Michael Gdalevich

Can parametrectomy be avoided in early cervical cancer? An algorithm for the identification of patients at low risk for parametrial involvement

AIMSnTo assess the rate of parametrial involvement in a large cohort of patients who underwent radical hysterectomy for cervical cancer and to suggest an algorithm for the triage of patients to simple hysterectomy or simple trachelectomy.nnnMETHODSnMulticenter retrospective study of patients with cervical cancer stage I through IIA who underwent radical hysterectomy and pelvic lymphadenectomy. The patients were divided into 2 groups according to whether or not the parametrium was involved. The two groups were compared with regard to the clinical and histopathological variables. Logistic regression of the variables potentially assessable prior to definitive hysterectomy such as age, tumor size, lymph-vascular space invasion (LVSI) and nodal involvement was performed.nnnRESULTSnFive hundred and thirty patients had specific histological data on parametrial involvement and in 58 (10.9%) patients, parametria was involved. Parametrial involvement was significantly associated with older age, tumors larger than 2 cm, deeper invasion, LVSI, involved surgical margins, and the presence of nodal metastasis. By triaging patients with a tumor ≤ 2 cm and no LVSI, the parametrial involvement rate was 1.8% (2/112 patients). With further triage of patients with negative nodes, the rate of parametrial involvement was 0% (0/107 patients).nnnCONCLUSIONnUsing a pre-operative triage algorithm, patients with early small lesions, no LVSI and no nodal involvement may be spared radical surgical procedures and parametrectomy. Further prospective data are urgently needed.

A multicenter validation of computerized tomography models as predictors of non- optimal primary cytoreduction of advanced epithelial ovarian cancer.

AIMSnTo compare the validity of four predictive models of preoperative computerized tomography (CT) scans in predicting suboptimal primary cytoreduction in patients treated for advanced ovarian cancer.nnnPATIENTS AND METHODSnPreoperative CT scans of patients with stage III/IV epithelial ovarian cancer who underwent primary cytoreductive surgery at one of four medical centers were reviewed by radiologists blinded to surgical outcome. The validity of each set of CT criteria previously published by Nelson, Bristow, Dowdy, and Qayyum as predictors of suboptimal cytoreduction was assessed.nnnRESULTSnData of 123 patients were evaluated. Optimal cytoreduction (largest diameter of residual tumor < or =1cm) was obtained in 90 (73.2%) patients. All CT models were able to significantly predict surgical outcome (p<0.02). The respective sensitivity, specificity, and accuracy of the CT models to predict sub-optimal cytoreduction was 64%, 64% and 64% for Nelsons criteria, 70%, 64% and 66% for Bristows criteria, 79%, 60%, and 65% for Dowdys criteria, and 67% 57% and 60% for Qayyums criteria.nnnCONCLUSIONSnApart from Dowdys criteria, the accuracy rates of CT predictors of suboptimal cytoreduction in the original cohorts could not be confirmed in this cross validation. This study underscores the difficulty in devising universally applicable selection criteria or models that reliably predict surgical outcome across institutions and surgeons.

The reproducibility of histological parameters employed in the novel binary grading systems of endometrial cancer.

OBJECTIVEnTo compare the interobserver reproducibility and prognostic value of the FIGO grading system with the histological parameters employed in the various recently proposed binary grading systems of endometrial cancer.nnnMETHODSnSeventy two consecutive stage I endometrioid endometrial carcinomas from hysterectomy specimens were independently graded by two pathologists. Clinical data and outcome were obtained from the patients records. The following histological parameters were evaluated: FIGO grade (dichotomized to grades 1 and 2 vs. grade 3), nuclear atypia, presence of more than 50% solid growth, diffusely infiltrative rather than expansive growth pattern, presence of tumor cell necrosis, and mitotic count. Interobserver agreement was measured by the kappa (k) statistics. Kaplan-Meier survival analysis, log-rank tests and Cox proportional hazard regression were used to evaluate the equality of survival distributions and to model the overall effects of the various predictor variables on survival.nnnRESULTSnThe interobserver reproducibility was as follows: FIGO grade, k=0.65; nuclear atypia, k=0.63; solid growth, k=0.51; infiltrative growth pattern, k=0.38; tumor necrosis, k=0.52; and mitotic index, k=0.44. In the comparison of the Kaplan-Meier curves, the following parameters were associated with a significantly poorer survival: FIGO grade 3, p=0.02; presence of more than 50% solid growth, p=0.01; and a high mitotic index, p=0.01. The other binary histological parameters were not significantly predictive of survival.nnnCONCLUSIONSnThe proposed novel binary grading parameters are not advantageous in terms of interobserver reproducibility and prognostic significance over dichotomization to FIGO grades 1 and 2 vs. grade 3. A simple binary grade based solely on presence of more than 50% solid growth has a comparable reproducibility and prognostic value.

Temporal pattern of recurrence of stage I endometrial cancer in relation to histological risk factors

OBJECTIVEnTo study the temporal pattern of endometrial cancer recurrence in relation to histological risk factors in a large multicenter setting.nnnMETHODSn843 patients with apparent stage I endometrial cancer were followed for a median time of 38 months, documenting all recurrences. Patients were stratified as high risk based on the presence of at least one of the established histological risk factors: high tumor grade, penetration to the outer half of the myometrium, lymphvascular space involvement, lower uterine segment involvement and non endometroid histology. Survival analysis, including Kaplan-Meier curves, log-rank tests and multi-variate Cox proportional hazard regression were used to evaluate the equality of recurrence-free distributions for different levels of risk.nnnRESULTSnRecurrence was documented in 66 cases. The presence of one or more of the histological risk factors was associated with significantly shorter recurrence free survival, not attenuating over time (p < 0.001). Age-adjusted Cox regression model demonstrated a significantly decreased recurrence-free survival (HR = 2.8 95% CI 1.5, 5.1) in the presence of risk factors.nnnCONCLUSIONSnIn patients with stage I endometrial cancer, the presence of histological risk factors is associated with a significantly higher recurrence rate, which does not attenuate over follow up time. This may allow for a selective approach in the follow- up of endometrial cancer patients.

Lower uterine segment involvement is associated with adverse outcome in patients with stage I endometroid endometrial cancer: Results of a multicenter study

OBJECTIVEnTo quantify the relative risk associated with lower uterine segment involvement (LUSI) on outcome measures in patients with apparent stage I endometroid endometrial cancer.nnnMETHODSnA cohort of 769 consecutive patients with endometroid endometrial carcinoma apparent stage I, who underwent surgery in five gynecological oncology centers in Israel; 138 patients with and 631 without LUSI were followed for a median time of 51 months. Local recurrence, recurrence-free and overall survival were compared between the two groups.nnnRESULTSnLUSI was associated with grade 3 tumor (p=0.002), deep myometrial invasion (p<0.001), and the presence of lymphvascular space involvement (p=0.01). There were 22 cases of local recurrences, 40 cases of distal recurrences and 80 patients died. Univariate survival analysis showed that patients with LUSI had trend toward lower regional recurrence-free survival (p=0.09), and significant lower distant recurrence-free survival (p=0.04) and lower overall survival (p=0.002). The Cox proportional hazards model demonstrated a significantly decreased overall survival (HR=2.3; 95% CI 1.3, 3.9; p=0.003) in cases with LUSI.nnnCONCLUSIONSnIn patients with apparent stage I endometroid endometrial cancer, the presence of LUSI is a poor prognostic factor, associated with a significantly higher risk of distal recurrence and death. The presence of LUSI warrants consideration when deciding upon surgical staging or postoperative management.

The influence of early diagnosis of endometrioid endometrial cancer on disease stage and survival

ObjectiveTo evaluate whether the presence or duration of uterine bleeding is associated with disease stage, and survival of patients with endometrioid endometrial carcinoma (EEC).MethodsThe records of 220 patients with EEC who underwent surgery were reviewed. The patients were divided into three groups according to the presence and duration of vaginal bleeding at the time of surgery. Group 1, without vaginal bleeding; group 2, vaginal bleeding up to 3xa0months; group 3, vaginal bleeding exceeding 3xa0months prior to surgery. Disease stage and survival were between the three groups.ResultsOf the 220 patients, 42 (19xa0%) were asymptomatic; 95 (43xa0%) had symptom duration of up to 3xa0months and 83 (38xa0%) experienced bleeding for >3xa0months. There were no significant differences between groups 1, 2 and 3 regarding the proportion of patients with deep invasion in stage I (21, 24, 26xa0%, pxa0=xa00.84; respectively), with grade 3 tumors (10, 13, 14xa0%, pxa0=xa00.42; respectively) or with advanced stage disease (12, 14, 15xa0%, pxa0=xa00.92; respectively). Survival analysis demonstrated a non-significant trend toward better survival in asymptomatic patients and in patients with a shorter duration of symptoms (pxa0=xa00.172).ConclusionsDiagnosis of EEC in asymptomatic patients or in patients with a short duration of bleeding is associated with comparable stage and survival.

The outcome of patients with stage I endometrial cancer involving the lower uterine segment

The objective of this study was to evaluate whether lower uterine segment involvement (LUSI) correlates with recurrence and survival in women with stage I endometrial adenocarcinoma and whether it is associated with poor prognostic histopathologic features. Three hundred seventy-five consecutive patients with endometrial carcinoma stage I compromised the study population. The patients were divided into two groups according to the presence of LUSI with endometrial carcinoma. The two groups were compared with regard to prognostic factors and outcome measures by using the Pearson χ2 test, log-rank test, and Cox proportional hazards model. LUSI was present in 89 (24%) patients with stage I endometrial carcinoma. LUSI was significantly associated with grade 3 tumor (P= 0.022), deep myometrial invasion (P< 0.0001), and the presence of capillary space-like involvement (CSLI) (P= 0.003). Kaplan–Meier survival curves demonstrated that patients with LUSI had a lower recurrence-free survival (log-rank test; P= 0.009) and a worse overall survival (log-rank test; P= 0.0008). In the Cox proportional hazards model, only a trend toward higher recurrence rate (HR = 2.4, 95% CI 0.7, 8.2; P= 0.16) and a trend toward poorer overall survival (HR = 1.54, 95% CI 0.82, 2.91; P= 0.18) were noted when LUSI was present. In patients with stage I endometrial cancer, the presence of LUSI is associated with grade 3 tumor, deep myometrial invasion, and the presence of CSLI. A larger group of patients is necessary to conclude whether higher recurrence rate and poorer overall survival are associated with the presence of LUSI.

Misoprostol treatment for early pregnancy failure does not impair future fertility

Abstract Aims: To examine whether misoprostol treatment for first trimester missed abortion affects future fertility. Patients and methods: In a historical prospective approach, we analyzed our database for patients treated with misoprostol. All eligible patients underwent an interview according to a questionnaire, which includes their demographic characteristics, obstetric, gynecologic and infertility history. They were asked about the side effects, intention and subsequent ability to conceive. Their future pregnancy rates were calculated and compared to the acceptable figures in the literature. Results: The infertility rates among our patients were similar to those reported in the general population. Pregnancy rates 2 years after treatment were similar to the previously published reports, except for lower rates during the first three months post-treatment. Although no between-group differences were observed in the subsequent pregnancy rates, 2 years following misoprostol treatment in ≤35 versus >35 years old patients, primi- versus multigravida and nulli- versus parous women, higher pregnancy rates were observed in patients ≤35 versus >35 years old, primi- versus multigravida and nulli- versus, parous, during the first 3 months following misoprostol treatment. Conclusion: Misoprostol treatment, for women with first trimester missed abortion and favorable reproductive history, is an acceptable treatment with no detrimental effect on future fertility.

Evaluation of Clinical and Pathologic Risk Factors May Reduce the Rate of Multimodality Treatment of Early Cervical Cancer.

Objective:To assess the rate of postoperative adjuvant treatment in patients who underwent radical hysterectomy for early cervical cancer and to suggest criteria for the triage of patients who have a high probability of multimodality treatment. Methods:This was a multicenter retrospective study of 514 patients with FIGO stages IA2-IIA cervical cancer who underwent radical hysterectomy between 1999 and 2010. The patients were divided into 2 groups according to whether or not postoperative radiation was administered. The 2 groups were compared with regard to clinical and histopathologic variables divided into major and minor criteria (intermediate risk factors) based on lymph nodes status, parametrial involvement, tumor size, deep stromal invasion, and lymph-vascular space invasion. Results:We identified 294 (57.2%) patients who received adjuvant postoperative radiotherapy (RT) or chemoradiation. Fifty-three percent of these patients who were treated by adjuvant radiation had only intermediate risk factors. Combining the various combinations of 2 out of 3 of the following criteria, we found that 89% of patients with tumors ≥2 cm and lymph-vascular space invasion received RT, 76% of patients with tumors ≥2 cm and depth of invasion >10 mm received RT, and 87% of patients with tumors depth of invasion >10 mm and lymph-vascular space invasion received RT. Conclusions:This study suggests that in patients with early cervical cancer, clinicopathologic evaluation of tumor size and lymph-vascular space invasion should be undertaken before performing radical hysterectomy. This approach can serve to tailor treatment, reducing the rate of employing both radical hysterectomy and chemoradiation.

Are Ultrasonographic Findings Suggestive of Ovarian Stromal Edema Associated with Ischemic Adnexal Torsion

Objective: To study whether sonographic findings suggestive of ovarian stromal edema are associated with tissue ischemia in patients with adnexal torsion. Methods: A study of 79 patients with adnexal torsion was performed. Patients were divided into an ischemic group, in which the twisted adnexa were seen as blue or black, and a non-ischemic group, in which the adnexa retained normal color and appeared viable. Clinical and ultrasonographic findings, specifically the presence of ultrasonographic signs suggestive of ovarian stromal edema, were compared between the two groups. Results: Of the 79 patients with torsion, in 44 (55.7%) the adnexa appeared ischemic at surgery. The presence of ischemia was not associated with age, pregnancy, duration of pain, vomiting or findings at physical examination. There was no significant difference between the ischemic and the non-ischemic group in the proportion of patients with signs of ovarian stromal edema (59 vs. 40%, p = 0.11), in the proportion of patients with absent/diminished stromal Doppler flow (36 vs. 28%, p = 0.12%) or in the proportion of patients with both signs of stroma edema and absent/diminished stromal Doppler flow (20 vs. 12%, p = 0.36). Conclusion: Ultrasonographic signs of ovarian stromal edema do not assist in differentiating between ischemic and non-ischemic adnexal torsion.