Hospital Admission Less than 30 Days after Chemotherapy: Results from a Chemotherapy-Specific Morbidity and Mortality Conference in Gynecologic Oncology

Introduction: Morbidity and Mortality (M&M) rounds can identify adverse events and improve patient safety however adoption in cancer centers is not routine. Herein we report the results of a chemotherapy-specific gynecologic oncology M&M rounds and identify reasons for hospital admission < 30 days after chemotherapy treatment. Methods: Between July 2014 and April 2016, all admissions < 30 days from chemotherapy administration were prospectively collected along with clinical data. Admissions were described and classified as planned or unplanned and as associated with chemotherapy or with underlying disease. Results: 585 patients were admitted, 78% of whom had ovarian cancer and 43% of whom had recurrent disease. Overall, 47% of admissions were unplanned and these were significantly longer than planned admissions (5.6 vs. 2.4 days, p = 0.0003). Of unplanned admissions, 43% were due to chemotherapy, and 57% were due to disease burden. 74% of patients had received >1 prior line of chemotherapy, and 22% were on clinical trial. The most common causes of unplanned admission were nausea, vomiting or failure to thrive (28.9%), fever (17.9%) and small bowel obstruction (19.9%). Conclusions: There is a high rate of unplanned admission < 30 days after chemotherapy and patients with ovarian cancer and recurrent disease are at the highest risk. This information can be used to counsel patients about complications of chemotherapy and to improve supportive management. M&M conferences surrounding unplanned admissions after chemotherapy may help guide therapy, encourage best supportive care, and prompt re-evaluation of treatment goals in heavily pretreated patients with recurrent.

Shanghai Gynecologic Oncology Group’s consensus on the academic and industry’s clinical trial types

Shanghai Gynecologic Oncology Group(SGOG,www.ShanghaiGOG.org),[1]established in 2009,is a non-profit organization of clinical research and the full member of Gynecology Cancer Intergroup(GCIG)since 2012.It was guided by Drs.Jinghe Lang(China),Gavin Stuart(Canada)(2009-2020);Drs.Jinghe Lang(China),Ding Ma(China)(2021-)and was supported by Dr.Zeyi Cao(2009-2012).The mission of SGOG is to actively promote the investigator-initiated trial(IIT)in gynecologic cancers,particularly the innovative phase II clinical trials.Followed by the high quality of management in investigators’training,trial development,human resources.

Gynecologic Oncologic Surgery for the Palliation of Life-Limiting Cancer Crises—The Importance of Education and Training in Palliative Care for the Gynecologic Oncologist

Introduction: Palliative care expertise is an important component of the comprehensive care of women with gynecologic cancers. Palliative care ranges from treatment of symptoms experienced by people with cancer such as constipation, nausea, anxiety, pain to careful and the skillful discussion of prognosis and goals of care. The purpose of this review is to summarize the basic issues in palliative care faced by healthcare providers caring for people with cancer and then focus on some examples of diagnostic and treatment dilemmas faced by gynecologic oncologists caring for women with recurrent cancers. Review Summary: Palliative and hospice care strategies are described. Palliative care refers to symptom management from diagnosis through active treatment, problems encountered by survivors, and concerns at the end of life. Hospice care pertains to care during the last six months of life and includes the alleviation of suffering of those dying from cancer and the support for family members. The symptoms at the end of life including pain, anorexia, and intestinal complications are reviewed. Palliative surgical procedures range from the drainage of pleural and abdominal fluid, including the management of intestinal obstruction via drains, diversionary procedures, or the creation of an ostomy. A comparison of outcomes between medical (when surgery was not feasible) and surgical management of bowel obstruction shows the average survival of 54 days compared to 193 days respectively. Conclusion: Gynecologic oncologists are uniquely positioned among other oncologists in managing intestinal obstruction, malignant ascites and pleural effusions, and oligometastatic recurrences where they must decide whether a medical or surgical approach will be effective in palliation and alleviation of suffering. The combination of traditional surgical gynecologic oncology training with palliative care is crucial to become the most effective clinician for each patient with advanced or recurrent gynecologic cancer.

Diagnostic challenges and individualized treatment of cervical adenocarcinoma metastases to the breast:A case report

BACKGROUND Cervical cancer is a rare primary tumor resulting in metastases to the breast with few cases reported in literature.Breast metastases are associated with poor prognosis.The following case highlights the diagnostic challenges associated with metastatic cervical cancer to the breast along with individualized treatment.CASE SUMMARY A 44-year-old G7P5025 with no significant past medical or surgical history presented with heavy vaginal to an outside emergency department where an exam and a pelvic magnetic resonance imaging showed a 4.5 cm heterogenous lobulated cervical mass involving upper two thirds of vagina,parametria and lymph node metastases.Cervical biopsies confirmed high grade adenocarcinoma with mucinous features.A positron emission tomography/computed tomography(PET/CT)did not show evidence of metastatic disease.She received concurrent cisplatin with external beam radiation therapy.Follow up PET/CT scan three months later showed no suspicious fluorodeoxyglucose uptake in the cervix and no evidence of metastatic disease.Patient was lost to follow up for six months.She was re-imaged on re-presentation and found to have widely metastatic disease including breast disease.Breast biopsy confirmed programmed death-ligand 1 positive metastatic cervical cancer.The patient received six cycles of carboplatin and paclitaxel with pembrolizumab.Restaging imaging demonstrated response.Patient continued on pembrolizumab with disease control.CONCLUSION Metastatic cervical cancer to the breast is uncommon with nonspecific clinical findings that can make diagnosis challenging.Clinical history and immunohistochemical evaluation of breast lesion,and comparison to primary tumor can support diagnosis of metastatic cervical cancer to the breast.Overall,the prognosis is poor,but immunotherapy can be considered in select patients and may result in good disease response.

Knockdown of circular RNA (CircRNA)_001896 inhibits cervical cancer proliferation and stemness in vivo and in vitro

Objective:Previous studies indicated that aberrant circular RNA(circRNA)expression affects gene expression regulatory networks,leading to the aberrant activation of tumor pathways and promoting tumor cell growth.However,the expression,clinical significance,and effects on cell propagation,invasion,and dissemination of circRNA_001896 in cervical cancer(CC)tissues remain unclear.Methods:The Gene Expression Omnibus(GEO)datasets(GSE113696 and GSE102686)were used to examine differential circRNA expression in CC and adjacent tissues.The expression of circRNA_001896 was detected in 72 CC patients usingfluorescence quantitative PCR.Correlation analysis with clinical pathological features was performed through COX multivariate and univariate analysis.The effect of circRNA_001896 downregulation on CC cell propagation was examined using the cell counting kit-8(CCK-8)test,clonogenic,3D sphere formation,and in vivo tumorigenesis assays.Results:Intersection of the GSE113696 and GSE102686 datasets revealed an increased expression of four circRNAs,including circRNA_001896,in CC tissues.Fluorescence quantitative PCR confirmed circRNA_001896 as a circular RNA.High expression of circRNA_001896 was considerably associated with lymph node metastasis,International Federation of Gynecologists and Obstetricians(FIGO)stage,tumor diameter,and survival period in CC patients.Proportional hazards model(COX)univariate and multivariate analyses revealed that circRNA_001896 expressions are a distinct risk factor affecting CC patients’prognosis.Cellular functional experiments showed that downregulating circRNA_001896 substantially suppressed CC cell growth,colony formation,and 3D sphere-forming ability.In vivo,tumorigenesis analysis in nude mice demonstrated that downregulating circRNA_001896 remarkably reduced the in vivo proliferation capacity of CC cells.Conclusion:CircRNA_001896 is highly expressed in CC tissues and is substantially related to lymph node metastasis,FIGO stage,tumor size,and survival period in patients.Moreover,downregulating circRNA_001896 significantly inhibits both in vivo and in vitro propagation of CC cells.Therefore,circRNA_001896 might be used as a biomarker for targeted therapy in cervical cancer.

Recurrent multisystem Langerhans cell histiocytosis involving the female genitalia: A case report

BACKGROUND Langerhans cell histiocytosis(LCH)is a histiocytic proliferative disease caused by clonal proliferation of Langerhans cells,which is currently defined as an inflam-matory myeloid tumor.It is rare in adults,with an incidence of 1–2 per million,and is highly heterogeneous in clinical presentation,with unpredictable disease progression and outcome.CASE SUMMARY A 52-year-old postmenopausal female patient presented to the gynecology department in July 2023 with bilateral vulvar masses.She was diagnosed with recurrent multisystem LCH.The patient had previously been diagnosed with a single-system and single-focal LCH in October 2021 due to a right maxillofacial mass,which resolved after surgical treatment.A chemotherapy regimen was developed after multidisciplinary consultation.Six cycles of chemotherapy resulted in partial remission,and maintenance chemotherapy is currently being administered.CONCLUSION Recurrent LCH involving the bilateral vulva has been poorly reported.Compre-hensive imaging and pathological evaluation is important for diagnosis.The model of joint multidisciplinary specialist diagnosis and treatment is worthy of clinical application.

Tankyrase 2 promotes lung cancer cell malignancy

BACKGROUND Tankyrase 2(TNKS2)is a potential candidate molecular target for the prognosis and treatment of non-small cell lung cancer(NSCLC),but its biological functions are unclear.AIM To investigate the biological functions of TNKS2 in NSCLC.METHODS Using a lentiviral vector,we generated H647 model cells with TNKS2 knockdown by RNA interference and A549 model cells with TNKS2 overexpression by tran-sfection with a TNKS2 overexpressing plasmid.Increased and decreased exp-ression levels of TNKS2 in the two cell lines were verified using real-time reverse transcriptase-polymerase chain reaction and Western blot analyses.Cell apopto-sis,proliferation,and migration were determined using flow cytometry,carbo-xyfluorescein succinimidyl ester staining,and scratch assay,respectively.Im-munofluorescence staining was conducted to examine TNKS2 andβ-catenin ex-pression levels in the two transfected cell lines and the non-transfected cells.RESULTS TNKS2 mRNA and protein expression was significantly higher in the highly malignant NCI-H647 cells,while it remained at a low level in the less malignant A549 cells.Lentivirus-mediated overexpression of TNKS2 in A549 cells resulted in a 3-fold increase in gene expression and a 1.7-fold increase in protein expression(P<0.01).Conversely,shRNA interference targeting TNKS2 Led to an 8-fold decrease in gene expression and a 3-fold decrease in protein expression(P<0.01)in NCI-H647 cells.Furthermore,the cell apoptosis rate was significantly reduced(50%)and cell migration rate was increased(35%)in the TNKS2 overexpression group than in the control group(P<0.05).In contrast,shTNKS2 promoted apoptosis by more than one fold and reduced migration by 60%(P<0.05).Immunofluorescence analysis revealed enhanced nuclear localization ofβ-catenin fluorescence signal associated with high TNKS2 expression levels.Western blot analysis investigating TNKS2/β-catenin-related proteins indicated consistent changes between TNKS2 andβ-catenin expression in lung cancer cells,whereas Axin displayed an opposite trend(P<0.05).CONCLUSION The obtained results revealed that TNKS2 may serve as an adverse prognostic factor and a potential therapeutic target in NSCLC.

Glycogen metabolism-mediated intercellular communication in the tumor microenvironment influences liver cancer prognosis

Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells and 65 glycogen metabolism genes were analyzed bya nonnegative matrix factorization(NMF).The prognosis and immune response of new glycogen TME cell dusters were predicted by using HCC and immunotherapy cohorts from public databases.HOC single cell analysis was divided into fibroblasts,NT T cells,macrophages,endothelial clls,and B cells,which were separately divided into new cell clusters by glycogen metabolism gene annotation.Pseudo temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell dusters.Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell.related subtypes and diferent glycogen subtype cell clusters.SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism.In addition,TME cell dusters of glycogen metabolism were found to be enriched in expression in CAF subtypes,CD8 depleted,M1,and M2 types.Bulk seq analysis showed the prognostic signifcance of glycogen metabolism.mediated TME cell dusters in HCC,while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade(ICB),especially for CAFs,T cells,and macrophages In summary,our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell dusters.

This pain drives me crazy:Psychiatric symptoms in women with interstitial cystitis/bladder pain syndrome

BACKGROUND Interstitial cystitis/bladder pain syndrome(IC/BPS)is an at least 6-mo noninfectious bladder inflammation of unknown origin characterized by chronic suprapubic,abdominal,and/or pelvic pain.Although the term cystitis suggests an inflammatory or infectious origin,no definite cause has been identified.It occurs in both sexes,but women are twice as much affected.AIM To systematically review evidence of psychiatric/psychological changes in persons with IC/BPS.METHODS Hypothesizing that particular psychological characteristics could underpin IC/BPS,we investigated in three databases the presence of psychiatric symptoms and/or disorders and/or psychological characteristics in patients with IC/BPS using the following strategy:("interstitial cystitis"OR"bladder pain syndrome")AND("mood disorder"OR depressive OR antidepressant OR depression OR depressed OR hyperthymic OR mania OR manic OR rapid cyclasterisk OR dysthymiasterisk OR dysphoriasterisk).RESULTS On September 27,2023,the PubMed search produced 223 articles,CINAHL 62,and the combined PsycLIT/PsycARTICLES/PsycINFO/Psychology and Behavioral Sciences Collection search 36.Search on ClinicalTrials.gov produced 14 studies,of which none had available data.Eligible were peer-reviewed articles reporting psychiatric/psychological symptoms in patients with IC/BPS,i.e.63 articles spanning from 2000 to October 2023.These studies identified depression and anxiety problems in the IC/BPS population,along with sleep problems and the tendency to catastrophizing.CONCLUSION Psychotherapies targeting catastrophizing and life stress emotional awareness and expression reduced perceived pain in women with IC/BPS.Such concepts should be considered when implementing treatments aimed at reducing IC/BPS-related pain.

Sarcopenia and Anemia Are Predictors of Poor Prognostic in Cervical Cancer Patients

Objective: Evaluate pretreatment sarcopenia and anemia as prognostic factors in women undergoing treatment for cervical cancer (CC) with concurrent chemoradiotherapy (CCRT). Methods: 151 women with CC were analysed in this cohort study. Pretreatment computed tomography (CT) images were analysed to assess skeletal muscle index (SMI). Hazard ratios (HR) and multivariate Cox proportional HR were used to analyse association between low SMI, age, body mass index (BMI), haemoglobin levels, histological type, and International Federation of Gynaecology and Obstetrics (FIGO) stage with PFS and OS. Results: A total of 151 patients were included, 53 (35.1%) presented pretreatment sarcopenia;51 (34%) stage I/II and 100 (66%) stage III/IV. Among those patients in advanced stage (III/IV) 37 (70%) (p = 0.28) were sarcopenic at the beginning of treatment. Sarcopenia was associated with worse progression-free survival (PFS) and overall survival (OS) in our cohort [HR 0.97 (p = 0.01)] [HR 0.73 (p = 0.001)], as well as anemia [HR 0.73 (p = 0.001)] [HR 0.78 (p = 0.001)]. Linear regression models indicated that despite showing no association with age, neutrophil or platelet counts, sarcopenia was associated with pretreatment anemia levels (p = 0.01). After a multivariate analysis, only haemoglobin (anemia) and complete CCRT remained associated with PFS and OS. Sarcopenia and anemia were associated with worse PFS and OS in FIGO stage I/II. Conclusion: Pretreatment sarcopenia was significantly associated with low haemoglobin levels. Anemia and incomplete CCRT were independently associated with poor prognosis in women with CC. Pretreatment sarcopenia, as low SMI, was a predictor of poor prognostic in early stages of CC.

Efficacy and safety of paclitaxel liposome versus paclitaxel in combination with carboplatin in the first-line chemotherapy for ovarian cancer:a multicenter,open-label,non-inferiority,randomized controlled trial

Background:The paclitaxel liposome formulation,encapsulating paclitaxel within a phospholipid bilayer,ad-dresses the insolubility of traditional paclitaxel formulations,thereby reducing toxicity without compromising its antitumor efficacy.Methods:This multicenter,open-label,non-inferiority randomized controlled trial(ChiCTR2000038555)evalu-ates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin(PLC vs.PC)as first-line therapy in patients with epithelial ovarian cancer.Results:An analysis of median progression-free survival(PFS)revealed non-inferior outcomes between 263 pa-tients in the PLC group and 260 patients in the PC group(32.3 vs.29.9 months,hazard ratio[HR],0.89[95%CI,0.64−1.25]),using a non-inferior margin of 1.3.Although the overall incidence of treatment-related adverse events was comparable between groups,the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen.Conclusion:The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of pa-clitaxel and carboplatin regarding therapeutic efficacy,with an enhanced safety profile marked by reduced non-hematologic toxicities.

Risk assessment and triage strategy of cervical cancer primary screening on HPV integration status:5-year follow-up of a prospective cohort study

Objective:We investigated the relation between man papillomavirus(HPV)integration status and the immediate risk of cervical intraepithelial neoplasia(CIN),as well as the triage strategy based on HPV integration test.Methods:4086 women aged 20 to 65 years in China were enrolled in 2015 for a prospective,population-based,clinical observational study to evaluate the triage performance of HPV integration.Cervical exfoliated cells were collected for HPV testing and cytologic test.If high-risk HPV was positive,HPV integration test was performed at baseline,2-year and 5-year follow-up.Results:At baseline,HPV integration was positively correlated with the severity of cervical pathology,ranging from 5.0%(15/301)in normal diagnosis,6.9%(4/58)in CIN1,31.0%(9/29)in CIN2,70%(14/20)in CIN3,and 100%(2/2)in cervical cancer(P<0.001).Compared with cytology,HPV integration exhibits comparable sensitivity and negative predictive value for the diagnosis of CIN3+,higher specificity(92.8%[90.2%-95.4%]vs.75.5%[71.2%-79.8%],P<0.001)and higher positive predictive value(36.4%[22.1%-50.6%]vs.15.2%[8.5%-21.8%],P<0.001).HPV integration testing strategy yielded a significantly lower colposcopy referral rate than cytology strategy(10.7%[44/410]vs.27.3%[112/410],P<0.001).The HPV integration-negative group exhibited the lowest immediate risk for CIN3+(1.6%)and accounted for the largest proportion of the total population(89.3%),when compared with the normal cytology group(risk,1.7%;proportion,72.7%).Conclusion:As a key molecular basis for the development of cervical cancer,HPV integration might be a promising triage strategy for HPV-positive patients.

Disseminated tumor cells in bone marrow as predictive classifiers for small cell lung cancer patients

Background: Small cell lung cancer (SCLC) is a highly aggressive disease characterized by early metastasis. Ane- uploid CD31- disseminated tumor cells (DTCs) and CD31+ disseminated tumor endothelial cells (DTECs) residing in the bone marrow are generally considered as the initiators of metastatic process. However, the clinical signifi- cance of DTCs and DTECs in SCLC remains poorly understood. The aim of this study is to investigate the clinical implications of diverse subtypes of highly heterogeneous DTCs and DTECs in SCLC patients. Methods: Subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) was applied to enrich and perform comprehensive morphologic, karyotypic, and phenotypic characterization of aneuploid DTCs and DTECs in 30 patients. Additionally, co-detection of circulating tumor cells (CTCs) and circulating tumor endothelial cells (CTECs) was conducted on 24 of the enrolled patients. Proof-of-concept of the whole exon sequencings (WES) on precisely selected different subtypes of CTCs or DTCs, longitudinally detected from a representative case with pathologically confirmed bone marrow metastasis, was validated to feasibly reveal genetic mutations in these cells. Results: DTCs, DTECs and their subtypes were readily detectable in SCLC patients. Comparative analysis re- vealed that the number of DTCs and DTECs was significantly higher than that of their corresponding CTCs and CTECs ( P < 0.001 for both). Positive detection of disseminated tumor microemboli (DTM) or disseminated tumor endothelial microemboli (DTEM) was associated with inferior survival outcomes ( P = 0.046 and P = 0.048). Pa- tients with EpCAM+ DTCs detectable displayed significantly lower disease control rate (DCR) (16.67% vs 73.33%, P = 0.019), reduced median progression-free survival (mPFS) and median overall survival (mOS) compared with those with EpCAM- DTCs ( P = 0.028 and P = 0.002, respectively). WES analysis indicated that post-treatment DTCs isolated from bone marrow at the time of disease progression shared more homologous somatic gene mu- tations with pre-treatment CTCs compared with post-treatment CTCs. Conclusions: Our findings suggest that bone marrow sampling and characterization of DTC subtypes provided a valuable tool for predicting treatment response and the prognosis in SCLC. Moreover, DTCs inherit a greater amount of homologous somatic information from pre-treatment CTCs, indicating their potential role in disease progression and treatment resistance.

Burden of malignant mesothelioma in China during 1990-2019 and the projections through 2029

Objective:To provide the most up-to-date data on the burden of malignant mesothelioma(MM)and the projections through 2029 in China.Methods:Data on patients diagnosed with MM from China during 1990-2019 were obtained from the Global Burden of Disease(GBD)2019 database,including annual cases and deaths data and age-standardized rates of incidence,mortality,and disability-adjusted life-years(DALYs)associated with MM among different age groups.Temporal trends during 1990-2019 were analyzed by the Joinpoint regression models using 95%confidence interval(CI),while the projections through 2029 were calculated by the Bayesian age-period-cohort model.Data on the production and consumption of asbestos in China were obtained from the United States Geological Survey on Mineral Commodity Summaries during 1996-2023.Results:We observed a significant elevation in incident new cases and deaths over the last 3 decades,increasing from 1193 in 1990 to 2815 in 2019 for incident cases and from 1134 in 1990 to 2773 in 2019 for death cases.We found a roughly 6%increase in the proportion of incident cases for those aged>70 years(30%in 2019 versus 24%in 1990),while for the proportion of deaths similar elevation for those aged>70 years was found.Additionally,men had significantly higher DALYs due to MM across age groups compared with women.Asbestos consumption in China dramatically dropped since 2012 and reached the bottom in 2017 with 230 kilotons.By 2029,the projected age-standardized rate for incidence and mortality is expected to reach 1.2 per million for both.Conclusion:We found,for the first time using GBD data on the Chinese population,that the burden of MM has been significantly increasing in China over the last three decades and will continue to increase in the upcoming decade,suggesting an urgent need for a complete ban on chrysotile asbestos in China.

Chemotherapy Use Is a Significant Predictor for Sexual Dysfunction in Women with Gynecologic Cancer

Objectives: Sexual dysfunction is a significant survivorship issue in women with gynecologic cancer. We examined the association between chemotherapy and impaired sexual functioning. Methods: A cross sectional study of women with gynecologic cancer was conducted with a 181-item survey of validated instruments. A sub-analysis of women with chemotherapy treatment was performed to examine factors associated with sexual function including age, menopause status, BMI, diagnosis, stage, surgery/radiation use, active disease status, number of regimens, and number of cycles. Sexual dysfunction was measured by change in the Female Sexual Function Index (FSFI) score from pre-treatment with a significant decline in sexual function determined to be a 5.6 point decrease using a Reliable Change Index Statistic (RCIS). Standard statistical tools were employed. Results: A total of 107 (63%) of the women in the larger study had received chemotherapy as part of their treatment and were included in the sub-study. Women undergoing chemotherapy were more likely to experience sexual dysfunction post-treatment (51% vs. 26%;OR 2.9, 95% CI 1.5 - 5.7). In bivariate analyses, sexual dysfunction following chemotherapy was associated with age Conclusions: Women treated with chemotherapy for gynecologic cancer are at a significant risk of impaired sexual function. Women with cervical cancer, early stage disease, those who are premenopausal, and those younger than age 50 are at the highest risk.

Phase 1/2 study of concurrent chemoradiotherapy with weekly irinotecan hydrochloride for advanced/recurrence uterine cancer:A multi-institutional study of Kansai Clinical Oncology Group

Objective:Concurrent chemoradiotherapy using cisplatin was thought to be standard treatment for squamous cell carcinoma of cervix,but it had not been effective for adenocarcinoma.Concurrent chemoradiotherapy using irinotecan hydrochloride(CPT-11)had been effective for colorectal cancer,thus,we chose CPT-11 as a candidate for gynecologic adenocarcinoma.To evaluate the maximum tolerated dose(MTD)of weekly CPT-11 with external pelvic radiotherapy,a phase 1/2 study was conducted according to modified Fibonacci method.Methods:Eligible patients were advanced uterine cancer with measurable diseases[performance score(PS):0-2].Study period was from August 1 st,2002 to December 31 st,2008.The starting dose level(DL)of CPT-11 was 30 mg/m2(DL1)given weekly for 4 weeks.Subsequently,dose escalation was scheduled in 10 mg/m2 increments to 60 mg/m^2(DL4).The fixed radiotherapy consisted of whole pelvic 1.8 Gy/d,once a day in weekday for five weeks and it amounted to 45 Gy(25 fractions)in total.Results:Seventeen patients were enrolled.As for toxicities,one(1/17:5.9%)grade(G)4 neutropenia lasting 7 days had been seen in DL4.G2 diarrhea was identified in 35.3%(6/17)of the patients,and 11.8%(2/17)G3 diarrhea was observed in DL3 and DL4.Thus,the MTD of CPT-11 was defined as dose of 60 mg/m^2.The recommended dose was decided as 50 mg/m^2.The response rate was 88.2%[9 complete response(CR),3 partial response(PR),3 stable disease(SD),2 not evaluable(NE)].Disease control rate at 1 month after treatment completion was 100%but distant metastases were found in 24%(4/17)in longer outcome.Conclusions:MTD was 60 mg/m^2 and recommended dose was set as 50 mg/m2.This concurrent chemoradiation using weekly CPT-11 was feasible at 50 mg/m^2,and it might be effective even in adenocarcinoma of the uterus.

Care of survivors of gynecologic cancers

The number of cancer survivors is increasing and most healthcare providers will manage patients who have completed therapy for malignancy at some point. The care of survivors of gynecologic malignancies may seem daunting in a busy general gynecology practice. This paper intends to review the literature and suggest management of these women for the general gynecologist.

Modified Triple P Approach by Gynecologic Oncologist-Led Team for Placenta Accreta Spectrum Improves the Outcome: Non-Randomized Controlled Trial

Introduction: Placenta Accreta Spectrum (PAS) is associated with significant maternal and fetal morbidity and mortality. The ideal conservative management still does not exist. We aimed to compare the outcome of cesarean section for PAS by a gynecologic oncologist-led team using the modified triple P approach and by a non-gynecologic oncologist-led team. Material and Methods: This is non-randomized controlled trial. Group A had Cesarean Section by gynecologic oncologist. Gynecologic oncologist-led team did all Cesarean Section following a modified triple P approach. The first P is for “Plan” the uterine incision. The second P for “Pelvic” devascularization by internal iliac artery ligation. The third P is for Placenta non-separation with resection of the myometrium. Group B had Cesarean Section by non-gynecologic oncologist-led team. The main outcome measures were the need for hysterectomy, amount of blood loss, and the management-related complications. Results: Group A had significantly less estimated blood loss, and received less number of backed RBCs units, and less operative time than group B. The uterus is preserved in all cases of group A and in 50% of cases of group B. The overall maternal morbidity rate was 17.5% in group A and 72.2% in group B. Conclusion: This study provides evidence that the modified triple P approach for PAS by gynecologic oncologist-led team presents lower maternal morbidity in comparison to surgery by non-gynecologic oncologist-led team.

Minor Gynecologic Surgery: A Review of the Training Experience and Skill Building Opportunities for Providers in Low and Middle Income Countries

Purpose: Minor gynecologic surgery is the cornerstone of gynecologic evaluation and intervention in countries with a well-established medical infrastructure. Surgical training and exposure to minor procedures are not available in low and middle-income countries due to the complex challenges of patient delay and lack of access to healthcare, physician shortages, and the lack of ancillary services such as pathology and radiology. This paper reviews current training statistics, the international literature on minor gynecologic surgery and training strategies. Methods: PubMed searches using MESH terms cone biopsy, dilation and curettage, and loop electrosurgical excision procedure were performed. Statistics of minor surgical procedures among US Obstetrics and Gynecology Residency programs were tabulated. We then searched for data of training programs and surgical statistics in low resource countries. Results:Dilation and curettage is the most common minor gynecologic procedure in the United States but is performed with significantly lower frequency in low and middle-income countries. The most common procedure for the treatment of preinvasive disease was cryotherapy followed by loop electrosurgical excision procedure. There was no information about minor surgical procedures performed in hospitals in low and middle-income countries. Statistics from four-year American training programs showed an average of 209 minor cervical procedures performed annually. Conclusion: Expertise in minor gynecologic procedures is vital and requires the development of both adequate training programs and local medical infrastructure. Strategies for training in minor surgery for providers in low and middle-income countries include online curriculums, mentored relationships with senior physicians, and simulation models.

Immune evasion and therapeutic opportunities based on natural killer cells

Natural killer(NK)cells can elicit an immune response against malignantly transformed cells without recognizing antigens,and they also exhibit cytotoxic effects and immune surveillance functions in tumor immunotherapy.Although several studies have shown the promising antitumor effects of NK cells in immunotherapy,their function is often limited in the tumor microenvironment because tumor cells can easily escape NK cell-induced death.Thus,for efficient tumor immunotherapy,the mechanism by which tumor cells escape NK cell-induced cytotoxicity must be fully understood.Various novel molecules and checkpoint receptors that mediate the disruption of NK cells in the tumor microenvironment have been discovered.In this review,we analyze and detail the major activating and inhibitory receptors on the surface of NK cells to delineate the mechanism by which tumor cells suppress NKG2D ligand expression and increase tumor receptor and inhibitory receptor expression[NKG2A,programmed cell death1(PD-1),and T-cell immunoglobulin and immunoreceptor tyrosine inhibitory motif(TIGIT)]on the NK cell surface,and thus inhibit NK cell activity.We also reviewed the current status of treatments based on these surface molecules.By comparing the therapeutic effects related to the treatment status and bypass mechanisms,we attempt to identify optimal single or combined treatments to suggest new treatment strategies for tumor immunotherapy.