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Copyright of Fudan University Journal of Medical Sciences is the property of Fudan University Journal of Medical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Clinically and through auxiliary examinations, distinguishing uterine leiomyoma from early-stage uterine sarcoma presents significant challenges. A 48-year-old patient underwent a laparoscopic hysterectomy for uterine leiomyoma, during which a large uterus was excised through the vagina and extracted. Four months post-operation, the patient developed abdominal distension, indicative of extensive pelvic-abdominal dissemination of uterine sarcoma. We hypothesize that unprotected fibroid fragmentation increases the risk of uterine sarcoma spread, thereby worsening the prognosis. Our literature review aims to thoroughly understand the risks associated with unprotected transvaginal laparoscopic tumor division. [ABSTRACT FROM AUTHOR]

Objective: Patients with advanced epithelial ovarian cancer treated with salvage therapy using new combinations of systemic chemotherapy, radiation therapy, and systemic immunotherapy have had limited success. Since the most common site of relapse or failure to conventional systemic chemotherapy has been the peritoneal cavity, intraperitoneal (IP) chemotherapy was selected to treat small-volume residual disease., Methods: Sixty-five patients were entered on a protocol using intraperitoneal cisplatin and thiotepa following a response to intravenous cisplatin-based chemotherapy. Patients had surgically documented residual disease (0.5 cm or less maximum tumor diameter) at completion of preprotocol surgery and had no clinical, radiologic, or histologic evidence of extraperitoneal disease. Cisplatin (100 mg/m2) and thiotepa 30 mg/m2 was delivered intraperitoneally every 4 weeks for a maximum of six cycles. The dose of thiotepa was reduced to 12 mg/m2 due to unexpected severe myelosuppression., Results: Of the 52 evaluable patients, grade 4 neutropenia, thrombocytopenia, neurotoxicity, and nephrotoxicity were observed in 31, 19, 13, and 6% of patients, respectively. For all evaluable patients, the complete response rate was 19% and the partial response rate was 2% for a total response rate of 21%. Of 16 patients who had a reassessment laparotomy, 10 patients achieved a surgically documented complete response and 1 patient had a partial response. Four patients are still in response for 67+, 70+, 70+, and 73+ months after third-look surgery. Three patients who did not undergo third-look surgery after chemotherapy are alive and clinically free of disease at 49+, 69+, and 85+ months., Conclusion: Thiotepa, when used with cisplatin for IP salvage therapy in patients with advanced or recurrent ovarian cancer, may produce significant myelosuppression and doses must be adjusted accordingly. In cisplatin-sensitive patients with small-volume residual ovarian cancer, IP cisplatin and thiotepa appears to have activity. Determining the utility of this approach will require a randomized trial., (Copyright 1998 Academic Press.)

Objective: Our purpose was to evaluate the risk factors and prognosis in patients with stage IA squamous cell carcinoma of the cervix and 3 to 5 mm of invasion., Study Design: From 1981 to 1984 the Gynecologic Oncology Group conducted a prospective clinicopathologic study of patients with stage I carcinoma of the cervix. A selective study group that was previously defined and reported included patients with squamous cell carcinoma of the cervix who were treated with radical hysterectomy and pelvic lymphadenectomy and who had disease confined to the uterus, with or without microscopically positive lymph nodes., Results: One hundred eighty-eight patients had invasion of 3, 4, or 5 mm as determined by central pathology review. Patients who satisfied the 3 to 5 mm invasion definition of the current stage IA2 classification of the International Federation of Gynecology and Obstetrics (1995) are the subject of this report., Conclusions: Patients with stage IA2 carcinoma of the cervix who have 3 to 5 mm of invasion present on conization with no invasion in the hysterectomy specimen are at very low risk for lymph node metastases, recurrences, or death caused by cancer.

The influence of cell type on recurrence-free interval (RFI) and survival after radical hysterectomy for patients with Stage IB carcinoma of the cervix was investigated. Patients with Stage IB carcinoma of the cervix (>3-mm invasion) underwent a radical hysterectomy and pelvic lymphadenectomy. Patients with involved paraaortic nodes or gross extracervical disease were excluded. Of 813 evaluable patients, 645 had squamous, 104 with adenocarcinoma, and 64 had adenosquamous cell type. The time to failure and the following clinical/pathologic characteristics were compared among the three cell types: age, Gynecologic Oncology Group performance status (PS), gross versus occult tumor, histologic grade, depth of invasion, node status, uterine extension, parametrial extension, surgical margins, and capillary-lymphatic space (CLS) involvement. A Cox proportional hazards model was used to compare the patients with adenosquamous and adenocarcinoma to those with squamous while adjusting for prognostic factors. The median age was 40 years (range, 21-87). Pelvic nodes were involved in 119 (15%) of patients. There were no significant differences between cell types in distributions of the following factors: age, PS, positive nodes, depth of invasion, uterine extension, surgical margins, or parametrial extension. There were statistically significant differences between cell types with regards to grade (P < 0.001), gross versus occult primary status (P = 0.016), and CLS involvement (P = 0.005). There was no statistically significant difference detected between cell types in crude comparisons of RFI (P = 0.29); however, there was a difference in survival (P = 0.02) with shorter survival seen in the adenosquamous cell type. After adjusting for CLS involvement, PS, depth of invasion, and clinical tumor size, survival remained worse for patients with adenosquamous primaries when compared to squamous carcinoma (P = 0.02) and adenocarcinoma (P = 0.007). In conclusion, no statistically significant differences were seen in RFI among cell types; however, in patients with Stage I carcinoma of the cervix overall survival after radical hysterectomy may be slightly worse for those with adenosquamous cell type.

Purpose: Progestins represent the most widely used form of endocrine therapy in advanced or recurrent endometrial carcinoma. Based on encouraging response rates in breast cancer with high-dose megestrol acetate (MA) 800 mg/d, this phase II trial assessed response rates in patients with endometrial carcinoma treated with high-dose MA., Patients and Methods: Sixty-three patients with recurrent or advanced endometrial carcinoma were entered into this Gynecologic Oncology Group (GOG) study. Patients had either failed to respond to or were considered incurable with local therapy and had not received prior cytotoxic or hormonal therapy. MA 800 mg/d was administered orally in divided doses. Standard GOG toxicity criteria were used., Results: Of 63 patients entered, 58 were assessable for toxicity and 54 for response. Of 13 responders (24%), six (11%) had a complete and seven (13%) a partial response. Four of the responses lasted greater than 18 months. Twelve patients (22%) had stable disease. The response rate of patients with grade 1 or 2 lesions (11 of 30, 37%) was significantly higher (P = .02) than that of patients with more poorly differentiated tumors (two of 24, 8%). There was no difference in response rates comparing advanced versus recurrent disease, cell type, including papillary serous lesions, site of disease, prior radiation, age, or weight. The median progression-free survival (PFS) and overall survival intervals were 2.5 and 7.6 months, respectively. Grade 3 weight gain (> 20%) was seen in three patients and grade 3/4 hyperglycemia in three. Three deaths secondary to cardiovascular events were possibly related to therapy; diabetes was also a contributing factor in all three cases., Conclusion: High-dose MA is active in endometrial carcinoma, but appears to have no advantage over lower-dose progestins.

The Gynecologic Oncology Group (GOG) experience with second-look laparotomy in malignant ovarian germ cell tumors is reviewed. All patients in this study were enrolled prospectively on one of three protocols that employed relatively brief cisplatin-based chemotherapy after initial surgical staging and cyto-reduction. Forty-five surgical procedures were done in patients who received three courses of cisplatin-based adjuvant therapy after complete tumor resection. Findings were no tumor or mature teratoma in 43; 2 patients had immature teratomas. One of the latter patients received further chemotherapy and one did not. Both of these patients and 44 of the total are disease free. Seventy-two patients were treated with similar chemotherapy for advanced incompletely resected tumor. Forty-eight of these patients did not have teratoma elements in their primary tumor. At surgery, 45 patients had no tumor and 3 had persistent endodermal sinus tumor or embryonal carcinoma. All three of the latter patients are dead despite further treatment. Twenty-four patients had teratoma elements in their primary tumor. Of these patients, 16 had mature teratoma at second-look, which in 7 was bulky or progressive. Fourteen of the total 16 and 6 of the 7 with bulky residual tumor remain disease free after surgical resection. Second-look laparotomy is not necessary in patients completely resected initially or in those patients with advanced tumor that does not contain teratoma. However, enough patients with incompletely resected tumor which initially contains elements of teratoma benefit from the procedure to warrant its general use.

Background: A clinicopathologic evaluation of clinical Stage I and II uterine sarcoma was done by the Gynecologic Oncology Group from 1979-1988., Methods: After all eligibility criteria were met, 453 cases were evaluable and analyzed for prognostic factors., Results: Of the 301 mixed mesodermal tumors (MMT), 167 were homologous (HO), and 134 were heterologous (HE). Fifty-nine tumors were leiomyosarcomas (LM). The remaining 93 sarcomas were predominantly stromal cell and adenosarcomas. For this study, only the MMT or LM tumors were analyzed. The recurrence rate for all MMT was 53% (HO, 44%; HE, 63%). The recurrence rate for LM was 71%. The site of the first recurrence included the pelvis in 21% of MMT and 14% in LM. Factors significantly related to progression-free interval (PFI) by univariate analysis among MMT were adnexal spread, lymph node metastases, tumor size, lymphatic-vascular space involvement, histologic grade, cell type, age, peritoneal cytologic findings, and depth of uterine tumor site of invasion. The prognostic factors based on multivariate analysis were adnexal spread, lymph node metastases, histologic cell type (HO versus HE), and grade of sarcoma. For LM, the mitotic index was the only factor significantly related to PFI.

Surgical and pathologic findings at laparotomy for radical hysterectomy in 990 patients with clinical stage IB carcinoma of the cervix were analyzed to determine the frequency of metastases to the ovary. Ovarian spread was identified in 4 of 770 (0.5%) patients with squamous carcinoma and 2 of 121 (1.7%) with adenocarcinoma. No patients with adenosquamous carcinoma (n = 82) or other histologic types (n = 17) had ovarian metastases. Although the frequency of metastases was greater among patients with adenocarcinoma, this was not statistically significant (p = 0.19, Fisher's exact test). All 6 patients with ovarian metastases had other evidence of extracervical disease. Three underwent radical hysterectomy and bilateral salpingo-oophorectomy. Of these, one patient received extended field radiotherapy and died of disease 18 months after diagnosis. Two patients, one treated with combination chemotherapy and one with no adjunctive therapy, are alive without evidence of disease at 59 and 62 months, respectively. Three patients underwent exploratory laparotomy with salpingo-oophorectomy and lymphadenectomy without hysterectomy. All three patients died of disease at 2, 3, and 30 months; the first and last patient received adjunctive radiotherapy. Not all patients underwent oophorectomy. Of 347 patients with at least unilateral ovarian preservation, no postoperative pelvic radiotherapy, and no gross extracervical disease or metastasis to the paraaortic nodes, pelvic recurrence developed in 16. There was no excess of pelvic recurrences in patients with adenocarcinoma (0/41) or adenosquamous carcinoma (1/29, 3.4%) when compared with those with squamous carcinoma (15/270, 5.6%). This suggests no excess of occult ovarian metastases in nonsquamous tumors of the cervix. There is no evidence in these data of an increased risk of ovarian preservation in patients with stage IB carcinoma of the cervix with no gross extracervical disease.

We report on the clinical and pathologic findings in 31 cases of adenosarcoma of the uterus subjected to hysterectomy and staging laparotomy. Nine of 30 patients (30%) have had recurrent tumor and six of 30 (20%) have already died of tumor in a relatively short follow-up period (mean, 38.3 months). Seventeen of 31 cases were diagnosed as adenosarcoma with sarcomatous overgrowth (SO). Ten of these 17 with SO contained focal or extensive rhabdomyosarcoma. In six cases, extrauterine spread was identified as follows (two patients had two sites each): vaginal involvement (two cases), pelvic lymph node metastases (two), positive peritoneal cytologic findings (two), parametrial invasion (one), and ovarian metastasis (one). Extrauterine spread (stage III) (p less than 0.001) and myometrial invasion (p = 0.04) were associated with higher rates of recurrence. The presence of lymphatic and/or vascular invasion, SO, and rhabdomyosarcomatous differentiation also indicated poor prognosis but did not attain statistical significance. Based on this experience, staging laparotomy including peritoneal cytology is suggested in cases of clinical stages I and II adenosarcoma. The differential diagnosis of these tumors is also discussed.

Long-term follow-up was obtained on 726 women with advanced ovarian carcinoma (suboptimal stage III and stage IV) who had received primary chemotherapy on two Gynecologic Oncology Group (GOG) protocols between 1976 and 1982. The first study compared melphalan alone versus melphalan plus hexamethylmelamine versus cyclophosphamide plus doxorubicin (CA). The second study evaluated the same CA regimen with or without cisplatin. Eligibility for the two studies was the same. At last contact, 76 patients were alive. In a multivariate analysis, cell type other than clear cell or mucinous, cisplatin-based treatment, good performance status, younger age, lower stage, clinically nonmeasurable disease, smaller residual tumor volume, and absence of ascites were favorable characteristics for overall survival (P less than .05). Second-look laparotomy was negative significantly more often among those with endometrioid tumors; there were no negative second-look laparotomies among those with mucinous or clear cell tumors. There were 30 patients with suboptimal stage III disease who had a negative second-look laparotomy; 18 (60%) have experienced recurrence, and 13 (43%) have died. Although cisplatin treatment was beneficial, new treatments are clearly needed.

Objective: The purpose of the study was to analyse the role of prognostic factors on the risk of recurrence and overall survival of patients with uterine adenosarcoma. Methods: A retrospective international multicentre study involving 46 centres collected 32 cases of uterine adenosarcoma, and these cases were included in the present subanalysis. Clinical and demographic features and tumour characteristics were gathered, as well as information on treatment and relapse. Disease-free and overall survival were analysed. Results: The 5-year disease-free survival (DFS) was 85.3% and the 5-year overall survival (OS) rate was 89.5%. The risk factors significantly associated with overall survival were age (HR 1.09, 95% CI 1.03-1.15; p = 0.004) and FIGO stage II-III (HR 17.75, 95% CI 2.87-109.93; p = 0.002). Patients who experienced early relapse (within 12 months) had a tumour size >30 mm and advanced stage. The majority of recurred cases were treated with radiotherapy or surgery and obtained a good response rate. Conclusion: The most significant prognostic factors in uterine adenosarcoma were age and FIGO stage and, indirectly, tumour size at diagnosis. The use of secondary surgery and/or radiotherapy could help in prolonging the disease-free status of the patients. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To elucidate prognostic factors, determine the best course of treatment methods, and assess oncological results in individuals diagnosed with uterine sarcoma. STUDY DESIGN: Between January 2001 and August 2023, 30 patients with uterine sarcomas (US) were included and analyzed in this cross-sectional study. Sixteen patients (53.3%) had uterine leiomyosarcoma, 6 patients (20%) had high-grade endometrial stromal sarcoma, 8 patients (26.7%) had low-grade endometrial stromal sarcoma. RESULTS: The median follow-up of all participants was 50 months. Recurrence was detected in 43.3% of the patients. 5-year survival ratio was 73.3%, 5-year disease-free survival ratio was 66.7%, the overall survival ratio was 70% and the overall disease-free survival rate was 56.6%. No difference was observed between groups in terms of survival comparisons. No statistically significant effect of adjuvant systemic chemotherapy, adjuvant radiotherapy, and combined treatments on median overall survival and median disease-free survival was detected (p>0.05). CONCLUSION: Uterine sarcomas are uncommon malignancies characterized by a poor prognosis, even in early stages, and they are associated with a high recurrence ratio. The most effective treatment method remains unclear to date. [ABSTRACT FROM AUTHOR]

Background: Uterine sarcoma (US) is a highly malignant cancer with poor prognosis and high mortality in women. In this study, we evaluated the expression of human fibroblast growth factor 23 (FGF23) in different US subtypes and the relationship between survival and clinicopathological characteristics. Methods: We conducted a comparative analysis of FGF23 gene expression in different pathological types of US. Utilizing a cohort from The Cancer Genome Atlas of 57 patients, a 50-patient microarray dataset (GSE119043) from the Gene Expression Omnibus and a Suining cohort of 44 patients, we analyzed gene expression profiles and corresponding clinicopathological information. Immunohistochemistry was used to examine the expression level of FGF23 in four US subtypes. Survival analysis was used to assess the relationship between FGF23 expression and prognosis in US patients. Results: Compared with uterine normal smooth muscle and uterine leiomyoma, FGF23 expression was significantly upregulated in US and was differentially expressed in four US subtypes. Uterine carcinosarcoma exhibited the highest expression of FGF23 among the subtypes. Survival analysis revealed no correlation between FGF23 expression and either overall survival or progression-free survival in US (P > 0.05). Similar results were obtained from the validation cohorts. Univariate and multivariate analyses showed no significant correlation between FGF23 expression and the US prognosis. Tumor stage, CA125, and tumor recurrence were independent prognostic factors for survival of US patients. Conclusion: FGF23 was highly expressed in US and was promising as a novel potential biomarker for the diagnosis and prognosis of US. [ABSTRACT FROM AUTHOR]

Patients with postmolar nonmetastatic gestational trophoblastic disease were entered into this Gynecologic Oncology Group study to determine the relationship of efficacy and toxicity to a rapidly escalating dose of weekly intramuscular methotrexate. The treatment was initiated at 40 mg/m2 weekly of intramuscular methotrexate. If no major toxicity was encountered, the weekly dose was escalated 5 mg/m2 at 2-week intervals until a maximum dose of 50 mg/m2 per week was achieved. Complete response was defined as three normal beta-hCG values measured on consecutive weeks. Forty-six of sixty-two (74%) evaluable patients had a complete response to this regimen. Duration of therapy ranged from 3 to 16 weeks with a median of 7 weeks. No major toxicity occurred. Eight patients experienced leukopenia at a median of 3200/microliters (range 2100-3900). Two patients had platelet nadirs of 128,500 and 131,000. Only 50% (8/16) of the nonresponders subsequently responded to second-line 5-day methotrexate every 2 weeks. Fifteen of the sixteen weekly intramuscular methotrexate failures ultimately had complete responses after treatment with subsequent chemotherapy. In this study, second-line therapy results support administration of another agent such as dactinomycin rather than 5-day methotrexate. This higher dose (1.36 relative dose intensity to median complete response) of weekly intramuscular methotrexate therapy (40 mg/m2) is no more effective and of similar toxicity to a lower-dose regimen (30 mg/m2) reported earlier.

We report on the pathologic findings in primary tumors and metastases in 203 cases of stage I and II endometrial carcinosarcoma (malignant mixed mesodermal tumor) subjected to hysterectomy and staging laparotomy. Metastases were studied in 40 of these cases, including 34 with positive findings in the pelvic and/or para-aortic lymph nodes. Features of the stromal component of the primary tumors, including grade, mitotic index, and the presence and types of heterologous elements, showed no relation to the presence of metastases at operation. High-grade, serous, and clear cell carcinomatous components, on the other hand, were associated with a higher frequency of metastases, as were deep myometrial invasion, lymphatic or vascular space invasion, and involvement of the isthmus or cervix. The current concepts of histogenesis and differentiation of these tumors are discussed, and the suggestion is made that they might represent metaplastic carcinomas.

Opinion Statement: Among cervical cancers, adenocarcinoma is less common than squamous cell carcinoma of the cervix; however, the incidence of these cancers is rising. The incidence has changed largely due to a shift in risk factors as well as the evolution of the diagnosis and classification of adenocarcinoma. Adenocarcinoma of the cervix is composed of a diverse group of neoplasms that can be classified by various factors. In this review article, preinvasive disease, updated classifications of adenocarcinoma, and treatment options for cervical adenocarcinoma are discussed with a focus on current and future therapies. Advances in antibody-drug conjugates (ADC) and immunotherapy have increased the treatment options available for usual-type adenocarcinoma but there is still a lack of variety of treatment options for the remaining 25% of non-usual-type adenocarcinomas., Competing Interests: Declarations Conflict of Interest The authors declare no competing interests. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors, (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Visceral obesity (VO), characterized by excess fat around internal organs, is a recognized risk factor for gynecological tumors, including benign uterine leiomyoma (ULM) and malignant uterine leiomyosarcoma (ULS). Despite this association, the shared molecular mechanisms remain underexplored. This study utilizes an integrated bioinformatics approach to elucidate common molecular pathways and identify potential therapeutic targets linking VO, ULM, and ULS. We analyzed gene expression datasets from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) in each condition. We found 101, 145, and 18 DEGs in VO, ULM, and ULS, respectively, with 37 genes overlapping across all three conditions. Functional enrichment analysis revealed that these overlapping DEGs were significantly enriched in pathways related to cell proliferation, immune response, and transcriptional regulation, suggesting shared biological processes. Protein-protein interaction network analysis identified 14 hub genes, of which TOP2A, APOE, and TYMS showed significant differential expression across all three conditions. Drug-gene interaction analysis identified 26 FDA-approved drugs targeting these hub genes, highlighting potential therapeutic opportunities. In conclusion, this study uncovers shared molecular pathways and actionable drug targets across VO, ULM, and ULS. These findings deepen our understanding of disease etiology and offer promising avenues for drug repurposing. Experimental validation is needed to translate these insights into clinical applications and innovative treatments., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Several studies have demonstrated that secondary cytoreductive surgery (SCS) for patients with recurrent uterine malignancies may improve the survival. However, the selection criteria for SCS remain to be defined. This study aimed to assess the outcome of SCS and to explore factors that may influence the prognosis. Methods: Data of patients with recurrent uterine malignancies who received SCS in our hospital between January 2005 and January 2015 were retrospectively analyzed. Patients were assigned into endometrial carcinoma (EC) group and uterine sarcoma (US) group. Results: 84 cases in total were involved in the study, including 47 cases with recurrent EC and 37 cases with recurrent US. The 5-year survival of cases with recurrent EC and recurrent US was 59.6% and 33.3%, respectively. Recurrent EC cases with a lower tumor grade (G1/G1-G2/G2), size of the largest tumor ≤ 6 cm, single recurrent tumor, a history of adjuvant therapy, as well as recurrent US cases with younger age, a longer disease-free interval (DFI) before SCS (≥ 12 months), no peritoneal dissemination, and a history of complete cytoreduction were associated with a longer survival. The number of recurrent tumors was found as an independent prognostic factor of SCS. Conclusion: Recurrent EC cases with a lower tumor grade, smaller tumor size, single tumor, a history of adjuvant therapy, as well as recurrent US cases with younger age, a longer DFI before SCS, no peritoneal dissemination, and a history of complete cytoreduction were more likely to benefit from SCS. [ABSTRACT FROM AUTHOR]

A carcinosarcoma is a rare form of cancer characterised by the presence of both carcinomatous and sarcomatous components. Here, we present our experience with an extremely rare case of an uterine carcinosarcoma with immature teratoid-like differentiation. The patient was a woman in her 60s. She was referred for the evaluation of a uterine tumour. She underwent total abdominal hysterectomy with bilateral adnexectomy and received postoperative treatment with paclitaxel and carboplatin. On microscopic examination, the tumour had a heterogeneous appearance with a combination of carcinomatous and sarcomatous elements, and teratoid features. The tumour included immature squamous epithelial cells and immature epithelial glands, and focal atypical fused glands, which are consistent with endometrioid carcinoma, were identified in the endometrium. Pathological differentiation from extrarenal Wilms’ tumour and teratocarcinosarcoma was challenging. The final pathological diagnosis was uterine carcinosarcoma with immature teratoid-like differentiation. At 14 months after the surgery, the patient has not experienced recurrence. [ABSTRACT FROM AUTHOR]

Background: High-complexity and low-prevalence procedures benefit from treatment by referral centers. The volume of cases necessary to maintain high training in the treatment of gynecologic sarcoma is currently unknown. This study aimed to determine differences in survival and recurrence as a function of the volume of patients treated per center. Methods: The multicentric cross-sectional SARComa of the Uterus (SARCUT) study retrospectively collected cases of uterine sarcomas from 44 centers in Europe from January 2001 to December 2007. The survival of patients treated in high case-volume (HighCV) centers was compared with the survival of patients treated in low case-volume (LowCV) centers. Results: The study enrolled 966 patients: 753 in the LowCV group and 213 in the HighCV. Overall survival (OS) was 117 months, and cancer-specific survival (CSS) was 126 months. The difference was significant (respectively p = 0.0003 and 0.0004, log rank). After adjustment for other confounding factors, the remaining significant factors were age (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.03–1.05), histology (HR, 1.19; 95% CI, 1.06–1.34), extrauterine involvement (HR, 1.61; 95% CI, 1.24–2.10) and persistent disease after treatment (HR, 3.22; 95% CI, 2.49–4.18). The cytoreduction performed was significantly associated with the CSS and OS in both groups. The log rank for surgical cytoreduction was a p value lower than 0.0001 for OS, lower than 0.0001 for the LowCV centers, and 0.0032 for the HighCV centers. Conclusions: The prognosis for patients with uterine sarcoma is directly related to complete tumor cytoreduction, histologic type, and FIGO stage, with significant differences between low and high case-volume centers. Patients with uterine sarcomas should be centralized in HighCV centers to improve their oncologic outcomes. [ABSTRACT FROM AUTHOR]

Objective: Endocrine therapy is frequently administered in patients with hormone dependent (HR+) metastatic endometrial cancer. ESR1 mutations have emerged as a key mechanism of aromatase inhibitor (AI) resistance in HR + metastatic breast cancer and can be monitored using circulating tumor DNA (ctDNA). The aim of this study was to explore the incidence and clinical relevance of circulating ESR1 mutations in patients treated by AI or megestrol acetate (M) for advanced endometrial carcinoma. Methodology: This single-center retrospective study was performed at the Henri Becquerel Center (Rouen) and looked for circulating ESR1 gene mutations by droplet digital PCR (E380Q, L536R, Y537S, Y537N, Y537C, D538G, S463P) in patients with advanced HR + endometrial carcinoma treated between 2008 and 2020 for at least 30 days by AI or M. Analyses were performed before exposure and at progression/during endocrine therapy. Results: Twenty-two patients were included: 13 were treated with AI, 12 of whom progressed; 9 patients were treated with M, 8 of whom progressed. 68.1% of the patients had low-grade endometrial carcinoma and 54.5% had received chemotherapy in the metastatic setting. The median duration of treatment was 152 days (min 47 – max 629) with AI and 155 days (min 91-max 1297) with M. Under AI, there was no ESR1 mutation at baseline, and one Y537C mutation at progression with a variant allele frequency (VAF) of 0.14%. Under M, one patient had a Y537C (VAF 0.2%) at baseline that disappeared during treatment. Another patient had a Y537S mutation emergence at progression after 91 days of treatment (VAF 1.83%). There was no significant difference between the circulating DNA concentration before and after hormone therapy (p = 0.16). Conclusion: ESR1 mutations do not seem to be involved in the mechanisms of resistance to AI or M in HR+ endometrial cancer. The clinical relevance of their detection is not demonstrated. [ABSTRACT FROM AUTHOR]

Copyright of Obstetrică şi Ginecologie is the property of MEDICHUB MEDIA, S.R.L. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The year 2023 was an extraordinary year for the further development and expansion of novel treatments for all patients with cervical cancer, ranging from early stage to later stage and metastatic or recurrent disease. Individuals with early-stage disease will benefit from less invasive surgery with subsequent improvement in quality of life. The effectiveness of immunotherapy has been demonstrated in upfront, locally advanced cervical cancer and confirmed in advanced metastatic disease. Induction chemotherapy will play a role in some patients with locally advanced disease, particularly those in low resource areas of the world. Novel therapeutics including antibody-drug conjugates have shown efficacy even in pretreated patients. As we continue to explore innovative therapeutics in this space, however, we must also continue to improve the diversity of clinical trial accrual to allow for generalizable results. At the same time, we must focus on eradicating this disease with appropriate screening and vaccination., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Cervical cancer accounts for most deaths due to cancer in women, majorly in developing nations. The culprit behind this disease is the human papillomavirus (HPV) which accounts for more than 90% of cervical cancer cases. The viral strains produce proteins that favor the knocking down of the apoptosis process and continuous growth of cells in the cervix leading to tumor growth. Proangiogenic growth factors, such as fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), angiopoietins, and other endothelial growth factors (EGF), are secreted by tumor cells and the surrounding microenvironment, which further advances the development of cancer. The extracellular domain of receptor tyrosine kinases is employed by ligands (like VEGF and EGF) to engage and activate them by inducing receptor dimerization, which facilitates the cascade impact of these factors. The tyrosine kinase domains of each receptor autophosphorylate each other, activating the receptor and initiating signaling cascades that promote angiogenesis, migration, proliferation, and survival of endothelial cells. Cancer cells benefit from its modified signaling pathways, which cause oncogenic activation. Upon early cervical cancer detection, the second-line therapy strategy involves blocking the signaling pathways with VEGF and small molecule tyrosine kinase inhibitors (TKIs). This review paper highlights the genesis of cervical cancer and combating it using VEGF and tyrosine kinase inhibitors by delving into the details of the currently available inhibitors. Further, we have discussed the inhibitor molecules that are currently in various phases of clinical trials. This paper will surely enhance the understanding of cervical cancer and its treatment approaches and what further interventions can be done to alleviate the disease currently serving as a major health burden in the developing world., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Female genital system carcinosarcomas are rare gynecologic diseases that most commonly involve the corpus uteri. This study aimed to investigate the differences between uterine and ovarian carcinosarcomas in terms of histological, clinicopathological, and survival characteristics and evaluate the adjuvant treatment options received by patients, particularly at the sites of the first relapse. Material and Method: This retrospective study was conducted on patients with the diagnosis of uterine carcinosarcomas and ovarian carcinosarcomas treated between January 1, 2006, and December 31, 2020. Records of 54 patients (42 patients with uterine carcinosarcoma and 12 patients with ovarian carcinosarcoma) who underwent debulking surgery were analyzed. Results: No difference was found in terms of mean tumor diameter, lymphovascular space invasion, lymph node involvement, and omental assessment. Recurrence occurred in 18 patients with uterine carcinosarcoma and eight patients with ovarian carcinosarcoma. Distant organ metastases such as lung or brain were not detected in any of the patients during the follow-ups. Kaplan-Meier analysis showed that disease-free survival (DFS) and overall survival (OS) in the uterine carcinosarcoma and ovarian carcinosarcoma groups were similar (p=0 .938 for OS and p=0.328 for DFS). Conclusion: Ovarian carcinosarcomas can be seen at an earlier age than uterine carcinosarcomas, and it has fewer signs that may indicate disease. It should be underlined that 41.7% of patients with ovarian carcinosarcoma were in the premenopausal period. [ABSTRACT FROM AUTHOR]

Objective: To compare leiomyoma variants and leiomyosarcoma (LMS) in terms of clinicopathological characteristics. Material and Methods: We evaluated the clinical and pathology outcomes of 57 patients who underwent myomectomy or hysterectomy between September 2013 and August 2022 and were diagnosed with cellular leiomyoma (CL), mitotically active leiomyoma (MAL), leiomyoma with bizarre nuclei (LBN), or LMS. Intraoperative frozen results were compared with the final pathology results. Leiomyoma variants (CL, MAL, and LBN) were compared with each other and with LMS. Results: Patients in the LMS group were older than those in the leiomyoma variants group (p<0.001). Frozen results in the variant group was 6.7% malignant, whereas 100% in the LMS group. Age (p=0.207), menopausal status (p=0.347), fibroid size (p=0.432), and number (p=0.598) did not differ between CL, MAL, and LBN groups. The median follow-up of leiomyoma variants and LMS groups was 61 months (4-105 months) and 20.5 months (6-85 months), respectively. No recurrence was observed in leiomyoma variants group whereas, recurrence was observed in 5 patients, and 3 patients died after recurrence in the LMS group. Conclusion: In this study, no recurrence was observed in the leiomyoma variants groups during the follow-up period and the prognosis is favorable. Not all tumors in the group of leiomyoma variants already meet the diagnostic criteria for LMS. Therefore, the detailed naming of the leiomyoma variants by subgroups does not seem to be of additional benefit for patient follow-up. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the characteristics of recurrence pattern and survival of patients with non-endometrioid endometrial cancer (NEEC) and attempted to identify prognostic and treatment factors affecting disease-free survival (DFS) and overall survival (OS) of these patients. Methods: Fifty-seven patients with histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stage IA–IVA NEEC from February 2003 to December 2021 were retrospectively analyzed. Results: The 5‑year DFS and OS rates of the total cohort were 50.6% and 56.1%, respectively. Recurrence occurred in 28 patients (49.1%) during follow-up, and the most common recurrence pattern was distant metastasis (DM; 78.6% of total recurrences). The occurrence of relapse significantly reduced 5‑year OS (recurrence group vs. non-recurrence group: 12.5% vs. 100%; p < 0.001). In univariate analysis, adjuvant radiotherapy (RT) group showed significantly higher 5‑year DFS (56.7% vs. 37.9%; p = 0.04), local recurrence-free survival (91.6% vs. 50.5%; p = 0.01), and regional recurrence-free survival (88.2% vs. 56.5%; p < 0.01) than the non-RT group. In multivariate analysis, advanced FIGO stage was identified as a negative prognostic factor for DFS and OS. Lymphovascular space invasion (LVSI) and adjuvant RT were independent prognostic factors for DFS. Conclusion: The most common recurrence pattern observed in patients with NEEC was DM. FIGO stage and LVSI were identified as prognostic factors for survival, and RT was identified as a therapeutic modality that could increase DFS. To improve the OS of patients with NEEC, the addition of effective chemotherapy that can reduce DM may be important. [ABSTRACT FROM AUTHOR]

Cervical adenocarcinoma accounts for 10%-25% of total cases of cervical carcinoma. But in recent years, the incidence of adenocarcinoma has risen both proportionally and absolutely. Clinically, most cervical adenocarcinoma show no symptom or present with abnormal uterine bleeding or vaginal discharge, similar to squamous cell carcinoma. What different about it is that cervical cytological testing demonstrates a high false-negative rate of cervical adenocarcinoma, potentially leading to the failure in detecting in early stage. This report presents two cases both with pelvic masses, and massive ascites served as the initial symptom, which is similar to the clinical symptom of ovarian cancer, but ultimately diagnosed with cervical adenocarcinoma through surgical specimens. There are few literature reports on this situation. Hence, a literature review also has been performed to improve the recognition for cervical adenocarcinoma presenting with pelvic masses and massive ascites, and to avoid misdiagnosis. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study is to determine primary survival endpoints in women with recurrent and metastatic endometrial carcinoma (RMEC) treated with progestins. Methods: A retrospective chart review was conducted at The Ottawa Hospital using electronic medical records. Inclusion criteria were a diagnosis of RMEC between 2000 and 2019, endometrioid histology, and ≥one line of progestin treatment. Progression‐free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Results: Of 2342 cases reviewed, 74 met inclusion criteria. Sixty‐six (88.0%) patients received megestrol acetate and 9 (12.0%) received a progestin alternative. The distribution of tumors by grade was: 1: 25 (33.3%), 2: 30 (40.0%), and 3: 20 (26.7%). The PFS and OS for the entire study sample was 14.3 months (95% CI 6.2–17.9) and 23.3 months (14.8–36.8), respectively. The PFS for patients with Grade 1–2 RMEC was 15.7 months (8.0, 19.5), compared to 5.0 months (3.0, 23.0) with Grade 3 disease. The OS for patients with Grade 1–2 versus Grade 3, was 25.9 months (15.3, 40.3) versus 12.5 months (5.7, 35.9), respectively. Thirty‐four (45.9%) and 40 (54.1%) patients were treated with 0 and ≥1 line of chemotherapy. The PFS for chemotherapy‐naïve patients was 17.9 months (14.3, 27.0), versus 6.2 months (3.9, 14.8) following ≥1 line of treatment. The OS was 29.1 months (17.9, 61.1) for chemotherapy‐naïve patients versus 23.0 months (10.5, 37.6) for patients previously exposed. Conclusions: This real‐world data on RMEC suggests there is a role for progestins in select subgroups of women. The PFS for chemotherapy‐naïve patients was 17.9 months (14.3, 27.0), versus 6.2 months (3.9, 14.8) following ≥1 line of treatment. The OS was 29.1 months (17.9, 61.1) for chemotherapy‐OS was 29.1 months (17.9, 61.1) for chemotherapy‐naïve patients versus 23.0 months (10.5, 37.6) for patients previously exposed. This real‐world data on recurrent and metastatic endometrial carcinoma (RMEC) suggests there is a role for progestins in select subgroups of women. The PFS for chemotherapy‐naïve patients was 17.9 months (14.3, 27.0), versus 6.2 months (3.9, 14.8) following>=1 line of treatment. The OS was 29.1 months (17.9, 61.1) for chemotherapy‐OS was 29.1 months (17.9, 61.1) for chemotherapy‐naïve patients versus 23.0 months (10.5, 37.6) for patients previously exposed. [ABSTRACT FROM AUTHOR]

Purpose: Uterine carcinosarcomas (UCSs) are aggressive biphasic malignancies, with a carcinomatous/epithelial component and a sarcomatous/mesenchymal counterpart. The aim of this study was to evaluate the impact of the sarcomatous component (homologous vs heterologous) on the overall survival (OS) and progression-free survival (PFS). Methods: This is a multicenter observational retrospective study conducted in patients with stage I and II UCSs. Results: Ninety-five women with histological diagnosis of early-stage UCSs were retrieved: 60 (63.2%) had tumors with homologous sarcomatous components, and 35 (36.8%) with heterologous. At univariate analysis, a stromal invasion ≥ 50%, the presence of clear cell, serous or undifferentiated carcinomatous component, the heterologous sarcomatous component and FIGO stage IB and II were shown to be variables with a statistically significant negative impact on PFS. Similarly, a depth of invasion ≥ 50%, the heterologous sarcomatous component and FIGO stage IB and II were statistically negative prognostic factors also concerning OS. At multivariate analysis, only the heterologous sarcomatous component was confirmed to be a statistically significant negative prognostic factor both on PFS (HR 2.362, 95% CI 1.207–4.623, p value = 0.012) and on OS (HR 1.950, 95% CI 1.032–3.684, p = 0.040). Conclusion: Carcinomatous and sarcomatous components both played a role in tumor progression and patients' survival. However, only the sarcomatous component retained a statistical significance at the multivariable model suggesting its preeminent prognostic role in early-stage UCSs. [ABSTRACT FROM AUTHOR]

Uterine leiomyosarcoma (uLMS) is an aggressive mesenchymal neoplasm associated with a poor prognosis. Systemic chemotherapy is the standard therapy for patients with uLMS. However, it is unclear which treatment regimen results in the most favorable clinical outcome. We performed a meta‐analysis and meta‐regression analysis to assess the efficiency of different treatments received by patients with advanced, metastatic, and relapsing uLMS by evaluating the objective response rate (ORR) and disease control rate (DCR) as primary endpoints. The frequentist random effects meta‐analysis model was used to compare the outcomes of different treatment regimens for advanced uLMS. A meta‐regression analysis was performed to estimate the association between the study‐specific hazard ratios and specific demographic variables. A meta‐analysis of 51 reports including 1664 patients was conducted. Among patients who received adjuvant chemotherapy (916 patients; 55%), gemcitabine and docetaxel were the most frequently used drugs. First‐line monotherapy with alkylating agents (pooled ORR = 0.48; 95% confidence interval [CI]: 0.44–0.52) and second‐line monotherapy with protein kinase inhibitors (pooled ORR = 0.45; 95% CI: 0.39–0.52) resulted in favorable prognoses. The combinations of anthracycline plus alkylating therapy (pooled DCR = 0.74; 95% CI: 0.67–0.79) and of gemcitabine plus docetaxel (pooled DCR = 0.70; 95% CI: 0.63–0.75) showed the greatest benefits when used as first‐line and second‐line chemotherapies, respectively. Subgroup meta‐analysis results revealed that dual‐regimen therapies comprising anthracycline plus alkylating therapy and gemcitabine plus docetaxel are practical therapeutic choices for International Federation of Gynecology and Obstetrics stages III–IVb with distant metastases when assessed by computed tomography (p = 0.001). Furthermore, neoadjuvant chemotherapy and local radiotherapy resulted in favorable outcomes for patients with earlier stages of distant relapsed uLMS (p < 0.001). Our findings provide a basis for designing new therapeutic strategies and can potentially guide clinical practice toward better prognoses for uLMS patients with advanced, metastatic, and relapsing disease. [ABSTRACT FROM AUTHOR]

From November 1973 through July 1982, 225 women with Stage I or II uterine sarcoma were entered on a protocol which evaluated the use of doxorubicin in the adjuvant setting. Of these, 157 patients had a minimum follow-up of 2 years. Following complete surgical removal of all known clinical disease, consenting patients were randomized to receive either 60 mg/m2 of doxorubicin every 3 weeks for eight courses or no further therapy. The use of radiation therapy in this protocol was optional, and a review of protocol cases was undertaken to determine progression-free interval, survival rates, and site of first recurrence in the radiation therapy and no radiation therapy groups. In patients with Stage I or II leiomyosarcoma of the uterus, there was no difference in the progression-free interval, absolute two-year survival rate, or site of first recurrence in the two groups. There was no difference in the progression-free interval or absolute survival rates for cases with Stage I and II uterine mixed mesodermal sarcomas in the two treatment groups. However, those who received radiation therapy to the pelvis experienced a statistically significant reduction of recurrences within the radiation treatment field.

Twenty cases of immature teratoma of the ovary with a neural component are analyzed. A plea is made for use of the nomenclature adopted from the new World Health Organization classification of ovarian tumors, the past confusion over terminology and histogenesis of this rare tumor is discussed. All the primary tumors in the present series contained at least some immature tissues (predominantly of neural origin) and were thus graded from 1 to 3 according to the criteria of Thurlbeck and Scully. No grade 0 tumors ("benign solid teratomas") were identified. We believe that thorough sectioning almost always insures the identification of immature elements. The prognosis was closely related to the histologic grade, but correlated poorly withthe clinical stage, the latter being influenced by the common finding (25 per cent of the cases in this series) of peritoneal implants composed exclusively of mature glial tissue, which is associated with a benign clinical evolution. This phenomenon of maturation or differentiation appears to be the rule rather than the exception in this tumor, since implants are usually of better or equal differentiation when compared with their primary tumors and older patients tend to have lower grade tumors than younger patients. Since the majority of patients with this tumor are young, primary surgical therapy should be conservative, unilateral salpingooophorectomy often being sufficient. Spontaneous or operative rupture of the tumor capsule carries an increased risk of subsequent dissemination. We have noted impressive clinical responses in patients with disseminated tumors of a high histologic grade after treatment with triple chemotherapy (vincristine, actinomycin D, and cyclophosphamide) but do not recommend adjuvant therapy in patients with only grade 0 implants.

Three patients with Stage III serous cystadenocarcinoma of the ovary were successfully treated with estrogen antagonist therapy after failure of cytotoxic chemotherapy. All had histologic confirmation of progressive or persistent disease. High titers of estrogen receptor protein (ERP) and progesterone receptor protein (PRP) were detected in one patient prior to tamoxifen therapy. One patient had a complete remission lasting for 18 months. The other patients had partial responses and were able to return to normal activities. Simultaneous or prior sequential cytotoxic chemotherapy did not negate the effectiveness of the estrogen antagonists.

The present report of 16 new cases of fallopian tube carcinoma also includes 2 new cases of adenoacanthoma, an exceedingly rare tumor. The histologic evaluation of tubal carcinoma is discussed. A meticulous search at surgery for occult disease is urged, because penetration of the tubal serosa seems to be the most important determinant of prognosis. Suggestions are made for adjunctive therapy, although the authors believe the time has come for a multicentered attempt to evaluate treatment protocols randomly.

This report describes the detection of human papillomavirus type 16 or 18 deoxyribonucleic acid (DNA) in nine of 15 invasive tumors of the cervix, including three squamous carcinomas, four adenosquamous carcinomas, one glassy cell carcinoma, and one adenocarcinoma. The viral DNA was identified by Southern blotting and DNA hybridization. Human papillomaviruses may play an etiologic role in the development of at least some adenocarcinomas and adenosquamous carcinomas as well as most squamous tumors of the cervix.

Patients with nonmetastatic gestational trophoblastic disease were entered into this Gynecologic Oncology Group study to determine the efficacy, toxicity, and cost-effectiveness of weekly intramuscular (IM) methotrexate. Treatment was initiated with 30 mg/m2 of weekly IM methotrexate. If no major toxicity was encountered, the weekly dose was escalated 5 mg/m2 at three-week intervals until a maximum dose of 50 mg/m2 each week was achieved. Complete response was defined as three normal beta-hCG values measured on consecutive weeks. Fifty-one of 63 evaluable patients (81%) had a complete response to weekly IM methotrexate. Duration of therapy ranged from three to 19 weeks, with a median of seven. No major toxicity occurred. Thirteen patients experienced leukopenia at a median of 3300/microL, with a range of 2300-3900. Three patients had platelet nadirs of 66,000, 127,000, and 135,000/microL. Eleven patients with weekly IM methotrexate failure had a complete response after one to eight courses of dactinomycin administered 0.5 mg/m2 intravenously daily for five days; one refused therapy after three courses. Weekly IM methotrexate for nonmetastatic gestational trophoblastic disease is efficacious, minimally toxic, and cost-effective.

The Gynecologic Oncology Group has conducted a randomized prospective trial comparing cisplatin 50 mg/m2 every 21 days (regimen 1), 100 mg/m2 every 21 days (regimen 2), and cisplatin 20 mg/m2 for five consecutive days repeated every 21 days (regimen 3). Four hundred ninety-seven evaluable patients have been accrued on this study. The response rates were 20.7%, 31.4%, and 25.0%, for regimens 1, 2, and 3, respectively; the complete remission rates were 10.0%, 12.7%, and 8.6% for regimens 1, 2, and 3, respectively. The median duration of response ranged from 3.9 to 4.8 months, the median progression-free interval from 3.7 to 4.6 months, and the median survival time from 6.1 to 7.1 months. The difference in response rates for regimens 1 and 2 is statistically significant (P = .015) but less than the magnitude originally considered clinically significant. The differences in complete remission rates, response duration, progression-free interval, and survival times are not statistically significant. The following types of toxicity were observed: serum creatinine level greater than 2 mg/dL and/or BUN level greater than 40 mg/dL was 7%, 14%, and 17% on regimens 1, 2, and 3, respectively; leukocyte count less than 4,000/microL was 27%, 44%, and 41% on regimens 1, 2, and 3, respectively. Nausea and vomiting occurred in 74 patients (83%). The regimen consisting of a 100-mg/m2 single dose has produced a statistically significant higher response rate than the 50 mg/m2 regimen while producing no appreciable differences in complete remission rate, response duration, progression-free interval, or survival. In addition, the higher dose regimen was associated with greater myelosuppression and nephrotoxicity.