Immunohistochemical and molecular pattern of p53 in epithelial ovarian cancers negative for germline BRCA1/2 variants.

Epithelial ovarian cancers (EOC) associated with germline or somatic BRCA pathogenetic variants have a significantly higher rate of TP53aberrations. The majority of TP53 mutations are detectable by immunohistochemistry and several studies demonstrated that an abnormal p53 pattern characterized high-grade EOCs. An abnormal p53 immunohistochemical staining in fallopian tube (serous tubal intraepithelial carcinoma (STIC) and "p53 signature" is considered as a precancerous lesion of high-grade EOCs and it is often found in fallopian tube tissues of BRCA germline mutated patients suggesting that STIC is an early lesion and the TP53 mutation is an early driver event of BRCA mutated high-grade EOCs. No relevant data are present in literature about the involvement of p53 abnormal pattern in EOC carcinogenesis of patients negative for germline BRCA variants. We describe TP53 mutation results in relationship to the immunohistochemical pattern of p53 expression in a series of EOCs negative for BRCA1 and BRCA2 germline mutations. In addition, we also investigated STIC presence and "p53 signature" in fallopian tube sampling of these EOCs. Our results demonstrate that TP53 alterations are frequent and early events in sporadic EOCs including also low-grade carcinomas. Also in this series, STIC is associated with an abnormal p53 pattern in fallopian tubes of high-grade EOCs. In summary, TP53 aberrations are the most frequent and early molecular events in EOC carcinogenesis independently from BRCA mutation status.

Surgical and survival outcomes in older women with endometrial cancer treated by laparoscopy.

OBJECTIVE: The aim of this study was to evaluate the feasibility and safety of laparoscopic surgical management of apparently early-stage endometrial cancer in older women and to compare clinical outcomes between older and younger women. METHODS: Our prospective oncological database was retrospectively reviewed to identify all consecutive women who underwent surgery for endometrial cancer from 2002. Data available included information about demography, comorbidities, surgical outcomes, histology, adjuvant therapies, and follow-up. Women were divided in two groups according to age (older, >65 y, and younger, < or =65 y). Univariate and multivariate analyses were performed to identify factors that negatively impact disease-free and overall survival. RESULTS: A total of 48 (44.4%) older and 60 (55.6%) younger women were included. Groups were comparable in operative time, blood loss, need for blood transfusions, nodal count, and intraoperative and postoperative complications. Cancer in older women was more frequently upstaged than that in younger women (17 [35.4%] vs 8 [13.3%], respectively; P = 0.01). The 2- and 5-year disease-free survival rates were 82% versus 96% (P = 0.003) and 74% versus 93% (P = 0.0005) and the overall 2- and 5-year survival rates were 87% versus 98% (P = 0.006) and 83% versus 95% (P = 0.01) for older and younger women, respectively. Multivariate analysis showed that advanced surgical stage, unfavorable histology, high-grade tumors (grade 3), and deep myometrial invasion (>50%) are independent risk factors for recurrence. CONCLUSIONS: In the absence of absolute anesthesia contraindications, laparoscopy seems to be feasible and safe in older women with endometrial cancer. Comprehensive surgical staging should be offered, regardless of age, to avoid understaging and to optimize treatment strategies.

Incorporating laparoscopy in the practice of a gynecologic oncology service: actual impact beyond clinical trials data.

BACKGROUND: Feasibility and safety of laparoscopic management of gynecologic cancers have been established by numerous clinical trials. However, the degree to which such results are achievable outside the context of formal research programs and the actual extent of laparoscopy uptake since its introduction are unclear. Purpose of this study was to examine the impact upon operative and cancer outcomes of the incorporation of laparoscopy into the surgical practice of our gynecologic oncology service. METHODS: Data from 383 consecutive women undergoing surgery for the treatment of an apparently early-stage gynecologic cancer between 2000 and 2008 were analyzed. Integration of minimally access surgery for the treatment of invasive malignancies began with borderline ovarian tumors in 2001 and proceeded sequentially to include endometrial, ovarian, and cervical cancer patients. RESULTS: The annual proportion of laparoscopic cases has increased significantly over the study period from 7.7% in 2001 to 90.9% in 2008 (P < 0.0001 for trend). A temporal trend toward reduction in estimated blood loss was observed in both endometrial cancer and cervical cancer patients (P < 0.0001). There was a significant decrease in the percentage of patients requiring blood transfusions [18 (17.1%) during the period 2000-2002, 19 (13.6%) during 2003-2005, and 8 (5.8%) during 2006-2008; P = 0.005 for trend]. Length of hospital stay has decreased significantly over time for all disease sites (P < 0.0001 for endometrial and cervical cancer; P = 0.02 for ovarian cancer). No difference was found in median operative time, number of lymph nodes harvested, complication rates, 1- and 2-year disease-free survival, and overall survival when data of subsequent time periods were compared. CONCLUSIONS: Substantial utilization of laparoscopy in the existing practice of a gynecologic oncology service provided benefits to patients without detrimental effects on clinical outcomes. The relatively short follow-up time of laparoscopic cases disallows firm conclusions on long-term survival.

Microlaparoscopy: a further development of minimally invasive surgery for endometrial cancer staging -- initial experience.

OBJECTIVES: To present our initial experience with micro-laparoscopy in the surgical treatment of endometrial cancer and to compare its outcomes with those of conventional laparoscopic approach. METHODS: Consecutive patients undergoing surgical staging of endometrial cancer using exclusively 3-mm working ports and a 3- or 5-mm laparoscope at the umbilicus (microlaparoscopy group; N=23) were compared with historical controls selected from consecutive women who have had staging with conventional laparoscopy (N=80). RESULTS: No difference was found in demographics and preoperative variables between the two groups. Conversion from microlaparoscopy to a conventional laparoscopic technique occurred in two cases (9.7%), while there was no conversion to open surgical staging in either group. There were no significant differences between the microlaparoscopy group and the control group with regard to estimated blood loss [100 (10-400) vs. 100 (10-400), P=0.09], number of pelvic lymph nodes (19.2+/-7.4 vs. 18. 6+/-7.2, P=0.79), and complication rate (intraoperative: 0% vs. 2.5%, P=1.0; postoperative: 8.7% vs. 13.7%, P=0.73). Operative time was similar between groups when analysis was restricted to the last 20 conventional procedures performed period prior to beginning of the microlaparoscopy trial [155 (110-300) vs. 160 (115-295), P=0.17]. The median length of hospital stay was 2 (1-10) days for women undergoing microlaparoscopic procedures compared to 3 (1-15) days for those undergoing conventional laparoscopy (P=0.001). CONCLUSIONS: These preliminary results suggest that microlaparoscopy is a safe and adequate surgical option for endometrial cancer staging, with the potential to further decrease invasiveness of the conventional laparoscopic approach.

Carcinosarcoma of the uterine cervix: case report and discussion.

BACKGROUND: Cervical carcinosarcomas are rare neoplasms; optimal treatment is unclear. CASE 1: A 42-year-old woman underwent abdominal hysterectomy because of bleeding, anaemia and uterine fibromatosis. Histology showed a homologous carcinosarcoma of the cervix. Laparoscopic re-staging (pelvic lymphadenectomy, bilateral salpingo-oophorectomy) was negative for neoplasia. Adjuvant chemotherapy with ifosfamide and cisplatin was performed. At 48 months of follow-up, the patient is NED. CASE 2: A 74-year-old woman reporting vaginal bleeding, with carcinosarcoma on the cervical biopsy, underwent radical hysterectomy, bilateral salpingo-oophorectomy, pelvic and paraortic lymphadenectomy. Histology confirmed a homologous carcinosarcoma of the cervix, stage IIb. Whole-pelvis irradiation and brachytherapy were carried out. Nine months later, the patient developed systemic recurrence and died of disease. Aggressive primary therapy can result in cure of early-stage cervical carcinosarcomas. Extracervical disease is associated with a poor prognosis.

A comparison of urinary complications following total laparoscopic radical hysterectomy and laparoscopic pelvic lymphadenectomy to open abdominal surgery.

OBJECTIVE: The objective of this study was to compare total laparoscopic radical hysterectomy (TLRH) and laparoscopic pelvic lymphadenectomy (LPS) to total abdominal radical hysterectomy (TARH) and pelvic lymphadenectomy (LPT) in terms of urinary tract lesions and postoperative urinary retention. METHODS: Starting in 2004, we treated all early stage cervical cancer patients with TLRH and LPS. The control group for this analysis was a historical cohort of patients treated with TARH+LPT. Within the TLRH+LPS group, we assessed whether the width of parametrial tissue removed was a risk factor for urinary tract injuries or postoperative urinary retention. RESULTS: Fifty women were included in the TLRH+LPS group and forty-eight were included in the TARH+LPT group. There were no conversions from laparoscopy to laparotomy. There was no statistically significant difference in intraoperative urinary complications between the groups. Four (8%) intraoperative urinary tract injuries in the LPS (3 cystotomies and 1 ureteral lesions all repaired laparoscopically) and 2 (4.2%) in the LPT group (2 cystotomies) occurred (p=0.68). Similarly, there was no statistically significant difference in postoperative urinary complications between groups. Urinary postoperative complications were: 1 (2%) ureterovaginal and 1 vesicovaginal fistulas, 1 delayed ureteric fistula in LPS group vs. 0 in LPT group (p=0.24). Urinary retention was complained by 7 (14%) and 7 (14.6%) patients in LPS and LPT groups respectively (p=1.00). The average width of parametrial tissue removed in the LPS group was 32.2+14.0 mm in patients with vs. 39.5+13.6 mm in patients without urinary complications (p=0.11). CONCLUSIONS: A laparoscopic approach is comparable to the laparotomy in terms of urinary lesions and postoperative retention. The width of parametrium removed does not affect the risk of urinary lesions or postoperative retention.