From January 2016 through December 2017, 18 patients received paclitaxel plus ramucirumab combination therapy and 1 patient received ramucirumab monotherapy. Thus, a total of 19 patients were analyzed in terms of both therapeutic effect and adverse events. The response evaluation of the targeted lesion was as follows; CR: 0, PR: 1, SD: 16, PD: 2. The median of overall survival and progression-free survival of the combination therapy was 9.9 months and 4.2 months, respectively. Although more than half of the patients were enforced after tertiary therapy in our department, the therapeutic effect of paclitaxel plus ramucirumab combination therapy was considerably satisfactory. Neutropenia as an adverse event was observed in 13(68.4%)out of 19 patients, and 8 patients(42.1%)had neutropenia greater than Grade 3. Non -hematologic toxicity was observed in 17 cases(89.5%), and anorexia, nausea, diarrhea, dysgeusia, peripheral neuropathy, hair loss, and fatigue were determined to be either Grade 1 or 2. Alternatively, 1 patient developed Grade 3 interstitial pneumonia, and 3 patients(15.8%)had complicated Grade 3 high blood pressure. Only 2 patients who had severe adverse events, one was interstitial pneumonia and the other was high blood pressure, discontinued paclitaxel plus ramucirumab combination therapy.

Immunological checkpoint inhibitors have effects on various advancedcancers. Nivolumab was approvedfor advanced gastric cancer after third-line treatment in 2017. In our hospital, 10 patients were treatedwith nivolumab from October 2017 to March 2018. Thus, we retrospectively examinedthe clinical background, treatment outcomes, andad verse events of those patients. The median age was 70 years; male-to-female ratio was 6:4; recurrence sites were peritoneal dissemination, liver, lymph nodes, brain, ovaries, and bone(8, 2, 2, 1, 1, and1 , respectively); andtreatment lines were third, fourth, andfifth(in 6, 3, and1 patients, respectively). The minimum number of cycles was 1 course, while the maximum was 11 courses. The best tumor response evaluation was SD, andthe adverse event was an itching sensation in only one patient. It was suggestedthat long-term SD couldbe maintainedwhen the nivolumab treatment was initiatedin a patient with goodPS. In the future, biomarker analysis is expectedto identify effective cases.

A 59-year-old woman was diagnosed with advanced gastric cancer with para-aortic and Virchow's lymph node metastases (L, Less, type 2, tub1, cT3N2H0P0M1[LYM: #16, Virchow's]). Four courses of S-1(80mg/m / 2, days 1-21)and CDDP(60mg/ m2, day 8)were administered. After the chemotherapy, CT showed that the primary tumor and para-aortic and Virchow's lymph nodes had reduced in size. The clinical stage was ycT3N1H0P0M0, stage III A. The patient underwent distalgastrectomy, D2 dissection, and sampling of the para-aortic lymph nodes(#16b1lat, #16a2int). The pathological diagnosis was L, less, type 1, por1/2, pT2N2H0P0M0CY0, pStage III B. The patient was treated with S-1(80mg/m2, days 1-28)as adjuvant chemotherapy. After 3 courses had been administered(6 months after the resection), swelling of a para-aortic lymph node (#16b1int)was detected using CT. Based on the diagnosis of recurrence in the lymph node, weekly paclitaxel(80mg/m2, days 1, 8, and 15)was administered. After receiving 9 courses of weekly paclitaxel, the swelling of the lymph node disappeared, and the response evaluation was complete response. She discontinued the chemotherapy 5 years and 9 months after the surgery. To date, she has survived more than 6 years after surgery without recurrence. We report a long-surviving patient with advanced gastric cancer with para-aortic lymph node metastasis who received combined modality therapy.

We report a case of recurrent colon cancer that achieved partial response with chemotherapy of combined 5-fluorouracil (5-FU), irinotecan, Leucovorin(FOLFIRI), and aflibercept. A 65-year-old man was diagnosed with colon cancer with lymph node metastasis. He underwent surgery, but after 1 year, he had a recurrence of peritoneal dissemination, nodal enlargement, and liver metastases. He received chemotherapy(mFOLFOX plus bevacizumab), but suffered progressive disease. Thereafter, FOLFIRI plus aflibercept was administered, and CT revealed a decrease in peritoneal dissemination after 2 cycles of chemotherapy. After 23 cycles, a PET-CT showed no evidence of the disease. We also examined 9 recent cases treated with aflibercept in terms of Grade 3 and 4 adverse effects, leukopenia, neutropenia, thrombocytopenia, hypertension, and sweating. Placentalderived growth factor(PIGF)has been reported to stimulate macrophages and induce production of IL-6, and thus it promotes inflammation and growth of extant cancer. Among the responses to chemotherapy based on the RECIST criteria, a partial response was significantly higher in patients with a low neutrophil-to-lymphocyte ratio(NLR)(p≤0.05)compared to those with high NLR. As regards the relationship between NLR and OS in patients treated with FOLFIRI plus aflibercept, OS was significantly worse in patients with high NLR than those with low NLR(p≤0.05). NLR may be a useful marker in conjunction with aflibercept treatment.

A 69-year-old man was administered S-1/oxaliplatin/trastuzumab as induction chemotherapy for advanced gastric cancer (cT4b[liver, pancreas], N2M1(H1P0CYX), cStage IV). After 4 courses, because contrast-enhanced computed tomography showed remarkable reduction of the tumor, distal gastrectomy, partial hepatectomy, and radiofrequency ablation for the liver metastasis were performed. The patient was histopathologically diagnosed with gastric neuroendocrine carcinoma(NEC). S- 1/oxaliplatin/trastuzumab was continued after surgery; however, recurrence in the remnant liver was observed after 4 cours- es. For recurrence, cisplatin/irinotecan as first-line and paclitaxel/ramucirumab as second-line treatment were administered, but progression of liver metastasis and ascites due to peritoneal dissemination were observed. As third-line treatment, nivolumab was initiated. Ascites decreased after 3 courses, but after 2 more courses, progression of ascites, liver recurrence, and multiple metastasis in the lumbar vertebra were observed.

We herein report a Stage IV case ofrectal cancer in a patient who achieved stable disease and was treated monthly with fluorouracil(FU)monotherapy plus bevacizumab(Bmab)against relapse after residual tumor resection and withdrawal because ofref usal to continue chemotherapy, even though a marked response was obtained with standard chemotherapy. A 73-year-old woman visited a former hospital in 2014, and was diagnosed with rectal cancer with liver and lung metastases (diagnosed with Rb, T3, M1b[liver, lung]cStage IV). Chemotherapy(mFOLFOX6 plus Bmab)was initiated with a consideration of conversion. After 5 courses, she moved to our hospital. Since she was not aggressive to chemotherapy from the beginning, an imaging examination was performed after 9 courses. The primary lesion and lung metastases had disappeared, and there was only one liver metastasis. Partial hepatic resection was performed to attempt chemotherapy withdrawal following informed consent. Six months after surgery with no therapy, since relapse in the rectum and lungs was confirmed, laparoscopic rectal amputation was performed to control the primary tumor. Chemotherapy containing FU monotherapy plus Bmab was reinitiated after 15 months of withdrawal because liver and lung metastases increased 5 months after rectal amputation. Two months after resuming chemotherapy, the metastatic lesion decreased in size, and the tumor marker level normalized. The same regimen is continued monthly, and the response has been maintained for 17 months(infusions of 5-FU/LV plus Bmab, 18 courses).

A 74-year-old woman was found to have a hepatic mass based on CT findings. She was diagnosed as having cecum cancer, and it was difficult to distinguish whether the hepatic mass was liver metastasis or biliary cystadenocarcinoma. We proceeded with the surgery for cecum cancer, and laparoscopic ileocecal resection with D3 lymph node dissection was performed. The histopathological diagnosis was mucinous adenocarcinoma, and the pathological stage was T3N2H1P0M1a, Stage IV. After the surgery, her CEA level was elevated, and we diagnosed the hepatic mass as a liver metastasis. A CapeOX plus bevacizumab regimen was administered but was discontinued for 2 courses due to the development of adverse effects and her decision. Gd-EOB-DTPA-enhanced MRI revealed a multilocular and lobulated mass, which was a low-intensity area in T1WI and high-intensity area in T2WI, and the mass had no significant contrast effects. These images were unspecific for liver metastasis of colorectal cancer, and we performed segmental 6 hepatectomy for diagnosis and curative surgery. A histopathological diagnosis of liver metastasis of cecum cancer was made. Here, we report a case of liver metastasis of colorectal cancer that was undifferentiated from biliary cystadenocarcinoma.

We report a case of effective treatment comprising mFOLFOX6 plus bevacizumab for neuroendocrine carcinoma of the ascending colon. A 60-year-old woman was admitted for diarrhea and abdominal pain. Colonoscopy showed a Type 2 tumor in the ascending colon. She was diagnosed with neuroendocrine cell carcinoma based on biopsy and immunostaining. CT and MRI showed liver metastasis and lymph node #12a metastasis. Right hemi-colectomy, lymphadenectomy, and partial hepatectomy were performed(T4a, N2, M1b, Stage IV). Neuroendocrine cell carcinoma(small-cell type)was finally diagnosed based on a histological examination because the nuclear fission image was 30(/10HPF)and the Ki-67 index was 42%. Three months after the surgery, multiple lymph node metastases were found using CT and MRI. mFOLFOX6 plus bevacizumab was initiated. After 4 courses of the chemotherapy, the metastases responded completely. A total of 10 courses of chemotherapy were administered. About 2 years and 6 months after the surgery, no recurrence is allowed.

A 57-year-old woman with a history of interstitial pneumonia since 5 years ago was diagnosed with a 10mm diameter tumor during the medical examination and consultation at the hospital. The tumor was palpable in the AC area of her right breast. An ultrasonography showed an irregular-shaped mass. A vacuum-assisted biopsy was performed, and the pathologicaldiagnosis was suspicious for malignancy. Then, we performed an excisionalbiopsy and confirmed the definitive diagnosis of invasive ductalcarcinoma. However, surgicalmargins were positive on the skin and lateralside; therefore, we conducted a two-stage surgery. Interstitialpneumonia was in the active phase, and she was administered sufficient amount of immunosuppressive drugs. Therefore, we performed additionalresection under localanesthesia, not generalanesthesia. Interstitial pneumonia did not worsen perioperatively, and the postoperative course was uneventful. Surgeries performed while the patient is administered with immunosuppressive drugs may cause infections and delayed wound healing. Thus, perioperative complications should be carefully considered.

Endocrine therapy is effective for elderly patients who are diagnosed with estrogen receptor-positive breast cancer and cannot receive surgical treatment or chemotherapy because of advanced age. The duration of response in patients receiving letrozole is approximately 10.3 months. There are few cases with more than 3 years of response. We evaluated the significance of indoleamine 2,3-dioxygenase(IDO)during letrozole therapy in long-term response. We measured IDO activity based on the tryptophan(Trp)/kynurenine(Kyn)ratio. Trp and Kyn levels were measured using high-performance liquid chromatography(HPLC). The Trp/Kyn ratio decreased along with tumor reduction after letrozole therapy. These results suggest that measuring the Trp/Kyn ratio may be useful for evaluating immunological status during endocrine therapy in elderly patients with locally advanced breast cancer.

The neutrophil lymphocyte ratio is reported to be a poor prognostic factor in each carcinoma, and the possibility of predicting the therapeutic effect of chemotherapy, for example, is being studied. In this study, we measured the NLR before and after administration of eribulin and the NLR before and after the final administration in breast cancer patients and examined the relationship with the therapeutic effect.

Although chemotherapy is the standard treatment for unresectable advanced gastric cancer, its prognosis is poor and the median survival time is only around 10 months. With some literature consideration, we report that ovarian metastasis triggered the diagnosis of unresectable advanced gastric cancer with long-term survival through multidisciplinary treatment. This is the case of a 69-year-old woman, who was diagnosed with ovarian tumor and underwent right extracorporectomy and omentum resection in 2011. Pathological diagnosis suspected adenocarcinoma. In February 2012, EGD found a type 4 tumor in the upper portion of the pyloric area of the stomach. She was diagnosed with gastric cancer with Stage IV(T4aN0M1 [ovary])ovarian metastasis. Because the primary tumor was HER2 positive, XP plus HER therapy(capecitabine 1,000mg/m2 twice a day for 14 days, CDDP 80mg/m2 every 3 weeks on the first day, and trastuzumab 8 mg/kg every 3 weeks on the first day)was administered since March 2012. No metastasis was found in the imaging examination after 8 courses of chemotherapy, and we also confirmed the reduction of the primary tumor in the EGD. Based on the images, primary resection was already possible. In December 2012, after a diagnostic laparoscopy, total gastrectomy with D2 lymph node dissection was performed. Postoperative pathology was diagnosed as Stage IV(pT4aN0M1). To control postoperative micrometastasis, capecitabine therapy(1,000mg/m2 twice a day for 14 days)was administered for 12 months starting from February 2013. Then, recurrence and metastasis were not observed during follow-up. However, in January 2017, a circumstellar stenotic tumor was found in the rectum and was diagnosed as recurrence of peritoneal dissemination through images. In February 2017, artificial ostomy(in the sigmoid colon, double-mouth type)was made. Then, the patient underwent an outpatient chemotherapy, with hospital visits, and she survives.

A 47-year-old woman presented with a hard umbilical nodule that appeared red and was painful. A biopsy of the umbilical nodule revealed adenocarcinoma. As a result of general examinations, the patient was diagnosed with umbilical, hepatic, and ovarian metastases from transverse colon cancer. She was treated with S-1 and oxaliplatin(SOX)plus bevacizumab chemotherapy. After 4 courses of chemotherapy, CT revealed that the primary lesion and umbilical and hepatic metastases had reduced in size. We considered this to be a partial response and thus administered 4 additional courses of SOX plus bevacizumab chemotherapy. Finally, she remained well for 22 months and achieved relatively good prognosis. An umbilical metastasis from an internal malignancy is known as a Sister Mary Joseph's nodule, and it has very poor prognosis. Most studies show that the survival period from the time of diagnosis is within 1 year. However, our case suggests that novel anti-cancer drugs or molecular-targeted agents may improve survival.

A 41-year-old woman with type 3 advanced gastric cancer and Virchow lymph node, para-aortic lymph node, and multiple bone metastases was diagnosed with U-less cType 3 cT4aN3M1, cStage IV. We administered docetaxel, cisplatin, and S-1 (DCS)therapy for unresectable gastric cancer. After 11 courses of DCS, we confirmed that the distant lymph node metasta- ses were significantly reduced. We performed radiotherapy(30 Gy/10 Fr)on the thoracic lumber vertebrae. Because the patient was successfully downstaged, we performed total gastrectomy with Roux-en-Y reconstruction. The histopathological diagnosis was ypT3N2M0, ypStage III A. In this case, DCS therapy successfully treated gastric cancer with distant metastases, including multiple bone metastases.

Esophageal carcinosarcoma is a rare malignant tumor. A 76-year-old man consulted near hospital about dysphagia. A gastrointestinal fiberscopy showed a stricture of the thoracic esophagus at approximately 34 cm from the incisor, and the macroscopic type of the tumor was 0-Ip. Biopsy results indicated carcinosarcoma. The patient underwent esophagectomy and regional lymphadenectomy with gastric tube reconstruction by laparoscopy-assisted surgery and thoracotomy. Pathological examination of the surgical specimen revealed that the majority of the tumor was composed of spindle-shaped atypical cells, but because a very small transitional area between squamous cell carcinoma and sarcoma was noted, a diagnosis of carcinosarcoma was made. The depth of invasion was small, and no region lymph node metastasis was detected. We classified the tumor as pT1b(SM)N0M0, pStage I. Immunohistochemically, the spindle-shaped sarcomatous cells displayed a posi- tive reaction to vimentin and cytokeratin AE1/AE3. Ki -67(MIB-1)labeling index was high. The patient was discharged after an uneventful postoperative course and remains well as an outpatient at his 6-month follow-up. We report this case with a review of the literature.

Concomitant myocardial and cutaneous metastases of squamous cell lung cancer after left pneumonectomy are very rare. Although nivolumab is used as a standard second-line chemotherapy for non-small cell lung cancer(NSCLC), its efficacy for concomitant myocardial and cutaneous metastases remains unclear.