Efficacy of regional cooling + oral dexamethasone for primary prevention of hand-foot syndrome associated with pegylated liposomal doxorubicin.

PURPOSE: Pegylated liposomal doxorubicin (PLD)-induced hand-foot syndrome (HFS) frequently lowers the quality of life of ovarian cancer patients. Wrist and ankle cooling, having a limited preventive effect, has been the commonest supportive HFS care. In this study, we retrospectively assessed the primary preventive effect of a combination of regional cooling and oral dexamethasone therapy (cooling + oral Dex) on HFS. METHODS: This study is a single-arm retrospective, observational study. Recurrent ovarian cancer patients were administered PLD ± bevacizumab. We retrospectively examined the efficacy of hands and feet cooling (from the start of PLD to the end) + oral Dex (day 1-5: 8 mg/day, day 6, 7: 4 mg/day) for primary HFS prevention. RESULTS: This study included 74 patients. The initial dose of PLD was 50 mg/m2 and 40 mg/m2 for 32 (43.2%) and 42 (56.8%) patients, respectively. HFS of Grade ≥ 2 and Grade ≥ 3 developed in five (6.8%) and one (1.4%) patient(s), respectively. The incidence of ≥ Grade 2 and ≥ Grade 3 HFS was much lower than those reported in previous studies. Dose reduction was required in 13 patients (17.6%) mainly because of neutropenia or mucositis; there was no HFS-induced dose reduction. Meanwhile, PLD therapy was discontinued mainly because of interstitial pneumonia (4 patients) and HFS (one patient). CONCLUSIONS: We demonstrated the efficacy of regional cooling and oral Dex for primary prevention of PLD-induced HFS. Although future prospective studies are needed to confirm its efficacy, this combination therapy can be considered for primary prevention of HFS in ovarian cancer patients on PLD.

Histone arginine methyltransferase CARM1 selective inhibitor TP-064 induces apoptosis in endometrial cancer.

Histone modification is the key epigenetic mechanism that regulates gene expression. Coactivator-associated arginine methyltransferase 1 (CARM1) is an arginine methyltransferase that catalyzes dimethylation of histone H3 (H3R17) at arginine 17. Lately, it has been suggested that CARM1 is associated with human carcinogenesis, and the CARM1-selective inhibitor, TP-064, has been shown to be a potential therapeutic agent for multiple myeloma. However, the physiological significance of CARM1 in endometrial cancer remains unclear. Therefore, we aimed to explore the role of CARM1 and the effect of TP-064 in endometrial cancer. To this end, we analyzed CARM1 expression in endometrial cancer using quantitative real-time polymerase chain reaction and examined the antitumor mechanism with CARM1 knockdown endometrial cancer cells. Moreover, we evaluated the therapeutic capability of TP-064 in endometrial cancer cells. CARM1 was remarkably overexpressed in 52 endometrial cancer tissues compared to normal endometrial tissues. The growth of CARM1 knockdown endometrial cancer cells was suppressed and CARM1 knockdown induced apoptosis. TP-064 also inhibited endometrial cancer cell growth and declined the number of endometrial cancer cell colonies. These data suggest that CARM1 may be a powerful therapeutic target for endometrial cancer.

Endometrial cancer with concomitant endometriosis is highly associated with ovarian endometrioid carcinoma: a retrospective cohort study.

BACKGROUND: Endometriosis is assumed to be involved in ovarian cancer development, which is called endometriosis-associated ovarian cancer (EAOC). Uterine endometrial cells may be the cell of origin of EAOC. Accumulated carcinogenic changes in the uterine endometrial cells may increase the risk of developing EAOC. To further understand the pathogenesis of EAOCs, we focused on the clinicopathological characteristics of EAOCs in endometrial cancer patients with concomitant endometriosis. METHODS: We retrospectively reviewed 376 patients who were surgically treated for stage I-III endometrial cancer. Clinicopathological characteristics were compared between patients with and without endometriosis. Furthermore, the incidence of simultaneous endometrial and ovarian cancer (SEOC) and the histological characteristics of SEOC were compared between the two groups. RESULTS: Among 376 patients with endometrial cancer, 51 had concomitant endometriosis. Patients with endometriosis were significantly younger and more frequently had endometrioid G1/G2 tumors than those without endometriosis. The incidence of SEOCs was significantly higher in endometrial cancer patients with endometriosis than those without it (p < 0.0001); notably, 12 of 51 endometrial cancer patients with endometriosis (24%) had SEOCs. All of the ovarian cancers in endometrial cancer patients with endometriosis were endometrioid carcinomas. Moreover, even in those without endometriosis, endometrioid carcinoma was the most common histological type of SEOC. CONCLUSION: We revealed that endometrial cancer patients with endometriosis had a high probability of SEOC and that endometrioid carcinoma was the most common histological subtype of SEOC regardless of the presence of endometriosis. For patients with endometrial cancer and endometriosis, careful examination of ovarian endometriotic lesions may be important to detect EAOCs.

Recurrent cervical cancer with PD-L1 amplification treated with nivolumab: A case enrolled in the BELIEVE trial.

Patients with cervical cancer benefiting from immune checkpoint inhibitors (ICIs) are limited. Recently, PD-L1 amplification has been attracted attention as a reliable marker of ICIs. A 47-year-old woman with stage IIB cervical cancer experienced disease progression during postoperative adjuvant chemotherapy. Cancer genomic profiling revealed that the tumor was microsatellite stable with PD-L1 amplification, therefore, nivolumab was administered by enrolling in the BELIEVE trial. Despite nivolumab treatment, remarkable disease progression was observed. At the beginning of nivolumab treatment, the patient already had multiple liver metastases with severe systemic inflammation as indicated by a high neutrophil-to-lymphocyte ratio (NLR), both of which are negative predictive markers for ICI. Despite the presence of PD-L1 amplification, nivolumab was ineffective in cancer progression, which may be attributable to the presence of liver metastasis and high NLR. ICI is recommended to be administered at an early stage of cancer treatment to enhance its effectiveness.

Transiently elevated D-dimer levels post-concentrated ascites reinfusion therapy cannot be used to predict deep vein thrombosis-pulmonary embolism.

AIM: Cell-free and concentrated ascites reinfusion therapy (CART) is useful for treating malignant ascites. We have previously experienced cases with no DVT-PE despite a marked elevation in D-dimer post-CART. In this study, we assessed the changes in the D-dimer levels in patients who received CART and investigated the association between elevated D-dimer levels and occurrence of DVT-PE. METHODS: We performed an observational retrospective analysis of patients with gynecological malignancies treated with CART between March 2018 and April 2021. The selected patients had their D-dimer levels measured before and post-CART. The presence or absence of clinical DVT-PE findings was then examined, and contrast-enhanced computed tomography was performed using a DVT protocol in some cases. RESULTS: Eleven patients received 17 CART procedures in this study. Patients of 16 procedures (94.1%) showed a significant elevation in D-dimer levels on day 1 post-CART. Changes in D-dimer levels were monitored in these patients of 16 procedures. In all 16 cases, the D-dimer levels decreased after day 2 post-CART. Only one patient, who presented with respiratory failure, out of the patients of 16 procedures (6.2%) with elevated D-dimer levels on day 1 had PE. CONCLUSIONS: D-dimer elevation after CART is likely to be transient and a false-positive. None of the patients in this study had PE if they were asymptomatic after CART, there is no need to strongly suspect PE only by D-dimer elevation. In conclusion, D-dimer measurement immediately post-CART is not helpful in predicting the diagnosis of DVT-PE.

Manual vacuum aspiration (women's MVA) for endometrial biopsy for patients with suspected endometrial malignancies.

AIM: Endometrial biopsy is generally performed with a metal uterine curette sonde; however, recently, many types of vacuum aspirators are available, including the manual vacuum aspiration (MVA) system. We used the women's MVA system for endometrial sampling and evaluated its effectiveness in determining the presence of endometrial malignancy. METHODS: Forty-seven samples were examined using the following procedures after measuring endometrial thickness by transvaginal ultrasonography: fractional curettage biopsy (Bx; 20 samples), total curettage under general anesthesia (T/C; 13 samples), and MVA (14 samples). The quality of the endometrial samples was classified into four types: 1-4, where 1 denoted poor and 4, good quality. RESULTS: The mean score of the MVA group was significantly higher than that of the partial curettage biopsy group (p = 0.0065). No differences were observed between the MVA and total curettage groups (p = 1.00). When patients were divided into two groups according to endometrial thickness (<10 mm or ≥10 mm) and analyzed, both the MVA and T/C groups did not show a significant difference in their scores compared to the Bx group when the endometrial thickness was <10 mm. However, when the endometrial thickness was ≥10 mm, the MVA and T/C groups had significantly better scores than the Bx group (p = 0.0225 and p = 0.0244, respectively). Vagal reflex, as an adverse event, was observed only in two patients in the Bx group (2/20, 10%). CONCLUSION: Considering its quality and safety, Karman-type MVA for endometrial sampling could be an alternative to fractional curettage using a metallic uterine curette sonde.

A low preoperative albumin-to-globulin ratio is a negative prognostic factor in patients with surgically treated cervical cancer.

BACKGROUND: The albumin-to-globulin ratio reflects both the nutrition and inflammation and predicts prognosis in patients with various malignancies. However, in cervical cancer patients who undergo surgery, its significance has yet to be established. METHODS: A total of 247 cervical cancer patients who received surgical treatment at our institution between 2005 and 2017 were enrolled in this study. Preoperative data, such as the levels of serum albumin and serum globulin as well as the albumin-to-globulin ratio along with the other clinicopathological characteristics were retrospectively assessed, and their association with the overall survival was analyzed. RESULTS: Overall, 49 cases of recurrence and 26 deaths were observed during the median follow-up time of 58.6 months. A low albumin-to-globulin ratio (< 1.345) as well as low albumin (< 3.25 g/dL) and high globulin levels (≥ 3.25 g/dL) were significantly associated with poor prognosis. According to the multivariate analysis, a low albumin-to-globulin ratio was an independent prognostic factor for overall survival (HR = 2.59, 95% CI 1.12-5.96, P = 0.026); however, low albumin or high globulin levels was not associated with the overall survival. Among the clinicopathological characteristics, older age, diabetes mellitus, hypertension, larger tumor size, and parametrial invasion were associated with a low albumin-to-globulin ratio. CONCLUSION: A low albumin-to-globulin ratio was associated with a poor prognosis in patients with surgically treated invasive cervical cancer. Therefore, the albumin-to-globulin ratio may serve as a prognostic marker, which predicts a worse prognosis.

History of whole pelvis plus para-aortic radiation is a risk factor associated with febrile neutropenia during chemotherapy for recurrent cervical cancer.

BACKGROUND: Radiation-based therapy is widely used for advanced cervical cancer. Prior radiation-based therapy is a potential risk factor for febrile neutropenia (FN). However, the effect of irradiation field size on the incidence of FN during recurrent cervical cancer treatment is unclear. This study aimed to investigate the relationship between prior irradiation field size and FN development during recurrent chemotherapy. METHODS: This retrospective, observational study included cervical cancer patients who received recurrent chemotherapy between November 2006 and June 2020. The patients were classified into two groups based on the area of irradiation fields. The first group included patients with a history of whole pelvis (WP) irradiation (WP group). The second group had patients who underwent WP plus para-aortic lymph node (PAN) irradiation (WP + PAN group). The incidences of hematological toxicities and FN during the recurrent chemoradiotherapy were compared between the two groups. RESULTS: The FN incidence was significantly higher in the WP + PAN group than in the WP group (32.1% vs. 0%, P < 0.001). The incidence of Grade 4 neutropenia was not significantly different between the WP + PAN and WP groups. The nadir absolute neutrophil counts were significantly lower and the dose reduction or discontinuation rate of chemotherapy was significantly higher in the WP + PAN group than in the WP group. CONCLUSION: History of WP plus PAN radiation is a risk factor for developing FN during recurrent cervical cancer chemotherapy.

Application of artificial intelligence in gynecologic malignancies: A review.

With the development of machine learning and deep learning models, artificial intelligence is now being applied to the field of medicine. In oncology, the use of artificial intelligence for the diagnostic evaluation of medical images such as radiographic images, omics analysis using genome data, and clinical information has been increasing in recent years. There have been increasing numbers of reports on the use of artificial intelligence in the field of gynecologic malignancies, and we introduce and review these studies. For cervical and endometrial cancers, the evaluation of medical images, such as colposcopy, hysteroscopy, and magnetic resonance images, using artificial intelligence is frequently reported. In ovarian cancer, many reports combine the assessment of medical images with the multi-omics analysis of clinical and genomic data using artificial intelligence. However, few study results can be implemented in clinical practice, and further research is needed in the future.

Targeting Epigenetic Regulators for Endometrial Cancer Therapy: Its Molecular Biology and Potential Clinical Applications.

Endometrial cancer is one of the most frequently diagnosed gynecological malignancies worldwide. However, its prognosis in advanced stages is poor, and there are only few available treatment options when it recurs. Epigenetic changes in gene function, such as DNA methylation, histone modification, and non-coding RNA, have been studied for the last two decades. Epigenetic dysregulation is often reported in the development and progression of various cancers. Recently, epigenetic changes in endometrial cancer have also been discussed. In this review, we give the main points of the role of DNA methylation and histone modification in endometrial cancer, the diagnostic tools to determine these modifications, and inhibitors targeting epigenetic regulators that are currently in preclinical studies and clinical trials.

Production of an anti-angiogenic factor sFLT1 is suppressed via promoter hypermethylation of FLT1 gene in choriocarcinoma cells.

BACKGROUND: Soluble Fms-like tyrosine kinase-1 (sFLT1) as an anti-angiogenic factor is abundantly expressed in placental trophoblasts. Choriocarcinoma, a malignant tumor derived from trophoblasts, is known to be highly angiogenic and metastatic. However, the molecular mechanism underlying angiogenesis in choriocarcinoma pathogenesis remains unclear. We aimed to investigate the mRNA expression and DNA methylation status of the FLT1 gene in human choriocarcinoma cells and trophoblast cells. METHODS: qRT-PCR, Western blotting and ELISA were conducted to evaluate the mRNA and protein expression levels of sFLT1. 5-aza-2'-deoxycytidine (5azadC) treatment and bisulfite sequencing were used to study the FLT1 gene promoter methylation. The effect of sFLT1 on choriocarcinoma growth and angiogenesis was evaluated in a xenograft mouse model. RESULTS: Expression of the FLT1 gene was strongly suppressed in choriocarcinoma cell lines compared with that in the primary trophoblasts. Treatment of choriocarcinoma cell lines with 5azadC, a DNA methyltransferase inhibitor, markedly increased in mRNA expression of three FLT1 splice variants and secretion of sFLT1 proteins. Bisulfite sequencing revealed that the CpG hypermethylation was observed at the FLT1 promoter region in choriocarcinoma cell lines and a human primary choriocarcinoma tissue but not in human trophoblast cells. Interestingly, in 5azadC-treated choriocarcinoma cell lines, sFLT1 mRNA expression and sFLT1 production were further elevated by hypoxic stimulation. Finally, as expected, sFLT1-expressing choriocarcinoma cells implanted into nude mice showed significantly slower tumor growth and reduced microvessel formation compared with GFP-expressing control choriocarcinoma cells. CONCLUSIONS: Inhibition of sFLT1 production by FLT1 silencing occurs via the hypermethylation of its promoter in choriocarcinoma cells. The stable expression of sFLT1 in choriocarcinoma cells resulted in the suppression of tumor growth and tumor vascularization in vivo. We suggest that the FLT1 gene may be a cell-type-specific tumor suppressor in choriocarcinoma cells.

Desensitization strategy for hypersensitivity reactions to carboplatin in five patients with gynecological cancer.

AIM: Carboplatin is a key drug for gynecologic cancers. However, hypersensitivity reactions (HSR) are major adverse effects that might necessitate carboplatin discontinuation. Desensitization is an effective method in patients who developed initial HSR and further required carboplatin treatment. Here, we aimed to evaluate our experience with the use of the carboplatin desensitization protocol in five patients at the University of Tokyo Hospital. METHODS: We established a four-step, 5-h desensitization protocol for our hospital. Observational and retrospective analyses were performed. Additionally, we have shared the patients' clinical information with the emergency department to ensure the safety of this protocol. RESULTS: Five patients with recurrent gynecological cancer were treated using this protocol. Four of the five patients were treated effectively and 28 of 29 desensitization protocols were completed successfully. In one patient, we switched to olaparib successfully after two courses of our protocol. One patient who developed grade 4 HSR during initial carboplatin administration developed grade 2 HSR and we discontinued the protocol. CONCLUSION: The carboplatin desensitization protocol is very efficient. The outcome of our protocol was on a par with other protocols. To the best of our knowledge, this is the first study to indicate that switching to olaparib can be considered a suitable option in patients who develop HSR to carboplatin.

Reconstructed uterine length is critical for the prevention of cervical stenosis following abdominal trachelectomy in cervical cancer patients.

AIM: Although the procedure of abdominal trachelectomy has been remarkably improved, preventing subsequent cervical stenosis remains challenging. In this study, we analyzed the clinicopathological risk factors for cervical stenosis to explore the appropriate surgical procedures for the prevention of cervical stenosis following trachelectomy. METHODS: Thirty-two patients who underwent abdominal extended and radical trachelectomy were assessed retrospectively (median follow-up period = 33 months). To evaluate the risk factors, the clinicopathological factors were analyzed by univariate and multivariate analyses. The reconstructed uterine length (UtL), that is, the length between the vaginal end of the neo-cervix and the uterine fundus, was measured by transvaginal ultrasound after surgery. The cut-off value for the UtL was assessed by a receiver operating characteristic (ROC) curve analysis. RESULTS: Cervical stenosis of any grade was observed in 12 patients (grade 1 = 9, grade 3b = 3). Among the various clinicopathological factors, the UtL and cervical length (CL) were significantly related to cervical stenosis following trachelectomy. The multivariate analysis revealed that the UtL, but not CL, is an independent risk factor for stenosis. The ROC curve analysis revealed that stenosis was significantly more likely to occur in patients with a UtL shorter than 53 mm (area under the ROC curve = 0.902). UtL in the patients who became pregnant was longer than that in the patients who did not. No evidence of recurrent cancer was observed during the follow-up period. CONCLUSION: Our proposed method may provide a functional reconstructed uterus with preserving fertility by remaining UtL more than 53 mm.

Interleukin-17 is associated with expression of programmed cell death 1 ligand 1 in ovarian carcinoma.

The programmed cell death 1/programmed cell death 1 ligand 1 pathway was successfully targeted in cancer immunotherapy. Elevated interleukin-17 (IL-17), which is known in autoimmune diseases, has recently been recognized in cancer patients. We investigated the role of IL-17 in the regulation of expression of programmed cell death 1 ligand 1 in ovarian cancer by evaluating changes in the number of IL-17-producing cluster of differentiation 4 helper T cells (Th17) and γδT cells (γδT17) in PBMC of 52 gynecological cancer patients (including 30 ovarian cancer patients) and 18 healthy controls. The occupancy ratio of Th17 and γδT17 was higher in ovarian cancer and endometrial cancer patients than in controls, determined by multi-color flow cytometry (Th17: P < 0.0001 and P = 0.0002, respectively; γδT17: P = 0.0020 and P = 0.0084, respectively). IL-17 mRNA level was elevated in PBMC of ovarian cancer patients (P = 0.0029), as measured by RT-PCR. The neutrophil-to-lymphocyte ratio, which is a prognostic biomarker of ovarian cancer, correlated with Th17 occupancy ratio in patients (P = 0.0068). We found that programmed cell death 1 ligand 1 expression and its associated factors (IL-6 and phospho-signal transducer and activator of transcription 3) were induced by IL-17 in an ovarian cancer cell line. These results suggest that increased Th17 counts and IL-17 level, which correlated with high neutrophil-to-lymphocyte ratio and programmed cell death 1 ligand 1 expression, are potential biomarkers for poor prognosis in ovarian cancer and likely indications for application of programmed cell death 1 ligand 1 pathway inhibitors.

The histone methyltransferase WHSC1 is regulated by EZH2 and is important for ovarian clear cell carcinoma cell proliferation.

BACKGROUND: Wolf-Hirschhorn syndrome candidate gene-1 (WHSC1), a histone methyltransferase, has been found to be upregulated and its expression to be correlated with expression of enhancer of zeste homolog 2 (EZH2) in several cancers. In this study, we evaluated the role of WHSC1 and its therapeutic significance in ovarian clear cell carcinoma (OCCC). METHODS: First, we analyzed WHSC1 expression by quantitative PCR and immunohistochemistry using 23 clinical OCCC specimens. Second, the involvement of WHSC1 in OCCC cell proliferation was evaluated by MTT assays after siRNA-mediated WHSC1 knockdown. We also performed flow cytometry (FACS) to address the effect of WHSC1 on cell cycle. To examine the functional relationship between EZH2 and WHSC1, we knocked down EZH2 using siRNAs and checked the expression levels of WHSC1 and its histone mark H3K36m2 in OCCC cell lines. Finally, we checked WHSC1 expression after treatment with the selective inhibitor, GSK126. RESULTS: Both quantitative PCR and immunohistochemical analysis revealed that WHSC1 was significantly overexpressed in OCCC tissues compared with that in normal ovarian tissues. MTT assay revealed that knockdown of WHSC1 suppressed cell proliferation, and H3K36me2 levels were found to be decreased in immunoblotting. FACS revealed that WHSC1 knockdown affected the cell cycle. We also confirmed that WHSC1 expression was suppressed by EZH2 knockdown or inhibition, indicating that EZH2 is upstream of WHSC1 in OCCC cells. CONCLUSIONS: WHSC1 overexpression induced cell growth and its expression is, at least in part, regulated by EZH2. Further functional analysis will reveal whether WHSC1 is a promising therapeutic target for OCCC.

Anti-tumor activity of dual inhibition of phosphatidylinositol 3-kinase and MDM2 against clear cell ovarian carcinoma.

INTRODUCTION: PI3K pathway signaling has received attention as a molecular target in clear cell ovarian carcinoma (CCOC). MDM2 is one of the AKT effectors in the PI3K pathway, which binds to and degrades p53. In this study, we aimed to clarify the prognostic significance of PIK3CA and MDM2 expression, and potential therapeutic effect of a dual inhibition of the PI3K pathway and MDM2. MATERIALS AND METHODS: cDNA expression was evaluated by using microarray data using 75 samples of CCOC. DS-7423 (dual inhibitor of pan-PI3K and mTOR) and RG7112 (MDM2 inhibitor) were used on CCOC cell lines to evaluate cell proliferation, expression level of MDM2 related proteins, and apoptosis by MTT assay, western blotting, and flow cytometry. DS-7423 (3 mg/kg) and/or RG7112 (50 mg/kg) were orally administrated every day for three weeks, and the anti-tumor effect was evaluated using tumor xenografts, along with immunohistochemistry. RESULTS: Tumors with high expression of both PIK3CA and MDM2 showed significantly worse prognosis in expression array of 71 CCOCs (P = 0.013). Dual inhibition of the PI3K pathway by DS-7423 and MDM2 by RG7112 showed synergistic anti-proliferative effect in 4 CCOC cell lines without TP53 mutations. The combination therapy more robustly induced pro-apoptotic proteins (PUMA and cleaved PARP) with increase of sub G1 population and apoptotic cells, compared with either single agent alone. The combination therapy significantly reduced tumor volume in mice (P < 0.001 in OVISE, and P = 0.038 in RMG-I) without severe body weight loss. Immunohistochemistry from the xenograft tumors showed that the combination treatment significantly reduced vascularity and cell proliferation, with an increase of apoptotic cell death. CONCLUSION: A combination therapy targeting the PI3K pathway and MDM2 might be a promising therapeutic strategy in CCOC.

Usefulness of cell-free and concentrated ascites reinfusion therapy in the therapeutic management of advanced ovarian cancer patients with massive ascites.

BACKGROUND: The management of refractory ascites in advanced ovarian cancer (AOC) is vital for patients with abdominal distention, respiratory distress, and anorexia due to massive ascites with cancer peritonitis. We analyzed the benefits of concentrated ascites reinfusion therapy (CART) in the management of AOC. METHODS: We reviewed records of AOC patients who underwent CART between January 2011 and March 2017. We retrospectively analyzed patients' backgrounds and physiological changes, including body weight, abdominal girth, urine volume, blood component values, blood pressure, heart rate, and body temperature before and after CART. We investigated the clinicopathological significance of CART by measuring the mean number of ascites tumor cell (ATC) clusters before CART. RESULTS: A retrospective analysis was performed on 29 cases of AOC with massive ascites involving 47 CART sessions. The patients' mean age was 56.6 ± 12.8 years, and the mean number of sessions was 1.7 ± 1.2. The mean volume of the processed ascites was 2,937 ± 820 mL, which was concentrated to 272 ± 84 mL containing 85.0 ± 33.2 g protein on average. Significant reductions in abdominal girth (- 5.30 ± 0.65 cm; p < 0.0001) and body weight (- 2.97 ± 0.26 kg; p = 0.0011), increased urine volume (+ 824.29 ± 145.21 mL; p < 0.0001), and improved serum albumin levels (+ 0.18 ± 0.34; p < 0.0001) were observed after CART. Analysis of variance revealed significant elevations in body temperature after CART in 11 patients with a small number of ATC clusters. CONCLUSIONS: CART is useful for the therapeutic management of AOC patients with refractory massive ascites. Elevations of body temperature after CART may be avoided by the investigation of patients' peritoneal cytology before CART.

Mixed endometrioid and clear cell carcinoma arising from laparoscopic trocar site endometriosis.

Laparoscopic port site endometriosis is less common in abdominal wall endometriosis, and malignant transformation of abdominal wall endometriosis is rare. We reported a case of mixed endometrioid and clear cell carcinoma arising from port site endometriosis. The patient was a 49-year-old woman with a history of laparoscopic excision of ovarian endometrioma. Physical examination revealed a subcutaneous solid tumor around the laparoscopic surgical scar. Imaging showed a suspicious malignancy. She underwent radical marginal resection of the abdominal wall tumor, flap reconstruction of the abdominal wall, hysterectomy, bilateral salpingo-oophorectomy and omental biopsy. Histological examination revealed mixed endometrioid and clear cell carcinoma. Computed tomography scan showed no evidence of recurrence after six cycles of chemotherapy. This is the first case of malignant transformation from laparoscopic trocar site endometriosis.

Radical hysterectomy with or without para-aortic lymphadenectomy for patients with stage IB2, IIA2, and IIB cervical cancer: outcomes for a series of 308 patients.

BACKGROUND: Although many studies have already shown that lymph node metastasis is one of the major prognostic factors for cervical cancer, the therapeutic significance of para-aortic lymphadenectomy for the surgical treatment of cervical cancer remains controversial. METHODS: A total of 308 patients diagnosed with stage IB2, IIA2, or IIB cervical cancer and treated with radical hysterectomy were retrospectively investigated to assess the incidence of para-aortic lymph node metastasis and the clinicopathological factors linked to cervical cancer prognosis. RESULTS: Para-aortic lymph node metastases were pathologically confirmed in 13 of the 136 patients (9.6 %) who underwent para-aortic lymphadenectomy. The incidence of para-aortic lymph node metastasis was significantly higher in the patients who had common iliac lymph node metastases (odds ratio 31.5, p < 0.001) according to logistic regression analysis. Common iliac lymph node metastasis was related to risk of recurrence (hazard ratio 2.43, p = 0.003) and death (hazard ratio 2.62, p = 0.007) in Cox regression analysis. Kaplan-Meier analysis and Cox regression analysis showed that para-aortic lymphadenectomy did not have a positive impact on survival in 308 patients or 140 pN1 patients, but para-aortic lymphadenectomy was related to better overall survival with a marginal trend toward significance (p = 0.053) in 30 patients with common iliac lymph node metastasis. CONCLUSIONS: Indication for para-aortic lymphadenectomy in the surgical treatment of stage IB2, IIA2, or IIB cervical cancer needs to be individualized. Patients with common iliac lymph node metastasis are possible candidates, and a prospective study is needed to clarify this issue.

Minimization of curative surgery for treatment of early cervical cancer: a review.

Surgery is effective and useful for curative treatment of patients with early invasive cervical cancer, yet minimization of surgical procedures provides many additional advantages for patients. Because the mean age of patients diagnosed with cervical precancer and invasive cancer has been decreasing, the need for minimization of surgery to reduce disruption of fertility is increasing. Trachelectomy is an innovative procedure for young patients with invasive cancer. Minimally invasive procedures are increasingly implemented in the treatment of patients with early cervical cancer, such as laparoscopic/robotic surgery and sentinel lymph node navigation. The use of modified radical hysterectomy may not only be curative but also minimally invasive for Stage IA2-IB1 patients with a tumor size <2 cm in diameter. Here, we have summarized and discussed the minimally invasive procedures for the treatment of patients with early cervical cancer.