Immunosuppressive tumor microenvironment in uterine serous carcinoma via CCL7 signal with myeloid-derived suppressor cells.

Serous carcinoma of the uterus (USC) is a pathological subtype of high-grade endometrial cancers, with no effective treatment for advanced cases. Since such refractory tumors frequently harbor antitumor immune tolerance, many immunotherapies have been investigated for various malignant tumors using immuno-competent animal models mimicking their local immunities. In this study, we established an orthotopic mouse model of high-grade endometrial cancer and evaluated the local tumor immunity to explore the efficacy of immunotherapies against USC. A multivariate analysis of 62 human USC cases revealed that the tumor-infiltrating cell status, few CD8+ cells and abundant myeloid-derived suppressor cells (MDSCs), was an independent prognostic factor (P < 0.005). A murine endometrial cancer cell (mECC) was obtained from C57BL/6 mice via endometrium-specific deletion of Pten and Tp53, and another high-grade cell (HPmECC) was established by further overexpressing Myc in mECCs. HPmECCs exhibited higher capacities of migration and anchorage-independent proliferation than mECCs (P < 0.01, P < 0.0001), and when both types of cells were inoculated into the uterus of C57BL/6 mice, the prognosis of mice bearing HPmECC-derived tumors was significantly poorer (P < 0.001). Histopathological analysis of HPmECC orthotopic tumors showed serous carcinoma-like features with prominent tumor infiltration of MDSCs (P < 0.05), and anti-Gr-1 antibody treatment significantly prolonged the prognosis of HPmECC-derived tumor-bearing mice (P < 0.05). High CCL7 expression was observed in human USC and HPmECC, and MDSCs migration was promoted in a CCL7 concentration-dependent manner. These results indicate that antitumor immunity is suppressed in USC due to increased number of tumor-infiltrating MDSCs via CCL signal.

[Is Surgery Really Useful for Breast Cancer Management in Elderly Patients?]

PURPOSE: The Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer 2018 indicated that operation is the standard treatment for breast cancer in elderly patients. This study aimed to assess the safety and efficacy of surgery for elderly patients with breast cancer. METHODS: Between April 2009 and November 2019, 545 patients underwent surgery in our hospital. The medical records of the elderly group(≥80 years, n=62)and the control(55-65 years, n=128)groups were compared and analyzed retrospectively. RESULTS: The elderly group had more comorbidities(p<0.001)than those of the control group. Although no significant difference in the pathological stage was noted between the 2 groups, dermal infiltrations were more common(p=0.003)in the elderly group than those of the other, and 27% of them did not undergo any surgery to the axilla. This group experienced more post-surgery complications than those of the other; however, such complications did not extend beyond the duration of hospital stays. No difference in the recurrence rate between the groups was noted. In the elderly group, 64% died of comorbidities. The 3-year survival rate was 88.3% and 95.4% in the elderly and control groups, respectively(p=0.18). CONCLUSIONS: Our study revealed that surgery was safe for the management of breast cancer in elderly patients. However, their prognosis was poor owing to their comorbidities. Hence, careful therapy for their comorbidity is also important.

A Novel Direct Approach to the Deep Uterine Vein in Laparoscopic Radical Hysterectomy.

STUDY OBJECTIVE: To describe a direct approach to the deep uterine vein in laparoscopic radical hysterectomy. DESIGN: Demonstration of the laparoscopic technique with narrated video footage. SETTING: Securing sufficient radicality is extremely important when performing a radical hysterectomy for cervical cancer, either by laparotomy or by minimally invasive surgery. The nerve-sparing Okabayashi radical hysterectomy (NS-RH) was originally aimed at achieving both radical resection and function preservation [1-3]. A key procedure when performing NS-RH is intraoperative identification of the relationship between the deep uterine vein and pelvic splanchnic nerve fibers [4]. With this in mind, a safe and easy method for identifying the crossing point of the deep uterine vein and pelvic splanchnic nerve in the initial phase of the surgery may greatly improve the safety and efficacy of functional preservation in NS-RH. Herein, we describe a minimally invasive "direct approach" to the deep uterine vein. INTERVENTIONS: Before undergoing the pelvic lymphadenectomy, all steps of laparoscopic radical hysterectomy were performed. First, we identified the ureter on the posterior peritoneum, and the peritoneum was dissected just above the ureter. By continuously exploring the pelvic cavity along the ureter, especially through the opening of the space below the ureter in a cranial to caudal direction, we could easily identify the deep uterine vein. This procedure also exposed the fibers of the hypogastric nerve, clarifying the relationship of these structures. CONCLUSION: Because the relationship between the deep uterine vein and nerve fibers is the most important guidepost of this surgery, their identification in the early phase of the surgery enables us to perform the subsequent procedure precisely and securely. This direct approach to the deep uterine vein can be easily and safely performed.

Management of an obstructed recurrent inguinal hernia using a hybrid method: a case report.

BACKGROUND: For recurrent incarcerated and strangulated hernias, the optimal treatment strategy for each case is needed. CASE PRESENTATION: The study patient was a 70-year-old man. TAPP repair was performed for a left inguinal hernia (JHS Classification II-1) 7 years earlier. The patient experienced transient pain and swelling of the left inguinal region for 5 months and visited our emergency department for abdominal pain and vomiting. A CT scan showed a recurrent left inguinal hernia and small bowel incarceration, and emergency surgery was performed. Laparoscopic observation of the abdominal cavity revealed recurrent left inguinal hernia (Rec II-1) with small bowel incarceration. The small bowel was reduced after pneumoperitoneum, and no findings suggested intestinal tract necrosis. Adhesions around the herniated sac were dissected using an extraperitoneal approach and then shifted to mesh plug repair. No perioperative complications or hernia recurrence were observed in the 10 months after the surgery. CONCLUSIONS: This report describes a novel, successful surgical treatment for a recurrent incarcerated hernia. In our patient, we could easily perform dissection and understand the positional relationship by hybrid surgery using the TEP method. Additionally, in patients with incarcerated hernias, we believe that performing hybrid surgery by combining the TEP method would be useful because bowel dilation caused by intestinal obstruction would not disturb the operative field.

[A Case of Stage â £ Cholangiocarcinoma with an Improved Quality of Life after Resection of a Symptomatic Giant Ovarian Teratoma].

An 82‒year‒old female presented to our hospital with abdominal fullness and loss of appetite. Abdominal computed tomography revealed a cholangiocarcinoma(Stage Ⅳ)with liver metastases and multiple lymph node metastases. In addition, we found a left ovarian teratoma(approximately 33 cm in diameter)occupying most of the abdominal cavity. She did not want an aggressive treatment for cholangiocarcinoma, but hoped to receive the best supportive care. She was treated with a fentanyl patch, although there was no symptomatic improvement. We explained that resection of the giant ovarian tumor may improve the symptoms. As a result, she accepted the surgery. The laparotomy was performed, and a left ovarian tumor(approximately 10,600 g in weight)was resected. Operation time was 2 hours and 35 minutes, and the amount of blood loss was small. No postoperative complications were observed. She started oral intake at POD 2. The abdominal symptom was relieved by the surgery, and she was discharged to her own home on POD 12. She was readmitted on POD 46 for general malaise, and died of advanced cholangiocarcinoma on POD 66. It was suggested that the QOL may be improved by resecting symptomatic benign tumors even in terminal cancer patients.

Anti-VEGF therapy resistance in ovarian cancer is caused by GM-CSF-induced myeloid-derived suppressor cell recruitment.

BACKGROUND: The mechanism of resistance development to anti-VEGF therapy in ovarian cancer is unclear. We focused on the changes in tumour immunity post anti-VEGF therapy. METHODS: The frequencies of immune cell populations and hypoxic conditions in the resistant murine tumours and clinical samples were examined. The expression profiles of both the proteins and genes in the resistant tumours were analysed. The impact of granulocyte-monocyte colony-stimulating factor (GM-CSF) expression on myeloid-derived suppressor cell (MDSC) function in the resistant tumours was evaluated. RESULTS: We found a marked increase and reduction in the number of Gr-1 + MDSCs and CD8 + lymphocytes in the resistant tumour, and the MDSCs preferentially infiltrated the hypoxic region. Protein array analysis showed upregulation of GM-CSF post anti-VEGF therapy. GM-CSF promoted migration and differentiation of MDSCs, which inhibited the CD8 + lymphocyte proliferation. Anti-GM-CSF therapy improved the anti-VEGF therapy efficacy, which reduced the infiltrating MDSCs and increased CD8 + lymphocytes. In immunohistochemical analysis of clinical samples, GM-CSF expression and MDSC infiltration was enhanced in the bevacizumab-resistant case. CONCLUSIONS: The anti-VEGF therapy induces tumour hypoxia and GM-CSF expression, which recruits MDSCs and inhibits tumour immunity. Targeting the GM-CSF could help overcome the anti-VEGF therapy resistance in ovarian cancers.

Phosphorylation of STAT1 serine 727 enhances platinum resistance in uterine serous carcinoma.

Uterine serous carcinoma (USC) is a highly aggressive histological subtype of endometrial cancers harboring highly metastatic and chemoresistant features. Our previous study showed that STAT1 is highly expressed in USC and acts as a key molecule that is positively correlated with tumor progression, but it remains unclear whether STAT1 is relevant to the malicious chemorefractory nature of USC. In the present study, we investigated the regulatory role of STAT1 toward platinum-cytotoxicity in USC. STAT1 suppression sensitized USC cells to increase cisplatin-mediated apoptosis (p < 0.001). Furthermore, phosphorylation of STAT1 was prominently observed on serine-727 (pSTAT1-Ser727), but not on tyrosine-701, in the nucleus of USC cells treated with cisplatin. Mechanistically, the inhibition of pSTAT1-Ser727 by dominant-negative plasmid elevated cisplatin-mediated apoptosis by increasing intracellular accumulation of cisplatin through upregulation of CTR1 expression. TBB has an inhibitory effect on casein kinase 2 (CK2), which phosphorylate STAT1 at serine residues. Sequential treatment with TBB and cisplatin on USC cells greatly reduced nuclear pSTAT1-Ser727, enhanced intracellular accumulation of cisplatin, and subsequently increased apoptosis. Tumor load was significantly reduced by combination therapy of TBB and cisplatin in in vivo xenograft models (p < 0.001). Our results collectively suggest that pSTAT1-Ser727 may play a key role in platinum resistance as well as tumor progression in USC. Thus, targeting the STAT1 pathway via CK2 inhibitor can be a novel method for attenuating the chemorefractory nature of USC.

VISTA expressed in tumour cells regulates T cell function.

BACKGROUND: V-domain Ig suppressor of T cell activation (VISTA) is a novel inhibitory immune-checkpoint protein. VISTA expression on tumour cells and the associated regulatory mechanisms remain unclear. We investigated VISTA expression and function in tumour cells, and evaluated its mechanism and activity. METHODS: VISTA in tumour cells was assessed by tissue microarray analysis, immunohistochemical staining and western blot. A series of in vitro assays were used to determine the function of tumour-expressed VISTA. In vivo efficacy was evaluated in syngeneic models. RESULTS: VISTA was highly expressed in human ovarian and endometrial cancers. Upregulation of VISTA in endometrial cancer was related to the methylation status of the VISTA promoter. VISTA in tumour cells suppressed T cell proliferation and cytokine production in vitro, and decreased the tumour-infiltrating CD8+ T cells in vivo. Anti-VISTA antibody prolonged the survival of tumour-bearing mice. CONCLUSIONS: This is the first demonstration that VISTA is highly expressed in human ovarian and endometrial cancer cells, and that anti-VISTA antibody treatment significantly prolongs the survival of mice bearing tumours expressing high levels of VISTA. The data suggest that VISTA is a novel immunosuppressive factor within the tumour microenvironment, as well as a new target for cancer immunotherapy.

[A Case of Multiple Laparoscopic Surgeries Performed for Disseminated Peritoneal Recurrence of Primary Peritoneal Carcinoma].

A 61-year-old woman presented to our hospital with abdominal distension. Abdominal CT showed massive ascites and disseminated peritoneal nodules. The patient was diagnosed with primary peritoneal cancer based on ascites and disseminated peritoneal nodules following laparoscopic surgery(initial operation). After receiving neoadjuvant chemotherapy, she underwent hysterectomy, bilateral salpingo-oophorectomy, and omentectomy(2nd operation). During chemotherapy, she experienced small bowel obstruction owing to disseminated peritoneal recurrence and splenic metastasis. Therefore, she underwent a laparoscopic partial small bowel resection(3rd operation)and laparoscopic splenectomy(4th operation). Treatment of primary peritoneal carcinoma consists of debulking surgery and chemotherapy. Laparoscopic debulking surgery may be useful for preventing adhesions and facilitating early postoperative recovery.

Genomic profile predicts the efficacy of neoadjuvant chemotherapy for cervical cancer patients.

BACKGROUND: Neoadjuvant chemotherapy (NAC) using platinum and irinotecan (CPT-11) followed by radical excision has been shown to be a valid treatment for locally advanced squamous cervical cancer (SCC) patients. However, in NAC-resistant or NAC-toxic cases, surgical treatment or radiotherapy might be delayed and the prognosis may be adversely affected. Therefore, it is important to establish a method to predict the efficacy of NAC. METHODS: Gene expression microarrays of SCC tissue samples (n = 12) and UGT1A1 genotyping of blood samples (n = 23) were investigated in terms of their association with NAC sensitivity. Gene expression and drug sensitivity of SCC cell lines were analyzed for validation. RESULTS: Microarray analysis revealed that the glutathione metabolic pathway (GMP) was significantly up-regulated in NAC-resistant patients (p < 0.01), and there was a positive correlation between 50 % growth inhibitory concentrations of CPT-11 and predictive scores of GMP activation in SCC cells (r = 0.32, p < 0.05). The intracellular glutathione (GSH) concentration showed a highly positive correlation with GMP scores among 4 SCC cell lines (r = 0.72). UGT1A1 genotyping revealed that patients with UGT1A1 polymorphisms exhibited significantly higher response rates to NAC than those with the wild-type (79.5 vs. 49.5 %, respectively, p < 0.05). CONCLUSIONS: These results indicate that GMP scores of cancerous tissue combined with UGT1A1 genotyping of blood samples may serve as highly potent markers for predicting the efficacy of NAC for individual SCC patients.

[A Case of Malignant Lymphoma of the Spleen Infiltrating the Diaphragm Treated with Splenectomy].

A 67-year-old man was treated for diabetes mellitus by his family doctor. A splenic tumor was suspected based on his pain in the left side of the abdomen. He was admitted to our hospital for close inspection and medical treatment. Abdominal CT and MRI scans showed a tumor, 10 cm in diameter, in the spleen. An opaque boundary with the diaphragm was also observed. On PET-CT, accumulations of FDG were observed in the left supraclavicular fossa and the left axilla. The serum levels of LDH and sIL-2R were elevated, and therefore a diagnosis of malignant lymphoma was suspected. Due to the risk of splenic rupture, a splenectomy was performed. After pathological examination, the patient was diagnosed with diffuse large B-cell malignant lymphoma. He is currently being treated with chemotherapy at another medical institute. Splenic rupture occurs in some cases of splenic malignant lymphoma, although the number of reported cases is low. In some of the cases, splenic rupture occurred during treatment of the malignant lymphoma. There is no specific way to measure the risk of splenic rupture; however, performing a prophylactic splenectomy is one option in cases where tumor cells have extended to the capsula lienis, similar to that in our patient.

Up-regulation of Kv7.1 channels in thromboxane A2-induced colonic cancer cell proliferation.

Thromboxane A2 (TXA2) is known to stimulate colonic cancer cell proliferation, although the mechanism has not been clarified. In this study, we compared the expression levels of Kv7.1 K(+) channels between human colorectal cancer tissue and the accompanying non-tumor mucosa. Kv7.1 proteins were found to be consistently up-regulated in the cancer tissues from different patients. Kv7.1 was also expressed in human colonic cancer cell lines. Treatment of colonic cancer cells with 9,11-epithio-11,12-methano-thromboxane A2 (STA2), a stable analogue of TXA2, significantly increased whole-cell K(+) currents sensitive to chromanol 293B, an inhibitor of Kv7.1 channels, in parallel with an increased expression of Kv7.1 proteins. In contrast, TXB2, an inactive metabolite of TXA2, had no effects on expression level and function of Kv7.1. A TXA2 receptor antagonist (SQ29548) and an inhibitor of cAMP-dependent protein kinase (Rp-8-Br-MB-cAMPS) inhibited STA2-induced increases in both Kv7.1 expression and chromanol 293B-sensitive K(+) currents. Interestingly, STA2-stimulated proliferation of colonic cancer cells was inhibited by chromanol 293B. These results suggest that Kv7.1 channels are involved in the TXA2-induced cancer cell proliferation and that they are up-regulated by the TXA2 receptor-mediated cAMP pathway.

Predictive value of optimal morphologic response to first-line chemotherapy in patients with colorectal liver metastases.

BACKGROUND: It has been reported that morphologic response to preoperative chemotherapy is an independent prognostic factor in patients who undergo hepatic resection of colorectal liver metastases (CLM). The aim of this study was to evaluate the predictive value of morphologic response to first-line chemotherapy in patients with CLM. METHODS: We assessed 41 patients with CLM who received fluorouracil-based chemotherapy with or without bevacizumab as the first-line chemotherapy between April 2006 and June 2012. Three blinded radiologists evaluated computed tomography images and classified them as optimal, incomplete or no response according to the morphologic criteria. Response to systemic chemotherapy was also evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST). Predictive factors associated with progression-free survival (PFS) were identified in multivariate analysis. RESULTS: Twenty-three patients (56%) received chemotherapy with bevacizumab, while 18 patients (44%) received chemotherapy without bevacizumab. Optimal morphologic response was observed in 11 patients (48%) treated with bevacizumab and in 5 patients (28%) treated without bevacizumab (p = 0.19). Eight patients (20%) underwent hepatic resection after chemotherapy. The median follow-up period was 31.3 months. The median PFS was 13.3 months for patients with optical morphologic response and 8.7 months in those with incomplete/no morphologic response (p = 0.0026). On multivariate analysis, performance status and morphologic response were significant independent predictors of PFS. CONCLUSION: Optimal morphologic response was significantly associated with PFS in patients with CLM who were treated with fluorouracil-based chemotherapy as the first-line chemotherapy.

Case Report: The first case of successful pregnancy and live birth following laparoscopic resection of adenomyosis under real-time intraoperative ultrasound elastography guidance.

Objective: Adenomyosis-related infertility is increasingly being diagnosed, and surgical intervention has been suggested to improve fertility. Elastography, a noninvasive ultrasound technique, is promising for diagnosing and guiding the resection of adenomyosis. This report presents the first case of successful delivery after twin pregnancies achieved with IVF following intraoperative elastography-guided laparoscopic adenomyomectomy. Case report: A 35-year-old Japanese woman with uterine adenomyosis received a gonadotropin analog before surgery. Preoperative MRI revealed a 5.0 × 7.0 cm adenomyoma, leading to scheduled laparoscopic adenomyomectomy with intraoperative elastography. During surgery, elastography ensured the complete resection of the adenomyotic tissue while preserving the endometrium. Postoperative MRI confirmed the absence of residual adenomyosis. The patient underwent in vitro fertilization and embryo transfer, leading to a successful twin pregnancy after double blastocyst transfer. Despite a stable perinatal course, she required hospitalization to prevent preterm labor. At 32 weeks, an elective cesarean section delivered healthy twins. The intra- and post-operation was uncomplicated, and the patient and infants had an optimal health. Conclusion: This is the first reported case of a twin pregnancy resulting from vitrified-warmed embryo transfer after elastography-guided laparoscopic adenomyomectomy, culminating in a successful delivery via cesarean section. This technique allows precise resection and mitigates the risks of uterine rupture and placenta accreta spectrum disorders. Although promising, further studies are required to validate the safety and efficacy of this innovative surgical approach.

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.

Efficacy of weekly paclitaxel in patients with advanced gastric cancer refractory to docetaxel-based chemotherapy.

BACKGROUND: Only partial cross-resistance between docetaxel and paclitaxel has been demonstrated in breast and ovarian cancers. Whether weekly paclitaxel is effective in patients with advanced gastric cancer refractory to docetaxel-based chemotherapy remains unclear, and we aimed to clarify the efficacy and safety of weekly paclitaxel in such patients. METHODS: Patients who had received docetaxel-based regimens were assigned to the prior-docetaxel group, and those who had never received docetaxel were designated as the non-docetaxel group. Paclitaxel at 80 mg/m(2) was administered by intravenous infusion in all patients, and this was repeated weekly for 3 weeks out of 4. RESULTS: Between April 2006 and June 2011, 65 patients were studied: 26 in the prior-docetaxel group and 39 patients were non-docetaxel group. The median age, gender, performance status, histological type, history of gastrectomy, and the locations and numbers of metastatic sites did not differ significantly between the two groups. In the prior-docetaxel group, the response rate (RR) was 14.2% (3/21) among patients with measurable lesions, median progression-free survival (PFS) was 79 days [95% confidence interval (CI), 47-135 days], and overall survival (OS) was 123 days (95% CI, 90-215 days) from the initiation of paclitaxel treatment. In the non-docetaxel group, the RR was 11.5% (3/26) among patients with measurable lesions, PFS was 82 days (95% CI, 52-106 days), and OS was 143 days (95% CI, 121-178 days). The efficacy of weekly paclitaxel thus appeared to be similar in the two groups. CONCLUSIONS: Weekly paclitaxel was modestly active in patients with gastric cancer refractory to docetaxel-based chemotherapy.

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.

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.

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.