Pathological process has a crucial role in sentinel node biopsy for vulvar cancer.

OBJECTIVES: To report the interim findings of an audit of the outcomes of sentinel node (SN) biopsy performed as a replacement for groin node dissection in women with early stage vulvar cancer in routine clinical practice in Australia and New Zealand. METHODS: A prospective multi-center study in 8 participating centers. Eligible patients had squamous cell carcinomas clinically restricted to the vulva <4 cm in diameter. SN procedures and pathological assessment were to be performed in accordance with the methods published by the GROINSS-V collaboration [1]. RESULTS: 130 women with apparent early stage vulvar cancer were enrolled. Seventeen women subsequently did not meet the eligibility criteria and were excluded. SNs were identified in 111/113 of the remaining women. Twenty-two women had positive nodes. Sixteen of these women had at least 12 months follow up and 7 (44%) had recurrent disease. Eighty-nine women had only negative nodes. Seventy-four of these women had at least 12 months follow up and 6 (8%) had recurrent disease (including 2 [2.7%] with recurrence in the groin). On subsequent review of the two women with negative SNs who had groin recurrences, it was found that the recommended pathology protocol had not been followed. In both cases, SN metastases were identified following serial sectioning of the nodes. CONCLUSIONS: SN biopsy is feasible in routine clinical practice. However, undetected metastases in a removed SN may be associated with groin recurrence. To ensure patient safety, strict adherence to the pathology protocol is an essential component in the utilization of the sentinel lymph node technique in vulvar cancer.

Family history of cancer predicts endometrial cancer risk independently of Lynch Syndrome: Implications for genetic counselling.

OBJECTIVE: To determine endometrial cancer (EC) risk according to family cancer history, including assessment by degree of relatedness, type of and age at cancer diagnosis of relatives. METHODS: Self-reported family cancer history was available for 1353 EC patients and 628 controls. Logistic regression was used to quantify the association between EC and cancer diagnosis in ≥1 first or second degree relative, and to assess whether level of risk differed by degree of relationship and/or relative's age at diagnosis. Risk was also evaluated for family history of up to three cancers from known familial syndromes (Lynch, Cowden, hereditary breast and ovarian cancer) overall, by histological subtype and, for a subset of 678 patients, by EC tumor mismatch repair (MMR) gene expression. RESULTS: Report of EC in ≥1 first- or second-degree relative was associated with significantly increased risk of EC (P=3.8×10-7), independent of lifestyle risk factors. There was a trend in increasing EC risk with closer relatedness and younger age at EC diagnosis in relatives (PTrend=4.43×10-6), and with increasing numbers of Lynch cancers in relatives (PTrend≤0.0001). EC risk associated with family history did not differ by proband tumor MMR status, or histological subtype. Reported EC in first- or second-degree relatives remained associated with EC risk after conservative correction for potential misreported family history (OR 2.0; 95% CI, 1.24-3.37, P=0.004). CONCLUSION: The strongest predictor of EC risk was closer relatedness and younger EC diagnosis age in ≥1 relative. Associations remained significant irrespective of proband MMR status, and after excluding MMR pathogenic variant carriers, indicating that Lynch syndrome genes do not fully explain familial EC risk.

Circulating 25-hydroxyvitamin D and survival in women with ovarian cancer.

BACKGROUND: Vitamin D status might be associated with cancer survival. Survival after ovarian cancer is poor, but the association with vitamin D has rarely been examined. OBJECTIVE: We evaluated the association between serum 25-hydroxyvitamin D [25(OH)D], a marker of vitamin D status, and ovarian cancer survival. DESIGN: Participants were women with invasive ovarian cancer diagnosed between 2002 and 2005 who participated in the Australian Ovarian Cancer Study. Serum samples, collected at diagnosis (n = 670) or after completion of primary treatment and before recurrence (n = 336), were assayed for 25(OH)D. Sociodemographic, dietary, and lifestyle data came from questionnaires self-completed at recruitment, and clinical and survival data were from medical records, supplemented by linkage to the Australian National Death Index (October 2011). Cox proportional hazards regression was used to estimate HRs and 95% CIs for the association between circulating 25(OH)D and survival. RESULTS: Overall, 59% of the women died during follow-up, with 95% of deaths resulting from ovarian cancer. Circulating 25(OH)D concentrations (mean: 44 nmol/L) were significantly associated with age, state of residence, season of blood collection, and body mass index but not with tumor histology, stage or grade, or comorbidities. Higher 25(OH)D concentrations at diagnosis were significantly associated with longer survival (adjusted HR: 0.93; 95% CI: 0.88, 0.99 per 10 nmol/L), but there was no significant association with progression-free survival or for 25(OH)D measured after primary treatment. CONCLUSIONS: In our cohort, higher serum 25(OH)D concentrations at diagnosis were associated with longer survival among women with ovarian cancer. If confirmed in other studies, this suggests that vitamin D status at diagnosis may be an independent predictor of prognosis. Furthermore, if the association is found to be causal, improving vitamin D status may improve ovarian cancer survival rates.

Tumor mismatch repair immunohistochemistry and DNA MLH1 methylation testing of patients with endometrial cancer diagnosed at age younger than 60 years optimizes triage for population-level germline mismatch repair gene mutation testing.

PURPOSE: Clinicopathologic data from a population-based endometrial cancer cohort, unselected for age or family history, were analyzed to determine the optimal scheme for identification of patients with germline mismatch repair (MMR) gene mutations. PATIENTS AND METHODS: Endometrial cancers from 702 patients recruited into the Australian National Endometrial Cancer Study (ANECS) were tested for MMR protein expression using immunohistochemistry (IHC) and for MLH1 gene promoter methylation in MLH1-deficient cases. MMR mutation testing was performed on germline DNA of patients with MMR-protein deficient tumors. Prediction of germline mutation status was compared for combinations of tumor characteristics, age at diagnosis, and various clinical criteria (Amsterdam, Bethesda, Society of Gynecologic Oncology, ANECS). RESULTS: Tumor MMR-protein deficiency was detected in 170 (24%) of 702 cases. Germline testing of 158 MMR-deficient cases identified 22 truncating mutations (3% of all cases) and four unclassified variants. Tumor MLH1 methylation was detected in 99 (89%) of 111 cases demonstrating MLH1/PMS2 IHC loss; all were germline MLH1 mutation negative. A combination of MMR IHC plus MLH1 methylation testing in women younger than 60 years of age at diagnosis provided the highest positive predictive value for the identification of mutation carriers at 46% versus ≤ 41% for any other criteria considered. CONCLUSION: Population-level identification of patients with MMR mutation-positive endometrial cancer is optimized by stepwise testing for tumor MMR IHC loss in patients younger than 60 years, tumor MLH1 methylation in individuals with MLH1 IHC loss, and germline mutations in patients exhibiting loss of MSH6, MSH2, or PMS2 or loss of MLH1/PMS2 with absence of MLH1 methylation.

Pyomyositis after chemotherapy for endometrial cancer.

Pyomyositis is a rare complication of chemotherapy that is commonly seen in tropical climates and in patients with immunodeficiency states. Owing to its rarity and subacute presentation, its diagnosis is often delayed. It has been reported after intense chemotherapy for hematological cancers. We present a case of a 58-year-old woman with endometrial cancer who developed pyomyositis after the first cycle of carboplatin and paclitaxel with no prior predisposing factor except for cancer and premedication with corticosteroids. The patient improved once the diagnosis was established and managed with antibiotics and drainage of abscess. Full recovery was made with a protracted course of antibiotics.Early diagnosis of this entity with appropriate investigations and treatment prevents septicemia, which can often be life threatening.

Intraperitoneal chemotherapy for advanced epithelial ovarian malignancy: lessons learned.

BACKGROUND: The administration of intraperitoneal (IP) chemotherapy as first-line adjuvant treatment for women with optimally debulked advanced ovarian malignancy results in improved median and overall survival when compared with intravenous (IV) chemotherapy. However, the number of adverse events and toxicities are increased in patients treated with IP chemotherapy. In addition, the administration of IP chemotherapy is technically more challenging and the schedule is more demanding in terms of time and resources. AIMS: We report on our initial experience with the administration of IP chemotherapy at two gynaecological oncology units in Australia. METHODS: We collected retrospective data from a series of 23 women undergoing IP chemotherapy as adjuvant treatment for advanced ovarian cancer. In addition to standard (Common Terminology Criteria for Adverse Events v3.0, CTCAE) toxicity data, we collected technical data specific to the administration of IP chemotherapy. RESULTS: The average number of IP chemotherapy cycles received was 4.3. Forty-three per cent of patients received all six planned IP chemotherapy cycles. Thirty-nine per cent of patients discontinued their IP treatment. Of those, 22% were discontinued because of drug-related toxicities and the remaining 17% experienced a port complication or toxicity directly related to the route of administration. CONCLUSIONS: This study demonstrates the feasibility and practicality of and lessons learned from initial experiences with IP chemotherapy for ovarian cancer in Australia.

Refinements in the lotus petal flap repair of the vulvo-perineum.

BACKGROUND: Many reconstructive techniques have been used to repair the vulval, vaginal and perianal areas after excision. These range from grafts to various types of flap repair. The authors have modified a procedure called the lotus petal flap repair to provide a simpler, equally reliable, yet aesthetically enhanced technique for vulvo-perineal reconstruction. METHODS: Where primary closure was not possible the modified lotus petal flap was employed. The present flap design was based on the dense perforators supplying the perineum. The flap resembles the petals of a lotus flower as in the design of Yii and Niranjan. However, the present modification uses a thinned cutaneous flap without identification of the blood supply. The flap is sited over an area of dense perforators. Transposition with this thinner design allows for easy coverage of the defects. RESULTS: In the present series of eight patients and 12 flaps no cases of partial or complete flap failure were recorded. The only complications encountered in the series were one case of cellulitis after discharge from hospital, and a single case of urethral incontinence. CONCLUSIONS: The modified lotus flap repair is a reliable, simple, and aesthetically appealing alternative to those already available to the plastic surgeon for vulval repair.