A preliminary study on the detection of lymph node metastasis in cervical cancer using a quantitative RT-PCR assay.

OBJECTIVE: This preliminary study aimed to assess the detection accuracy of sentinel lymph node metastasis in cervical cancer using quantitative reverse transcriptase-polymerase chain reaction. METHODS: We collected cervical cancer tissues and 70 pelvic lymph node samples from patients with cervical cancer. The quantitative reverse transcriptase-polymerase chain reaction assay was performed to investigate the expression of cytokeratin 19 mRNA in cervical cancer tissues and determine the cutoff value of cytokeratin 19 mRNA between the non-metastatic and metastatic lymph nodes. RESULTS: The expression of cytokeratin 19 mRNA in cancer tissues was detected in all (71/71) the tumours, with a median copy number of 7.56 × 105/µl of RNA by quantitative reverse transcriptase-polymerase chain reaction. Sixteen lymph nodes were diagnosed as positive by pathological examination. The median copy numbers of cytokeratin 19 mRNA for positive and negative lymph nodes were 43.3 × 104/µl and 121.1/µl, respectively. The expression of cytokeratin 19 mRNA in pathologically positive lymph nodes was higher than that in the negative lymph nodes (P < 0.0001) by quantitative reverse transcriptase-polymerase chain reaction analysis. Using a receiver operating characteristic plot, the maximum sensitivity (100%) and specificity (94.4%) were obtained when the cutoff value was set at 1169 copies/µl. CONCLUSIONS: After setting the cutoff value at 1169 copies/µl, a quantitative reverse transcriptase-polymerase chain reaction assay using cytokeratin 19 mRNA showed high accuracy in detecting lymph node metastasis in cervical cancer. We believe that the quantitative reverse transcriptase-polymerase chain reaction assay using cytokeratin 19 mRNA may be acceptable for lymph node metastasis detection in patients with cervical cancer.

Successful management of vulvar proximal-type epithelioid sarcoma in pregnancy.

Vulvar proximal-type epithelioid sarcoma during pregnancy is extremely rare; only two reports are available to date. Herein, we describe a 36-year-old woman who presented with a pigeon-egg-sized solid mass with cystic component on the left labia majora at 18 weeks of gestation. The patient underwent tumor resection at 23 weeks of gestation and was diagnosed with epithelioid sarcoma, proximal-type. At 29 weeks of gestation, elective cesarean section, radical local resection of the vulva and vagina, and inguinal lymphadenectomy were performed. After surgery, she underwent six courses of adjuvant chemotherapy (doxorubicin 60 mg/m2 and cisplatin 50 mg/m2) every four weeks. The patient and her baby survived with neither recurrence nor complications until 5 years. Aggressive management for proximal-type epithelioid sarcoma, such as early termination of pregnancy and operation, can improve maternal outcomes.

One-step nucleic acid amplification (OSNA) assay for detecting lymph node metastasis in cervical and endometrial cancer: a preliminary study.

OBJECTIVE: To evaluate the accuracy of the one-step nucleic acid amplification (OSNA) assay for the diagnosis of lymph node (LN) metastasis in uterine cancer. METHODS: A total of 116 LNs from 30 patients with cervical and endometrial cancer, enrolled in this prospective study, were used. Excised LNs were cut into 4 to 6 blocks at 2 mm intervals, and nonadjacent blocks were alternately subjected to either histological examination or the OSNA assay. RESULTS: The concordance rate between histological examination and the OSNA assay in cervical cancer and in endometrial cancer was 95.9% and 95.2%, respectively. The sensitivity, specificity, and negative predictive value of the OSNA assay were 80%, 97.7%, and 97.7% in cervical cancer, and 85.7%, 93.3%, and 98.2% in endometrial cancer, respectively. In cervical cancer, discordant results were observed in 2 out of 49 LNs (4.1%); 1 was OSNA assay-positive and histological examination-negative, and 1 was OSNA assay-negative and histological examination-positive. In endometrial cancer, discordant results were observed in 5 out of 67 LNs (7.5%); 4 were OSNA assay-positive and histological examination-negative, and 1 was OSNA assay-negative and histological examination-positive. CONCLUSION: The OSNA assay showed high concordance rate with histological examination, sensitivity, and specificity in uterine cancer, suggesting that it could enhance the accuracy of conventional pathological examination for the detection of LN metastasis by reducing false negative rate.

Comparison of radio-isotope method with 99m technetium and near-infrared fluorescent imaging with indocyanine green for sentinel lymph node detection in endometrial cancer.

BACKGROUND: We aimed to compare the detection rate of pelvic sentinel lymph node between the radio-isotope with 99m technetium (99mTc)-labeled phytate and near-infrared fluorescent imaging with indocyanine green in patients with endometrial cancer. METHODS: This study included 122 patients who had undergone sentinel lymph node mapping using 99mTc and indocyanine green. In the radio-isotope method, sentinel lymph nodes were detected using uterine cervix 99mTc injections the day before surgery. Following injection, the number and locations of the sentinel lymph nodes were evaluated by lymphoscintigraphy. In addition, indocyanine green was injected into the cervix immediately before surgery. RESULTS: The overall pelvic sentinel lymph node detection rate (at least one pelvic sentinel lymph node detected) was not significantly different between 99mTc (95.9% [117/122]) and indocyanine green (94.3% [115/122]). Similarly, the bilateral sentinel lymph node detection rate was not significantly different between 99mTc (87.7% [107/122]) and indocyanine green (79.5% [97/122]). More than two sentinel lymph nodes per unilateral pelvic lymph node were found in 12.3% (15/122) and 27% (33/122) of cases with 99mTc and indocyanine green, respectively, in the right pelvic side, and 11.5% (14/122) and 32.8% (40/122) of cases with 99mTc and indocyanine green, respectively, in the left pelvic side. indocyanine green showed that there were significantly more than two sentinel lymph nodes in either the left or right pelvic sentinel lymph nodes (P < 0.0001). There was a significant difference in the mean number of total pelvic sentinel lymph nodes between 99mTc (2.2) and indocyanine green (2.5) (P = 0.028) methods. CONCLUSION: Although indocyanine green is useful for sentinel lymph node identification, we believe it is better to use it in combination with 99mTc until the surgeon is accustomed to it.

Zinc supplementation during chemotherapy for gynecological malignancy.

OBJECTIVE: To determine the significance of zinc supplementation for zinc deficiency during chemotherapy for gynecologic malignancies. METHODS: Twenty-eight patients suspected of zinc deficiency before chemotherapy were prospectively evaluated. Gustatory test, serum zinc, blood count, and biochemical examinations were made pre-chemotherapy at 3- and 6-week intervals. Patients with serum zinc levels <70 µg were prescribed oral zinc acetate hydrate (167.8 mg/day) for 3 weeks. The primary outcome was efficacy of zinc supplementation, the secondary outcomes were zinc deficiency rates and adverse effects of the zinc supplement. RESULTS: Fifteen (mean serum zinc level: 67.4 ± 6.2 µg/dL) out of 28 patients were administered zinc supplementation pre-chemotherapy, and subsequent serum zinc levels reached 83.2 ± 15.3 µg/dL in 3 weeks. Factors associated with chemotherapy (vs. chemoradiation, p = 0.041) and taxane + platinum (p = 0.048) were significant risk factors for decreasing zinc levels following chemotherapy. Although patients that required zinc supplementation showed decreased serum zinc levels after chemotherapy and tended to experience taste alteration (sour: p = 0.041), zinc supplementation for zinc deficiency during chemotherapy did not alter taste perception. CONCLUSION: Zinc supplementation promptly increased serum levels without major complications and may prevent an alteration in taste perception.

The use of bevacizumab is correlated with improved post-progression survival in advanced recurrent ovarian cancer.

BACKGROUND: The recent improvements in anti-cancer therapy following first-line treatment can potentially impact post-progression survival. We evaluated the factors that influence post-progression survival in advanced recurrent ovarian cancer. METHODS: Eighty-nine patients who underwent first-line treatment between June 2005 and December 2017 were included. The post-progression survival was defined as the difference between overall survival and initial progression-free survival. The effects of age, histology, stage, optimal surgery, secondary debulking surgery, bevacizumab administration, platinum sensitivity, and olaparib maintenance in recurrence were compared and independent risk factors were determined. RESULTS: The median follow-up duration was 60.0 months (range: 2-181). Platinum-sensitive recurrence had longer post-progression survival than platinum-resistant (P < 0.001). Inclusion of bevacizumab in first-line treatment did not produce a significant difference in post-progression survival (P = 0.462). Secondary debulking surgery (P = 0.013), bevacizumab administration (P < 0.001), and olaparib maintenance (P = 0.001) during recurrence increased post-progression survival. In multivariate analysis, histologies other than serous or endometrioid (hazard ratio = 2.389; 95% confidence interval = 1.200-4.754; P = 0.013) and non-bevacizumab usage in recurrence (hazard ratio = 4.484; 95% confidence interval = 1.939-10.370; P < 0.001) were independently correlated with poorer prognosis. Bevacizumab administration beyond progressive disease elicited improved post-progression survival (P < 0.001). In patients receiving bevacizumab in first-line treatment, exclusion of bevacizumab in the recurrent therapy (hazard ratio = 5.507; 95% confidence interval = 2.301-12.124; P < 0.001) was independently correlated with poorer prognosis. CONCLUSIONS: The continuous use of bevacizumab beyond progressive disease improves post-progression survival suggesting its important role in first-line and recurrence treatment for ovarian cancer.

Importance of Cervical Elongation Assessment for Laparoscopic Sacrocolpopexy.

Cervical elongation in patients with pelvic organ prolapse (POP), who previously underwent laparoscopic sacrocolpopexy (LSC), is not fully understood. We report a case of a second surgery for endometrial cancer complicated with POP recurrence, which seemed to be related to cervical elongation following LSC. A 65-year-old woman was referred for invasive treatment following LSC. Although preoperative endometrial cytology was negative, the resected uterine specimen revealed endometrioid carcinoma. The patient also had complications of cervical prolapse with cystocele Stage III. Repeat surgery was performed with a trachelectomy, anterior-posterior colporrhaphy, and vaginal apex suspension. Mesh had been adequately sutured to the upper cervix in the previous surgery, and the resected cervix was elongated up to 9 cm. Cervical elongation may be correlated with the inaccurate preoperative endometrial examination, and it may also promote POP recurrence leading to a poorly supported pelvic floor. We suggest that cervical elongation should be identified before POP surgery.

Association Between Positive Human Papillomavirus Status After Conization and Disease Recurrence in Patients with Cervical Intraepithelial Neoplasia Grade 3.

OBJECTIVE: This study aimed to examine the associations of cone margin and human papillomavirus (HPV) status after conization with cytological abnormalities and disease recurrence in patients with cervical intraepithelial neoplasia grade 3 (CIN3). METHODS: This is a retrospective study of 366 women with CIN3 who underwent conization at Kagoshima University Hospital between 2004 and 2017. Conization was performed using an ultrasonic scalpel. The polymerase chain reaction for detecting HPV genotypes was performed using fresh cervical cell samples. We examined the associations of margin status and HPV status after conization with cytological abnormalities and recurrence. RESULTS: Among 224 women with CIN3, 193 (86.2%) underwent HPV genotype testing before conization. The HPV-positive rate was 84.9%. The most common HPV genotypes before conization were HPV 16, 31, 58, 52, 18, 35, and 33. In 191 patients, the uterus was preserved after conization. Sixteen patients had pathologically positive margins, 165 had negative margins, and 10 had unclear margins. There was no significant difference in abnormal cytology and recurrence rate after conization between the three groups. Five patients with positive margins and abnormal cytology during follow-ups were HPV16- or HPV58-positive in the preoperative HPV testing. Of the 191 women, 91 (47.6%) underwent pre- and postoperative HPV genotype testing, among whom 14 (15.4%) were HPV-positive after conization. No significant difference in abnormal cytology based on HPV status after conization was found. The recurrence rate tended to be higher in HPV-positive patients than in HPV-negative patients after conization (21.4% vs. 1.3%, p < 0.05). Three patients with HPV positivity after conization and recurrence during follow-up were HPV16- or HPV58-positive. CONCLUSIONS: HPV positivity after conization for CIN3 was associated with a high recurrence rate, especially in HPV16- and HPV58-positive patients. HPV58 has not received much attention thus far, but abnormalities in cytology and recurrence may be as likely as those associated with HPV16. Thus, a careful follow-up in such patients is recommended.

Molecular Evaluation of Endometrial Dedifferentiated Carcinoma, Endometrioid Carcinoma, Carcinosarcoma, and Serous Carcinoma Using a Custom-Made Small Cancer Panel.

It is often difficult to histologically differentiate among endometrial dedifferentiated carcinoma (DC), endometrioid carcinoma (EC), serous carcinoma (SC), and carcinosarcoma (CS) due to the presence of solid components. In this study, we aimed to categorize these carcinomas according to The Cancer Genome Atlas (TCGA) classification using a small custom-made cancer genome panel (56 genes and 17 microsatellite regions) for integrated molecular diagnosis. A total of 36 endometrial cancer cases with solid components were assessed using IHC, next-generation sequencing (NGS), and the custom-made panel. Among 19 EC cases, six were categorized as MMR-deficient (MMR-d) and eight were classified as having a nonspecific molecular profile. Three EC cases were classified as POLE mutation (POLEmut)-type, which had a very high tumor mutation burden (TMB) and low microsatellite instability (MSI). Increased TMB and MSI were observed in all three DC cases, classified as MMR-d with mutations in MLH1 and POLD1. Except for one case classified as MMR-d, all SC cases exhibited TP53 mutations and were classified as p53 mutation-type. SC cases also exhibited amplification of CCND1, CCNE1, and MYC. CS cases were classified as three TCGA types other than the POLEmut-type. The IHC results for p53 and ARID1A were almost consistent with their mutation status. NGS analysis using a small panel enables categorization of endometrial cancers with solid proliferation according to TCGA classification. As TCGA molecular classification does not consider histological findings, an integrated analytical procedure including IHC and NGS may be a practical diagnostic tool for endometrial cancers.

Comparison of survival outcomes between laparoscopic and open surgery in patients with low-risk endometrial cancer.

OBJECTIVE: To evaluate the feasibility, safety and surgical outcomes of laparoscopic surgery for the treatment of low-risk endometrial cancer. METHODS: Of 155 patients with low-risk endometrial cancer, who were included in this retrospective study between May 2008 and March 2017, 82 and 73 underwent laparoscopic and open surgery, respectively. Clinicopathological and surgical data, recurrence-free survival and overall survival were analyzed. RESULTS: No statistically significant differences in median age, final pathological type, International Federation of Gynecology and Obstetrics stage and lymphovascular space involvement were observed between the laparoscopic and open surgery groups. No procedure in the laparoscopic surgery group was converted to open surgery. The median follow-up period was 60 months, with oncologic recurrence identified in three cases (one lung carcinoma and two pelvic cavity carcinomas) in the laparoscopic surgery group. There was no significant between-group difference in 5-year recurrence-free survival (laparoscopic surgery group: 96.3%, open surgery group: 92.6%) and overall survival (laparoscopic surgery group: 100%, open surgery group: 95.4%). CONCLUSIONS: Laparoscopic surgery is a feasible and safe treatment for endometrial cancer and should be considered as a standard treatment option for low-risk endometrial cancer.

Next-generation sequencing analysis of endometrial screening liquid-based cytology specimens: a comparative study to tissue specimens.

BACKGROUND: Liquid-based cytology (LBC) is now a widely used method for cytologic screening and cancer diagnosis. Since the cells are fixed with alcohol-based fixatives, and the specimens are stored in a liquid condition, LBC specimens are suitable for genetic analyses. METHODS: Here, we established a small cancer gene panel, including 60 genes and 17 microsatellite markers for next-generation sequencing, and applied to residual LBC specimens obtained by endometrial cancer screening to compare with corresponding formalin-fixed paraffin-embedded (FFPE) tissues. RESULTS: A total of 49 FFPE and LBC specimens (n = 24) were analyzed, revealing characteristic mutations for endometrial cancer, including PTEN, CTNNB1, PIK3CA, and PIK3R1 mutations. Eight cases had higher scores for both tumor mutation burden (TMB) and microsatellite instability (MSI), which agree with defective mismatch repair (MMR) protein expression. Paired endometrial LBC, and biopsied and/or resected FFPE tissues from 7 cases, presented almost identical mutations, TMB, and MSI profiles in all cases. CONCLUSION: These findings demonstrate that our ad hoc cancer gene panel enabled the detection of therapeutically actionable gene mutations in endometrial LBC and FFPE specimens. Endometrial cancer LBC specimens offer an alternative and affordable source of molecular testing materials.

Risk factors for lymphatic complications following lymphadenectomy in patients with endometrial cancer.

OBJECTIVE: Lymph node (LN) metastasis is among the important prognostic factors for survival in endometrial cancer (EC). This study aimed to evaluate the occurrence of lymphatic complications following lymphadenectomy in patients with EC. MATERIALS AND METHODS: EC patients were retrospectively evaluated. Lower extremity lymphedema (LEL) and pelvic lymphocele (PL) were evaluated according to the International Society of Lymphology guidelines and the National Cancer Institute Common Terminology Criteria for Adverse Events, respectively. RESULTS: A total of 289 patients were enrolled. Surgery was performed via laparotomy and laparoscopy in 200 (69.2%) and 89 (30.8%) patients, respectively. LEL and PL occurred in 43 (14.9%) and 33 (11.4%) patients, respectively. In multivariate logistic regression analysis, circumflex iliac node (CIN) removal (odds ratio [OR]: 3.22; 95% CI: 1.43-7.98; P = 0.004) was an independent risk factor for LEL, while the surgical approach (OR: 4.46; 95% CI: 1.13-29.9; P = 0.004) was an independent risk factor for PL. CONCLUSION: CIN dissection was a significant risk factor for LEL, while laparotomy was an independent risk factor for PL compared to laparoscopy in EC patients. This suggests that laparoscopic surgery combined with sentinel lymph node navigation surgery will prevent lymphatic complications in low-risk EC patients.

Comparison of lymphoscintigraphy and single photon emission computed tomography with computed tomography (SPECT/CT) for sentinel lymph node detection in endometrial cancer.

BACKGROUND: Endometrial cancer is the most common gynecologic cancer, and lymph node metastasis is one of the most important prognostic factors. Increasing evidence shows that sentinel lymph node (SLN) mapping is an effective alternative to comprehensive lymphadenectomy. Single photon emission CT with computed tomography (SPECT/CT) is associated with a high SLN detection rate. OBJECTIVE: To compare the clinical efficacy of SPECT/CT with that of lymphoscintigraphy in detecting SLNs in patients with endometrial cancer. METHODS: Between May 2014 and October 2018, 151 patients with endometrial cancer were enrolled in this study at the Department of Obstetrics and Gynecology of the Kagoshima University Hospital. Inclusion criteria were patients with endometrial cancer, older than 18 years, and with pre-operative International Federation of Gynecology and Obstetrics (FIGO) staging of I and II. All patients underwent pre-operative CT, and patients with suspected peritoneal dissemination and lymph node metastasis were excluded from this study. Pelvic SLNs were detected by injection of tecnetium-99m-labeled phytate into the uterine cervix. The number and locations of SLNs detected using lymphoscintigraphy and SPECT/CT were evaluated. JMP software (version 14, SAS Institute Inc., Cary, North Carolina, USA) was used for statistical analysis. RESULTS: A total of 151 patients who underwent pre-operative lymphoscintigraphy and SPECT/CT were included in the study. The median age was 57 years (range 24-79), and the median body mass index was 24.3 kg/m2 (range 16-40). The final pathology was as follows: 135 (89%) endometrioid carcinoma, 11 (7%) serous carcinoma, one (1%) clear cell carcinoma, and four (3%) other histotypes. Based on SPECT/CT, 204 pelvic SLNs were detected. The bilateral pelvic SLN detection rate was better for SPECT/CT (43% (65/151)) than for lymphoscintigraphy (32% (48/151)) (p<0.0001). The overall pelvic SLN detection rate (at least one pelvic SLN detected) was also better with SPECT/CT (77% (16/151)) vs lymphoscintigraphy (68% (102/151)) (p<0.0001). The distribution of SLN locations detected using SPECT/CT was as follows: external iliac, 91 (45%); obturator, 61 (30%); common iliac, 28 (14%); internal iliac, 19 (9%); para-aortic, 2 (1%); parametrium, 2 (1%), and presacral, 1 (1%). The SLN detection rate using SPECT/CT was significantly worse in patients of advanced age (p<0.0001). DISCUSSION: Overall and bilateral SLN detection rate was better with SPECT/CT than with lymphoscintigraphy in patients with stage I/II endometrial cancer.

Comparison of lymphatic complications between sentinel node navigation surgery and pelvic lymphadenectomy in patients with cervical cancer.

BACKGROUND: Sentinel node navigation surgery (SNNS) has been frequently used in early cervical cancer. However, the incidence and potential reduction of lymphatic complications following the removal of the sentinel lymph node remain unknown. Thus, this study aimed to evaluate the occurrence of lymphatic complications post sentinel node navigation surgery in patients with early cervical cancer. METHODS: A total of 167 patients, including 70 and 97 patients who had undergone SNNS and pelvic lymphadenectomy (PLA), respectively, were enrolled in this study. We compared the lymphatic complications (lower extremity lymphedema and pelvic lymphocele) between the SNNS and PLA groups. RESULTS: The median number of sentinel lymph nodes removed was 2 (range: 1-14). Among the 70 patients in the SNNS group, there were 0 (0%) and 3 (4.3%) occurrences of lower extremity lymphedema and pelvic lymphocele, respectively. The occurrences of lower extremity lymphedema and pelvic lymphocele were significantly lower in the SNNS group than in the PLA group, despite circumflex iliac node removal. CONCLUSIONS: The occurrence of lymphatic complications (lower extremity lymphedema and pelvic lymphocele) was significantly lower in the SNNS group than in the PLA group. We found that SNNS, and not PLA, was the best treatment option for preventing the development of lower extremity lymphedema and pelvic lymphocele, despite circumflex iliac node preservation.

Impact of taxane plus bevacizumab for ovarian sex cord tumor with annular tubules.

Sex cord tumor with annular tubules (SCTAT) is rare, and 20% of SCTAT cases, excluding those associated with Peutz-Jeghers syndrome, are clinically malignant. Limited data is available regarding the role of chemotherapy in the management of SCTAT. We encountered a 44-year-old woman with recurrent SCTAT complicated by peritoneal dissemination following a right adnexectomy. The surgical resection could not be performed completely due to the wide extension of the tumor. Considering the potential of becoming malignant, we chose a combination of bleomycin, etoposide and cisplatin (BEP) as postoperative chemotherapy treatment. However, the patient showed partial response following a complete BEP regimen. The patient received three courses of chemotherapy with docetaxel and carboplatin plus bevacizumab. After the combination chemotherapy, positron emission tomography-computed tomography scan confirmed a complete response, and is currently continuing bevacizumab treatment without relapsing and having no major adverse effects from complications. This case proved the potential of a combination of taxane and bevacizumab in patients with recurrent SCTAT.

Learning curve and surgical outcomes for laparoscopic surgery, including pelvic lymphadenectomy, for early stage endometrial cancer.

BACKGROUND: The purpose of this study was to determine the learning curve of laparoscopic surgery for the treatment of early endometrial cancer and report the surgical outcomes. METHODS: Patients: Data were retrospectively extracted from the medical charts of patients who underwent laparoscopic surgery. INTERVENTION: Laparoscopic surgery, including pelvic lymphadenectomy, was performed using the same technique and instruments for all patients. OUTCOMES: The learning curve for the surgical technique, characterized by the operative time, number of lymph nodes removed, and volume of intra-operative blood loss, was analyzed. RESULTS: Over the period of observation, 82 patients were enrolled. For analysis, cases were classified into four groups, based on their surgery date. Between-group comparisons identified a significant decrease in operative time and volume of blood loss between Groups 1 and 4 (P < 0.05). However, the number of lymph nodes removed, and the length of hospital stay were not influenced by learning. CONCLUSION: The operative time and the amount of blood loss significantly decreased with an increase in the surgeon's experience but with no effect of learning on the number of lymph nodes removed and length of hospital stay.

Clostridium difficile infection in fever patients with gynecological malignancies.

BACKGROUND: Although Clostridium difficile infection (CDI) often results in severe manifestations due to toxin-producing clostridium, the correlation between CDI and having a fever in gynecological malignancies is not completely understood. AIMS: The incidence, and clinical features, and clinical management of CDI in patients with gynecological malignancies who have fevers were investigated, and the clinical managements of this complication are discussed. METHODS AND RESULTS: We retrospectively reviewed 485 patients newly diagnosed with invasive gynecological cancers who underwent anticancer treatment between July 2012 and December 2016. The diagnosis of CDI was performed using enzyme immunoassays for C difficile glutamate dehydrogenase and toxin A/B enzyme immunoassay. The cumulative risk of CDI was 9.5% (six of 63) in overall fever patients and 6.3% (six of 95) in patients with fever episodes. Two CDI patients (33.3%) did not show diarrheal symptoms, with the fever of unknown origin criteria prompting their CDI testing and diagnosis. CDI patients were treated using vancomycin or metronidazole without suffering from fatal clinical course. Overall, eight patients with gynecological malignancies were diagnosed with CDI, including two patients with fever lower than 38.5°C. The cumulative risk of CDI was 0.48% (eight of 1652) for all admitted patients and 1.6% (eight of 485) in those with gynecological malignancies. Of all the patients with confirmed CDI, only one had a history of administration of antibiotics prior to onset of CDI symptoms. CONCLUSION: CDI does not always present with typical manifestations in malignancy patients. Investigation of CDI, regardless of gastrointestinal symptoms or history of antibiotic use, is warranted in cases of fever of unknown origin in gynecological malignancy.