TGF-β-regulated different iron metabolism processes in the development and cisplatin resistance of ovarian cancer

The impact of different iron metabolism processes(DIMP)on ovarian cancer remains unclear.In this study,we employed various gene chips and databases to investigate the role of DIMP in the initiation and development of ovarian cancer.cBioPortal was used to determine mutations in DIMP-associated genes in ovarian cancer.Kaplan-Meier plotter was used to examine the influence of DIMP on the prognosis of ovarian cancer.By analyzing 1669 serous ovarian cancer cases,we identified a range of mutations in iron metabolism genes,notably in those coding for the transferrin receptor(19%),melanotransferrin(19%),and ceruloplasmin(10%)in the iron import process,and glucose-6-phosphate isomerase(9%),hepcidin antimicrobial peptide(9%),metal regulatory transcription factor 1(8%),and bone morphogenetic protein 6(8%)in the iron regulation process.Compared to the unaltered group,the group with gene alterations exhibited a higher tumor mutation burden count(43 vs.54)and more advanced histologic grade(78.19%vs.87.90%).Compared to the normal ovarian counterparts,a reduction in expression was observed in 9 out of the 14 genes involved in iron utilization and 4 out of the 5 genes involved in iron export in ovarian cancer;in contrast,an increase in expression was observed in 2 out of the 3 genes involved in iron storage in ovarian cancer.Furthermore,in cisplatin-resistant cells compared to cisplatin-sensitive ones,the expression of all genes in iron storage and 13 out of 14 genes in iron import was decreased,while that of 8 out of the 10 genes in iron utilization was increased.In addition,survival curve analysis indicated that a higher expression in the majority of genes in the iron import process(12/21),or a reduced expression in most genes in the iron export process(4/5)correlated with poor progression-free survival.Additionally,TGF-βcould regulate the expression of most iron metabolism-associated genes;particularly,expression of genes involved in the iron storage process(2/2)was inhibited after TGF-β1 or TGF-β2 treatment.In conclusion,DIMP plays multifaceted roles in the initiation,chemo-resistance,and prognosis of ovarian cancer.Therapeutically targeting DIMP may pave the way for more tailored treatment approaches for ovarian cancer.

Deciphering resistancemechanisms and novel strategies to overcome drug resistance in ovarian cancer:a comprehensive review

Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy.Drug resistance(DR)poses the most significant challenge in treating patients with existing drugs.The Food and Drug Administration(FDA)has recently approved three new therapeutic drugs,including two poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib and niraparib)and one vascular endothelial growth factor(VEGF)inhibitor(bevacizumab)for maintenance therapy.However,resistance to these new drugs has emerged.Therefore,understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management.In this review,we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.

Immune pathway through endometriosis to ovarian cancer

Endometriosis is an estrogen-dependent inflammatory disease,defined by the presence of functional endometrial tissue outside of the uterine cavity.This disease is one of the main gynecological diseases,affecting around 10%-15%women and girls of reproductive age,being a common gynecologic disorder.Although endometriosis is a benign disease,it shares several characteristics with invasive cancer.Studies support that it has been linked with an increased chance of developing endometrial ovarian cancer,representing an earlier stage of neoplastic processes.This is particularly true for women with clear cell carcinoma,low-grade serous carcinoma and endometrioid.However,the carcinogenic pathways between both pathologies remain poorly understood.Current studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers(EAOCs)via pathways associated with oxidative stress,inflammation,and hyperestrogenism.This article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis,specifically focusing on the complex relationship between the immune response to endometriosis and cancer,including the molecular mechanisms and their ramifications.Examining recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.

Advances in the Diagnosis and Treatment of Appendiceal Mucinous Neoplasms

Primary appendiceal neoplasms represent a relatively low percentage of all gastrointestinal cancers. A subset of these neoplasms, those of epithelial origin, are characterised by the production of a considerable amount of mucus, which is referred to as appendiceal mucinous neoplasms (AMN). Appendiceal mucinous neoplasms (AMN) have a low incidence, are easily misdiagnosed, depend on postoperative examination for confirmation of the diagnosis, are prone to form a “diagnosis”, and have a high incidence of the disease. Furthermore, they are prone to form peritoneal pseudomyxoma peritonei (PMP), are controversial in surgical decision-making, are prone to recurring after surgery alone, and are tricky to manage clinically. In this paper, we review the pathological characteristics, diagnosis and treatment of appendiceal mucinous tumours in the light of recent literature reports, with a view to providing certain references for the clinical diagnosis and treatment of this disease. .

Symptom Experience and Quality of Life in Colorectal Cancer Patients Undergoing Chemotherapy-A Secondary Publication

Objective:To evaluate symptom experience and quality of life(QoL)and to identify the predictors of QoL among colorectal cancer patients undergoing chemotherapy.Methods:A cross-sectional study was conducted on 107 colorectal cancer patients at a university-affiliated hospital between June 1 and July 30,2021.Functional Assessment of Cancer Therapy-Colorectal(FACT-C)and Memorial Symptom Assessment Scale-Short Form(MSAS-SF)were used to assess symptom experience and QoL of these patients.Data were analyzed using Pearson’s correlation,t-test,ANOVA,and hierarchical multiple regression.Results:The mean QoL score for colorectal cancer patients was 88.78±20.08.The most frequently experienced physical and psychological symptoms were numbness/tingling and worrying.Physical and psychological symptoms have a significant negative association with QoL.Perceived economic status was significantly associated with QoL in patients’general characteristics.The regression analyses showed that high psychological symptoms(β=-0.63,P<0.001),middle perceived economic status(β=-0.22,P=0.009),and low perceived economic status(β=-0.36,P<0.001)were statistically significant in predicting patients’low QoL.Conclusion:Symptom experience and QoL are essential variables that should be acknowledged when delivering health care to colorectal cancer patients.More attention to the reduction and comprehensive symptom management of psychological distress could improve QoL among colorectal cancer patients.

Primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery for patients with advanced ovarian cancer

Objectives： To compare the survival and perioperafive morbidity between primary debulking surgery （PDS） and neoadjuvant chemotherapy followed by interval debulking surgery （NAC/IDS） in treating patients with advanced epithelial ovarian cancer （EOC）. Methods： We retrospectively reviewed 67 patients with stage IIIC or iV EOC treated at Peking University Cancer Hospital from January 2006 to June 2009. VVherein, 37 and 30 patients underwent PDS and NAC/ IDS, respectively. Results： No difference in overall survival （OS） or progression-free survival （PFS） was observed between NAC/IDS group and PDS group （OS： 41.2 vs. 39.1 months, P=0.23; PFS： 27.1 vs. 24.3 months, P=0.37）. The optimal debulking rate was 60% in the NAC/IDS group, which was significantly higher than that in the PDS group （32.4%） （P=0.024）. The NAC/IDS group had significantly less intraoperative estimated blood loss and transfusion, lower nasogastric intubation rate, and earlier ambulation and recovery of intestinal function than the PDS group （P〈0.05）. Conclusions： NAC/IDS is less invasive than PDS, and offers the advantages regarding optimal cytoreduction rate, intraoperative blood loss, and postoperative recovery, without significantly impairing the survival compared with PDS in treating patients with stage IIIC or IV EOC. Therefore, NAC/IDS may be a valuable treatment alternative for EOC patients.

Ability of human umbilical cord mesenchymal stem cells to repair chemotherapy-induced premature ovarian failure

BACKGROUND Premature ovarian insufficiency(POI)and premature ovarian failure(POF)have become one of the major problems threatening women of childbearing age.Studies have shown that stem cells transplanted from bone marrow,umbilical cord,peripheral blood and amniotic fluid can migrate and proliferate to the ovary,promote ovarian function repair,increase the number of follicles and granulosa cells at all levels of ovary,improve endocrine function,and can differentiate into oocytes in specific ovarian environment to restore fertility to some extent.AIM To study the ability of human umbilical cord mesenchymal stem cells(hUCMSCs)to repair ovarian injury after chemotherapy.METHODS A total of 110 female BALB/c mice(aged 7-8 wk old)with body masses of 16.0-20.0 g were selected.The mice were fed until 12 wk of age,and cyclophosphamide was administered by intraperitoneal injection for 14 consecutive days to induce premature ovarian failure in mice.Seventy-five mice with estrous cycle disorder were screened and randomly divided into 3 groups according to their body weight:model group,positive control group and hUCMSC group,and each group had 25 mice.Another 25 mice were used as negative controls.The mice in the hUCMSC group were injected with hUCMSCs in the tail vein,and the mice in the positive control group were given an oestradiol valerate solution and a medroxyprogesterone acetate solution in the tail vein.On the 1^st,15^th,30^th,45^th,and 60^th days after intravenous administration,vaginal smears were made to monitor the estrous cycles of the mice.The ovaries were weighed,and pathological sections were made to observe the morphology of the follicles;blood samples were collected to monitor the concentration of sex hormones(oestradiol and follicle-stimulating hormone).RESULTS The estrous cycles of the model group mice were disrupted throughout the experiment.Mice in the hUCMSC group and the positive control group resumed normal estrous cycles.The ovarian weight of the model group mice continued to decline.The ovarian weight of the hUCMSC group mice and the positive control group mice decreased first and then gradually increased,and the ovarian weight of the hUCMSC group mice was heavier than that of the positive control group mice.The difference was statistically significant(P<0.05).Compared with the negative control group,the model group experienced a decrease in oestradiol and an increase in follicle-stimulating hormone,and the difference was statistically significant(P<0.05).Compared with the model group,the hUCMSC and positive control groups experienced a slight increase in oestradiol and a decrease in follicle-stimulating hormone;the difference was statistically significant(P<0.05).The pathological examination revealed that the mouse ovaries from the model group were atrophied,the volume was reduced,the cortical and medullary structures were disordered,the number of follicles at all stages was significantly reduced,the number of atretic follicles increased,the number of primordial follicles and corpus luteum significantly decreased,and the corpus luteum had an irregular shape.Compared with those of the model group,the lesions of the hUCMSC and positive control groups significantly improved.CONCLUSION hUCMSCs can repair ovarian tissue damaged by chemotherapy to a certain extent,can improve the degree of apoptosis in ovarian tissue,and can improve the endocrine function of mouse ovaries.

Clinical benefit and tolerability of adjuvant intraperitoneal chemotherapy in patients who have or have not received neoadjuvant chemotherapy for advanced ovarian cancer

BACKGROUND Adjuvant chemotherapy using intraperitoneal(IP)treatment has demonstrated survival benefit over intravenous(IV)therapy alone in patients treated with upfront debulking surgery for advanced stage ovarian cancer.Neoadjuvant chemotherapy followed by interim surgery and adjuvant chemotherapy has similar outcome in survival as compared to upfront surgery followed by adjuvant IV chemotherapy.IP chemotherapy has not been widely adopted in clinical practice for a number of reasons.Whether IP chemotherapy delivered in the patients who received neoadjuvant chemotherapy can be well tolerated or confers any clinical benefit has not been well studied.AIM To evaluate the experience of adjuvant IP chemotherapy in the community cancer clinic setting,and the clinical benefit and tolerability of incorporating IP chemotherapy in patients who received neoadjuvant treatment.METHODS We retrospectively evaluated toxicities and outcomes of patients with stage III and IV ovarian cancer diagnosed at our institution between 07/2007 and 07/2015 who received intraperitoneal chemotherapy after cytoreductive surgery(group 1)or after neoadjuvant chemotherapy followed by interim surgery(group 2).RESULTS Thirty eight patients were treated with IP chemotherapy,median age was 54 years old(range 38.6 to 71 years).In group 1(n=25),12(48%)of the patients completed 4 or more cycle of IP treatment after upfront debulking surgery;while in group 2(n=13),8(61.5%)of the patients completed all 3 cycles of the assigned IP chemotherapy after receiving neoadjuvant IV chemotherapy followed by surgery,and 2(15.4%)more patients tolerated more than 3 cycles.In those patients who did not get planned IP chemotherapy,most of them were treated with substitutional IV chemotherapy,and the completion rate for 6 cycles of IV+IP was 92%.Abdominal pain,(64%in group 1 and 38%in group 2),vomiting,(36%in group 1 and 30.8%in group 2),dehydration(16%in group 1 and 15.4%in group 2),and hypomagnesemia(12%in group 1 and 15.4%in group 2)were the most common adverse effects in all patients,while patients who have received neoadjuvant chemotherapy were more likely to get hypokalemia,fatigue and renal insufficiency.Progression free survival(PFS)was 26.5 mo(95%CI 14.9,38.0)in group 1 and 27.6 mo(95%CI 13.1,42.1)in group 2.The overall survival was 100.2 mo(95%CI 67.9,132.5)for group 1 and 68.2 mo(95%CI 32.2,104.0)for group 2.For the entire cohort,PFS was 26.5 mo(95%CI 15.9,37.0)and OS was 78.8 mo(95%CI 52.3,105.4).CONCLUSION The use of IP/IV chemotherapy can be safely administrated in the community cancer clinic setting.The use of IP/IV chemotherapy in patients who have received neoadjuvant chemotherapy followed by surgery is feasible and tolerable.Despite various modification of the IP regimen,incorporation of IP chemotherapy in the adjuvant setting appears to be associated with improved PFS and overall survival.

Accuracy of Intraoperative Frozen Section in the Diagnosis of Ovarian Neoplasms

Objective: The aim of the work is to evaluate the accuracy of intraoperative frozen section in the diagnosis of ovarian neoplasms in Zagazig University. Design: A prospective cross sectional cohort study. Method: This study was performed between March 2011 and March 2012, on 50 patients presented with ovarian mass. Gross examination of the tumor removed was done by inspection and palpation. The specimen was then cut with a sharp knife into two halves. The most appropriate area thought to be representative of lesion was chosen. The number of sections frozen was depended on the type and size of the tumor. Seven to eight μm sections were obtained and stained with hematoxylin-eosin. The specimens were then fixed in formalin. Paraffin blocks of the sections were processed in the routine way and sections were stained with hematoxylin and eosin (H and E). The diagnosis obtained by intraoperative frozen section based on cellularity and cell morphology was compared with final histopathological diagnosis in terms of diagnostic sensitivity, to differentiate between benign and malignant lesions. Assessment of the overall accuracy of the intraoperative diagnosis was classified as concordant or discordant. Results: There was no statisticaly significant differencre in the studied patients as regard the clinical data, macroscopic and intraoperative picture, while there was statisticaly significat association as regard the laterality of the ovarian masses. The validity of frozen section in the diagnosis of benign tumour was 100% with 100% accuracy, specificity, positive predictive value, negative predictive value, while sensitivity & negative prediction for borderline tumour and specificity & positive prediction of malignant tumour were 100%, specifecity for borderline tumours was 95% while the positive predictive value was 33.3% with 96% accuracy for both malignant and borderline tumours. Conclusion: Intraoperative frozen section is accurate for rapid diagnosis of ovarian tumors. It can help surgeons avoid under-treatment or overtreatment of patients. Our study was designed prospectively using a small number of patients. The door is open to larger studies using a larger number of patients to be performed in order to substantiate our results.

PHASE Ⅱ STUDY OF GEMCITABINE COMBINED WITH PLATINUM CHEMOTHERAPY FOR RECURRENT EPITHELIAL OVARIAN CANCER

Objective To evaluate the anti-tumor effect and toxicity of gemcitabine combined with platinum chemotherapy on recurrent epithelial ovarian cancer. Methods Phase Ⅱ study of gemcitabine combined with platinum chemotherapy was carried out in 22 patients with recurrent epithelial ovarian cancer. Median age of patients was 50. 5 years old. Seven patients were platinum-sensitive and 15 patients were platinum-resistant or -refractory. All patients received gemcitabine combined with carboplatin or oxa/iplatin chemotherapy. Patients＇ response rate （RR） and toxicity of gemcitabine combined with platinum chemotherapy were evaluated. Results A total of 98 gemcitabine-based chemotherapy cycles were performed. Total RR was 36. 4%, RR of platinum-sensitive patients was 4/7 and platinum-resistant and -refractory patients was 4/15. The estimated median survival time was 10.0 months （95% CI. 7.0-13.0） after initiation of gemcitabine combined with platinum chemotherapy. There was no significant difference in survival time between platinum-resistant/refractory group and platinum-sensitive group （P = 0. 061 ）. Side effects of gemcitabine combined with platinum chemotherapy were observed in 81.8% of patients. Grade Ⅱ/Ⅲ anemia （54. 5% ） and grade Ⅲ/Ⅳ neutropenia （54. 5% ） were most common toxicities. Ten （45.5%） patients had to delay their chemotherapy cycles or reduce the dose of chemotherapeutic drugs because of the severe side effects. Fourteen （63.6%） patients received granulocyte colony-stimulating factor to relieve neutropenia, and 8 （ 36. 4% ） patients received component blood transfusion to treat anemia or thrombocytopenia. There was no treatment-associated death. Conclusion Gemcitabine combined with platinum chemotherapy appears to be an effective and well-tolerant treatment for recurrent epithelial ovarian cancer, including platinum-resistant or -refractory diseases.

Chemotherapy of ovarian cancer in elderly patients

Epithelial ovarian cancer is primarily a disease of older women. Advanced age is risk factor for decreased survival. Optimal surgery and the safe and effective administration of chemotherapy are essential for prolonged progression-free and overall survival(OS). In this article, the available regimens in both the primary treatment and relapsed setting are reviewed.

Treatment Free Intervals after Subsequent Chemotherapy Lines in Recurrent Ovarian Cancer

Aim: Despite recent advances in the treatment of ovarian cancer, recurrence of the disease is still frequent. This study evaluated whether multiple lines of chemotherapy have impact on overall survival (OS), progression free survival (PFS) or on treatment free intervals (TFIs) after serial chemotherapy lines in recurrent settings. Methods: A total of 189 patients with ovarian cancer (including fallopian tube and primary peritoneal cancer), who were treated in Kuopio University Hospital in Finland during 2009-2014, were enrolled. The medical files of these patients were retrospectively reviewed. Results: Median OS and PFS were significantly higher at the time of the first relapse compared to subsequent relapses (p < 0.001). TFIs shortened significantly after the first relapse (p < 0.001). The differences in TFIs were also seen when comparing platinum sensitive, semi-sensitive and platinum resistant patients. The total amount of TFI times during the whole follow-up time was significantly reduced in those patients that received at least one form of aggressive care at the end of life (p = 0.004). Conclusions: Ovarian cancer patients received often multiple lines of chemotherapy. TFIs after subsequent chemotherapy lines decreased during the disease course. More efforts should be taken to avoid unnecessary and ineffective treatments especially in recurrent phase of the disease.

Risk factors for postoperative delayed gastric emptying in ovarian cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

BACKGROUND Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy(CRSHIPEC)has shown promising results in improving the survival of ovarian cancer patients.Although the safety profiles of CRS-HIPEC exist,more attention should be paid to gastrointestinal complications,as the procedure involves a considerable proportion of bowel resection and anastomosis.AIM To identify the risk factors for delayed gastric emptying in ovarian cancer treated with CRS-HIPEC.METHODS A cross-sectional study was conducted.According to the inclusion and exclusion criteria,we retrospectively analyzed 77 patients admitted between March 2014 and April 2018 with advanced and recurrent ovarian cancer treated with CRSHIPEC in Beijing Shijitan Hospital of Capital Medical University.Risk factors for delayed gastric emptying were analyzed using univariate analysis.All of the statistically significant variables in the univariate analysis were entered into the multivariable logistic regression model to determine factors independently associated with delayed gastric emptying.RESULTS Among the 77 included patients,36.4%(28/77)had delayed gastric emptying after CRS-HIPEC.The median age and body mass index of all patients were 59 years and 22.83 kg/m^(2),respectively.Preoperative chemotherapy was administered in 55 patients(71%).Sixty-two patients(81%)had a history of at least one previous pelvic surgery.The median operation time and intraoperative hemorrhage volume were 630 min and 600 mL,respectively.Omentectomy was performed in 32 cases of primary ovarian cancer and 24 cases of recurrence.The median peritoneal cancer index was 16.The risk factors for delayed gastric emptying from the univariate analysis were body mass index<23 kg/m2(X2=5.059,P=0.025),history of pelvic surgery(X^(2)=4.498,P=0.034),history of chemotherapy(X^(2)=4.334,P=0.037),operation time≥7 h(X2=4.827,P=0.047),and intraoperative hemorrhage≥800 mL(X^(2)=7.112,P=0.008).Multivariable analysis revealed that age≥70 years(HR=7.127;95%CI 1.122-45.264;P=0.037)and intraoperative hemorrhage≥800 mL(HR=3.416;95%CI 1.067-10.939;P=0.039)were independently associated with postoperative delayed gastric emptying after CRS-HIPEC.CONCLUSION Postoperative gastrointestinal management,including prolonged nasogastric intubation,should be promoted for patients over 70 years or those with intraoperative bleeding exceeding 800 mL.

Combination of docetaxel-carboplatin for adjuvant chemotherapy of epithelial ovarian,primary peritoneal and fallopian tube cancers:a meta-analysis

Objective： The aim of this study was to compare the efficacies and safeties of the combination of docetaxel- carboplatin with the combination of non docetaxel-carboplatin as first-line chemotherapy for advanced epithelial ovarian, pri- mary peritoneal or fallopian tube cancers. Methods： Relevant articles were identified from MEDLINE （1993-2010）, EMBASE （1980-2010）, MEDION, the Cochrane library, Science Citation Index Expanded databases, hand searching of reference lists from primary articles and reviews, conference abstracts and contact with experts in the field. The review included 5 relevant primary studies （1430 women）. Data was extracted for study characteristics and quality. Bivariate random-effect model meta- analysis was used to estimate diagnostic accuracy of the various index tests. A quantitative meta-analysis was carried out by two reviewers based on the inclusion criteria from all available studies. Results： The frequency of the subgroup analysis of toxicity showed that toxicity action of combination of docetaxel-carboplatin was more severe than that of non docetaxel- carboplatin group （OR = 1.33, 95% CI = 1.13-1.56, P = 0.0005）, whereas that of clinical responses was equivalent in com- parison combination of docetaxel-carboplatin with combination of paclitaxel-carboplatin or docetaxel-cisplatin （OR = 1.0, 95% CI = 0.87-1.16, P = 0.95）. There were heterogeneity （X2 = 79.36, P 〈 0.00001） and inconsistency （83.6%） in toxicity analysis among the trials, while neither heterogeneity （x2 = 3.21, P = 0.99） nor inconsistency （F = 0%） in clinical responses among the trials. Conclusion： The safety of combination of docetaxel-carboplatin is less than that of combination of paclitaxel- carboplatin or docetaxel-cisplatin. However, the clinical responses of combination of docetaxel-carboplatin are comparable with combination of paclitaxel-carboplatin or docetaxel-cisplatin.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in epithelial ovarian cancer: State of the art

Advanced stage epithelial ovarian cancer(EOC) is diffi cult to treat with low overall cure rates. A new strategy combining maximal cytoreductive surgery(CRS) with intraoperative hyperthermic intraperitoneal chemotherapy(HIPEC) has been proposed to treat advanced stage EOC in the primary setting. Numerous small, heterogeneous studies have been conducted exploring outcomes in patients with predominantly advanced, recurrent or refractory disease treated with CRS + HIPEC. Although morbidity rates approaching 35% have been reported, oncologic outcomes are promising. Incorporation of HIPEC for the treatment of primary EOC has continued to gain interest. Several prospective phase 2 clinical trials were recently completed evaluating the impact of CRS + HIPEC in the primary setting. This article will briefl y discuss the benefi ts of optimal surgical cytoreduction and the theoretical basis of intraperitoneal chemotherapy in patients with advanced stage EOC, and will then review existing literature describing oncologic outcomes in EOC patients treated with HIPEC in the primary setting.

Pharmacology of cancer chemotherapy drugs for hyperthermic intraperitoneal peroperative chemotherapy in epithelial ovarian cancer

The peritoneal parietal and visceral surfaces of the abdomen and pelvis are an important anatomic site for the dissemination of epithelial ovarian cancer(EOC). The transcoelomic spread of cancer cells gives rise to peritoneal carcinomatosis(PC) which, without special treatments, is a fatal manifestation of EOC. In order to control PC cytoreductive surgery to remove macroscopic disease is combined with perioperative intraperitoneal(IP) and perioperative intravenous chemotherapy to eradicate microscopic residual disease. Chemotherapy agents are selected to be administered by the IP or intravenous route based on their pharmacologic properties. A peritoneal-plasma barrier which retards the clearance of high molecular weight chemotherapy from the peritoneal cavity results in a large exposure of small cancer nodules on abdominal and pelvic surfaces. Tissue penetration is facilitated by moderate hyperthermia(41-42 ℃) of the IP chemotherapy solution. Timing of the chemotherapy as a planned part of the surgical procedure to maximize expo-sure of all peritoneal surfaces is crucial to success.

THE CORRELATION BETWEEN INCREASED APOPTOSIS AND DECREASED PERIPHERAL BLOOD WBC IN PATIENTS RECEIVING CHEMOTHERAPY FOR OVARIAN CANCER

The purpose of this study was to determine whether the decrease of WBC is correlated with theincrease of apoptosis induced by cytotoxic drugs in patients who received neoadjuvant polychemotherapy for ovariancancer and whether the reduction of peripheral blood WBC can be predicted by the detection of apoptosis. Methods:The study included 25 patients who received neoadjuvantpolychemotherapy for ovarian cancer after operation. Total 2 ml of venous blood was collected from these subjectswithin 24 hours before chemotherapy and at the fifth dayafter the beginning of chemotherapy. Peripheral bloodWBC count was performed and its apoptosis was analyzed using flow cytometry (FCM) and DNA electrophoresis.Results: 68% (17/25) of the patients had a decrease in WBC after chemotherapy. The average counts of WBC were5.191.36×109/L and 4.361.56×109/L, the distributionswere 4.10~8.60×109/L and 2.00~7.90×109/L before and after chemotherapy respectively. At the same time,64%(16/25) of the patients had an increase in apoptoticcells. The proportions of apoptosis were 4.012.59% and5.661.36%, the distributions were 1.05~11.02% and0.8~14.08% before and after chemotherapy respectively.Both the decrease of WBC and the increase of apoptosiswere statistical significant (P<0.05). The coefficient between the decrease of WBC and the increase of apoptosis is0.646(P<0.05). The sensitivity of the quantitative analysis of apoptosis using FCM for clinical early diagnosis of thedecrease of WBC is 82%, the speciality is 75% and theaccuracy is 80%. Conclusion: The increased apoptosis induced by cytotoxic drugs contributed to the chemotherapy-associated reduction of WBC at some extend, there were somewhat correlation between them. The detection of peripheral apoptosis could be of some help to assess the decrease and scientific bases for the administration of G-CSF, GM-CSF to obtain the optimal cost-effectiveness of clinical chemotherapy.

Prolonged hyperthermic intraperitoneal chemotherapy duration with 90 minutes cisplatin might increase overall survival in gastric cancer patients with peritoneal metastases

BACKGROUND Advanced gastric cancer with synchronous peritoneal metastases(GC-PM)is associated with a poor prognosis.Although cytoreductive surgery with hyperthermic intraperitoneal chemotherapy(CRS-HIPEC)is a promising approach,only a limited number of Western studies exist.AIM To investigate the clinicopathological outcomes of patients who underwent CRSHIPEC for GC-PM.METHODS A retrospective analysis of patients with GC-PM was conducted.All patients were seen at the Department of General and Visceral Surgery,Hospital Barmherzige Brüder,Regensburg,Germany between January 2011 and July 2021 and underwent CRS-HIPEC.Preoperative laboratory results,the use of neoadjuvant trastuzumab,and the details of CRS-HIPEC,including peritoneal carcinomatosis index,completeness of cytoreduction,and surgical procedures were recorded.Disease-specific(DSS),and overall survival(OS)of patients were calculated.RESULTS A total of 73 patients were included in the study.Patients treated with neoadjuvant trastuzumab(n=5)showed longer DSS(P=0.0482).Higher white blood cell counts(DSS:P=0.0433)and carcinoembryonic antigen levels(OS and DSS:P<0.01),and lower hemoglobin(OS and DSS:P<0.05)and serum total protein(OS:P=0.0368)levels were associated with shorter survival.Longer HIPEC duration was associated with more advantageous median survival times[60-min(n=59):12.86 mo;90-min(n=14):27.30 mo],but without statistical difference.To obtain additional data from this observation,further separation of the study population was performed.First,propensity score-matched patient pairs(n=14 in each group)were created.Statistically different DSS was found between patient pairs(hazard ratio=0.2843;95%confidence interval:0.1119-0.7222;P=0.0082).Second,those patients who were treated with trastuzumab and/or had human epidermal growth factor receptor 2 positivity(median survival:12.68 mo vs 24.02 mo),or had to undergo the procedure before 2016(median survival:12.68 mo vs 27.30 mo;P=0.0493)were removed from the original study population.CONCLUSION Based on our experience,CRS-HIPEC is a safe and secure method to improve the survival of advanced GC-PM patients.Prolonged HIPEC duration may serve as a good therapy for these patients.

Expression and significance of tumor suppressor gene p16 in human ovarian neoplasm

To observe the relationship between tumor suppressor gene p16 expression and ovarian cancer occurrence and development. Metbods: Using ABC immunohistochemistry method, we investigated the expression of p16 in 72 cases of ovarian neoplasm. Results: The positive rates of p16 in malignant, benign, borderline tumors and normal ovarian tissue were 7. 89%, 60.00%, 66. 67% and 83. 33%, respectively (P<0.01). In the cases whose tumors were more malignant and poorly differentiated, and who relapsed and died, the positive stainings were not discovered. Conclusiou: p16 is well related with the occurrence and development of malignant ovarian tumor.

The “predictive molecule targeted chemotherapy” for relapsed ovarian cancer—a pilot study

Objective: How to choose chemotherapy regimen is a often-encountered and formidable problem in the setting of relapsed ovarian cancer. So far, it was usually according to the clinical trials and doctors’ experience and the response rate was very low. In the present study, we proposed a new treatment strategy–the “predictive molecule targeted chemotherapy, PMTC” to choose supposedly sensitive protocols and void supposedly resistant protocols based on the specific predictive molecule expression of individual tumor tissue. Methods: Retrospectively analysis of 16 cases of relapsed ovarian cancer patients from January 2002 to December 2003, as the experience-directed chemotherapy group (control group), to calculate the response rate. Prospectively recruit 9 cases of relapsed ovarian cancer patients after January 2004, whose chemotherapy drug choice was based on the expression of 6 predictive molecules (p53, et al) by means of immunohistochemistry, as the PMTC group, to calculate the response rate. χ2 test was used for the statistical analysis. Results: The response rate of control group was 26%, including 31% for second line and 14% for third line respectively. The response rate of PMTC group was 78%, in which 5 cases of early relapse all responded. The difference was significant (P=0.011). Conclusions: PMTC is a new effective method to treat the relapsed ovarian cancer.