Vascular endothelial growth factor (VEGF) targeting therapy for persistent, recurrent, or metastatic cervical cancer.

BACKGROUND: Cervical cancer ranks as the fourth leading cause of death from cancer in women. Historically, women with metastatic or recurrent cervical cancer have had limited treatment options. New anti-angiogenesis therapies, such as vascular endothelial growth factor (VEGF) targeting agents, offer an alternative strategy to conventional chemotherapy; they act by inhibiting the growth of new blood vessels, thereby restricting tumour growth by blocking the blood supply. OBJECTIVES: To assess the benefits and harms of VEGF targeting agents in the management of persistent, recurrent, or metastatic cervical cancer. SEARCH METHODS: We performed searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, online registers of clinical trials, and abstracts of scientific meetings up until 27 May 2020. SELECTION CRITERIA: We examined randomised controlled trials (RCTs) that evaluated the use of VEGF targeting agents alone or in combination with conventional chemotherapy or other VEGF targeting agents. DATA COLLECTION AND ANALYSIS: Three review authors independently screened the results of search strategies, extracted data, assessed risk of bias, and analysed data according to the standard methods expected by Cochrane. The certainty of evidence was assessed via the GRADE approach. MAIN RESULTS: A total of 1634 records were identified. From these, we identified four studies with a total of 808 participants for inclusion. We also identified two studies that were awaiting classification and nine ongoing studies. Bevacizumab plus chemotherapy versus chemotherapy Treatment with bevacizumab plus chemotherapy may result in lower risk of death compared to chemotherapy alone (hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.62 to 0.95; 1 study, 452 participants; low-certainty evidence). However, there are probably more specific adverse events when compared to chemotherapy alone, including gastrointestinal perforations or fistulae (risk ratio (RR) 18.00, 95% CI 2.42 to 133.67; 1 study, 440 participants; moderate-certainty evidence); serious thromboembolic events (RR 4.5, 95% CI 1.55 to 13.08; 1 study, 440 participants; moderate-certainty evidence); and hypertension (RR 13.75, 95% CI 5.07 to 37.29; 1 study, 440 participants; moderate-certainty evidence). There may also be a higher incidence of serious haemorrhage (RR 5.00, 95% CI 1.11 to 22.56; 1 study, 440 participants; low-certainty evidence). In addition, the incidence of serious adverse events is probably higher (RR 1.44, 95% CI 1.16 to 1.79; 1 study, 439 participants; moderate-certainty evidence). The incremental cost-effectiveness ratio was USD 295,164 per quality-adjusted life-year (1 study, 452 participants; low-certainty evidence). Cediranib plus chemotherapy versus chemotherapy Treatment with cediranib plus chemotherapy may or may not result in similar risk of death when compared to chemotherapy alone (HR 0.94, 95% CI 0.53 to 1.65; 1 study, 69 participants; low-certainty evidence). We found very uncertain results for the incidences of specific adverse events, including gastrointestinal perforations or fistulae (RR 3.27, 95% CI 0.14 to 77.57; 1 study, 67 participants; very low-certainty evidence); serious haemorrhage (RR 5.45, 95% CI 0.27 to 109.49; 1 study, 67 participants; very low-certainty evidence); serious thromboembolic events (RR 3.41, 95% CI 0.14 to 80.59; 1 study, 60 participants; very low-certainty evidence); and serious hypertension (RR 0.36, 95% CI 0.02 to 8.62; 1 study, 67 participants; very low-certainty evidence). In addition, there may or may not be a similar incidence of serious adverse events compared to chemotherapy alone (RR 1.15, 95% CI 0.75 to 1.78; 1 study, 67 participants; low-certainty evidence). Apatinib plus chemotherapy or chemotherapy/brachytherapy versus chemotherapy or chemotherapy/brachytherapy Treatment with apatinib plus chemotherapy or chemotherapy/brachytherapy may or may not result in similar risk of death compared to chemotherapy alone or chemotherapy/brachytherapy alone (HR 0.90, 95% CI 0.51 to 1.60; 1 study, 52 participants; low-certainty evidence). However, hypertension events may occur at a higher incidence as compared to chemotherapy alone or chemotherapy/brachytherapy alone (RR 5.14, 95% CI 1.28 to 20.73; 1 study, 52 participants; low-certainty evidence). Pazopanib plus lapatinib versus lapatinib Treatment with pazopanib plus lapatinib may result in higher risk of death compared to lapatinib alone (HR 2.71, 95% CI 1.16 to 6.31; 1 study, 117 participants; low-certainty evidence). We found very uncertain results for the incidences of specific adverse events, including gastrointestinal perforations or fistulae (RR 2.00, 95% CI 0.19 to 21.59; 1 study, 152 participants; very low-certainty evidence); haemorrhage (RR 2.00, 95% CI 0.72 to 5.58; 1 study, 152 participants; very low-certainty evidence); and thromboembolic events (RR 3.00, 95% CI 0.12 to 72.50; 1 study, 152 participants; very low-certainty evidence). In addition, the incidence of hypertension events is probably higher (RR 12.00, 95% CI 2.94 to 49.01; 1 study, 152 participants; moderate-certainty evidence). There may or may not be a similar incidence of serious adverse events as compared to lapatinib alone (RR 1.45, 95% CI 0.94 to 2.26; 1 study, 152 participants; low-certainty evidence). Pazopanib versus lapatinib Treatment with pazopanib may or may not result in similar risk of death as compared to lapatinib (HR 0.96, 95% CI 0.67 to 1.38; 1 study, 152 participants; low-certainty evidence). We found very uncertain results for the incidences of specific adverse events, including gastrointestinal perforations or fistulae (RR 1.03, 95% CI 0.07 to 16.12; 1 study, 150 participants; very low-certainty evidence); haemorrhage (RR 1.03, 95% CI 0.31 to 3.40; 1 study, 150 participants; very low-certainty evidence); and thromboembolic events (RR 3.08, 95% CI 0.13 to 74.42; 1 study, 150 participants; very low-certainty evidence). In addition, the incidence of hypertension events is probably higher (RR 11.81, 95% CI 2.89 to 48.33; 1 study, 150 participants; moderate-certainty evidence). The risk of serious adverse events may or may not be similar as compared to lapatinib (RR 1.31, 95% CI 0.83 to 2.07; 1 study, 150 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: We found low-certainty evidence in favour of the use of bevacizumab plus chemotherapy. However, bevacizumab probably increases specific adverse events (gastrointestinal perforations or fistulae, thromboembolic events, hypertension) and serious adverse events. We found low-certainty evidence that does not support the use of cediranib plus chemotherapy, apatinib plus chemotherapy, apatinib plus chemotherapy/brachytherapy, or pazopanib monotherapy. We found low-certainty evidence suggesting that pazopanib plus lapatinib worsens outcomes. The VEGF inhibitors apatinib and pazopanib may increase the probability of hypertension events.

Gastric mucormycosis complicated by a gastropleural fistula: A case report and review of the literature.

RATIONALE: Mucormycosis is a rare opportunistic fungal infection with poor prognosis. The incidence of mucormycosis has been increasing, and it is a threat to immunocompromised hosts. We present a case of gastric mucormycosis complicated by a gastropleural fistula during immunosuppressive treatment for adult-onset Still disease (AOSD). PATIENT CONCERNS: An 82-year-old woman diagnosed with AOSD who developed gastric ulcers during the administration of an immunosuppressive therapy with corticosteroids, cyclosporine, and tocilizumab complained of melena and epigastralgia. Esophagogastroduodenoscopy showed multiple ulcers covered with grayish or greenish exudates. DIAGNOSES: The patient diagnosed with mucormycosis based on culture and biopsy of the ulcers, which showed nonseptate hyphae branching at wide angles. Mucor indicus was identified using polymerase chain reaction. INTERVENTIONS AND OUTCOMES: Although liposomal amphotericin B was administered, gastric mucormycosis was found to be complicated by a gastropleural fistula. The patient died because of pneumonia due to cytomegalovirus infection, and autopsy revealed the presence of Mucorales around the fistula connecting the stomach and diaphragm. LESSONS: Gastric mucormycosis is refractory to treatment and fatal. Surgical resection, if possible, along with antifungal drugs can result in better outcomes.

Gastrocolic fistula in a child following corrosive acid ingestion.

Gastrocolic fistulas in children are most commonly seen after placement of a percutaneous endoscopic gastrostomy. We present a 14-year-old girl who developed a gastrocolic fistula following accidental corrosive acid ingestion. On evaluation of her symptoms, a barium swallow identified the gastrocolic fistula. It healed spontaneously in 3 months. This was both unexpected and remarkable. To the best of our knowledge this is the first case of a gastrocolic fistula occurring following corrosive ingestion.

Gastro-splenic fistula as a complication of chemotherapy for large B cell lymphoma.

AIM: Gastro-splenic fistula is a rare entity in which malignant tumors are the primary cause, followed by perforated peptic ulcers and Crohn's disease. CASE REPORT: A 66 years old patient undergoing chemotherapy for gastric large cells B lymphoma presented fever, fatigue and worsening of general conditions. A CT scan showed the presence of an abdominal abscess resulting from a pathological communication between stomach and spleen. RESULTS: En - bloc splenectomy and gastric wedge resection was performed; gastric wall was sutured with a linear stapler. Postoperative stay was uneventful; alimentation was restarted 5 days after the surgical procedure, and the patient was discharged 2 days later CONCLUSION: We have described an unusual case of gastric fistula complicating chemotherapy early diagnosed and successfully treated. KEY WORDS: Chemothera Gastrosplenic fistula, Lymphoma, Surgery.

Gastrosplenic fistula following chemotherapy for lymphoma.

Gastrosplenic fistula resulting from erosion of a primary splenic lymphoma is a very rare cause of massive upper gastrointestinal hemorrhage as compared to benign peptic ulcer disease, gastric Crohn's disease, gastric adenocarcinoma, and primary gastric and splenic lymphomas. This hemorrhage can be successfully managed by splenic artery embolization, followed by splenectomy and gastric resection. A 50-year-old patient developed a gastrosplenic fistula during a course of chemotherapy for differentiated histiocytic lymphoma. The fistula was demonstrated by CT scan with oral contrast. The fistula was followed endoscopically and noted to have closed spontaneously with confirmed closure at laparotomy. The clinical management of this complication is discussed, and the literature pertaining to this rare condition is reviewed.

Gastrocolic fistula secondary to nonsteroidal anti-inflammatory drugs abuse in a cirrhotic patient.

Gastrocolic fistula is rarely described in the literature. It has been associated with a variety of diseases and recently with benign gastric ulcers related to the use of nonsteroidal anti-inflammatory drugs (NSAIDs'). The present case represents the first report of gastrocolic fistula due to NSAIDs in a cirrhotic patient. This is in keeping with the established knowledge that cirrhotic patients constitute a high-risk group of patients when treated with NSAIDs'. Review of the literature shows that this condition warrants a complete diagnostic work-up to exclude more ominous underlined diseases.

Elective surgery for corrosive-induced gastric injury.

Gastric cicatrization is a well recognized late sequela of corrosive gastric injury, but the optimum timing and type of surgery for this complication are still unclear. Over a 7-year period (1988-1994) 34 patients underwent elective surgery for gastric lesions secondary to corrosive ingestion. A total of 18 (53%) patients had an associated esophageal stricture and presented with dysphagia, 15 (44%) patients had features of gastric outlet obstruction, 6 (18%) had diffuse gastric injury, and 28 (82%) had a segmental lesion. A tube jejunostomy was done in 23 (68%) patients to improve nutrition and resulted in a significant increase in weight and in the serum protein level after 8 weeks of tube feeding. Elective surgery was performed 3 to 24 months (average 7 months) after ingestion of the corrosive substance. Gastric resection was done in 20 (59%) patients and gastrojejunostomy (without vagotomy) in 11 (32%); at follow-up the latter group did not exhibit development of a stomal ulcer. In patients with an associated esophageal stricture, endoscopic dilatation was successful in 89% patients and simplified the surgical approach. In conclusion, the success of surgery for corrosive-induced gastric injury depends on selecting the right procedure and intervening at the appropriate time.

Gastrocolic fistula-secondary to aspirin abuse.

Gastrocolic fistula is a rare complication of benign gastric ulcer disease. It has been associated more commonly, in the past, with marginal ulceration following gastrojejunostomy for peptic ulcer disease. We will describe a classic case of gastrocolic fistula as a complication of acetylsalicylic acid abuse in a middle aged female with a remote history of aspirin induced ulcer. Her presentation was classic and required a surgical approach with excellent recovery. We will describe the clinical, radiographic, endoscopic and surgical aspects of this interesting and unusual disorder.

Gastrocolic fistulas: the increasing role of aspirin.

Eight patients had gastrocolic fistulas depicted on barium studies at the authors' hospital during a 10-year period between 1982 and 1992. Seven of those patients (88%) had benign disease, including aspirin-induced gastric ulcers of the greater curvature (n = 4), granulomatous colitis (n = 1), tuberculosis (n = 1), and a penetrating anastomotic ulcer after partial gastrectomy (n = 1). The remaining patient had a malignant gastrocolic fistula caused by carcinoma of the transverse colon. Two patients (25%) experienced classic symptoms of gastrocolic fistulas (ie, feculent vomiting or foul-smelling eructations), but the other six (75%) experienced abdominal pain or other nonspecific clinical findings. In the four patients who were taking aspirin, upper gastrointestinal examinations revealed giant penetrating ulcers of the greater curvature that communicated with the superior border of the transverse colon via a fistula. Three of these patients exhibited marked clinical improvement after conservative medical treatment and did not need surgery. This experience suggests that aspirin-induced gastric ulcers of the greater curvature have become a more common cause of gastrocolic fistulas than is carcinoma of the stomach or transverse colon.

Iatrogenic gastrocolic fistula associated with non-steroidal anti-inflammatory drug administration.

An unusual case is presented of a benign gastrocolic fistula occurring in a 70-year-old man treated with piroxicam for arthritis for a period of only two months. This report illustrates that significant upper gastrointestinal complications can occur, even with short-term treatment, with non-steroidal anti-inflammatory drugs (NSAIDs).