic heart disease between fistula and control groups. CONCLUSIONS: Nicorandil is associated with fistula formation in diverticular disease.

Spontaneous rectovaginal fistula during bevacizumab therapy for ovarian cancer: a case report.

Recent studies have demonstrated efficacy of bevacizumab for recurrent ovarian cancer, but few data on its use and gastrointestinal potential complications when administered as adjuvant chemotherapy after cytoreductive surgery are available. In this study, we report the first case of a rectovaginal fistula in this indication.

A prospective phase I-II trial of the cyclooxygenase-2 inhibitor celecoxib in patients with carcinoma of the cervix with biomarker assessment of the tumor microenvironment.

PURPOSE: To evaluate the toxicity and effectiveness of celecoxib in combination with definitive chemoradiotherapy (CRT) in women with locally advanced cervical cancer. METHODS AND MATERIALS: Thirty-one patients were accrued to a phase I-II trial of celecoxib 400 mg by mouth twice per day for 2 weeks before and during CRT. Tumor oxygenation (HP(5)) and interstitial fluid pressure (IFP) were measured before and 2 weeks after celecoxib administration alone. The median follow-up time was 2.7 years (range, 1.1-4.4 years). RESULTS: The most common acute G3/4 toxicities were hematologic (4/31, 12.9%) and gastrointestinal (5/31, 16.1%) largely attributed to chemotherapy. Late G3/4 toxicity was seen in 4 of 31 patients (13.7% actuarial risk at 2 yr), including fistulas in 3 patients (9.7%). Within the first year of follow-up, 25 of 31 patients (81%) achieved complete response (CR), of whom 20 remained in CR at last follow-up. After 2 weeks of celecoxib administration before CRT, the median IFP decreased slightly (median absolute, -4.6 mm Hg; p = 0.09; relative, -21%; p = 0.07), whereas HP(5) did not change significantly (absolute increase, 3.6%; p = 0.51; median relative increase, 11%; p = 0.27). No significant associations were seen between changes in HP(5) or IFP and response to treatment (p = 0.2, relative HP(5) change and p = 0.14, relative IFP change). CONCLUSIONS: Celecoxib in combination with definitive CRT is associated with acceptable acute toxicity, but higher than expected late complications. Celecoxib is associated with a modest reduction in the angiogenic biomarker IFP, but this does not correspond with tumor response.

[Surgical treatment of high anorectal and rectovaginal fistulas with the use of transanal endorectal advancement flaps]. / Chirurgische Therapie hoher anorectaler und rectovaginaler Fisteln mittels transanaler endorectaler Verschiebelappenplastik.

INTRODUCTION: Sphincterotomy can be avoided in the repair of high anorectal or rectovaginal fistulas by use of rectal advancement flaps. METHODS: Between 1986 and 1998, 22 patients with high anorectal and 15 patients with rectovaginal fistulas underwent fistulectomy without sphincterotomy and consecutive transanal rectal advancement flap repair. RESULTS: Primary healing was achieved in 81% (30/37 patients). There was no disturbance of continence though anal resting pressures decreased postoperatively. Recurrences occurred in 4 of 12 patients with Crohn's disease (2 anorectal, 2 rectovaginal) and in 1 patient with traumatic anorectal fistula. There were no recurrences in patients with cryptoglandular disease, while the operation failed in 2 patients with ergotamine-induced fistulas. CONCLUSIONS: This operative approach achieves a high primary healing rate with optimal functional outcome. Despite good results the indication should be set carefully in patients with Crohn's disease.

Ergotamine-induced complex rectovaginal fistula. Report of a case.

PURPOSE: This report stresses the importance of local complications caused by ergotamine abuse for the treatment of migraine headaches. METHODS: We present an unusual case of a complex rectovaginal fistula (RVF) caused by long-term ergotamine suppository abuse. RESULTS: A 39-year-old female was referred after she had undergone a transverse colostomy for temporary fecal diversion. Evaluation, including proctoscopy, gastrograffin enema, vaginogram, and pelvic computerized tomography revealed a RVF 6 cm proximal to the dentate line with distal rectal stricture. Surgical intervention included take down of the transverse colostomy with reanastomosis, proctectomy with excision of the fistula, creation of a colonic "J-pouch" with a coloanal anastomosis, and construction of a temporary loop ileostomy. The patient had an uneventful recovery, and her ileostomy was closed three months later. Pathologic examination of the surgical specimen failed to reveal any specific etiology of the RVF. However, her ten-year use of up to five ergotamine suppositories per day for migraine treatment is associated with a local ischemic effect. Pathophysiology of this rare cause of RVF and the surgical procedure are discussed. CONCLUSION: If evidence of any side effects of ergotamine suppositories is seen, early discontinuation of the drug should be considered to avoid complications such as RVF and/or strictures.

[Proctomucosectomy and colo-anal anastomosis in rectovaginal fistula following the use of suppositories containing ergotamine]. / Proktomucosektomie und coloanale Anastomose bei recto-vaginaler Fistel nach Anwendung ergotaminhaltiger Suppositorien.

We observed a rectovaginal fistula in 2 patients who had applied ergotamine suppositories against migraine headaches. The local effect of ergotamine on the rectum mucosa as well as the higher systemic concentration after rectal application seem to promote the development of a rectovaginal fistula. Different methods for the surgical fistula repair are discussed, depending on location and diameter of the fistula. In our patients we have carried out the abdomino-transanal resection of the rectum with sutured colo-anal anastomosis.

Medical and psychosocial aspects of the habilitation of thalidomide children.

The habilitation of 34 thalidomide children, begun in 1963 at the Rehabilitation Institute of Montreal, involved the contribution of many medical and paramedical disciplines. These individual contributions are described.Habilitation of congenitally deformed children must be initiated at an early age. The early prescription of a prosthesis is desirable. Their care involves a broad range of services that must be continued over many years. Parents require support before they can accept the misfortune that has befallen them and their deformed child. Despite the necessity of frequent hospitalizations, children should be reared in a home setting. From their experience, the authors conclude that children born with malformations, and their parents, should be thoroughly evaluated and followed up for many years; and recommend that governments should finance programs for the complete habilitation of all children born with congenital malformations. National registries for the compulsory recording of birth deformities should also be established.