[Case of Unresectable Gastric Mixed Neuroendocrine Neoplasm(MiNEN)Treated with Chemotherapy].

A 68-year-old man diagnosed with gastric mixed neuroendocrine-non-neuroendocrine neoplasia(MiNEN)concomitant with liver metastasis received chemotherapy using ramucirumab and paclitaxel. A decrease in tumor marker levels and size of the metastatic liver lesions was observed after 3 courses of treatment. However, the patient developed progressive disease after 9 courses of chemotherapy; hence, nivolumab chemotherapy was initiated. Although liver metastases were reduced after 2 courses of nivolumab, the patient developed new liver lesions after 18 courses of treatment; irinotecan, S-1 and oxaliplatin, and trifluridine/tipiracil were then administered. Liver metastases progressed despite changing the regimen, and the patient died 25 months after the initiation of chemotherapy. Gastric MiNEN usually shows poor prognosis, and there is lack of consensus regarding optimal treatment. Ramucirumab and nivolumab are relatively well-tolerated and may be effective for chemotherapy.

[A Case of Metastatic Pancreatic Ductal Adenocarcinoma Successfully Treated with Modified FOLFIRINOX and Concurrent Radiotherapy].

A 70-year-old man with metastatic pancreatic ductal adenocarcinoma(cT4N1bM1, cStage Ⅳ)underwent chemotherapy with modified FOLFIRINOX without any severe adverse event to 20 cycles. In the middle of that, concurrent irradiation toward primary lesion(total dose, 43.2 Gy)was administered. Grade 1 adverse events include anemia, thrombocytopenia, hypoalbuminemia, hypokalemia, alkaline phosphatase increased, hypertension, peripheral sensory neuropathy, fatigue, anorexia and nausea. The relative dose intensities of oxaliplatin, irinotecan and fluorouracil at 6 months after beginning of treatment were 77.6, 84.0 and 88.3 percent, respectively. The total dose of administered oxaliplatin was 825 mg to the square meter. The primary lesion had been stable for the 20 cycles, although peritoneal dissemination had progressively increased in size. For 17 months, opioid was not necessary for the control of abdominal or back pain to the end of third-line treatment. Though safety or clinical benefits of modified FOLFIRINOX plus concurrent radiotherapy for metastatic pancreatic ductal adenocarcinoma have not been reported, in this case, such treatment might contribute to prolong prognosis or prevent developing abdominal or back pain.

[A Case of Malignant Thyroid Lymphoma That Was Difficult to Differentiate from Methotrexate-Associated Lymphoproliferative Disorders(MTX-LPD)].

A female patient in her 60s was going to get treatment for rheumatoid arthritis(RA). Considering the possibility of using biologics, CT examination was performed for screening of malignant diseases. A mass shadow in the left lobe of the thyroid gland was detected. The patient was followed up, and ultrasonography did not reveal any malignant findings. She was treated with methotrexate(MTX), and 1 year later, the thyroid mass was enlarged on CT. Ultrasonography revealed an enlarged hypoechoic region. Fine needle aspiration cytology revealed malignant lymphoma. Excisional biopsy was performed to determine the treatment plan. The pathological diagnosis was follicular lymphoma, and the possibility of methotrexate- associated lymphoproliferative disorders(MTX-LPD)persisted. It was difficult to discontinue MTX because of the high activity of RA. She was treated with rituximab for malignant lymphoma and concurrently with MTX for RA. The thyroid tumor disappeared for 3 months. Four years later, there is no sign of tumor recurrence.

[A Case of Intraductal Apocrine Carcinoma of the Breast].

A female in her 60s who complained of nipple discharge in her left breast for 1 year. A soft mass ill-defined margin in the border of AB area was observed. Mammography showed a focal asymmetric density. Ultrasonography disclosed an irregular heterogenous low echoic lesion in the AB area of her left breast. MRI image showed an enhanced lesion in the inner area. The pathological diagnosis by core needle biopsy was non-invasive ductal carcinoma with apocrine metaplasia. Mastectomy with sentinel lymph node biopsy of the left breast was performed. Post operative histopathological examination revealed intraductal apocrine carcinoma without lymph node metastasis. Estrogen and progesterone receptors were negative. Three years after operation without any adjuvant treatment, she has no recurrence of lesion.

[Investigation of marginal ulcer after pancreatoduodenectomy].

BACKGROUND: Marginal ulcer after pancreatoduodenectomy (PD) is a relatively common complication, but if massive bleeding or ulcer perforation occurs together with the marginal ulcer, this condition may be fatal. OBJECTIVE: To identify the risk factors and management of marginal ulcer after PD. METHODS: In all, 438 patients who underwent PD from 2003 to 2017 were retrospectively reviewed and analyzed. After surgery, all patients were administered a histamine H2 receptor antagonist (H2RA) or a proton pump inhibitor (PPI), which was continued after discharge. Marginal ulcer was diagnosed by endoscopy or surgery. The risk factors for marginal ulcer were then investigated using univariate and multivariate analyses. RESULTS: After a median follow-up time of 2.7 years, 29 patients (6.6%) developed marginal ulcer. Seventeen patients developed marginal ulcer within 1 year after PD, and 7 patients developed marginal ulcer more than 3 years after PD. All 8 patients who underwent surgery for the treatment of marginal ulcer developed acute peritonitis. Two patients with acute peritonitis died within 1 month after surgery. A multivariate analysis found that discontinuation of PPI treatment was the only independent risk factor for marginal ulcer development (P<0.001). In contrast, sex, age, primary disease, procedure, operation time, volume of blood loss, pancreatic texture, development of postoperative pancreatic fistula, postoperative complications, poor glycemic control after PD, and discontinuation of H2RA therapy after PD were not significantly different between the patient group that developed marginal ulcer and the patient group that did not. Sixteen patients were not treated with antacids at the time of marginal ulcer development. The reason for discontinuation of antacids was the decision of the family physician in 8 cases and the decision of the patient in 3 cases. CONCLUSION: Marginal ulcer can still develop a long time after PD, and sometimes, it may be fatal. PPI administration should be continued even after a long time has passed, although this therapy is often discontinued for various reasons. It is therefore important for family physicians and patients to recognize the danger of marginal ulcer after PD.

[A Case of Unresectable Intrahepatic Cholangiocarcinoma Successfully Treated with Chemoradiotherapy].

A 69-year-old woman with unresectable intrahepatic cholangiocarcinoma(T3N1M1, Stage Ⅳ)underwent chemoradiotherapy with gemcitabine, cisplatin and irradiation toward primary lesion(total dose, 36 Gy). Grade 3 or 4 adverse events include leukopenia, neutropenia, and anemia. The relative dose intensities at 6 months after beginning of treatment were 58.9%(gemcitabine)and 80.2%(cisplatin), respectively. The total dose of administered cisplatin was 525 mg to the square meter. Partial response was obtained, and after that, the representative lesions have been stable with continuous administration of gemcitabine. As some studies have reported clinical benefits of chemoradiotherapy for unresectable intrahepatic cholangiocarcinoma, further clinical investigations are expected.