Response to treatment and prognostic significance of supradiaphragmatic disease in patients with high-grade serous ovarian cancer.

OBJECTIVES: This study was designed to investigate the response to chemotherapy of supradiaphragmatic disease diagnosed by preoperative imaging. As secondary objectives, oncologic outcomes of patients affected by supradiaphragmatic disease and their pattern of recurrence were also evaluated. METHODS: Data of consecutive patients with newly diagnosed FIGO stage IV (for supradiaphragmatic disease) epithelial ovarian cancer undergoing either primary debulking surgery or neoadjuvant chemotherapy plus interval debulking surgery between 2004 and 2021, were retrospectively collected. All patients were preoperatively evaluated by chest/abdominal CT scan or 18F-FDG PET/CT preoperatively and at follow-up to evaluate response to chemotherapy. At follow-up visits, site of recurrence diagnosed by imaging techniques was systematically recorded as it occurred. Progression-free and overall survival were measured by using Kaplan-Meier and Cox models. RESULTS: A total of 130 patients was included in this study with a median (range) follow-up of 32.9 (12.8-176.7) months. Complete or partial response was achieved in most of the patients after 3 cycles (77.7%) and 6 cycles (85.4%) of chemotherapy. At follow-up, recurrence occurred in 96 (73.8%) patients and the main site of recurrence was abdomen only in 64 (66.7%) patients. At multivariate analysis, residual disease after surgery was the only variable influencing survival outcomes. CONCLUSIONS: Supradiaphragmatic disease respond to chemotherapy in most patients affected by advanced EOC and recurrence mainly occurs in the abdomen. Results from this study confirms that abdominal optimal cytoreduction is the main surgical goal in the treatment of women affected by FIGO stage IV EOC.

Using rADioMIcs and machine learning with ultrasonography for the differential diagnosis of myometRiAL tumors (the ADMIRAL pilot study). Radiomics and differential diagnosis of myometrial tumors.

OBJECTIVE: To develop and evaluate the performance of a radiomics and machine learning model applied to ultrasound (US) images in predicting the risk of malignancy of a uterine mesenchymal lesion. METHODS: Single-center retrospective evaluation of consecutive patients who underwent surgery for a malignant uterine mesenchymal lesion (sarcoma) and a control group of patients operated on for a benign uterine mesenchymal lesion (myoma). Radiomics was applied to US preoperative images according to the International Biomarker Standardization Initiative guidelines to create, validate and test a classification model for the differential diagnosis of myometrial tumors. The TRACE4 radiomic platform was used thus obtaining a full-automatic radiomic workflow. Definitive histology was considered as gold standard. Accuracy, sensitivity, specificity, AUC and standard deviation of the created classification model were defined. RESULTS: A total of 70 women with uterine mesenchymal lesions were recruited (20 with histological diagnosis of sarcoma and 50 myomas). Three hundred and nineteen radiomics IBSI-compliant features were extracted and 308 radiomics features were found stable. Different machine learning classifiers were created and the best classification system showed Accuracy 0.85 ± 0.01, Sensitivity 0.80 ± 0.01, Specificity 0.87 ± 0.01, AUC 0.86 ± 0.03. CONCLUSIONS: Radiomics applied to US images shows a great potential in differential diagnosis of mesenchymal tumors, thus representing an interesting decision support tool for the gynecologist oncologist in an area often characterized by uncertainty.

Predictors of recurrence following laparoscopic radical hysterectomy for early-stage cervical cancer: A multi-institutional study.

OBJECTIVE: To assess predictors of recurrence following laparoscopic radical hysterectomy (LRH) for apparent early stage cervical cancer (CC). METHODS: This is a retrospective multi-institutional study reviewing data of consecutive patients who underwent LRH for FIGO 2009 stage IA1 (with lymphovascular space invasion (LVSI)), IA2 and IB1(≤4 cm) CC, between January 2006 and December 2017. The following histotypes were included: squamous, adenosquamous, and adenocarcinoma. Multivariable models were used to estimate adjusted odds ratio (OR) and corresponding 95% CI. Factors influencing disease-free survival (DFS) and disease-specific survival (DSS) were also explored. RESULTS: 428 patients were included in the analysis. With a median follow-up of 56 months (1-162) 54 patients recurred (12.6%). At multivariable analysis, tumor size (OR:1.04, 95%CI:1.01-1.09, p = .02), and presence of cervical residual tumor at final pathology (OR: 5.29, 95%CI:1.34-20.76, p = .02) were found as predictors of recurrence; conversely preoperative conization reduced the risk (OR:0.32, 95%CI:0.11-0.90, p = .03). These predictors remained significant also in the IB1 subgroup: tumor size: OR:1.05, 95%CI:1.01-1.09, p = .01; residual tumor at final pathology: OR: 6.26, 95%CI:1.58-24.83, p = .01; preoperative conization: OR:0.33, 95%CI:0.12-0.95, p = .04. Preoperative conization (HR: 0.29, 95%CI: 0.13-0.91; p = .03) and the presence of residual tumor on the cervix at the time of surgery (HR: 8.89; 95%CI: 1.39-17.23; p = .01) independently correlated with DFS. No independent factors were associated with DSS. CONCLUSIONS: In women with early stage CC the presence of high-volume disease at time of surgery represent an independent predictor of recurrence after LRH. Conversely, preoperative conization and the absence of residual disease at the time of surgery might play a protective role.

Bevacizumab as maintenance treatment in BRCA mutated patients with advanced ovarian cancer: A large, retrospective, multicenter case-control study.

OBJECTIVE: The aim of this study was to investigate the correlation between BRCA mutational status and response to bevacizumab in a large advanced ovarian cancer (AOC) series. METHODS: This is a multicenter, retrospective case-control study including upfront AOC treated between January 2015 and June 2019. The main inclusion criteria were: having received three weekly carboplatin-paclitaxel as first-line treatment, with or without Bevacizumab maintenance, knowledge of the BRCA mutational status. RESULTS: Overall, 441 patients were included; 183 (41.5%) patients received bevacizumab (Cases), and 258 (58.5%) did not receive it (Controls). The BRCA mutated patients (BRCAmut) were 58 (39%) in the Cases group and 90 (34.9%) in the Controls group (p = .77). Patients who received bevacizumab had a significant 4-months increase in median progression free survival (mPFS: 21 vs. 17 months, p = .033). Concerning BRCAmut patients, no differences were shown between those who received bevacizumab or not in terms of mPFS (24 vs. 22 months, p = .3). Conversely, in BRCA wild-type (BRCAwt) population bevacizumab administration significantly prolonged mPFS (20 vs 15 months, p = .019). At multivariate analysis, independent factors of prolonged PFS were BRCA status (OR = 0.60), having received PDS (OR = 0.69), and complete cytoreduction (OR = 0.50), but not the bevacizumab administration (OR = 0.83, p = .22). CONCLUSIONS: No evidence of oncological benefit in terms of PFS and OS related to bevacizumab maintenance therapy was found in BRCAmut patients. Differently, BRCAwt patients seem to benefit from antiangiogenic treatment in terms of mPFS.

Is aortic lymphadenectomy indicated in locally advanced cervical cancer after neoadjuvant chemotherapy followed by radical surgery? A retrospective study on 261 women.

OBJECTIVES: The aim of this study was to estimate the rate of aortic lymph nodes (LN) metastases/recurrences among patients affected by locally advanced stage cancer patients (LACC), treated with neoadjuvant chemotherapy (NACT) and radical surgery. METHODS: Retrospective evaluation of consecutive 261 patients affected by LACC (stage IB2-IIB), treated with NACT followed by radical surgery at National Cancer Institute, Milan, Italy, between 1990 and 2011. RESULTS: Stage at presentation included stage IB2, IIA and IIB in 100 (38.3%), 50 (19.2%) and 111 (42.5%) patients, respectively. Squamous cell carcinoma accounted for more than 80%, followed by adenocarcinoma or adenosquamous cancers (20%). Overall, 56 women (21.5%) had LN metastases. Four out of 83 women (5%) who underwent both pelvic and aortic LN dissection had aortic LN metastases, and all women had concomitant pelvic and aortic LN metastases. Only one woman out of 178 (0.5%) who underwent pelvic lymphadenectomy only, had an aortic LN recurrence. Overall 2% of women (5/261) had aortic LN metastases/recurrence. CONCLUSIONS: Our data suggest that aortic lymphadenectomy at the time of surgery is not routinely indicated in LACC after NACT, but should reserved in case of bulky LN in both pelvic and/or aortic area. The risk of isolated aortic LN relapse is negligible. Further prospective studies are warranted.

How often parametrial involvement leads to post-operative adjuvant treatment in locally advanced cervical cancer after neoadjuvant chemotherapy and type C radical hysterectomy?

OBJECTIVE: Parametrial involvement (PMI) is one of the most important factors influencing prognosis in locally advanced stage cervical cancer (LACC) patients. We aimed to evaluate PMI rate among LACC patients undergoing neoadjuvant chemotherapy (NACT), thus evaluating the utility of parametrectomy in tailor adjuvant treatments. METHODS: Retrospective evaluation of consecutive 275 patients affected by LACC (IB2-IIB), undergoing NACT followed by type C/class III radical hysterectomy. Basic descriptive statistics, univariate and multivariate analyses were applied in order to identify factors predicting PMI. Survival outcomes were assessed using Kaplan-Meier and Cox models. RESULTS: PMI was detected in 37 (13%) patients: it was associated with vaginal involvement, lymph node positivity and both in 10 (4%), 5 (2%) and 12 (4%) patients, respectively; while PMI alone was observed in only 10 (4%) patients. Among this latter group, adjuvant treatment was delivered in 3 (1%) patients on the basis of pure PMI; while the remaining patients had other characteristics driving adjuvant treatment. Considering factors predicting PMI we observed that only suboptimal pathological responses (OR: 1.11; 95% CI: 1.01, 1.22) and vaginal involvement (OR: 1.29 (95%) CI: 1.17, 1.44) were independently associated with PMI. PMI did not correlate with survival (HR: 2.0; 95% CI: 0.82, 4.89); while clinical response to NACT (HR: 3.35; 95% CI: 1.59, 7.04), vaginal involvement (HR: 2.38; 95% CI: 1.12, 5.02) and lymph nodes positivity (HR: 3.47; 95% CI: 1.62, 7.41), independently correlated with worse survival outcomes. CONCLUSIONS: Our data suggest that PMI had a limited role on the choice to administer adjuvant treatment, thus supporting the potential embrace of less radical surgery in LACC patients undergoing NACT. Further prospective studies are warranted.

Class II versus Class III radical hysterectomy in early cervical cancer: an observational study in a tertiary center.

AIMS: The purpose of this observational study was to evaluate disease free survival (DFS), overall survival (OS), and local recurrence rate (LRR) in patients submitted to Class II RH compared with Class III RH in early FIGO stage cervical cancer (ECC). MATERIALS AND METHODS: We investigated 127 patients with CC admitted to the National Cancer Institute of Milan from June 2001 to October 2011 treated with Class II RH, and compared them with 202 patients operated with Class III RH between March 1980 and March 2001. A total of 329 patients were collected. RESULTS: Median follow-up time was 91 months (IQ range:58-196). Five-year OS and DFS estimates were 89.5% (95%CI: 86.0-93.2%) and 85.6% (95%CI: 81.6-89.7%), respectively. Estimates of effect of surgical treatment (Class III RH versus Class II RH) on OS showed a HR of death = 3.38 (95%CI: 1.18-9.63, P = 0.0228), at univariable Cox analysis, and a HR = 3.08 (95%CI: 0.96-9.93; P = 0.0595) at multivariable analysis. For DFS, a HR of relapse = 2.51 (95%CI 1.10-5.72; P = 0.0290) comparing Class III vs Class II was found at multivariable analysis. Overall recurrence rate was 12.8%, whilst it was 16.3% for Class III and 7.1% for Class II respectively. CONCLUSIONS: The present data suggest that the outcomes of Class II RH are comparable in terms of LRR and OS to those of Class III RH, according to literature data. The opportunity of extending the indication to all women with ECC needs further investigations. Clearer data are warranted by prospective controlled studies.

Secondary cytoreductive surgery for isolated lymph node recurrence of epithelial ovarian cancer: a multicenter study.

INTRODUCTION: Chemotherapy is the standard treatment of recurrent epithelial ovarian cancer (EOC), but its use in nodal relapses is still debated. On the other hand, the role of secondary cytoreductive surgery (SCS) remains controversial. Aim of this study is to evaluate feasibility and outcomes of SCS for the specific setting of recurrent ovarian cancer, exclusively relapsing in lymph nodes. PATIENTS AND METHODS: We conducted a retrospective analysis in five Italian Institutions (University of Torino, INT of Milano, CRO of Aviano, University of Pisa and INT of Napoli) from 2000 to 2012. Patients with EOC who underwent secondary surgery for isolated lymph node recurrence (ILNR) were selected. RESULTS: Seventy-three patients were identified. At first diagnosis, patients received debulking surgery and platinum-based chemotherapy. The median disease free interval from completion of primary chemotherapy to nodal recurrence was 18 months. Nodal recurrence was para-aortic in 37 patients (50.7%), pelvic in 21 (28.8%), pelvic and para-aortic in 9 (12.3%), pelvic and inguinal in 3 (4.1%) and inguinal in 3 (4.1%). During SCS, in 1 patients nephrectomy was necessary for renal vein injury. No significant postoperative morbidity occurred. Median follow-up is 50 months. After secondary surgery, 32 (43.8%) are alive without disease, 18 (24.6%) are alive with disease and 23 patients (31.5%) are dead of disease. Five-year overall survival from the time of treatment of recurrent disease is 64%. CONCLUSIONS: Secondary surgery for ILNR of ovarian cancer is feasible, safe, with low morbidity and it is associated with a favorable outcome.

The different impact of BRCA mutations on the survival of epithelial ovarian cancer patients: a retrospective single-center experience.

OBJECTIVES: The objective of this study was to examine whether the oncologic outcomes of BRCA1-associated and BRCA2-associated ovarian cancers correlate differently. METHODS: Genetic data and clinical characteristics were correlated with progression-free survival (PFS) and overall survival (OS). RESULTS: Data from 147 BRCA-mutated patients (119 BRCA1-positive and 28 BRCA2-positive) were analyzed. At a median follow-up of 69 months, the median PFS was 27.2 and 45.46 months for BRCA1 and BRCA2 patients, respectively (p = 0.03). Median OS was 77.23 and 111.47 months for BRCA1 and BRCA2 patients, respectively (p = 0.08). CONCLUSION: BRCA2 mutations confer PFS and a trend to OS advantage compared with the BRCA1 mutation in BRCA-mutated epithelial ovarian cancer patients.

Nanoparticle deposition onto biofilms.

We develop a mathematical model of nanoparticles depositing onto and penetrating into a biofilm grown in a parallel-plate flow cell. We carry out deposition experiments in a flow cell to support the modeling. The modeling and the experiments are motivated by the potential use of polymer nanoparticles as part of a treatment strategy for killing biofilms infecting the deep passages in the lungs. In the experiments and model, a fluid carrying polymer nanoparticles is injected into a parallel-plate flow cell in which a biofilm has grown over the bottom plate. The model consists of a system of transport equations describing the deposition and diffusion of nanoparticles. Standard asymptotic techniques that exploit the aspect ratio of the flow cell are applied to reduce the model to two coupled partial differential equations. We perform numerical simulations using the reduced model. We compare the experimental observations with the simulation results to estimate the nanoparticle sticking coefficient and the diffusion coefficient of the nanoparticles in the biofilm. The distributions of nanoparticles through the thickness of the biofilm are consistent with diffusive transport, and uniform distributions through the thickness are achieved in about four hours. Nanoparticle deposition does not appear to be strongly influenced by the flow rate in the cell for the low flow rates considered.

Weekly topotecan and cisplatin (TOPOCIS) as neo-adjuvant chemotherapy for locally-advanced squamous cervical carcinoma: Results of a phase II multicentric study.

OBJECTIVES: The aim of this phase II multicentric study was to evaluate the efficacy and toxicity of neo-adjuvant chemotherapy with weekly topotecan and cisplatin in locally-advanced squamous cervical cancer. PATIENTS AND METHODS: From November 2008 to January 2011, 92 patients met the inclusion criteria and were enrolled. Eligibility criteria were: squamous or adenosquamous cervical cancer; clinical stages IB2, IIA, IIB; Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)≤ 2; neutrophils ≥1500/µL; platelets ≥100,000/µL, normal renal and liver function. Treatment consisted of six courses of weekly topotecan (2mg/m(2)) and cisplatin (40 mg/m(2)). All responsive and stable patients were submitted to radical surgery, while progressed cases underwent definitive radiotherapy±chemotherapy. Primary end-point was evaluation of efficacy and toxicity. All patients are evaluable for toxicity and efficacy. RESULTS: Ninety-six percent of patients completed the six planned courses of chemotherapy, and 95% of courses were administered at a full dose and without interruption or delay. Mean age was 49 years (35-64 years). FIGO Stage distribution was 30 IB2, 13 IIA and 49 IIB. Treatment was well tolerated and no death occurred. G3-G4 haematological toxicity was observed in 28% of patients (5% out of cycles). Support therapies (blood transfusions and/or erythropoietin and/or Granocyte-Colony Stimulating Factor) were given to 24% of patients. Clinical response rate was 77%. The nine progressed cases were irradiated, while the remaining 83 patients were submitted to radical surgery. An overall pathologic response was observed in 67% of patients, with an optimal response rate of 32% and a disease downstage in 57% of patients. Nodal metastases occurred in 36% of patients. Adjuvant therapy (radiotherapy and or chemotherapy) was prescribed in 55% of patients, because of lymph node metastases, parametrial or vaginal involvement or cut-through margins. Median follow-up was 18 months: 76% of patients are alive and free from recurrence, 24% of patients relapsed and 13% died. CONCLUSIONS: Weekly topotecan and cisplatin showed an acceptable toxicity profile; the promising response rate warrants further investigation.

Ligand-dependent EGFR activation induces the co-expression of IL-6 and PAI-1 via the NFkB pathway in advanced-stage epithelial ovarian cancer.

The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kinases, is expressed in up to 70% of epithelial ovarian cancers (EOCs), where it correlates with poor prognosis. The majority of EOCs are diagnosed at an advanced stage, and at least 50% present malignant ascites. High levels of IL-6 have been found in the ascites of EOC patients and correlate with shorter survival. Herein, we investigated the signaling cascade led by EGFR activation in EOC and assessed whether EGFR activation could induce an EOC microenvironment characterized by pro-inflammatory molecules. In vitro analysis of EOC cell lines revealed that ligand-stimulated EGFR activated NFkB-dependent transcription and induced secretion of IL-6 and plasminogen activator inhibitor (PAI-1). IL-6/PAI-1 expression and secretion were strongly inhibited by the tyrosine kinase inhibitor AG1478 and EGFR silencing. A significant reduction of EGF-stimulated IL-6/PAI-1 secretion was also obtained with the NFkB inhibitor dehydroxymethylepoxyquinomicin. Of 23 primary EOC tumors from advanced-stage patients with malignant ascites at surgery, 12 co-expressed membrane EGFR, IL-6 and PAI-1 by immunohistochemistry; both IL-6 and PAI-1 were present in 83% of the corresponding ascites. Analysis of a publicly available gene-expression data set from 204 EOCs confirmed a significant correlation between IL-6 and PAI-1 expression, and patients with the highest IL-6 and PAI-1 co-expression showed a significantly shorter progression-free survival time (P=0.028). This suggests that EGFR/NFkB/IL-6-PAI-1 may have a significant impact on the therapy of a particular subset of EOC, and that IL-6/PAI-1 co-expression may be a novel prognostic marker.

Photodynamic therapy using a methyl ester of 5-aminolevulinic acid in recurrent Paget's disease of the vulva: a pilot study.

OBJECTIVE: In the past, treating vulvar Paget's disease through surgery has resulted in a high recurrence rate of the disease. Photodynamic therapy (PDT) using 5-aminolevulinic acid (5 ALA) is an effective treatment for some conditions such as Bowen's disease, subsets of basal cell carcinomas and vulvar carcinoma. Methyl 5-aminolevulinate (MAL) is an ester of 5 ALA that seems to be more effective and produces fewer side effects than 5 ALA. This paper outlines a pilot study designed to test the feasibility of using MAL-PDT in the treatment of recurrent vulvar Paget's disease. METHODS: 5 MAL-PDT was applied for 3 h and than irradiated with red-light (620 nm) using a total light dose of 37 J/cm2 for a period of 10 min. Patients taking part in the study were treated once every 3 weeks, for a total of three treatments. Vulvar biopsies were obtained before and 1 month after the PDT-treatment. RESULTS: Seven patients were enrolled in the study. Four cases had a complete clinical response, and this was pathologically confirmed in two of the cases. The cosmetic outcome was acceptable and the treatment was well tolerated. All the patients developed local edema and mild local pain, controlled with non-steroidal antiinflammatory drugs (NSAIDS). One patient experienced severe pain and a mild local phototoxicity reaction. CONCLUSIONS: MAL-PDT is a feasible treatment and seems to offer a reliable strategy in the control of vulvar Paget's disease and of its symptoms.

Cytoreduction combined with intraperitoneal hyperthermic perfusion chemotherapy in advanced/recurrent ovarian cancer patients: The experience of National Cancer Institute of Milan.

AIMS: We report the effects of cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP) in the treatment of advanced/recurrent epithelial ovarian cancer (EOC) on survival, morbidity and mortality. PATIENTS: Forty EOC patients were studied. Median age was 52.5 years (range: 30-68) and median follow-up 26.1 months (range: 0.3-117.6). Most patients presented advanced disease (stage III/IV). Previous systemic chemotherapy included cisplatin-based, taxol-based or taxol/platinum containing regimens. RESULTS: After the CRS, 33 patients presented no macroscopic residual disease. Five-year overall survival was 15%; the mean overall and progression-free survivals were 41.4 and 23.9 months, respectively. The morbidity, toxicity and mortality rates were 5%, 15% and 0%, respectively. CONCLUSION: Our results suggest that CRS + IPHP merits further evaluation by a formal prospective trial.

Administration of recombinant human erythropoietin in patients with gynecological cancer before radical surgery.

UNLABELLED: The purpose of this prospective study was to investigate the efficacy of preoperative administration of recombinant human erythropoietin in patients with gynecological cancer. METHODS: The study included 38 women with gynecological cancer who were divided randomly in two groups. Study group A included 20 women with gynecological cancer who received recombinant human erythropoietin (rHuEPO) plus iron supplementation for ten days before surgery and five days postoperatively. Group B (controls) included 18 patients who received only iron supplementation for the same time period. Blood samples were obtained on days -10, -3, 0, +3, +5, +10. RESULTS: The mean hemoglobin level was significantly higher in group A than in group B on the day of the operation and remained significantly higher postoperatively while an inverse relationship was observed for mean ferritin values in the two groups. CONCLUSION: Preoperative administration of rHuEPO in patients with gynecological cancer seems to be effective in the blood management of these patients.

p53 Gene status and response to topotecan-containing chemotherapy in advanced ovarian carcinoma.

OBJECTIVE: Since the p53 gene has been identified as a determinant of response to chemotherapy in ovarian carcinoma in previous studies, we investigated the significance of the p53 status in response to topotecan as second-line therapy. METHODS: Twenty-eight patients with advanced ovarian carcinoma, pretreated with standard platinum/paclitaxel chemotherapy, received topotecan as single-agent second-line therapy. Tumors were investigated by molecular analysis for p53 mutations in tumor samples obtained at primary surgery (i.e. before first-line therapy). RESULTS: Wild-type p53 tumors responsive to first-line therapy maintained substantial responsiveness to topotecan. In contrast, p53 mutation was associated with a low responsiveness to second-line therapy. CONCLUSIONS: The better outcome in relapsed patients with wild-type p53 suggests that the presence of a functional wild-type p53 confers stability of the drug-sensitive phenotype. This outcome is consistent with the clinical observation that the efficacy of topotecan in the treatment of relapsed ovarian carcinoma patients is dependent on platinum sensitivity, because platinum-sensitive tumors are expected to carry wild-type p53. Although untreated mutant p53 tumors may be responsive to first-line paclitaxel-containing therapy, it is likely that loss of p53 leads to genomic instability resulting in rapid progression to drug resistance.

Prognostic factors in microinvasive cervical squamous cell cancer: long-term results.

We examined tumor-related pathologic factors and cone-related characteristics to identify parameters related to recurrence in microinvasive squamous cell carcinoma of the cervix treated with conization. This is a retrospective study on 67 consecutive cases of microinvasive carcinoma of the cervix [depth of invasion (DI) < 3 mm] treated with conization. The mean follow-up was 121 months (range 72-276 months). Four (6%) invasive recurrences were observed. Presence of lymphvascular space involvement (LVSI) was significantly related with recurrences (P < 0.05). The mean distance between tumor margin and apex of the cone (apical clearance) was 10.6 mm (range 5-22 mm), and the mean distance between lateral border of the cone and tumor margin (lateral clearance) was 6.5 mm (range 1.7-15 mm). We adopted cut-off values of 10 and 8 mm for apical and lateral clearances, respectively. We found a statistically significant difference between apical clearance and recurrence rate (P < 0.02). The LVSI was, other than DI, an important prognostic factor. Apical clearance was significantly correlated with recurrence. The cone-related characteristics, other than tumor-related pathologic factors, could help the decision concerning the definitive therapy for microinvasive carcinoma of the cervix.

Outcome analysis of endoscopic sinus surgery in patients with nasal polyps and asthma.

OBJECTIVE: To investigate the efficacy of endoscopic sinus surgery (ESS) in the management of chronic sinusitis and asthma in patients with nasal polyps and steroid-dependent asthma. STUDY DESIGN: Retrospective chart review. METHODS: The study included 17 patients who underwent ESS with nasal polyps, steroid-dependent asthma with or without aspirin sensitivity and a minimum of 1 year postoperative follow-up. Nine patients were ASA sensitive, and eight patients were ASA tolerant. Chronic sinusitis and asthma were evaluated using subjective (patient complaints) and objective (computed tomography scans, pulmonary function tests, steroid doses) criteria. Preoperative data were compared with data obtained 12 to 18 months postESS. Tissue samples were graded for degree of inflammation and edema. RESULTS: Thirteen of the 17 (76.5%) patients reported improved clinical symptoms postESS. The postoperative Lund-Mackay scores were statistically lower for the 17 patients (P <.0001). The group experienced improvement in postoperative forced expiratory volume at 1 second (FEV1) (P <.014). Twelve of 17 (70.6%) experienced reduction in systemic steroid usage (P <.048). The ASA sensitive patients did not have a statistical improvement in postoperative FEV1 (P >.08) and sinonasal symptoms (P >.16) compared with the ASA tolerant group. Polyp tissue from the ASA sensitive patients demonstrated more edema and more inflammation on average than ASA tolerant polyps, but the results were not statistically significant. CONCLUSION: ESS demonstrates a beneficial effect on the sinonasal and asthma symptomatology in patients with nasal polyps and asthma using objective measures. Subset of aspirin-tolerant patients have statistically better outcome for sinonasal symptoms and pulmonary function testing than aspirin-sensitive patients.