[A Case of Effective Chemoradiotherapy for the Treatment of Distant Recurrence of Squamous Cell Carcinoma in the Anal Canal].

A 75-year-old woman diagnosed with squamous cell carcinoma of the anal canal was treated using chemoradiotherapy and revealed a complete response to the tumor. After 6 months of treatment, swollen para-aortic lymph nodes were found to develop. The patient received the same regimen of chemoradiotherapy again, resulting in lymph node disappearance. However, 2 months later, PET-CT revealed accumulation of FDG in the axillary and cervical lymph nodes. Chemoradiotherapy was performed for the third time. Swollen lymph nodes were found to disappear. After 12 months, para-aortic, axillary, and cervical lymph nodes developed, following which she received BSC; subsequently, she died after 38 months of the carcinoma diagnosis.

[A Case of Isolated ACTH Deficiency Induced by Nivolumab in a Patient with Gastric Cancer Metastasis of the Peritoneum].

Nivolumab induces several immune-related adverse events. Isolated adrenocorticotropic hormone(ACTH)deficiency has low frequency. A 73-year-old woman with gastric cancer metastasis of the peritoneum was treated with nivolumab as the third-line chemotherapy. After 5 courses of nivolumab, she developed hypothyroidism. After completing 12 courses, peritoneal metastasis increased. We evaluated the metastasis as progression of disease, so treatment with nivolumab was discontinued. Two weeks after the last dosage of nivolumab, she developed general fatigue and appetite loss. At first, we considered that these symptoms were caused by peritoneal metastasis, but progression was not indicated in the CT. Blood levels of cortisol and ACTH were very low. We suspected secondary adrenocortical insufficiency induced by nivolumab. Endocrinological examinations and the results of brain MRIsuggested isolated ACTH deficiency. This is the first report of isolated ACTH deficiency induced by nivolumab in a patient with gastric cancer metastasis of the peritoneum. The symptoms of adrenocortical insufficiency induced by nivolumab overlap with those of peritoneal metastasis, and thus, it may be difficult to confirm a differential diagnosis. When adrenocortical insufficiency is suspected, we should check the blood levels of cortisol and ACTH.

[A Case of FOLFOXIRI plus BV Therapy Responding to Liver Metastasis of Rectal Cancer with the Portal Venous Tumor Thrombi(Vp4)as Oncologic Emergency].

A 65-year-old woman was diagnosed with simultaneous hepatic metastasis of rectal cancer with portal venous tumor thrombi(Vp3)that developed in the bifurcation of the portal vein. Four days from the first visit, abdominal dynamic contrastenhanced CT image on the portal venous phase shows that the tumor thrombi progressed in the main trunk of the portal vein (Vp4). We decided that it was a condition of oncologic emergency and initiated FOLFOXIRI plus BV therapy. After 12 courses, tumor shrinkage and regression of the portal venous tumor thrombi were achieved, but conversion surgery was impossible because the collateral circulation of the hepatic portal region remained. The treatment target was changed to the extension of the survival period. The initiation and reinitiation of FOLFOXIRI plus BV therapy and maintenance of 5-FU/l-LV plus BV therapy contributed to disease control in 24 months and survival period of 36months.

Epithelial to mesenchymal transition might be induced via CD44 isoform switching in colorectal cancer.

BACKGROUND: Isoform switching of CD44 is associated with epithelial to mesenchymal transition (EMT) in several cancers; however, the clinical implications of this remain unclear for colorectal cancer (CRC). METHODS: We measured expression levels of E-cadherin, vimentin, CD44 standard (CD44s) and CD44 variant 9 (CD44v9) transcripts in 14 CRC cell lines and 150 CRC patients. We determined EMT and CD44 status by calculating vimentin/E-cadherin and CD44s/CD44v9 expression ratios, respectively. Associations between EMT status and CD44 isoform switching, and between clinicopathological factors and prognosis were analyzed. RESULTS: CD44s was highly expressed in mesenchymal-type cell lines, while CD44v9 was highly expressed in epithelial-type cell lines. CD44 knockdown resulted in decreased levels of vimentin expression, and significantly reduced proliferation, migration and invasion of cells. In CRC patients, the mesenchymal group and the high CD44 status group exhibited significantly poorer survival than that for the epithelial group (5-year survival; 62.1% vs. 85.5%, P = 0.0085) and the low CD44 status group (5-year survival; 66.1% vs. 85.0%, P = 0.0251). On multivariate analysis, CD44 status was an independent prognostic factor. CONCLUSIONS: The status of EMT and CD44 is a critical prognostic factor, with CD44 isoform switching a possible trigger for EMT in CRC.

The impact of dose/time modification in irinotecan- and oxaliplatin-based chemotherapies on outcomes in metastatic colorectal cancer.

PURPOSE: This study was designed to evaluate (1) the impact of relative dose intensity (RDI) on tumor response and survival outcomes and (2) the influence of dose reduction and schedule modification on outcomes in patients with metastatic colorectal cancer (mCRC). METHODS: Pooled datasets from two previous phase II trials of FOLFIRI (CCOG-0502; n = 36) and mFOLFOX6 (CCOG-0704; n = 30) in patients with mCRC were analyzed retrospectively. The RDIs of irinotecan and oxaliplatin were compared to response rate (RR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). To assess the effects of dose reduction and schedule modification, the effects of dose index (DI) and time index (TI) on outcomes were evaluated. RESULTS: The median RDIs of irinotecan in FOLFIRI and oxaliplatin in mFOLFOX6 were 80 and 79 %, respectively. Higher RDI of irinotecan in FOLFIRI was associated with significant improvements in RR (65 vs. 6 %, p < 0.01), DCR (100 vs. 59 %, p < 0.01), PFS (9.9 vs. 5.6 months, p < 0.01) and OS (26.7 vs. 12.9 months, p = 0.01) and was the only independent factor associated with PFS [hazard ratio (HR) 8.48, p < 0.01). Higher RDI of oxaliplatin in FOLFOX was significantly associated with DCR (65 vs. 6 %, p < 0.01), and higher TI of oxaliplatin was the only independent factor associated with PFS (HR 2.74, p = 0.04). CONCLUSION: RDIs of irinotecan and oxaliplatin affected clinical outcomes. Dose reductions in irinotecan, as indicated by DI, and time delays in oxaliplatin, as indicated by TI, were the only independent prognostic factors predicting PFS in patients receiving FOLFIRI and FOLFOX6, respectively.