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BACKGROUND: Rectal neuroendocrine carcinomas (NECs) are rare and associated with poorer prognoses compared to conventional adenocarcinomas. The efficacy of adjuvant chemotherapy for resectable rectal NECs remains uncertain. Herein, we present a case of rectal NEC successfully treated with postoperative chemotherapy using irinotecan plus cisplatin. CASE PRESENTATION: A 48-year-old woman with a history of endometrial cancer presented with an intramural rectal tumour detected on follow-up imaging. Colonoscopy revealed a 30 mm submucosal tumour, and laparoscopic low anterior resection was performed. Histopathological examination showed poorly differentiated atypical cells with solid growth patterns. Metastasis from the uterine cancer was ruled out due to histological differences between the primary uterine tumour and the rectal lesion, as well as the absence of hormone receptor immunohistochemical expression. Further immunohistochemical analysis revealed diffuse CD56 positivity, a high mitotic rate (> 20/10 high power fields) and a Ki-67 labelling index exceeding 70%. Based on these findings, a diagnosis of rectal NEC, T3N0M0, Stage IIB (UICC 8th edition), was established. Given the aggressive nature of the tumour evidenced by a high Ki-67 labelling index, adjuvant chemotherapy comprising six cycles of irinotecan plus cisplatin was administered to mitigate the risk of recurrence. At the 3-year follow-up, the patient was free of disease recurrence. CONCLUSION: This case highlights the importance of multidisciplinary surgical interventions followed by adjuvant chemotherapy in managing rectal NECs.

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OBJECTIVE: Comprehensive genomic profiling testing using a hybrid-capture next-generation sequencing is commonly used in clinical practice to employ precision medicine in cancer treatment worldwide. In this study, we aimed to analyze the profiles obtained using comprehensive genomic profiling testing that was performed in Japanese castration-resistant prostate cancer patients and to discuss the genetic findings in a real-world setting. METHODS: A total of 60 cases and 57 castration-resistant prostate cancer patients underwent comprehensive genomic profiling testing between 1 January 2021 and 31 December 2022. Four types of comprehensive genomic profiling testing were selected, and clinically significant cancer-specific gene alterations were identified. RESULTS: The median age of patients was 74 years, and the median prostate-specific antigen value at the time of submission was 18.6 ng/ml. Fifty-seven (95%) of 60 cases were metastatic castration-resistant prostate cancers, and 3 cases (5%) were non-metastatic. Among all genetic alterations, androgen-receptor alteration was the most frequently detected in 17 cases (28.3%), followed by 15 cases of TP53 (25.0%), 14 cases of CDK12 (23.3%), 10 cases of phosphatase and tensin homolog (16.7%) and 9 cases of ATM (15.0%) mutations. A total of 13 patients (21.7%) received systemic therapy according to the comprehensive genomic profiling testing results. Overall, the survival rate was significantly greater in the group treated through systemic therapy based on comprehensive genomic profiling testing compared with the group without new therapeutic treatment (P = 0.041). CONCLUSIONS: Comprehensive genomic profiling testing is recommended in castration-resistant prostate cancer patients identified as resistant to standard therapy as this can provide a new therapeutic option.

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We herein report a patient with KRAS wild-type non-small-cell lung cancer (NSCLC) with concurrent STK11 and KEAP1 mutations. A 53-year-old man visited a local doctor with a complaint of left shoulder swelling and pain. He was diagnosed with NSCLC cT4N0M1c stage IVB. A comprehensive genome profile test revealed mutations in STK11 and KEAP1 but no KRAS mutations. The patient was refractory to radiotherapy, immunotherapy, and chemotherapy. Thus, STK11 and KEAP1 mutations can be considered resistance mutations that confer resistance to various anticancer therapies in KRAS wild-type NSCLC.

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Most epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) cells are killed within a few days after osimertinib treatment; however, surviving cells remain detectable and are called drug-tolerant cells. Plasminogen activator inhibitor-1 (PAI-1) was reported to be involved in chemotherapeutic or radiotherapeutic resistance. The purpose of the present study was to investigate whether PAI-1 is involved in osimertinib tolerance and whether it could be a therapeutic target for overcoming this tolerance. We showed that the PAI-1 mRNA expression levels and mesenchymal gene expression levels were significantly higher in drug-tolerant EGFR-mutated NSCLC cells than in control cells after 7 days of in vitro osimertinib treatment. Additionally, an RNA microarray analysis revealed upregulation of the integrin-induced EMT pathway in osimertinib-tolerant cells. Furthermore, we observed that PAI-1 inhibitors suppressed proliferation and the degree of epithelial-mesenchymal transition (EMT) in tolerant cells. Finally, in a subcutaneous tumor model, we showed that combining osimertinib with a PAI-1 inhibitor prevented the regrowth of tumors comprising EGFR-mutated cancer cells. The present study is the first to show PAI-1 to be involved in tolerance to osimertinib via EMT.

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A 77-year-old woman with postoperative recurrent non-small cell lung adenocarcinoma, which exhibited an epidermal growth factor receptor (EGFR) L858R mutation, was treated with gefitinib and erlotinib. Seven years after the start of treatment, the patient experienced a recurrence of malignant pleural effusion. However, 3 different genetic tests revealed that the lung adenocarcinoma cells in the pleural effusion had lost EGFR L858R mutation, suggesting that long-term treatment with EGFR-tyrosine kinase inhibitors (TKIs) converted EGFR mutation from positive to negative. The negative conversion of EGFR mutation as a mechanism of acquired resistance to EGFR-TKIs is considered rare and needs to be further investigated.

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We present the case of a 72‒year‒old male patient with anorexia who was diagnosed with advanced gastric cancer with multiple liver metastasis. He had marked hypoglycemia and lightheadedness from the time of admission. The serum insulin level was very low and other endocrinology test results were normal. He was finally diagnosed with non‒islet cell tumor hypoglycemia(NICTH)based on IHC findings that tumor cells expressed insulin‒like growth factor (IGF)Ⅱ. After the patient received intravenous glucocorticoid therapy along with S‒1 plus CDDP combination chemotherapy, the hypoglycemia was quickly resolved. However, he developed septic shock in reaction to the chemotherapy and died on the 35th day of hospitalization. The autopsy showed the presence of IGF‒Ⅱ in the liver metastasis, as well as in the primary tumor.

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Severe leukopenia, thrombocytopenia, and bi-cytopenia due to nivolumab have been reported. In this report, we present the first case of nivolumab-induced severe pancytopenia in a patient with lung adenocarcinoma. A 56-year-old Japanese man with lung adenocarcinoma received nivolumab therapy as second-line treatment. After 3 cycles of this therapy, although computed tomography (CT) showed a reduced tumor size, laboratory findings revealed pancytopenia and a bone marrow biopsy showed a severely hypoplastic marrow. The pancytopenia was diagnosed as an adverse effect of nivolumab; filgrastim (75 µg/day), steroid-pulse therapy (intravenous methylprednisolone: 500 mg/day), and subsequently intravenous prednisolone (50 mg/day) were administered. Furthermore, intravenous administration of immunoglobulins was also performed. However, these treatments were ineffective. He was further diagnosed with fungal pneumonia and a catheter-related bloodstream infection. Anti-bacterial chemotherapy was administered. Two months after hospitalization, the neutrophil count improved to 1000/µL, but multiple red blood cell and platelet transfusions were needed. Therefore, further chemotherapy for lung adenocarcinoma could not be initiated, and the patient died due to progression of lung cancer 118 days after the onset of pancytopenia. The possibility of severe pancytopenia as an immune-related adverse event should be considered as a mandatory prerequisite for nivolumab therapy.

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