Anthracycline-based hepatic arterial infusion chemotherapy achieved 17 months of disease regression in a patient with breast cancer liver metastases resistant to multiple systemic chemotherapies.

Hepatic arterial infusion chemotherapy (HAIC) for liver metastases (LMs) from breast cancer is not a standard of care, but its effectiveness in patients with extensive LMs who cannot tolerate systemic therapy has been reported. Herein, we report a case of breast cancer LMs that were controlled by anthracycline-based HAIC. A 46-year-old woman with estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer who had multiple LMs and bone metastases underwent seven lines of systemic therapy (paclitaxel/bevacizumab for 38 months; letrozole, nivolumab/fulvestrant, eribulin, gemcitabine/vinorelbine, high-dose toremifene/abemaciclib, and capecitabine for 21 months in total). However, owing to its adverse effects and the continued progression of the LMs, systemic therapy was switched to HAIC (40 mg/body epirubicin on day 1, 4 mg/body mitomycin C on days 1 and 15, and 500 mg/body 5-fluorouracil on days 1, 8, and 15; 28-day courses). In response to HAIC, the LMs remarkably regressed and were controlled for 17 months without severe adverse effects. HAIC was stopped when multiple brain metastases arose, and the patient died 2 months later. This case suggests that HAIC is a reasonable option for patients with extensive LMs, even in the late stage of treatment. HAIC recipients should be carefully selected through multidisciplinary discussions as the survival benefits of HAIC over systemic treatment remain unclear. Our findings identify a potential window for the use of traditional chemotherapeutic agents such as anthracyclines. Novel strategies to improve drug delivery are warranted in the future.

A case of rapidly progressing sarcomatous intrahepatic cholangiocarcinoma with suddenly appearing lymph node metastasis.

BACKGROUND: The sarcomatous variant of carcinoma is relatively rare in intrahepatic cholangiocarcinoma (ICC). Sarcomatous ICC (SICC) is associated with a poorer prognosis compared with ICC. SICC is rarely diagnosed before surgery due to non-descriptive findings; it progresses rapidly, resulting in miserable prognosis. Here, we report a case of rapidly progressing SICC that showed a clinically significant tumor growth rate. CASE PRESENTATION: A 77-year-old woman who had undergone ileocecal resection for cecal cancer 5 years previously was found to have elevated levels of the tumor marker carbohydrate antigen 19-9. Although an abdominal computed tomography (CT) scan did not detect any liver mass lesions until 3 months before this serum examination, the subsequent CT scan revealed a hypodensity 20 mm mass lesion in the right anterior section. Contrast-enhanced CT and magnetic resonance imaging revealed peripheral enhancement in the arterial-to-equilibrium phase. Fluorodeoxyglucose positron emission tomography revealed uptake in the lesion. None of the imaging modalities showed lymph node swelling or distant metastases. She underwent hepatectomy under the diagnosis of ICC or an atypical metastasis from previous cecal cancer. Although preoperative images showed no suspicious lymph node metastasis 3 weeks prior, the hilar lymph node swelled 3 cm and contained adenocarcinoma. Consequently, the patient underwent right anterior sectionectomy and lymph node dissection of the hepatoduodenal ligament. Histopathological examination revealed that the liver tumor was a poorly differentiated adenocarcinoma with sarcomatous pattern. While the patient received adjuvant gemcitabine and S-1 therapy, lymph node metastasis appeared in the mediastinum 13 months after the surgery. She received gemcitabine + cisplatin + S-1 therapy but died 20 months after surgery. CONCLUSION: SICC and lymph node metastasis clinically appeared within 3 months and 3 weeks, respectively. Suspected ICC that rapidly progresses should be considered SICC and treated with early resection. SICC is often missed in clinical diagnosis and has a poor prognosis, even after curative resection. While an alternative strategy involving preoperative biopsy and neoadjuvant therapy may be beneficial, it should be approached with discretion due to the potential risks of tumor progression and peritoneal dissemination.

Propensity Score Matching Analysis of the Safety of Completion Total Pancreatectomy for Remnant Pancreatic Tumors Versus that of Initial Total Pancreatectomy for Primary Pancreatic Tumors.

BACKGROUND: The safety and feasibility of completion total pancreatectomy (TP) for remnant pancreatic neoplasms remain controversial and are rarely compared with that of initial TP. Thus, we aimed to compare the safety of these two procedures inducing a pancreatic state. METHODS: Patients who underwent TP for pancreatic neoplasms between 2006 and 2018 at our institution were included in this study. Tumor pathologies were classified into three subgroups according to survival curves. We used 1:1 propensity score matching (PSM) to analyze age, sex, Charlson Comorbidity Index, and tumor stage. Finally, we analyzed the primary outcome Clavien-Dindo classification (CDC) grade, risks of other safety-related outcomes, and the survival rate of patients with invasive cancer. RESULTS: Of 54 patients, 16 underwent completion TP (29.6%) and 38 (70.4%) underwent initial TP. Before PSM analysis, age and Charlson Comorbidity Index were significantly higher, and T category and stage were significantly lower for the completion TP group. Upon PSM analysis, these two groups were equivalent in CDC grade [initial TP vs. completion TP: 71.4% (10/14) vs. 78.6% (11/14); p = 0.678] and other safety-related outcomes. Additionally, while the overall survival and recurrence-free survival of patients with invasive cancer were not significantly different between these two groups, the T category and stage tended to be remarkably severe in the initial TP group. CONCLUSIONS: PSM analysis for prognostic factors showed that completion TP and initial TP have similar safety-related outcomes that can be used as a decision-making reference in the surgery of pancreatic tumors.

Antagonist of sphingosine 1-phosphate receptor 3 reduces cold injury of rat donor hearts for transplantation.

Cold storage is widely used to preserve an organ for transplantation; however, a long duration of cold storage negatively impacts graft function. Unfortunately, the mechanisms underlying cold exposure remain unclear. Based on the sphingosine-1-phosphate (S1P) signal involved in cold tolerance in hibernating mammals, we hypothesized that S1P signal blockage reduces damage from cold storage. We used an in vitro cold storage and rewarming model to evaluate cold injury and investigated the relationship between cold injury and S1P signal. Compounds affecting S1P receptors (S1PR) were screened for their protective effect in this model and its inhibitory effect on S1PRs was measured using the NanoLuc Binary Technology (NanoBiT)-ß-arrestin recruitment assays. The effects of a potent antagonist were examined via heterotopic abdominal rat heart transplantation. The heart grafts were transplanted after 24-hour preservation and evaluated on day 7 after transplantation. Cold injury increased depending on the cold storage time and was induced by S1P. The most potent antagonist strongly suppressed cold injury consistent with the effect of S1P deprivation in vitro. In vivo, this antagonist enabled 24-hour preservation, and drastically improved the beating score, cardiac size, and serological markers. Pathological analysis revealed that it suppressed the interstitial edema, inflammatory cell infiltration, myocyte lesion, TUNEL-positive cell death, and fibrosis. In conclusion, S1PR3 antagonist reduced cold injury, extended the cold preservation time, and improved graft viability. Cold preservation strategies via S1P signaling may have clinical applications in organ preservation for transplantation and contribute to an increase in the donor pool.