Efficacy of Lidocaine Spray for Pain Reduction during Colposcopy-Directed Cervical Biopsies: A Randomized Controlled Trial.

Objectives: The objective of this study was to evaluate the efficacy of lidocaine spray in reducing the pain during colposcopy-directed cervical biopsy (CDB). Methods: From December 2017 to February 2019, 312 women undergoing CDBs were enrolled. The participants were randomized to three groups: group 1 (lidocaine spray), in which lidocaine spray was applied thoroughly to the cervix; group 2 (placebo), in which normal saline was applied thoroughly to the cervix; and group 3 (control), in which no anesthetic agent was applied to the cervix. Each woman completed a 10 cm visual analog scale to classify the subjective pain experience at three time points: baseline, immediately after biopsy, and 10 min after the procedure. The primary outcome of this study was the biopsy pain score. Results: The 312 enrolled women were randomly assigned to the three groups, amounting to 104 women per group. The clinical and pathological characteristics of the participants in all groups were comparable. The baseline, the biopsy, and the post-procedure pain scores were comparable among the three groups. There was a significant increase in the pain score from baseline to biopsy and from baseline to post-procedure in each group. The pain-score changes from baseline to biopsy in the lidocaine spray group significantly decreased when compared with the normal saline group (<0.001), and tended to decrease, though not significantly (p = 0.06), when compared with the control group. No complication with the intervention was observed. Conclusions: The application of lidocaine spray to the cervix has the benefit of reducing the pain associated with CDBs by a small amount. However, the intervention is safe and may be considered in nulliparous and/or overly anxious women undergoing the procedure.

Comparison of risk prediction scores for cancer-associated thrombosis in ambulatory cancer patients not receiving thromboprophylaxis: A prospective cohort study in a South-East Asian population.

INTRODUCTION: To date, there is limited data regarding the incidence and risk prediction of cancer-associated thrombosis among South-East Asian patients who do not receive thromboprophylaxis. MATERIALS AND METHODS: This was a prospective cohort study conducted at a tertiary medical center from June 2020 to December 2021 in Thailand. We enrolled cancer patients aged ≥ 18 years, with ECOG score ≤ 1, scheduled to receive the first cycle of chemotherapy. We measured incidence of venous thromboembolism (VTE), all-cause mortality and performance of risk prediction scores. RESULTS: A total of 457 patients were included with a mean age of 58.18 ± 12.60 years. By the end of 6 months period, VTE had occurred in 30 patients (6.56 %, 95%CI 4.36-9.21). The median time to the first thrombosis was 1.94 months (IQR 0.26-3.19). Cancer associated thrombosis incidence was 14.58 % for Khorana score ≥ 3, 6.67 % for scores 1-2 and 2.13 % for score 0. C-statistics were 0.50 (95%CI 0.41-0.60) for Khorana score cut-off ≥ 2, 0.57 (95%CI 0.49-0.65) for Khorana score ≥ 3, 0.55 (95%CI 0.46-0.65) for PROTECHT score ≥ 3, and 0.57 (95%CI 0.49-0.65) for CONKO score ≥ 3. Classifying cholangiocarcinoma as very-high-risk increased the Khorana score cut-off ≥ 3's C-statistic to 0.62 (95%CI 0.53-0.71). CONCLUSIONS: A significant proportion of ambulatory South-East Asian cancer patients without thromboprophylaxis developed VTE. Further prospective studies investigating the benefit of thromboprophylaxis in high-risk patients with active cancer are warranted.

Clear-Cell Mesothelioma of Uterine Corpus: Diagnostic Challenges in Intraoperative Frozen Sections.

The clear-cell variant of epithelioid mesothelioma is an extremely rare neoplasm of the peritoneum. It shares histomorphologic features overlapping with a wide variety of tumors including carcinomas and other non-epithelial neoplasms. The diagnosis of peritoneal clear-cell mesothelioma is not always straightforward, despite known immunohistochemistry (IHC) markers. Due to its rarity, this entity may be diagnostically confused with other clear-cell neoplasms, particularly in intraoperative frozen sections. Here, we present a case of clear-cell mesothelioma originating in the uterine serosa that was initially misdiagnosed as clear-cell adenocarcinoma in the intraoperative frozen section. Microscopically, the tumor showed diffuse tubulocystic spaces of variable size lined by clear cells with moderate nuclear atypia. Immunohistochemical staining confirmed the diagnosis of clear-cell mesothelioma. Recognition of this entity, albeit rare, is important as the diagnosis may significantly affect the management considerations. The judicious use of an IHC panel helps to distinguish this tumor from other mimickers.

Profiling the Expression and Prognostic Values of FYN, A Non-Receptor Tyrosine Kinase, in Different Histological Types of Epithelial Ovarian Cancer.

OBJECTIVE: This study was aimed at evaluating FYN expression among different histologic types of epithelial ovarian cancer (EOC) and its associated prognostics. METHODS: The FYN expression levels using quantitative real-time PCR method were evaluated in 98 primary EOC. Receiver operating characteristic curve were used to select an optimal cut-off value for determining the presence or absence of a disease progression. RESULT: The median level of FYN expression varied among different EOC types, being the highest in high-grade serous carcinomas and the lowest in clear cell carcinomas (CCC). Using the cutoff FYN value to predict disease progression, the FYN-positive group had a poorer progression-free survival (PFS) compared to the FYN-negative group (p = 0.001). In multivariate Cox regression analysis, FYN expression was an independent predictor for disease progression (Hazard ratio = 2.30; 95% CI: 1.21- 4.38; p = 0.011). In subgroup analysis, FYN expression was significantly associated with lower PFS in early stage CCC patients (p = 0.009). CONCLUSION: FYN expression is variable among different types of EOC while impacting on the prognostic values in patients with early stage CCC.

Micturition symptoms in gynecologic cancer patients receiving paclitaxel and platinum-based chemotherapy regimen: a prospective study.

OBJECTIVE: To evaluate the effect of paclitaxel and platinum-based chemotherapy (PT) on micturition symptoms. METHODS: All gynecologic cancer patients who were assigned to receive the PT regimen and understood the Thai language were invited to participate in this study. The exclusion criteria were as follows: abnormal urinary symptoms, retained urinary catheter or percutaneous nephrostomy, anticholinergic drug use, or scheduled to receive radiation therapy after the completion of chemotherapy. The participants were interviewed using three Thai validated questionnaires, the incontinence impact questionnaire-short form, urogenital distress inventory short form, and Sandvik score, on the day before receiving the first cycle of chemotherapy (pre-treatment), on the day before receiving the 4th cycle (mid-treatment), and 46 weeks after completing 69 cycles (post-treatment). The scores at the three time points were compared. Patients who received less than three cycles were not included in the analysis. RESULTS: One hundred and ten patients were included in this study. There were significant differences in the median questionnaire scores at the three time points for both carboplatin plus paclitaxel and cisplatin plus paclitaxel. However, when using a pairwise difference between the two treatment protocols, there were no significant changes in the score from pre-treatment to post-treatment. CONCLUSION: The PT regimen has an impact on micturition symptoms during chemotherapy which recover after treatment completion.

Oncology and reproductive outcomes over 16 years of malignant ovarian germ cell tumors treated by fertility sparing surgery.

BACKGROUND: Malignant ovarian germ cell tumors (MOGCT) are rare and frequently occur in women of young and reproductive age and the oncologic and reproductive outcomes after fertility-sparing surgery (FSS) for this disease are still limited. AIM: To evaluate the oncology and reproductive outcomes of MOGCT patients who underwent FSS. METHODS: All MOGCT patients who underwent FSS defined as the operation with a preserved uterus and at least one side of the ovary at our institute between January 2005 and December 2020 were retrospectively reviewed. RESULTS: Sixty-two patients were recruited for this study. The median age was 22 years old and over 77% were nulliparous. The three most common histology findings were immature teratoma (32.2%), dysgerminoma (24.2%), and yolk sac tumor (24.2%). The distribution of stage was as follows; Stage I, 74.8%; stage II, 9.7%; stage III, 11.3%; and stage IV, 4.8%. Forty-three (67.7%) patients received adjuvant chemotherapy. With a median follow-up time of 96.3 mo, the 10-year progression-free survival and overall survival were 82.4% and 91%, respectively. For reproductive outcomes, of 43 patients who received adjuvant chemotherapy, 18 (41.9%) had normal menstruation, and 17 (39.5%) resumed menstruation with a median time of 4 mo. Of about 14 patients who desired to conceive, four were pregnant and delivered good outcomes. Only one case was aborted. Therefore, the successful pregnancy rate was 28.6. CONCLUSION: The oncology and reproductive outcomes of MOGCT treated by FSS are excellent. Many patients show a long survival time with normal menstruation. However, the obstetric outcome is not quite satisfactory.

Prevalence and risk factor of post-operative lower extremities deep vein thrombosis in patients undergoing gynecologic surgery: a single-institute cross-sectional study.

BACKGROUND AND AIM: The study of prevalence and risk factors of postoperative lower limb deep vein thrombosis (DVT) in Thai gynecologic patients was limited. The present study was conducted to evaluate this issue. METHODS: The patients were age > 15 years old without a history of DVT or pulmonary emboli (PE) scheduled for laparotomy or vaginal gynecologic surgery between May and November 2020 were invited to participate. All of these patients were scheduled for a complete duplex ultrasound to detect lower limb DVT 72 h before and within 14 days after the operation. The patients without DVT were scheduled for an interview by telephone about DVT symptoms 30 days after the operation. The clinical variables were compared using univariate and multivariate analysis to identify the independent factors related to the development of DVT. RESULTS: One hundred and twelve patients met the inclusion criteria. Of these patients, 44 cases (39.3%) were diagnosed as malignancy and 102 patients underwent a hysterectomy. Post-operative DVTs were detected in six patients (5.4%) and all except one had a malignancy. Thus, the prevalence of DVT in malignancy cases was five in 44 patients (11.4%). The independent risk factors for postoperative DVT were age > 60-year-old and receiving a perioperative blood transfusion. Five of six DVT patients received low molecular-weight heparin for treatment of DVT and none developed PE. The rest of the participants reported no symptom-related DVTs from the interview 30 days after the operation. CONCLUSION: The prevalence of postoperative DVT in gynecologic patients was 5%, and the independent risk factors were elderly patients and receiving a perioperative blood transfusion.

Effectiveness of enhanced recovery after surgery protocol in open gynecologic oncology surgery: A randomized controlled trial.

OBJECTIVE: To examine the effectiveness of applying the recommended enhanced recovery after surgery (ERAS) protocol compared with our usual care in women with gynecologic malignancy undergoing elective laparotomy. METHODS: From June 2020 to May 2021, 93 women with gynecologic cancers (cervix, endometrium, and ovary) undergoing elective laparotomy at our institution were randomly assigned into an intervention group (ERAS protocol, 46 women) or control group (usual care, 47 women). For the intervention group, each woman was brought through the pre-specified ERAS protocol starting from preoperative counseling to postoperative management. For the control group, participants underwent routine standard care. The primary outcomes were length of hospital stay and postoperative pain. RESULTS: The intervention group demonstrated shorter hospital stay by 20 h (47.48 h vs 67.17 h, P = 0.02) with lower postoperative pain score at postoperative day 0 (1.58 vs 4.00, P < 0.01) and day 1 (1.00 vs 2.67, P < 0.01) while having decreased opioid consumption (P < 0.01). The intervention group also had faster recovery of gastrointestinal function. Overall, good compliance to most of the ERAS pathway domains was obtained. CONCLUSION: The ERAS protocol demonstrates benefits on shortening hospital stay, reducing pain, and bowel function recovery without increasing complications in our population. CLINICAL TRIAL REGISTRATION: The present study was registered at clinicaltrials.gov (NCT04201626) on December 3, 2019. Initial participant enrollment began on June 1, 2020. Access through URL of the registration site: https://clinicaltrials.gov/ct2/show/NCT04201626?cond=ERAS&cntry=TH&draw=2&rank=3.

Efficacy of Listening to Music on Pain Reduction during Colposcopy-Directed Cervical Biopsy: A Randomized, Controlled Trial.

Background and Objective: To investigate the efficacy of listening to music on pain reduction during colposcopy-directed cervical biopsy (CDB). Materials and Methods: From June 2020 to November 2021, 240 women undergoing CDB were enrolled. The participants were randomized into three groups: Group 1, colposcopic examination while wearing headphones and listening to music; Group 2, colposcopy while wearing headphones but not listening to music; Group 3 (control group), colposcopy while neither listening to music nor wearing headphones. All participating women completed a 10 cm visual analog scale for subjective pain at three time points: baseline, immediately after cervical biopsy, and 15 min after the procedure. The primary endpoint was the biopsy pain score. Result: Of the 240 women, a sample size of 80 was randomly assigned per group. The clinical-pathological and procedure-related characteristics of the participants in all groups were similar. The mean baseline pain score between each group was not significantly different (2.83 in the music group, 2.54 in group 2, and 2.94 in the control group, p = 0.47). There were no significant differences between each group in terms of mean biopsy pain score (4.21 in the music group, 4.24 in group 2, and 4.30 in the control group, p = 0.98). The differences in changes between the baseline pain score and the biopsy pain score were not statistically significant (1.39 in the music group, 1.70 in group 2, and 1.36 in the control group, p = 0.69). In the multiple comparison analysis, the differences in changes between the biopsy pain score and the baseline pain score between each group were also not statistically significant. There were no complications with the intervention observed. Conclusion: This study demonstrated that there was no beneficial effect of listening to music on pain reduction during colposcopy-directed cervical biopsies.

Prevalence of malnourishment and predictive factors associated with the nutritional status of gynecologic cancer patients undergoing chemotherapy: a cross-sectional analysis.

OBJECTIVE: To investigate the prevalence and predictive factors of malnourishment in patients with gynecologic cancer during chemotherapy. METHODS: A total of 101 patients treated with chemotherapy between April 2020 and February 2021 were interviewed using the patient-generated subjective global assessment (PG-SGA). Clinical and laboratory data were also collected. The total number of lymphocytes per cubic milliliter (total lymphocyte count, TLC) and serum albumin were calculated to provide an optimal cut-off point using receiver operating characteristic curves. Clinicopathological variables were compared using univariate and multivariate analyses to identify the independent predictive factors for malnourishment. RESULTS: The prevalence of good, moderate, and severe nourishment was 73.3%, 18.8%, and 7.9%, respectively. The optimal cut-off points for TLC and albumin were 1,450 cells/µL and for albumin was 3.9 g/dL. Univariate analysis indicated that the number of chemotherapy cycles ≤3, albumin level ≤3.95 g/dL, body mass index ≤25 kg/m2, TLC <1,450 cells/µL, anemia, and no neutropenia were significantly associated with malnutrition. However, only a serum albumin level ≤3.95 g/dL was independently associated with malnourishment. CONCLUSION: Patients with gynecologic cancer treated with chemotherapy were occasionally found to be malnourished, with the independent predictive predictor being a blood albumin level less than or equal to 3.95 g/dL.

Clinicopathological Prognostic Factors Influencing Survival Outcomes of Vulvar Cancer.

BACKGROUND: The prognostic factors for survival in squamous cell carcinoma (SCCA) of vulva cancer such as groin node involvement, postmenopausal status, tumor size, margin status, tumor grade, lymph vascular space invasion (LVSI) were reported in the past. However, with limited data from Southeast - Asian population, the present study was conducted to evaluate the clinicopathological prognostic factors for survival outcomes of this disease after treatment with surgery. METHODS: All SCCA vulva cancer patients who underwent surgery between January 2006 and December 2017 were reviewed. The clinicopathological factors were analyzed to identify the prognostic factors for the progression-free survival (PFS) and overall survival (OS) using the Kaplan- Meier method and Cox-Proportional Hazard model. RESULTS: One hundred twenty-five patients were recruited. The independent poor prognostic factors for PFS were groin node-positive and  pathologic tumor diameter of more than 25 mm. Whereas postmenopausal status and groin node positive were independent poor prognostic factors for OS. CONCLUSION: Groin node-positive was the only one independent poor prognostic factor for both PFS and OS. In addition, the tumor diameter longer than 25 mm. was independent poor prognostic factors for PFS while postmenopausal status was independent poor prognostic factors for OS. Special adjuvant treatment for patients with these factors should be further investigated. 
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iPMI: Machine Learning-Aided Identification of Parametrial Invasion in Women with Early-Stage Cervical Cancer.

Radical hysterectomy is a recommended treatment for early-stage cervical cancer. However, the procedure is associated with significant morbidities resulting from the removal of the parametrium. Parametrial cancer invasion (PMI) is found in a minority of patients but the efficient system used to predict it is lacking. In this study, we develop a novel machine learning (ML)-based predictive model based on a random forest model (called iPMI) for the practical identification of PMI in women. Data of 1112 stage IA-IIA cervical cancer patients who underwent primary surgery were collected and considered as the training dataset, while data from an independent cohort of 116 consecutive patients were used as the independent test dataset. Based on these datasets, iPMI-Econ was then developed by using basic clinicopathological data available prior to surgery, while iPMI-Power was also introduced by adding pelvic node metastasis and uterine corpus invasion to the iPMI-Econ. Both 10-fold cross-validations and independent test results showed that iPMI-Power outperformed other well-known ML classifiers (e.g., logistic regression, decision tree, k-nearest neighbor, multi-layer perceptron, naive Bayes, support vector machine, and extreme gradient boosting). Upon comparison, it was found that iPMI-Power was effective and had a superior performance to other well-known ML classifiers in predicting PMI. It is anticipated that the proposed iPMI may serve as a cost-effective and rapid approach to guide important clinical decision-making.

Prevalence of Tissue BRCA Gene Mutation in Ovarian, Fallopian Tube, and Primary Peritoneal Cancers: A Multi-Institutional Study.

BACKGROUND AND OBJECTIVE: Ovarian, fallopian tube, or primary peritoneal cancer patients with BRCA gene mutation have enhanced sensitivity to platinum-based regimens and PARP inhibitors. However, the knowledge regarding BRCA mutation in Thai patients is limited. This study aimed at identifying the prevalence and characteristics of somatic and germline BRCA 1 and 2 mutations in Thai patients with these cancers. MATERIALS AND METHODS: The paraffin blocks of tumors with histology of high grade serous, high grade endometrioid, or clear cell carcinoma obtained between June 2016 and December 2017 were analyzedto evaluate BRCA mutation using next-generation sequencing system. Blood or normal tissue paraffin blocks of positive patients were further tested for germline BRCA mutation. RESULTS: Tissue paraffin blocks of 178 patients were collected but only 139 were analyzed. Positive BRCA mutation was identified in 24 patients (17.3%): BRCA1 in 13 cases, BRCA2 in 10 cases, and BRCA1 and 2 in the rest one. Germline mutation study in blood or normal tissue in 23 positive patients revealed BRCA mutation in 14 cases, BRCA1 in 8 cases and BRCA 2  in 6 cases. Overall, the prevalence of somatic and germline mutation was 6.5% (9 out of 138 patients) and 8.7% (14 out of 138 patients), respectively. The most common histology associated with BRCA mutation was high grade serous cancer (27.3%). No significant difference was found between patients with or without BRCA mutation in terms of stage, outcome, platinum status, and survival outcome. CONCLUSION: BRCA mutation was demonstrated in less than 10% of Thai ovarian cancer patients. Higher rate of mutation was found in high grade serous cancer.
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Potential predictors for chemotherapeutic response and prognosis in epithelial ovarian, fallopian tube and primary peritoneal cancer patients treated with platinum-based chemotherapy.

OBJECTIVE: This study aimed to investigate the potential predictive factors for platinum resistance and poor prognosis in epithelial ovarian, fallopian tube, and primary peritoneal cancer treated with platinum-based chemotherapy. METHODS: Medical records of 306 patients with the above mentioned cancers treated with platinum-based chemotherapy between 2007 and 2017 were retrospective reviewed. Clinical data, preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platinum-free interval, and survival time were recorded. NLR, PLR, and cancer antigen 125 (CA125) levels were calculated for an optimal cutoff point using receiver operating characteristic curves. The clinicopathological variables were compared using univariate and multivariate analyses to identify independent predictive factors for platinum resistance and poor survival outcomes. RESULTS: The optimal cutoff points for NLR, PLR, and CA125 were 3.38, 210, and 365 IU/L, respectively. Univariate analysis indicated that NLR >3.38, PLR >210, CA125 >365, advanced stage, suboptimal disease, serous type, and ascites were significant predictive factors for platinum resistance. However, only NLR >3.38 and advanced stage were independent predictive factors with an adjusted odds ratio of 1.880 and 3.333, respectively. Regarding factors associated with poor survival outcomes, only PLR >210 and advanced stage were independent factors, with a hazard ratio of 1.578 and 3.994, respectively. CONCLUSION: High NLR and advanced stage were potential independent predictive factors for platinum resistance, whereas high PLR and advanced stage were potential independent predictive factors for poor survival outcomes.

Primary signet ring cell carcinoma with neuroendocrine differentiation arising in mucinous borderline tumor of the ovary.

•Primary signet ring cell carcinoma in ovarian mucinous tumor is rare.•The most important differential diagnosis is metastatic carcinoma.•We report a case of primary ovarian signet ring cell carcinoma in mucinous tumor.•Clinicopathological correlation is essential to establish the correct diagnosis.

Treatment Outcomes of Patients with Squamous Cell Carcinoma of the Vulva: The Largest Series from a Tertiary Care Hospital.

OBJECTIVE: To evaluate the outcomes of squamous cell carcinoma (SCCA) of the vulva treated at our tertiary care center. METHODS: The medical records of SCCA patients treated between January 2006 and December 2015 were retrospectively reviewed. RESULTS: One hundred forty-five patients met the criteria with the median age of 57 years old, and 58.6% had an underlying disease. The distribution of stages was as follows: IA 6.2%, IB 21.4%, II 26.2%, IIIA 14.5%, IIIB 6.2%, IIIC 9.7%, IVA 9.0%, and IVB 6.9%. One hundred and nine patients underwent surgical intervention and radical local excision with bilateral groin node dissection as the most frequent procedure. Approximately half of the patients received combined treatment with surgery followed by radiation with or without chemotherapy. Recurrence developed in 127 patients after the median follow-up time of one year with the common sites in the groin and vulva region. However, no significant difference in survival occurred in patients with and without groin node recurrence (15 vs. 28 months, P=0.109). The five-year overall survival was 50.8%. CONCLUSIONS: The survival of patients with SCCA vulvar cancer was modest. The common failure sites were groin and vulva regions with unfavorable outcomes.

Cancer Antigen 125 during Pregnancy in Women without Ovarian Tumor Is Not Often Rising.

OBJECTIVE: To determine the percentage of rising serum cancer antigen (CA-125) in singleton pregnant women whose ultrasonographical findings were normal. METHODS: Singleton pregnant women who received antenatal care at our institute with a normal ultrasonographical examination in their first and/or second trimester were invited to participate in blood testing for CA-125. The conditions that might affect the CA-125 level were excluded. The normal level of CA-125 was defined as ≤35 U/ml. RESULTS: 136 pregnant women met the inclusion criteria. Of these cases, 87 cases received a blood test for CA-125 in both their first and second trimesters while 46 and 3 cases received a blood test for CA-125 in only the first and second trimester, respectively. The median serum CA-125 levels in the first and second trimester were 16.44 (range 5.94-77.54) U/ml and 16.76 (range 5.26-35.81) U/ml, respectively. Only 9.1% of the studied patients showed an abnormal CA-125 level in the first trimester period and only one case showed an abnormal CA-125 level in the second trimester period. CONCLUSION: Few of normal pregnancies showed rising CA-125. Therefore, when it elevated in pregnant women, other causes such as the adnexal lesion should be investigated.

Relationships of Ex-Vivo Drug Resistance Assay and Cytokine Production with Clinicopathological Features in the Primary Cell Culture of Thai Ovarian and Fallopian Tube Cancer Patients

Objective: Our goal was to determine the ex-vivo drug resistance assay, as well as the cytokine production, in response to platinum-based chemotherapy treatment in primary culture cells established from the tumor tissue of ovarian or fallopian tube carcinoma patients, and to predict the clinical responses to chemotherapy. Methods: Sensitivity to the platinum-based drug was analyzed in two ovarian cancer cell lines and 19 tumor samples using the primary cell culture obtained from 19 patients having ovarian or fallopian tube cancer that had undergone surgery from 2014 to 2017. Results: Our findings in the ovarian cancer cell lines showed that SKOV3 cells displayed 10-fold greater resistance to cisplatin and 5.8 times more resistance to carboplatin than A2780 cells. SKOV3 cells displayed platinum-induced IL-6 and IL-8 overproduction whereas wild type A2780 displayed no detectable cytokine production. Regarding the primary cell culture obtained from patients, ex-vivo drug resistance assay results revealed that although extreme drug resistance was correlated with late stage ovarian cancer (P= 0.031), it could not independently predict or alter the outcomes of patients with ovarian or fallopian tube cancer. No relationship was found between basal cytokine secretion and the clinical parameters. However, carboplatin-induced IL-6 and IL-8 production had a significant association with the clinical response to chemotherapy (P=0.016 and P=0.038 respectively). Carboplatin-induced IL-8 overproduction was correlated with FIGO staging III-IV (P=0.026), but no correlation between carboplatin-induced IL-6 and FIGO staging (P= 0.061) was noted. Conclusion: These results suggest that cytokine production in response to platinum-based chemotherapy in primary culture cells may be useful as a predictive marker for the therapeutic outcomes among ovarian or fallopian tube cancer patients.

Randomized, Controlled Trial of Dexamethasone Versus Dexamethasone Plus Hydrocortisone as Prophylaxis for Hypersensitivity Reactions Due to Paclitaxel Treatment for Gynecologic Cancer.

OBJECTIVE: The aim of this study was to assess intravenous hydrocortisone (HCT) added to standard dexamethasone (DXM) prophylaxis for paclitaxel-associated hypersensitivity reactions (HSRs). METHODS: Paclitaxel naives scheduled for 6 cycles of paclitaxel (plus platinum) were randomized to DXM alone (20 mg intravenously [IV]) versus DXM plus HCT (100 mg IV) as premedication including chlorpheniramine (10 mg IV), diphenhydramine (25 mg orally), and ranitidine (50 mg IV) 30 minutes before infusion. Clinic nurses observed for HSRs. Groups were well balanced for cancer type, stage, drug allergy, chemotherapy naivete, mean age, body mass index, and paclitaxel dose. RESULTS: The 44 DXM controls underwent 213 cycles and the 42 investigational DXM plus HCT group 192 per protocol cycles. Hypersensitivity reactions were observed among 9 (4.2%) DXM only cycles compared with 1 (0.5%) among DXM plus HCT cycles (P = 0.022). Hypersensitivity reactions occurred in 8 (18%) DXM only patients and in 1 (2.4%) among those correctly receiving DXM plus HCT (P = 0.030). All HSRs occurred in cycles 1 to 3, within 10 to 40 minutes after infusion initiation, and peaked in cycle 2 (5/39) for DXM recipients and in cycle 3 (1/30) for DXM plus HCT. Hypersensitivity reaction severity was grade 1 in 3 DXM only recipients and grade 2 in 6 DXM and 1 DXM plus HCT. A sole grade 3 HSR was in an intention-to-treat DXM-HCT patient, who erroneously received no HCT. Hypersensitivity reaction symptoms were facial flushing (8 episodes), dyspnea (7), palmar rash (1), and transient hypotension (1). Paclitaxel infusion was suspended for treatment of HSRs; in all cases, symptoms mitigated and infusion successfully restarted for the remaining dose. CONCLUSIONS: Adding HCT to routine DXM prophylaxis significantly decreased paclitaxel HSR frequency.

Prognostic Value of Tumor Budding in Early-Stage Cervical Adenocarcinomas

Background: Tumor budding has recently been reported as an independent adverse prognostic factor for colorectal adenocarcinomas and other types of carcinoma in the digestive tract. This study aimed to evaluate the prognostic value of tumor budding in patients with early-stage cervical adenocarcinomas and any associations with other clinical and pathological features. Methods: Histological slides of patients with early-stage (IB-IIA) usual-type endocervical adenocarcinoma who underwent radical hysterectomy and pelvic lymph node dissection, without preoperative chemotherapy, between January 2006 and December 2012 were reviewed. Tumor budding was evaluated in routinely-stained sections and defined as detached single cells or clusters of fewer than 5 cells in a tumor invasive front and was stratified based on the number of bud counts in 10-high-power fields as low (<15 buds) and high (≥15 buds). Correlations between tumor bud count and other clinical and pathological variables including follow-up outcomes were assessed. Results: Of 129 patients, a high tumor bud count was observed in 15 (11.6%), positively associated with histologic grade 3 (p<0.001), invasive pattern C (Silva System) (p=0.004), lymph node metastasis (p=0.008), stage IB2-IIA (p=0.016), and tumor size >2 cm (p=0.036). Kaplan-Meyer analysis showed a significant decrease in both disease-free survival and cancer-specific survival for patients with a high tumor bud count (p=0.027 and 0.031, respectively). On multivariate analysis, histologic grade 3 was the only independent predictor for decreased disease-free survival (p=0.004) and cancer-specific survival (p=0.003). Conclusions: A high tumor budding count based on assessment of routinely-stained sections was found to be associated with decreased disease-free and cancer-specific survival in patients with early-stage cervical adenocarcinomas. However, it was not found to be an independent prognostic predictor in this study.