OBJECTIVE: To explore the difference in chemotherapy completion and reasons for discontinuation between older (≥70 years) and younger (<70 years) patients.
METHODS: Retrospective cohort study.
METHODS: Single tertiary centre in Thailand.
METHODS: The patients who received chemotherapy from 1 January 2009 to 30 June 2021 were included and followed up until 30 June 2022. Of the 757 patients with epithelial ovarian, fallopian tube and primary peritoneal cancer (EOC), 108 were in the older group and 649 were in the younger group.
METHODS: The difference in chemotherapy completion, the association between younger and older patients and early discontinuation of chemotherapy.
RESULTS: The proportion of chemotherapy completion was significantly lower in older versus younger patients (84.3% versus 92.6%, p=0.007). Excluding discontinuation due to disease progression, the chemotherapy completion was comparable (93.5 versus 95.7%, p=0.456). Dose reduction and grade 3-4 hematotoxicity occurred more often in the older group. The univariable logistic regression model showed that older age (≥70 years) was significantly associated with early chemotherapy discontinuation (OR 2.39; 95% CI 1.29-4.24). However, after adjusting for potential confounders, age was not significantly associated with early discontinuation (OR 1.20; 95% CI 0.54-2.66). Multiple comorbidities and types of surgery were identified as independent risk factors for chemotherapy discontinuation.
CONCLUSIONS: The completion of chemotherapy was observed in a majority of older adults with EOC. Age is not the only determinant of chemotherapy completion. Comorbidity and disease status are crucial for determining chemotherapy discontinuation.

BACKGROUND: Literature data present new studies about precancerous lesions of pelvic serous carcinoma that originate from the tubal secretory cells. It has long been thought that ovarian cancer cannot be prevented by prophylactic screening or surgery. In recent years, gynecologists have adapted to new principles and so, during routine hysterectomies in perimenopausal women for benign uterine pathologies, salpingo-oophorectomy is performed as a prophylactic approach.
OBJECTIVE: The purpose of our article was to draw attention to the association between abnormal fallopian tube pathology and the presence of serous ovarian neoplasia in perimenopausal women at risk.
METHODS: We report the case of a 45-year-old woman who had unspecific symptoms of abdominal pain and loss of appetite and weight. A pelvic magnetic resonance imaging was performed, and an ovarian mass was detected. Our case shows that the fallopian tube can be the primary point of origin for a pelvic disease, therefore prevention is possible with early computed tomography scan and annual ultrasound. The patient presented with a T1c staging post-surgery and her chances of survival could have decreased if she had postponed medical examination longer. We found a significant increase in the absolute number of tubal secretory cells in patients with ovarian neoplasia, which supports the assumption that serous tubal intraepithelial carcinoma lesions are found especially in the serous ovarian type.
CONCLUSIONS: Our article is a strong suggestion that serous ovarian cancer originates from the fallopian tube and can potentially serve as a sensitive biomarker for early serous carcinogenesis within the fallopian tube.

Ovarian high-grade serous carcinoma (HGSC) originates in the fallopian tube, with secretory cells carrying a TP53 mutation, known as p53 signatures, identified as potential precursors. p53 signatures evolve into serous tubal intraepithelial carcinoma (STIC) lesions, which in turn progress into invasive HGSC, which readily spreads to the ovary and disseminates around the peritoneal cavity. We recently investigated the genomic landscape of early- and late-stage HGSC and found higher ploidy in late-stage (median 3.1) than early-stage (median 2.0) samples. Here, to explore whether the high ploidy and possible whole-genome duplication (WGD) observed in late-stage disease were determined early in the evolution of HGSC, we analysed archival formalin-fixed paraffin-embedded (FFPE) samples from five HGSC patients. p53 signatures and STIC lesions were laser-capture microdissected and sequenced using shallow whole-genome sequencing (sWGS), while invasive ovarian/fallopian tube and metastatic carcinoma samples underwent macrodissection and were profiled using both sWGS and targeted next-generation sequencing. Results showed highly similar patterns of global copy number change between STIC lesions and invasive carcinoma samples within each patient. Ploidy changes were evident in STIC lesions, but not p53 signatures, and there was a strong correlation between ploidy in STIC lesions and invasive ovarian/fallopian tube and metastatic samples in each patient. The reconstruction of sample phylogeny for each patient from relative copy number indicated that high ploidy, when present, occurred early in the evolution of HGSC, which was further validated by copy number signatures in ovarian and metastatic tumours. These findings suggest that aberrant ploidy, suggestive of WGD, arises early in HGSC and is detected in STIC lesions, implying that the trajectory of HGSC may be determined at the earliest stages of tumour development. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Endometrial serous carcinoma (ESC) and tubo-ovarian high-grade serous carcinoma (HGSC) are characterized by late-stage presentation and high mortality. Current guidelines for prevention recommend risk-reducing salpingo-oophorectomy (RRSO) in patients with hereditary mutations in cancer susceptibility genes. However, HGSC displays extensive genetic heterogeneity with alterations in 168 genes identified in TCGA study, but current germline testing panels are often limited to the handful of recurrently mutated genes, leaving families with rare hereditary gene mutations potentially at-risk.
To determine if there are rare germline mutations that may aid in early identification of more patients at-risk for ESC and/or HGSC by evaluating patients with concurrent ESC, HGSC or precursor lesions, and endometrial atypical hyperplasia (CAH) or low-grade endometrial endometrioid adenocarcinoma (LGEEA).
We performed targeted next-generation sequencing using TSO 500, a 523 gene panel, on formalin-fixed paraffin-embedded tumor and matched benign non-tumor tissue blocks from 5 patients with concurrent ESC, HGSC or precursor lesions, and CAH or LGEEA.
We identified germline pathogenic, likely pathogenic or uncertain significance variants in cancer susceptibility genes in 4 of 5 patients - affected genes included GLI1, PIK3R1, FOXP1, FANCD2, INPP4B and H3F3C. Notably, none of these genes were included in the commercially available germline testing panels initially used to evaluate the patients at the time of their diagnoses.
Comprehensive germline testing of patients with concurrent LGEEA or CAH and ESC, HGSC or precursor lesions may aid in early identification of relatives at-risk for cancer who may be candidates for RRSO with hysterectomy.

Objective: To investigate the clinical and pathological characteristics of primary mucinous gland lesions of the fallopian tubes. Methods: The clinical data, pathomorphological characteristics and immunophenotype of 14 cases of primary mucinous gland lesions of the fallopian tube diagnosed at Obstetrics and Gynecology Hospital of Fudan University from 2015 to 2023 were analyzed retrospectively. In addition, a comprehensive review of relevant literature was conducted. Results: The age of 14 patients ranged from 53 to 83 years, with an average of 65 years. Among them, 13 cases exhibited unilateral involvement while one case showed bilateral presentation. Nine cases were mucinous metaplasia of the fallopian tube, four cases were invasive mucinous adenocarcinoma and one case was mucinous carcinoma in situ. Morphologically, mucinous metaplasia of the fallopian tube was focal, with or without inflammation. The cells of mucinous adenocarcinoma or mucinous carcinoma in situ exhibited characteristics indicative of gastrointestinal differentiation. Immunohistochemical analysis revealed diffuse positive expression of CK7, and negative expression of SATB2. CDX2 demonstrated positive staining in two cases. One case exhibited diffuse and strongly positive mutant expression of p53, whereas the remaining cases displayed wild-type expression. MUC6 showed diffuse or focally positive staining in mucinous gland lesions characterized by gastric differentiation. Some cases of mucinous adenocarcinoma of fallopian tube were subject to AB-PAS staining, resulting in red to purple cytoplasmic staining. Conclusions: Primary mucinous lesions of the fallopian tube are exceedingly uncommon. All cases of mucinous adenocarcinoma of fallopian tubes in this study exhibit the morphology and immunohistochemical characteristics of gastrointestinal differentiation. Mucinous metaplasia of the fallopian tube is a benign lesion of incidental finding, which is closely related to inflammation or gastric differentiation. Mucinous lesions of cervix, ovary and digestive tract are excluded in all patients, confirming the independent existence of mucinous lesions within fallopian tubes.
目的： 探讨输卵管原发性黏液腺体病变的临床病理学特征。 方法： 回顾性分析复旦大学附属妇产科医院2015—2023年诊治的14例输卵管原发性黏液腺体病变的临床资料、病理形态学特征及免疫表型特点，并复习相关文献。 结果： 14例患者年龄53~83岁，平均65岁。13例为单侧，1例为双侧。9例为输卵管黏液上皮化生，4例为浸润性黏液腺癌，1例为黏液性原位癌。镜下观察，输卵管黏液上皮化生呈局灶性，伴或不伴有炎症。输卵管黏液腺癌或原位癌细胞具有胃肠型分化的黏液上皮特征。免疫组织化学显示所有病例细胞角蛋白（CK）7均阳性，SATB2均阴性。2例CDX2阳性表达，1例局灶表达CK20。1例p53呈弥漫强阳性突变型表达，余均呈野生型表达。伴有胃型分化的黏液腺体病变MUC6弥漫或局灶阳性。部分输卵管黏液腺癌行阿辛蓝-过碘酸雪夫染色，细胞质呈红至紫红色。 结论： 输卵管原发性黏液性病变非常罕见，本组输卵管黏液腺癌均见胃肠型分化形态及免疫组织化学特征，输卵管黏液上皮化生为偶然发现的良性病变，与炎症或胃型分化相关。所有患者均排除宫颈、卵巢及消化道黏液性病变，从而证实输卵管黏液性病变是可以独立存在的。.

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of pseudocarcinomatous hyperplasia of the fallopian tubes. Methods: Sixteen cases of pseudocarcinomatous hyperplasia of the fallopian tubes diagnosed at Obstetrics and Gynecology Hospital of Fudan University from January 2011 to January 2024 were collected.The pathological sections were reviewed, the clinical and pathological data were consulted, and immunohistochemical examination was conducted along with follow-up. Results: The patients were aged from 19 to 57 years, with an average age of 41 and a median age of 38. Among the 16 cases, 4 were located in the right fallopian tubes, 6 in the left fallopian tubes, while the remaining cases presented bilaterally. The general manifestations were tubal edema, crispness and purulent secretion in the lumen. Morphologically, the fallopian tube mucosa exhibited a significant infiltration of neutrophils, lymphocytes and plasma cells. The epithelial cells of the fallopian tube displayed evident proliferation, stratification and disorganized arrangement leading to formation of small glandular cavity with back-to-back, fissure-like and sieve-like structures. Immunohistochemical analysis revealed positivity for CK7 and WT1, along with wild-type p53 expression, Ki-67 index ranged from 5% to 20%. During the follow-up period ranging from 1 to 156 months, all the patients remained free of disease. Conclusions: Pseudocarcinomatous hyperplasia of the fallopian tube is a rare non-neoplastic lesion, which can lead to epithelial hyperplasia and atypical hyperplasia. The most important significance of recognizing this lesion lies in avoiding misdiagnosis of fallopian tube cancer during intraoperative and postoperative pathological examination. This ensures that clinicians can administer correct clinical interventions.
目的： 探讨输卵管假癌性增生的临床病理特征、诊断及鉴别诊断。 方法： 收集复旦大学附属妇产科医院2011年1月至2024年1月诊断的输卵管假癌性增生16例，复阅病理切片，查阅临床病理资料，并行免疫组织化学检查及随访。 结果： 16例患者年龄19~57岁，平均年龄41岁，中位年龄38岁。发生于右侧输卵管、左侧输卵管和双侧输卵管分别为4例、6例和6例。大体检查，输卵管水肿、质脆，管腔内见脓性分泌物。镜下观察，输卵管黏膜大量中性粒细胞、淋巴细胞及浆细胞浸润，输卵管上皮细胞明显增生、复层，排列紊乱，形成小腺腔、背靠背、裂隙样、筛孔状结构。免疫组织化学显示细胞角蛋白7、WT1阳性，p53均呈野生型表达，Ki-67阳性指数5%~20%。随访时间1~156个月，所有患者均无病生存。 结论： 输卵管假癌性增生是一种罕见的非肿瘤性病变，可以出现上皮增生和不典型，认识该类病变的最重要意义在于避免术中、术后病理检查中误判为输卵管癌，进而作出正确的临床处置。.

The use of bevacizumab has been hampered by safety concerns despite demonstrable progression-free survival (PFS) benefit in subjects with platinum-resistant ovarian cancer, highlighting the need for novel effective and safe antiangiogenic agents. This study aimed to characterize the tolerability, safety, and antitumor activities of escalating doses of anti-VEGF antibody suvemcitug plus chemotherapy in platinum-resistant ovarian cancer patients.
This open-label, dose-escalation trial enrolled adult patients (≥18 years) with platinum-resistant histologically or cytologically-confirmed epithelial ovarian, fallopian tube and primary peritoneal cancer. Eligible patients received paclitaxel or topotecan plus escalating doses of suvemcitug 0.5, 1, 1.5, or 2 mg/kg once every two weeks. The primary endpoints were safety and tolerability, and antitumor activities of suvemcitug.
Twenty-nine subjects received paclitaxel (n = 11) or topotecan (n = 18). No dose-limiting toxicities occurred. The most common adverse events of special interest were proteinuria (41.4%), hypertension (20.7%) and epistaxis (10.3%). No gastrointestinal perforations occurred. Nine subjects (31.0%, 95% CI 15.3-50.8) demonstrated investigators-confirmed objective response, including complete response in 1 and partial response in 8. The median PFS was 5.4 months (95% CI 2.2-7.4).
Suvemcitug demonstrated an acceptable safety profile and promising antitumor activities in platinum-resistant ovarian cancer patients, supporting its further clinical development.

Objective: To explore the sequential chemotherapy efficacy of different chemotherapeutic regimens in ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. Methods: A retrospective analysis was conducted on clinical and pathological data of 100 patients with platinum-sensitive ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma treated at Peking University Peopel\'s Hospital from January 1992 to January 2019. All patients underwent staging surgery or cytoreductive surgery followed by adjuvant chemotherapy. Based on different postoperative adjuvant chemotherapy regimens, patients were divided into the sequential chemotherapy group (70 cases) and the conventional chemotherapy group (30 cases). Clinical and pathological characteristics, chemotherapy efficacy, adverse reactions, and prognosis were compared between the two groups. Results: (1) Clinical and pathological characteristics: the age, tumor types (including ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma), pathological types, International Federation of Gynecology and Obstetrics (FIGO) stage, postoperative residual disease size, presence of neoadjuvant chemotherapy, and total number of chemotherapy cycles were compared between the sequential chemotherapy group and the conventional chemotherapy group. There were no statistically significant differences observed in these characteristics between the two groups (all P>0.05). (2) Chemotherapy efficacy: the median sum of complete response (CR)+partial response (PR) duration in the sequential chemotherapy group was 80.0 months (range: 39 to 369 months), whereas in the conventional chemotherapy group, it was 28.0 months (range: 13 to 52 months). A statistically significant difference was observed between the two groups (Z=-7.82, P<0.001). (3) Chemotherapy adverse reactions: in the sequential chemotherapy group, 55 cases (79%, 55/70) experienced bone marrow suppression and 20 cases (29%, 20/70) had neurological symptoms. In the conventional chemotherapy group, these adverse reactions occurred in 11 cases (37%, 11/30) and 2 cases (7%, 2/30), respectively. Statistically significant differences were observed between the two groups for both bone marrow suppression and neurological symptoms (all P<0.05). For the other chemotherapy adverse reactions compared between the two groups, no statistically significant differences were observed (all P>0.05). (4) Prognosis: during the follow-up period, the recurrence rate in the sequential chemotherapy group was 73% (51/70) and in the conventional chemotherapy group was 100% (30/30). The median sum of recurrence-free interval was 70.5 months (range: 19 to 330 months) in the sequential chemotherapy group and 15.0 months (range: 6 to 40 months) in the conventional chemotherapy group. Statistically significant differences were observed between the two groups for both recurrence rate and median recurrence-free interval (all P<0.01).In the sequential chemotherapy group, the median progression-free survival (PFS) time was 84.0 months (range: 34 to 373 months), and the median overall survival (OS) time was 87.0 months (range: 45 to 377 months). In contrast, in the conventional chemotherapy group, the median PFS time was 30.5 months (range: 14 to 60 months), and the median OS time was 37.5 months (range: 18 to 67 months). Statistically significant differences were observed between the two groups for both PFS and OS (all P<0.001). In the sequential chemotherapy group, the 3-year, 5-year, and 10-year OS rates were 100% (70/70), 93% (65/70), and 21% (15/70), respectively. In contrast, in the conventional chemotherapy group, the OS rates were 50% (15/30) at 3 years, 3% (1/30) at 5 years, and 0 at 10 years, respectively. The two groups were compared respectively, and the differences were statistically significant (all P<0.05). Conclusions: Sequential chemotherapy significantly prolongs PFS and OS in patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. The efficacy is superior to that of the conventional chemotherapy, with manageable adverse reactions. The use of sequential chemotherapy as first-line treatment for patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma is recommended.
目的： 探讨卵巢上皮性癌（卵巢癌）、输卵管癌和原发性腹膜癌序贯化疗的疗效。 方法： 回顾性分析1992年1月—2019年1月北京大学人民医院收治的行分期手术或肿瘤细胞减灭术且术后给予辅助化疗的100例铂敏感型卵巢癌、输卵管癌和原发性腹膜癌患者（分别为90、6、4例）的临床病理资料，根据术后辅助化疗模式不同分为序贯化疗组（70例）、常规化疗组（30例），比较两组患者的临床病理特征、化疗效果、化疗毒副反应及预后。 结果： （1）临床病理特征：序贯化疗组患者的年龄、肿瘤类型（包括卵巢癌、输卵管癌和原发性腹膜癌）、病理类型、国际妇产科联盟（FIGO）分期、术后残留灶大小、有无新辅助化疗、总化疗疗程数分别与常规化疗组比较，差异均无统计学意义（P均>0.05）。（2）化疗效果：序贯化疗组患者的中位完全缓解（CR）+部分缓解（PR）时间总和为80.0个月（范围：39~369个月），常规化疗组为28.0个月（范围：13~52个月），两组比较，差异有统计学意义（Z=-7.82，P<0.001）。（3）化疗毒副反应：序贯化疗组出现骨髓抑制55例（79%，55/70）、神经系统症状20例（29%，20/70），常规化疗组分别为11例（37%，11/30）、2例（7%，2/30），两组分别比较，差异均有统计学意义（P均<0.05）；其余化疗毒副反应两组间分别比较，差异均无统计学意义（P均>0.05）。（4）预后：随访期内，序贯化疗组、常规化疗组患者的复发率分别为73%（51/70）、100%（30/30），中位复发间隔时间总和分别为70.5个月（范围：19~330个月）、15.0个月（范围：6~40个月），两组分别比较，差异均有统计学意义（P均<0.01）。序贯化疗组70例患者的中位无进展生存（PFS）时间为84.0个月（范围：34~373个月）、中位总生存（OS）时间为87.0个月（范围：45~377个月），常规化疗组分别为30.5个月（范围：14~60个月）、37.5个月（范围：18~67个月），两组分别比较，差异均有统计学意义（P均<0.001）。序贯化疗组患者的3年、5年、10年OS率分别为100%（70/70）、93%（65/70）、21%（15/70），常规化疗组分别为50%（15/30）、3%（1/30）和0，两组分别比较，差异均有统计学意义（P均<0.05）。 结论： 采用序贯化疗可显著延长卵巢癌、输卵管癌和原发性腹膜癌患者的PFS和OS时间，疗效优于常规化疗患者，且毒副反应可控，建议用于卵巢癌、输卵管癌和原发性腹膜癌患者的一线化疗。.

The majority of high-grade serous carcinomas (HGSC) of the ovary, fallopian tube, and peritoneum arise from the precursor lesion called serous tubal intraepithelial carcinoma (STIC). It has been postulated that cells from STICs exfoliate into the peritoneal cavity and give rise to peritoneal HGSC several years later. While co-existent STICs and HGSCs have been reported to share similarities in their mutational profiles, clonal relationship between temporally distant STICs and HGSCs have been infrequently studied and the natural history of STICs remains poorly understood.
We performed focused searches in two national databases from the Netherlands and identified a series of BRCA1/2 germline pathogenic variant (GPV) carriers (n = 7) who had STIC, and no detectable invasive carcinoma, at the time of their risk-reducing salpingo-oophorectomy (RRSO), and later developed peritoneal HGSC. The clonal relationship between these STICs and HGSCs was investigated by comparing their genetic mutational profile by performing next-generation targeted sequencing.
Identical pathogenic mutations and loss of heterozygosity of TP53 were identified in the STICs and HGSCs of five of the seven patients (71%), confirming the clonal relationship of the lesions. Median interval for developing HGSC after RRSO was 59 months (range: 24-118 months).
Our results indicate that cells from STIC can shed into the peritoneal cavity and give rise to HGSC after long lag periods in BRCA1/2 GPV carriers, and argues in favor of the hypothesis that STIC lesions may metastasize.

We describe a case of bowel perforation secondary to a recurrence of primary fallopian tube carcinoma treated more than a decade ago. A woman in her 70s presented to a rural centre with an acute abdomen. An abdominal CT showed a perforated ileum secondary to a pelvic mass. Emergency laparotomy identified the pelvic mass that was adherent to the side wall and invading the ileum at the site of perforation. Its adherence to the external iliac vessels posed a challenge to achieve en-bloc resection; therefore, a defunctioning loop ileostomy was created. Final histopathology and immunopathology were consistent with the recurrence of her primary fallopian tube carcinoma. The patient was further discussed in a multidisciplinary team meeting at a tertiary referral hospital. This case highlighted the importance of having a high index of suspicion for cancer recurrence, the utility of rapid source control laparotomy and multidisciplinary team patient management.