[A Case of Neuroendocrine Carcinoma of the Stomach Treated with TAS-102].

A 77-year-old-woman underwent distal gastrectomy D2 lymph node dissection and cholecystectomy followed by Roux- en-Y reconstruction for Stage ⅢC gastric neuroendocrine cell carcinoma in January 2017. In July of the same year, an abdominal computed tomography scan revealed liver metastasis in segment 4. For treatment of recurrence, SP therapy(S-1 and cisplatin), ramucirumab plus weekly paclitaxel therapy, and nivolumab were administered in that order. TAS-102 was started as the fourth-line agent for multiple liver metastases, para-aortic lymph node metastases, and cancerous peritonitis. Although Grade 2 anemia, Grade 1 oral mucositis and general fatigue were observed during the treatment, both liver metastases and para-aortic lymph node metastases showed improvement after three courses, and the patient was able to continue 11 courses in 1 year. She died 1 year and 5 months after the first administration of TAS-102. TAS-102 can be effective after immune checkpoint inhibitor as a late treatment for gastric cancer and NEC. The appropriate timing for switching drug therapy may be important in the future. We report a favorable therapeutic effect of TAS-102 after immune checkpoint inhibitor treatment along with a review of the literature.

Feasibility of the Reconstruction with Fascia Lata Patch on the Abdominal Wall Defect After Resection of the Abdominal Desmoid Tumor.

INTRODUCTION: The abdominal desmoid tumor shows invasive development and high local recurrence rate. The primary treatment method is complete removal of the tumor because of the high recurrence rate; however, the problem for the surgeon is the reconstruction of the abdominal wall after resection of the abdominal desmoid tumor. CASE PRESENTATION: A 63-year-old man underwent open drainage and ileostomy for the perforation of ileocecal tumor. After 3 months, he underwent right hemicolectomy and ileostomy closure. Pathological examination revealed no malignancy, and the ileocecal tumor showed the presence of abscess. He noticed a palpable mass in the left abdomen. Enhanced abdominal computed tomography (CT) revealed a large abdominal incisional hernia and an enhanced mass of 40 mm in the left rectus muscle. Needle biopsy was performed and the diagnosis was desmoid tumor. He underwent resection of the desmoid tumor and repair of hernia. We performed wide local resection, with a 2-cm surgical margin. The hernia was repaired by simple closure, and the defect in the left abdomen was repaired with reconstruction using the fascia lata patch through plastic surgery. CONCLUSION: We encountered a case of abdominal wall desmoid tumor combined with a large abdominal incisional hernia. We selected the use of autologous fascia based on the risk of recurrence. The patient has not shown recurrence of incisional hernia or desmoid tumor 22 months after surgery. The use of fascia lata patch can be considered as a satisfactory alternative for such reconstruction cases.

[Effective S-1 plus Oxaliplatin(SOX)Therapy in Two Cases of Advanced Gastric Cancer That Was Difficult to Resect and R0 Surgery Could Be Performed].

Case 1: A 59-year-old man was diagnosed with type 3 gastric cancer cStage Ⅲ(MU, Gre, tub2>por, cT4aN2M0)induced by gastric perforation. The first surgery involving resection of the lesser curvature of stomach lymph node was judged to be difficult, and eventually exploratory laparotomy was performed. He received 3 courses of chemotherapy using S-1 plus oxaliplatin(SOX)(S-1 120mg/m2/day, day 1-14, oxaliplatin 100 mg/m2, day 1, followed by 7 days of rest). He subsequently underwent curative laparotomy gastrectomy plus D2(-No. 10)lymph node dissection, and Roux-en-Y reconstruction. Histological type was judged to be Grade 3. Case 2: A 69-year-old man was diagnosed with type 2 esophageal gastric junctional cancer,(GE, Less, tub2, cT4aN3M1[LYM])of cStage Ⅳ. He received 6 courses of chemotherapy using trastuzu- mab plus S-1 plus oxaliplatin(HER plus SOX)(trastuzumab 8mg/kg[2nd course 6mg/kg], day 1, S-1 120mg/m2/day, day 1-14, oxaliplatin 100mg/m2[5th course 80 mg/m2], on day 1, followed by 7 days of rest). He subsequently underwent laparotomy of the lower esophageal total gastrectomy plus D2(-No. 10, +No. 16, No. 110)lymph node dissection, and Roux-en-Y reconstruction as conversion surgery. Histological type was Grade 3. Both were impressive cases suggesting the usefulness of SOX therapy as a multidisciplinary treatment strategy for advanced gastric cancer.

[Hepatic Portal Vein Gas during Chemotherapy for Esophageal Cancer-A Report of Four Cases].

Case 1, a man in his 70s, was admitted because of a bleeding gastric ulcer during DCF therapy for esophageal cancer(EC). Three days after endoscopic hemostasis, abdominal pain and vomiting occurred.CT revealed hepatic portal venous gas (HPVG).No intestinal necrosis was observed on contrast-enhanced CT.Therefore, we selected a conservative treatment and found improvement.Case 2, a man in his 70s, developed frequent diarrhea during DCF therapy for EC.Case 3, a man in his 80s, developed hematochezie during DCF therapy for EC.Both cases 2 and 3 were diagnosed as HPVG using abdominal ultrasonography.The symptoms were mild, so we selected a conservative treatment and found improvement.Case 4, a man in his 60s, noticed sudden severe abdominal pain during DGS therapy for EC.Plain CT detected HPVG and gas in the small intestinal wall.We suspected intestinal necrosis due to HPVG with peritoneal irritation and performed emergency small intestine resection.We encountered 4 patients who developed HPVG during chemotherapy.The presence of HPVG is a poor prognostic sign, suggestive of intestinal necrosis, but some patients show improvement with conservative treatments.We also discuss previous reviews and reports.

Single-incision laparoscopic ileocecal resection in a 10-year-old child with appendiceal neuroendocrine tumor.

BACKGROUND: In Japan, the majority of gastrointestinal tract neuroendocrine tumors (NETs) have been reported to originate from the rectum, and appendiceal NETs are relatively rare. Preoperative diagnosis is very difficult and it is diagnosed after appendectomy. Pediatric appendiceal NET is a disease with a good prognosis. However, in rare cases, lymph node metastasis could occur and additional resection is required. CASE PRESENTATION: A 10-year-old boy complained of right lower quadrant abdominal pain and underwent an appendectomy under a diagnosis of acute appendicitis in previous hospital. The final diagnosis was appendiceal NET, so he was referred to our department for additional resection. The tumor was found in the base of the appendix and invasively reached the subserosal layer with obvious vascular invasion. His Ki-67 index was 1 to 2%, so we classified it as appendiceal NET G1 according to the WHO 2015 classification. We considered the possibility of a tumor remnant or lymph node metastasis, so we performed single-incision laparoscopy with D3 lymph node dissection. The pathological diagnosis revealed no tumor remnant but metastasis to one lymph node. He was discharged on the 9th postoperative day. There has been no recurrence at 3 years and 7 months after surgery. CONCLUSION: When the tumor size is 10-20 mm, the frequency of lymph node metastasis in some reports is variable, and there is no consensus yet on the indications for additional resection. However, there are definitely a certain number of cases with lymph node metastasis that require additional resection. In the present patient, long-term survival can be obtained by additional resection. At present, factors such as the presence of vascular or lymph node invasion and the malignancy grade and tumor's location must be considered on a case-by-case basis. Although the incidence rate of appendiceal NET is rare, the diagnosis can be made only during postoperative pathological examination; thus, reliable histopathological examination is required.

[Therapeutic Effect and Adverse Events of Ramucirumab in Patients with Gastric Cancer in Our Hospital].

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.

Regulation of cooperative function of the Il12b enhancer and promoter by the interferon regulatory factors 3 and 5.

The regulation of the Il12b gene, encoding the shared p40 subcomponent for IL-12 and IL-23, is critical for innate immune responses and subsequent T cell polarization. This gene is robustly induced upon Toll-like receptor (TLR) stimulation, wherein an enhancer located 10kb upstream of the transcription start site is required for promoter activity; however, the underlying mechanisms that regulate this enhancer in cooperation with the promoter has remained elusive. We show here that the Il12b enhancer contains functional ISREs for recognition by interferon regulatory factors (IRFs), and provide evidence that TLR-activated IRF5 mediates cooperativity of the enhancer with the promoter which also contains ISREs. By contrast, IRF3 activated by cytosolic RIG-I-like receptor (RLR) signaling binds to these ISREs and causes gene suppression. Consistently, IRF5 binding is accompanied with chromatin remodeling of both regulatory regions and the formation of a productive transcriptional complex containing other transcription factors, whereas these events are inhibited by IRF3 binding. We show that the ISREs embedded in the enhancer are indeed critical for its activation by IRF5. We also adduce evidence that the 5' sequences of the enhancer and promoter ISREs, all of which deviate from consensus ISREs, critically affect the function of IRF3. The dual commitment of these IRFs in the regulation of the Il12b enhancer and promoter is unique and may have implications for understanding the evolution of this gene.

Generation of mice deficient in RNA-binding motif protein 3 (RBM3) and characterization of its role in innate immune responses and cell growth.

The activation of innate immune responses is critical to host defense against microbial infections, wherein nucleic acid-sensing pattern recognition receptors recognize DNA or RNA from viruses or bacteria and activate downstream signaling pathways. In a search for new DNA-sensing molecules that regulate innate immune responses, we identified RNA-binding motif protein 3 (RBM3), whose role has been implicated in the regulation of cell growth. In this study, we generated Rbm3-deficient (Rbm3(-/-)) mice to study the role of RBM3 in immune responses and cell growth. Despite evidence for its interaction with immunogenic DNA in a cell, no overt phenotypic abnormalities were found in cells from Rbm3(-/-) mice for the DNA-mediated induction of cytokine genes. Interestingly, however, Rbm3(-/-) mouse embryonic fibroblasts (MEFs) showed poorer proliferation rates as compared to control MEFs. Further cell cycle analysis revealed that Rbm3(-/-) MEFs have markedly increased number of G2-phase cells, suggesting a hitherto unknown role of RBM3 in the G2-phase control. Thus, these mutant mice and cells may provide new tools with which to study the mechanisms underlying the regulation of cell cycle and oncogenesis.