Tomoyuki Kusumoto

Factors associated with parametrial involvement in stage IB1 cervical cancer and identification of patients suitable for less radical surgery

OBJECTIVE The purpose of the present study was to determine possible factors associated with parametrial spread in patients with stage IB1 cervical cancer and define parameters associated with a low risk for parametrial spread, in order to identify candidates for less radical surgery. PATIENTS AND METHODS We retrospectively reviewed 200 patients with stage IB1 cervical cancer who had undergone radical hysterectomy (class III) and pelvic lymphadenectomy. RESULTS Overall, 20 (10.0%) of the 200 patients revealed parametrial spread, of which 11 (55%) had only direct microscopic extension of the disease, 3 (15%) had only disease spread to parametrial lymph nodes, 1 (5%) had both direct microscopic extension and disease spread to parametrial lymph nodes, and 5 (25%) had only tumor emboli within the lymph vascular channels in the parametrial tissue. Elderly age, depth of invasion, tumor size, lymph vascular space invasion (LVSI), positive pelvic nodes, and ovarian metastasis were significantly associated with parametrial involvement. The multivariate analysis model included factors that could be determined by a cone biopsy and showed LVSI, deep stromal invasion, and elderly age to be the independent predictors of parametrial involvement. Ninety-one patients had a depth of invasion of ≤10 mm and no LVSI, of which only 1 (1.1%) had parametrial involvement. When patients aged ≤50 years were further stratified into those with a depth of invasion of ≤10 mm and no LVSI, parametrial involvement was found to be 0.0% (0/68). CONCLUSION Patients with a tumor depth of invasion of ≤10 mm, no LVSI, and aged ≤50 years, could be considered for less radical surgery such as modified radical hysterectomy or simple hysterectomy with pelvic lymphadenectomy.

The mean apparent diffusion coefficient value (ADCmean) on primary cervical cancer is a predictive marker for disease recurrence

OBJECTIVE The purpose of this study is to investigate the correlation of the max, mean and minimal apparent diffusion coefficient values (ADCmax, ADCmean, and ADCmin) on diffusion weighted imaging findings with prognostic factors in cervical cancer. METHODS A cohort of 80 cervical cancer patients underwent pelvic magnetic resonance imaging (MRI) within the 2 to 4 weeks prior to radical hysterectomy. The optimal cutoff value for segregating disease free survival (DFS) was determined by receiver operating characteristic (ROC) curve analysis. We used ROC curve analyses to evaluate whether preoperative ADCmax, ADCmean, ADCmin on MRI predicted the risk group of recurrence. RESULTS Analyses of ROC curves identified an optimal The ROC curves identified an optimal ADCmax, ADCmean, and ADCmin cutoff values of 1.122 × 10(-3)mm(2)/s, 0.852 × 10(-3)mm(2)/s, 0.670 × 10(-3)mm(2)/s and for predicting the recurrence of cervical cancer. The patients categorized into the lower ADCmean or ADCmin groups showed the shorter disease free survivals compared with the higher ADCmean or ADCmin, respectively (P<0.0001 or P=0.0210). In particular, the ADCmean of primary cervical cancer was an independent predictive factor for disease recurrence by a multivariate analysis (P=0.0133). CONCLUSIONS The ADCmean of primary cervical cancer calculated by MRI could be an important factor for identifying patients with a risk of disease recurrence.

Prognostic factors in stage IB-IIB cervical adenocarcinoma patients treated with radical hysterectomy and pelvic lymphadenectomy

The purpose of the present study was to identify prognostic factors and patterns of recurrence in patients with stage IB–IIB cervical adenocarcinoma who had undergone radical surgery and to compare these patterns with those observed in squamous cell carcinoma (SCC) patients.

The preoperative SUVmax is superior to ADCmin of the primary tumour as a predictor of disease recurrence and survival in patients with endometrial cancer

PurposeThe purpose of this study was to investigate the prognostic value of the minimum apparent diffusion coefficient (ADCmin) derived from diffusion-weighted MR imaging and of the maximum standardized uptake value (SUVmax) derived from PET/CT imaging of the primary tumour in patients with endometrial cancer.MethodsSUVmax reflects the highest tumour metabolism rate and ADCmin reflects the highest cellularity, and both parameters have been used for tumour grading and prediction of prognosis. The correlations between prognosis and SUVmax and ADCmin of the primary tumour were determined in 131 patients with endometrial cancer. The patients were divided into groups based on ADCmin and SUVmax cut-off values to predict recurrence and survival, which were derived from receiver operating characteristic curves. Disease-free survival (DFS) and overall survival (OS) of the groups were analysed using the Kaplan-Meier method, and differences between survival curves were evaluated using the log-rank test.ResultsThe median DFS and OS times of all patients were 19.2 and 20.5 months (follow-up periods 1–70 months for both DFS and OS), respectively. Patients with high SUVmax had significantly lower DFS (P < 0.0001) and OS (P = 0.0092) than patients with low SUVmax. Multivariate analysis showed that high SUVmax was an independent prognostic factor for both DFS (P = 0.0161) and OS (P = 0.0232).ConclusionThe SUVmax of the primary tumour derived from PET/CT imaging could be an important prognostic indicator of recurrence and survival in patients with endometrial cancer.

D-dimer level as a risk factor for postoperative venous thromboembolism in Japanese women with gynecologic cancer

BACKGROUND The purpose of the present study was to evaluate whether early postoperative D-dimer levels and certain pre-, intra-, and postoperative parameters can be used to predict venous thromboembolism (VTE) in gynecologic cancer patients. MATERIALS AND METHODS We prospectively evaluated 267 gynecologic cancer patients who underwent surgery at our institution. The plasma D-dimer level was measured serially before the operation and on certain postoperative days. After the operation, primary screening for VTE was undertaken by meticulous examination for clinical signs and elevation of the plasma D-dimer level. Seventy-five patients underwent multidetector row computed tomography and were subjected to further investigations. RESULTS VTE was detected in 21 of the 75 patients. There were significant differences in the D-dimer value between VTE-positive and VTE-negative patients on postoperative days 3, 5, and 7. The optimal cut-off value for the postoperative D-dimer level was determined as 5 mug/ml on day 3. Logistic regression multivariate analysis revealed that high D-dimer values on postoperative day 3, the use of recombinant human erythropoietin (rHuEPO), and non-O blood group were independent risk factors for postoperative VTE. CONCLUSION High plasma D-dimer level on postoperative day 3, the use of rHuEPO, and non-O blood group were independent risk factors for postoperative VTE.

Neutrophil to lymphocyte ratio in the pre-treatment phase of final-line chemotherapy predicts the outcome of patients with recurrent ovarian cancer

Inflammation and tumor immunology are associated with prognosis in a variety of cancers. The aim of the present retrospective study was to identify associations between the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), cancer antigen 125 (CA125) concentrations, tumor response, performance status (PS) and survival of patients that developed recurrent ovarian cancer subsequent to receiving chemotherapy. The NLR and PLR measured prior to fourth-line chemotherapy were significantly increased compared with those measured prior to second-line chemotherapy (P=0.029 and 0.049, respectively). By using receiver operating characteristic curves, the cut-off values were determined for the NLR, PLR and CA125 levels that were measured during the pre-treatment phase, which predicted the outcomes. According to univariate analyses, pre-treatment NLR >3.91, PLR >299.0 and PS 2 were each significantly associated with poor outcomes (P=0.001, 0.005 and 0.021, respectively). According to multivariate analyses, only pre-treatment NLR was associated with poor outcome (P=0.035). The present findings indicate that pre-treatment NLR is an important predictor of prognosis in patients with ovarian cancer that experience recurrence following chemotherapy.

The posttreatment mean apparent diffusion coefficient of primary tumor is superior to pretreatment ADCmean of primary tumor as a predictor of prognosis with cervical cancer

The objective of this study was to investigate the correlation of pretreatment and posttreatment measurements as the mean apparent diffusion coefficient (ADCmean) by diffusion‐weighted magnetic resonance imaging (DWI) findings with prognostic factors in patients with squamous cell carcinoma (SCC) of primary cervical cancer. The pretreatment and posttreatment ADCmean of the primary tumor were examined for their correlations with the prognosis in 69 patients with SCC of primary cervical cancer by radiotherapy (RT) with or without concurrent chemotherapy (CCRT). The median disease‐free survival (DFS) and overall survival (OS) times of patients were 20.97 and 23.47 months (follow‐up periods for DFS and OS: 1–72 and 1–72 months). The DFS and OS rates of patients with low pretreatment and posttreatment ADCmean of the primary tumor were also significantly worse than those of patients exhibiting high pretreatment and posttreatment ADCmean of the primary tumor (DFS; P = 0.0130 and P < 0.0001, OS; P = 0.0010 and P < 0.0001). Multivariate analyses showed that low posttreatment ADCmean of the primary tumor was an independent prognostic factor for DFS and OS (P < 0.0001 and P < 0.0001). The low posttreatment ADCmean of the primary tumor is a useful clinical prognostic biomarker for recurrence and survival in patients with cervical cancer.

Postoperative decreased levels of D-dimer in patients with gynecologic cancer with enoxaparin and fondaparinux thromboprophylaxis.

The purpose of the present study was to evaluate the effects of enoxaparin (ENO) and fondaparinux (FPX) on postoperative plasma D-dimer levels and risk factors associated with postoperative venous thromboembolism (VTE) and pulmonary thromboembolism (PTE) in patients with gynecologic cancer. For this study, 434 patients with gynecologic cancer were recruited and a surgical treatment strategy was employed. Plasma D-dimer levels were measured prior to surgery, as well as on a schedule up to 3 weeks postoperatively and again after day 28. Patients with clinical signs and elevation of the plasma D-dimer level underwent multidetector row computed tomography. The D-dimer value was significantly lower in patients with ENO or FPX on postoperative days 3–10 compared to patients with gynecologic cancers who were not receiving ENO or FPX. The D-dimer value was significantly lower in patients with FPX compared to patients with ENO on postoperative days 5–7. The D-dimer value on postoperative day 3, the use of erythropoiesis-stimulating agents (ESAs), advancing age and non-O blood group were independent risk factors for postoperative VTE. The D-dimer value on postoperative day 3 and the use of ESAs were independent risk factors for postoperative PTE. The postoperative D-dimer value was significantly lower in patients with gynecologic cancer who were administered ENO or FPX compared to patients were not administered either ENO or FPX. The use of ESAs and high plasma D-dimer levels on postoperative day 3 were independent risk factors for postoperative VTE and PTE.

Prognostic nutritional index as a predictor of survival in patients with recurrent cervical cancer

Systemic inflammatory responses (SIRs) can help predict survival in various cancers. The present study investigated the accuracy of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and prognostic nutritional index (PNI) in predicting survival for patients with recurrent cervical cancer. A retrospective review of prognoses examined the associations among NLR, PLR, and PNI, and clinical characteristics and survival in 79 patients with recurrent cervical cancer after undergoing concurrent chemoradiation therapy (CCRT) or radical hysterectomies with or without CCRT. The Mann-Whitney U-test was used for statistical analyses. In addition, 12-month, 24-month and overall survival were analyzed by the Kaplan-Meier method. Coxs proportional hazard regression was used for univariate and multivariate analyses. Median survival was 15.0 months over follow-up periods of 2–93 months. At the last follow-up point, 54 had succumbed to disease and 25 were alive with disease. In univariate analysis, NLR, PLR and PNI were significantly associated with 12-month, 24 month and overall survival (12 months: P=0.021, P=0.001 and P<0.001; 24 months: P=0.020, P=0.008 and P<0.001; overall; P=0.032, P=0.032 and P<0.001, respectively). In multivariate analyses, PNI was an independent prognostic factor for 12-month, 24-month and overall survival (P=0.001, P=0.001 and P<0.001, respectively). PNI is a useful predictor of survival of recurrent cervical cancer.

Radical Hysterectomy Plus Concurrent Chemoradiation/Radiation Therapy Is Negatively Associated With Return to Work in Patients With Cervical Cancer.

Objective Cervical cancer is one of the most common malignant diseases in working-age women. This study investigated the influence of adverse effects of various treatment modalities on return to work in women with cervical cancer. Methods Questionnaires and clinical data from medical records of 97 patients with early stage (stages I and II) cervical cancer were collected and assessed by treatment received. The following treatment groups were analyzed for correlations between time to return to work and various adverse effects: radical hysterectomy (RH) alone, RH group (n = 29); concurrent chemoradiation therapy (CCRT)/radiation therapy (RT) alone, CCRT/RT group (n = 21); and RH + CCRT/RT group (n = 47). The χ2 test was used to determine the significance of the correlations. Results The mean age at the time of diagnosis was 43.0 years and the average interval since treatment was 4.5 years. The RH + CCRT/RT group was the most strongly negatively associated with return to work in employed patients who had undergone CCRT/RT group of cervical cancer (P = 0.012). There was a significant association between failure to return to work and lower extremity lymphedema (P = 0.049). A more than–6-month interval between treatment and return to work and reduced personal income occurred in a significantly higher percentage of patients in the RH + CCRT group than in the CCRT/RT group (P = 0.034 and P = 0.034). Conclusions Of the treatments assessed, RH + CCRT/RT has the greatest negative effect on return to work in women with cervical cancer.