Endometrial Cancer Diagnosed at an Early Stage during Lynch Syndrome Surveillance: A Case Report.

Lynch syndrome is an autosomal dominant inherited disorder caused by a germline pathogenic variant in DNA mismatch repair genes, resulting in multi-organ cancer. Annual transvaginal ultrasonography and endometrial biopsy are recommended for endometrial cancer surveillance in patients with Lynch syndrome in several guidelines; however, evidence is limited. Here, we present the case of a 51-year-old woman with endometrial cancer who underwent robot-assisted laparoscopic simple hysterectomy at an early stage detected by Lynch syndrome surveillance. The patient was a 51-year-old gravida zero woman without any medical history or symptoms. Her sister suffered from bladder, breast, rectal, and endometrial cancer and was diagnosed with Lynch syndrome using a hereditary cancer panel test (VistaSeq®). During gynecologic surveillance, the patient's endometrial cytology was classified as Papanicolaou class III. Therefore, she underwent endometrial curettage with hysteroscopy and was diagnosed with atypical endometrial hyperplasia. Robot-assisted hysterectomy was performed with a final pathological diagnosis of endometrial cancer (endometrioid carcinoma, Grade 1), stage 1A. She has remained disease-free for more than 12 months. Owing to advances in genetic medicine, prophylactic and therapeutic surgeries for hereditary cancers are increasing. To achieve an early diagnosis and treatment of Lynch syndrome-associated cancers, the importance of Lynch syndrome surveillance should be more widely recognized.

A Case of Uterine Lymphangioleiomyomatosis Complicated by Tuberous Sclerosis Complex.

Lymphangioleiomyomatosis (LAM) is one of the presentations of perivascular epithelioid cell neoplasm that is frequently complicated by tuberous sclerosis complex (TSC). Here, we report an uncommon case of uterine LAM treated with everolimus, which is a mechanistic target of rapamycin (mTOR) inhibitor. A 42-year-old female patient (gravida 0) with a history of TSC presented with abdominal pain. Pelvic magnetic resonance imaging showed multiple masses in the uterine myometrium, suggesting tumors that may contain internal hemorrhagic components. The lesions were suspected as the root cause of her symptoms. After everolimus was administered for a previously diagnosed renal angiolipoma, her uterine tumors temporarily decreased in size. Subsequently, laparoscopic hysterectomy and bilateral salpingectomy were performed since she could not tolerate everolimus for a long period due to the medication's side effects. Furthermore, the patient was diagnosed with LAM through histopathological examination after surgical resection. Therefore, it is advisable to suspect and investigate uterine LAM when a patient with a history of TSC presents with irregular genital bleeding or abdominal pain. Moreover, mTOR inhibitors may be a treatment option, in addition to surgery, in cases of uterine LAM exacerbation.

Risk Factors for Septic Shock After Irinotecan-Containing Chemotherapy: An Exploratory Case-Control Study.

BACKGROUND AND OBJECTIVES: Irinotecan sometimes causes lethal septic shock but the risk factors remain unclear. This retrospective case-control study explored the potential risk factors for septic shock following irinotecan treatment. METHODS: All women who received irinotecan-containing chemotherapy for gynecologic malignancies at Shizuoka General Hospital from October 2014 to September 2020 were investigated. The clinical backgrounds and blood test results of those who developed septic shock after irinotecan-containing chemotherapy were compared with those who did not. Odds ratios (ORs) for developing septic shock after receiving irinotecan were calculated with 95% confidence intervals (CIs), using univariable logistic regression analysis. RESULTS: During the study period, 147 women received irinotecan-containing chemotherapy. Three women developed septic shock due to neutropenic enterocolitis after irinotecan treatment, and 144 did not. The three patients with septic shock had recurrent cervical cancer, heterozygous variants in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene (two patients had *1/*6, one had *1/*28 variants), a history of concurrent chemoradiation therapy, 50-60 Gy of pelvic irradiation, and platinum-combined chemotherapy. A history of pelvic irradiation was identified as a possible risk factor for developing septic shock after irinotecan-containing chemotherapy (OR 63.0, 95% CI 5.71-8635; p < 0.001). The OR of UGT1A1 polymorphism for septic shock was 9.09 (95% CI 0.86-1233; p = 0.070) in the complete case analysis. CONCLUSION: Medical personnel involved in cancer therapy should consider the possible risk of septic shock developing due to neutropenic enterocolitis when administering irinotecan-containing chemotherapy in patients with a history of pelvic irradiation.

Validity of Weekly Administration of Carboplatin after Carboplatin-Induced SIADH: Two Case Reports and Literature Review.

Chemotherapy-induced severe hyponatremia is a life-threatening condition. Platinum-based agents play a key role in ovarian cancer treatment but are more likely to cause hyponatremia than other anticancer agents. The optimal strategy for treating ovarian cancer in cases of severe platinum agent-induced hyponatremia remains unclear. We encountered 2 patients with ovarian cancer who developed syndrome of inappropriate antidiuretic hormone secretion (SIADH) after chemotherapy with involved carboplatin. Case 1 was a recurrent ovarian clear-cell carcinoma with peritoneal dissemination, and the patient developed severe hyponatremia due to SIADH on day 5 after receiving triweekly docetaxel and carboplatin (DC) therapy. The chemotherapy regimen was changed to weekly DC therapy, and she completed six cycles of regimen without electrolyte disturbance or tumor recurrence. Case 2 was a newly diagnosed advanced high-grade serous ovarian carcinoma, stage IIIC, with a BRCA1 mutation. She developed SIADH on day 8 after receiving triweekly paclitaxel and carboplatin (TC) therapy as adjuvant therapy after primary debulking surgery. The regimen was changed to weekly TC therapy, and she completed the schedule of chemotherapy without electrolyte disturbance and transitioned to maintenance therapy with a PARP inhibitor. In conclusion, weekly carboplatin administration might be a promising alternative to triweekly carboplatin administration after the development of carboplatin-induced SIADH.

Olaparib-induced cutaneous side effects in a patient with recurrent ovarian cancer.

Over the past decade, the treatment of ovarian cancer has been revolutionised by poly(ADP-ribose polymerase (PARP)) inhibitors. Based on the results from clinical trials, olaparib, a PARP inhibitor, is indicated for use in the first-line treatment for patients with BRCA gene mutations, and as a maintenance treatment in platinum-sensitive relapsed ovarian cancer after a complete or partial response to platinum-based chemotherapy. Although PARP inhibitors have been shown to be well tolerated, adverse side effects can affect the quality of life of patients and lead to the discontinuation of therapy. Here, we report a case of dermatosis of the left dorsal hand as a rare adverse side effect of olaparib. Dermatological adverse side effects may become the crux of a clinical problem that requires the cooperation of professionals in many fields.

Imiquimod for vaginal intraepithelial neoplasia 2-3: A systematic review and meta-analysis.

OBJECTIVE: The treatment strategy for vaginal intraepithelial neoplasia (VaIN) 2-3 has not been established. This study aimed to investigate the efficacy of imiquimod in VaIN 2-3. METHODS: Electronic databases (PubMed, EMBASE, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials) were searched from their inception until October 2019 and articles reporting imiquimod treatment for VaIN 2-3 were extracted. Additionally, the clinical records of women with VaIN 2-3 who had been treated with imiquimod in Shizuoka General Hospital from January 2016 to May 2020 were investigated. The data from the systematic search and the data from our hospital were analyzed, and a pooled complete response (CR) rate and response rate of imiquimod treatment for VaIN 2-3 were estimated. As a subgroup analysis, the CR rates and response rates were compared between women with and without a history of hysterectomy, and the rate ratio was calculated. RESULTS: Five articles described 28 women with VaIN 2-3 who underwent imiquimod treatment, and nine women with VaIN 2-3 were treated with imiquimod in our hospital. The discontinuation of the treatment was required in only one patient of the reported cases. The pooled CR rate and response rate of imiquimod, regardless of a history of hysterectomy, was 0.76 (95% CI, 0.59-0.87) and 0.89 (95% CI, 0.71-0.97), respectively. In the subgroup analysis, the CR rate in patients with hysterectomy was 0.98 (95% CI, 0.11-1.0) and in those without hysterectomy was 0.60 (95% CI, 0.30-0.84), and the rate ratio was 0.83 (95% CI, 0.48-1.19). The pooled response rates with and without a history of hysterectomy were not estimated, and the rate ratio was 0.83 (95% CI, 0.54-1.09). CONCLUSION: Imiquimod can be an effective treatment for vaginal intraepithelial neoplasia 2-3.

Recurrent vaginal intraepithelial neoplasia successfully treated with topical imiquimod: A case report.

Vaginal intraepithelial neoplasia (VAIN) is a rare disease associated with human papillomavirus infection. High-grade VAIN is typically treated with either excisional or ablative therapy. However, recurrent VAIN lesions are common and these treatments cause vaginal scarring. Recent studies have indicated that 5% imiquimod is an effective treatment for VAIN. The present report describes a case of a woman diagnosed with recurrent VAIN 3 who was treated with a 5% topical imiquimod cream and achieved a complete response after excision and CO2 laser vaporization. A 53-year-old, gravida 5, para 2 postmenopausal woman who was diagnosed with papillary squamous cell carcinoma by biopsy underwent conization, total abdominal hysterectomy and bilateral salpingo-oophorectomy. A histological examination revealed grade 3 cervical intraepithelial neoplasia with free surgical margins. At 3 years after the hysterectomy, the vaginal smear revealed atypical squamous cells, leading to a pathological diagnosis of VAIN 3. Partial vaginectomy was performed, and VAIN 3 was detected in the lesion with positive margins. At 4 months into follow-up, the vaginal smear revealed a high-grade squamous intraepithelial lesion (HSIL), and subsequent biopsy during colposcopy revealed a pathological diagnosis of VAIN 3. At 3 months after CO2 laser vaporization, the vaginal smear revealed HSIL with suspected recurrence and imiquimod treatment was initiated. One sachet of 5% imiquimod cream (0.25 g) was placed in the entire vagina three times per week for 14 weeks with no apparent complications. At 3 years after the treatment, there has been no recurrence. This case demonstrated that topical imiquimod with careful follow-up is an effective treatment for VAIN and is well-tolerated. Further clinical evidence of the effectiveness and safety of imiquimod in patients diagnosed with VAIN is required.