Clinical practice guidelines on the screening and treatment of precancerous lesions for cervical cancer prevention in Saudi Arabia

BACKGROUND: Cervical cancer is the third most common gynecological malignancy in Saudi women with an estimated incidence rate of 1.9 cases per 100 000 women-years. More than 40% of cervical cancer cases are diagnosed at advanced stages due to lack of a routine screening program in Saudi Arabia. Thus, national guidelines for routine screening and treatment of precancerous cervical lesions are needed. METHODS: The Saudi Centre for Evidence-Based Healthcare invited a panel of local experts and partnered them with a team from McMaster University in Canada for methodological support, to develop national clinical practice guidelines on the screening and treatment of precancerous lesions for cervical cancer. After the panel identified key clinical questions, the McMaster University working group updated existing systematic reviews that had been used for the 2013 WHO Guidelines for screening and treatment of precancerous lesions for cervical cancer prevention. Recommendations were based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. Those recommendations took into account the available evidence, patient values and preferences, and resource use in the Saudi context. The panel provided recommendations on two major issues: screening for precancerous lesions (cervical intraepithelial neoplasia 2 & 3) and treatment of those lesions to prevent cervical cancer in women who tested positive after screening. CONCLUSIONS: The Saudi expert panel recommends using the HPV DNA test followed by colposcopy or cytology (Pap test) followed by colposcopy to screen for CIN2+ in women at risk of cervical cancer. The panel recommends cryotherapy or loop excision electrosurgery procedure (LEEP) over cold knife cone biopsy to treat women at risk of cervical cancer that tests positive for CIN2+. Universal screening for precancerous cervical dysplasia in women in Saudi Arabia is recommended using HPV testing and or cytology. Either cryotherapy or LEEP are preferred for treatment. CONCLUSIONS: National studies on cervical cancer screening modalities and treatment of precancerous cervical lesions, including HPV prevalence and its association with cervical cancer, are scarce.

The chemosensitizing effect of aqueous extract of sweet fennel on cisplatin treated HeLa cells.

BACKGROUND: Cisplatin is an important chemotherapeutic agent that is widely used in treatment of several malignancies, but its side effects on normal tissues and organs limit its use. The aim of this study was to evaluate the effect of aqueous extract of sweet fennel alone and in combination with cisplatin on human cervical cancer adenocarcinoma cell line (HeLa cells) searching for an effective, inexpensive therapy with minimal side effects. MATERIALS AND METHODS: HeLa cell line was used to study the cytotoxic effect of different concentrations of the aqueous extract of sweet fennel alone and in combination with 50 µg/ml cisplatin. Quantitative measure of drug interaction was quantified by the combination index. Gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) were used to analyze the sweet fennel decoction. MTT assay was used to examine cell viability percentage. Electron microscopy was applied to study the ultrastructure of the cells. RESULTS: The phenyl propanoids (23%) and phenols (12%) constituted the highest percentage of the aqueous extract. Increasing the concentration of sweet fennel from 50 µg/ml to 80 µg/ml, decreased the percentage of the cell viability of HeLa cells from 86.74% to 78.28%, respectively. Further decrease to 11.31% was demonstrated when 50 µg/ml of fennel was combined with 50 µg/ml cisplatin (additive effect). In addition to the signs of apoptosis observed in HeLa cells at 50 µg/ml of fennel, disruption of both nuclear and cytoplasmic membranes and presence of autophagolysosomes were noticed at a dose of 80 µg/ml. Combination of 50 µg/ml of cisplatin with 60, 70, and 80 µg/ml of sweet fennel revealed no significant difference in comparison to cisplatin alone. The combination with 50 µg/ml of sweet fennel revealed marked vacuolization of the cytoplasm, fragmentation of the nucleus, and complete disruption of nuclear membrane. CONCLUSIOn: Combination of cisplatin and the 50 µg/ml of the fennel could enhance cervical cancer growth inhibition. This combination could be effective in lowering the dose of single or repeated cumulative courses of cisplatin and hence decreases its hazardous side effects. In vivo studies and the evaluation of different combination doses of cisplatin and sweet fennel are recommended.

Management of aggressive histologic variants of endometrial carcinoma at the Tom Baker Cancer Centre between 1984 and 1994.

OBJECTIVE: The aim of this study was to determine the patient characteristics and outcome of patients with aggressive histologic variants (AV) of endometrial carcinoma, including uterine papillary serous carcinoma (UPSC), uterine clear cell carcinoma (UCCC), and mixed type. METHODS AND MATERIALS: All cases with AV histological type of endometrial carcinoma from January 1984 to December 1994 at the Tom Baker Cancer Centre were identified using the Alberta Cancer Registry. Relevant data from the charts of these patients were entered into a study database (Microsoft Excel) and analyzed for presentation, demography, treatment parameters, and outcome of treatment. All pathology was reviewed at the time of diagnosis. Statistical analysis was performed using the S-plus statistics computer program. Univariate and multivariate analyses were used to assess independent prognostic factors using the Cox proportional hazards model. RESULTS: A total of 103 patients with AV histological type were identified and analyzed; there were 61, 31, and 11 cases of UPSC, CCC, and mixed tumors, respectively. Sixty-three patients had Stage I, 11 had Stage II, 15 had Stage III, and 14 had Stage IV disease. The median age of patients was 67 years with a range of 36 to 86 years. Median follow-up was 60 months with a range of 36 to 156 months. The Cox proportional hazards model showed that lymphvascular space invasion and stage are the two independent prognostic factors affecting recurrence and survival. Forty six percent of all cases underwent surgery alone, 39% underwent treatment which included pelvic RT, and 17% underwent treatment which included chemotherapy. Pelvic recurrence was reduced significantly by radiotherapy in Stages I, II, and III (19% recurrence with no RT vs 7% recurrence with RT, P < 0.005). Chemotherapy improved overall survival, but made little difference in distant relapse rates. CONCLUSIONS: Stage Ia cases treated by surgery alone have a low risk of relapse and need not be offered adjuvant systemic therapy or pelvic radiation. Patients with Ib, Ic, II, and III have significantly lower pelvic failure rates if treated with pelvic radiation, but still have a high distant failure rate. Systemic therapy did not significantly improve distant relapse-free survival, but did extend overall survival. Stage IV patients usually died within 6 months with a few responding to systemic chemotherapy. These results suggest that there is a need for randomized trials for these patients.

Urolithiasis following formation of a continent urostomy: case report and review of the literature.

BACKGROUND: Formation of urinary stones in a continent urostomy (Indiana pouch) has been described as a late complication. Management of a patient with symptomatic multiple large stones and review of the literature are outlined. CASE REPORT: A 32-year-old woman presented with recurrent urinary tract infections and pyelonephritis 6 years after a total pelvic exenteration and creation of a continent urostomy for central recurrent carcinoma of the cervix after radical pelvic radiation. Multiple large stones were found to be the underlying etiology. Laparotomy, enterocystotomy, and removal of stones were performed without apparent complication. CONCLUSION: It is recommended that for single calculi or multiple small stones, electroshock wave lithotripsy or the percutaneous endoscopic approach be considered. For larger stones the use of laparotomy and enterocystostomy may be appropriate.