[Results of Surgical Treatment for Gastric Cancer in the Elderly Over 85 Years Old].

Although the number of gastric cancers in elderly is increasing with the aging population, the indications of surgical treatment depend on the individual cases and the decisions of doctors. We investigated the outcomes of gastrectomy in elderly patients aged 85 years and older who underwent surgery at our hospital. From 2014 to 2022, 72 cases of gastrectomy were performed in the elderly. The approaches were laparotomy in 28 cases, laparoscopic in 42, and robot-assisted in 2. There were 57 cases of distal gastrectomy, 7 cases of proximal gastrectomy, and 8 cases of total gastrectomy. The median operation time was 200 minutes, and the postoperative hospital stay was 14 days. There were 14 cases of complications of Grade Ⅱ or higher according to the Clavien-Dindo classification. Although intra-abdominal complications were not many, respiratory and circulatory complications were occasionally observed. The median follow-up period was 14.6 months, there were 10 deaths from other diseases. Risk factors for death from other diseases were laparotomy, postoperative complications, and outcomes other than discharging home. Although gastrectomy may be performed safely even in the elderly, it is important to pay attention to the patients' conditions particular to the elderly and to plan the surgery accordingly.

[A Case of Primary Somatostatin-Producing Tumor of the Duodenum with Liver Metastases with Long-Term Survival of More than 20 Years].

A 52-year-old woman underwent esophagogastroduodenoscopy after an abnormal medical examination, which revealed a mass lesion over half the circumference of the superior duodenal angulus. Immunostaining was diffusely positive for somatostatin, synaptophysin, and chromogranin A. A 3 cm-sized mass in the pancreaticoduodenal region and multiple nodular lesions of a few mm in both lobes of the liver were revealed by CT. The diagnosis is primary somatostatin-producing tumor of the duodenum with multiple liver metastases. She underwent gastric jejunal bypass for impaired transit. Afterwards hepatic infusion and systemic chemotherapy were continued, and 5 years passed without progression. When she stopped chemotherapy for 6 months, she started somatostatin analogue therapy because of the increase of the tumors. The tumors did not increase, and 20 years have passed since the start of treatment. We report a case of primary somatostatin-producing tumor of the duodenum with liver metastases that is still alive for a long period of time, with a review of the literature.

[A Case of HER2-Positive Gastric Cancer with Multiple Lung and Liver Metastases Showing Long-Term Survival].

A male patient in his 70s visited our hospital with a complaint of tarry stool. A detailed examination revealed gastric cancer( pap, tub1, HER2[3+]), with multiple lungs and liver metastases. Chemotherapy with 4 courses of capecitabine, cisplatin, and trastuzumab(Tmab)and 4 courses of weekly paclitaxel(wPTX)plus 3w-Tmab were administered, and CR was achieved. Thereafter, Tmab was administered alone; however, local recurrence of the primary lesion was observed 24 months after diagnosis, and treatment with PTX and Tmab was resumed. After 68 months of diagnosis, the recurrent tumor increased in size. Therapy with nab-PTX plus ramucirumab was initiated, following which, the tumor growth was restricted. Eventually, the patient died of another disease after 6 years and 5 months of diagnosis. Chemotherapy for unresectable advanced/recurrent gastric cancer has a remarkable antitumor effect; however, a complete cure with chemotherapy alone is difficult. Therefore, a multimodal treatment, including chemotherapy, surgical treatment, and radiation therapy, is important.

[Intraductal Papillary Mucinous Carcinoma with Penetration in the Colon and Retrograde Infection-A Case Report].

We report a case of intraductal papillary mucinous carcinoma(IPMC)penetrating the colon in an 82-year-old man. He visited our hospital with left upper abdominal pain. Abdominal CT showed IPMC of the pancreatic tail, measuring 7 cm, with tumor penetration to the colon and retrograde infection. After the antibacterial treatment, we performed distal pancreatectomy with colectomy. Pathological examination showed proliferation of adenocarcinoma of the gastrointestinal tract with penetration to the colon. Severe fibrosis and calcification surrounding the invasive cancer cells suggested a long disease duration. Despite adjuvant chemotherapy, he developed recurrence of peritoneal dissemination after 9 postoperative months, and subsequently, systemic chemotherapy was started. As intraductal papillary mucinous neoplasm(IPMN)might penetrate the adjacent organs, leading to a poor prognosis, even over a prolonged time period, IPMN should be followed-up appropriately and resected soon after the suspicion of malignant transformation.

[A Case of Type 4 Ascending Colon Cancer Showing Early Postoperative Lymphangitis Carcinomatosa].

A 56-year-old man was admitted to our hospital because abdominal CT showed wall thickening of the ascending colon. Colonoscopyshowed type 4 colon cancer, diagnosed as poorlydifferentiated adenocarcinoma bybiopsy , with circumferential stenosis. Enhanced CT after admission also showed obstructive ileus and lymphadenopathy leading to a paraaortic lesion, but no other distant metastases were seen. Right hemicolectomywas performed. Histological examination showed poorlydifferentiated adenocarcinoma extending from the hepatic flexure to the terminal ileum, with marked invaded vessels and stromal fibrosis, which was diagnosed as type 4 colon cancer of scirrhous and lymphangiosis types. On the 10th postoperative day, he developed lymphangitis carcinomatosa. Intensive treatment including steroid therapy was not effective, and he died of respiratory failure on the 26th day. Type 4 colon cancer is rare and has very poor prognosis. We report a case and literature review.

[A Case of Type 4 Gastric Cancer with Esophageal Invasion That Responded to Neoadjuvant Chemotherapy Containing S-1 and Oxaliplatin followed by Surgery].

We encountered a case of type 4 gastric cancer with esophageal invasion that responded to neoadjuvant chemotherapy containing S-1 and oxaliplatin(SOX)followed by surgery, which could be curative resection. A 46-year-old man was referred to our hospital because of abnormal upper gastrointestinal series findings. He was diagnosed with type 4 advanced gastric cancer with esophageal invasion, cT4b(diaphragm)N2M0, Stage ⅢC, and 3 courses of neoadjuvant SOX therapy were administered. Adverse events were minor. After NAC, the primary lesion and lymph nodes showed marked reductions on CT; total gastrectomy and subtotal thoracic esophagectomy were performed. The pathological response to NAC was evaluated as Grade 2 in the primary tumor and Grade 3 in the lymph node; overall, NAC showed considerable antitumor effects. The final diagnosis was ypT3N0M0P0CY0H0, StageⅡA, and was judged as curatively resected. Currently, we are continuing to administer adjuvant chemotherapy containing S-1.

[A Case of Multiple Bevacizumab-Related Colonic Perforations during Opioid Use].

We present the case ofa 54-year-old man who had been treated with bevacizumab-containing chemotherapy for a postoperative recurrence of lung cancer for 5 months; he had used opioids for cancer pain in his right lateral chest for 2 months. He was admitted to the hospital because his chest pain had worsened 5 days earlier and he was experiencing a dull pain in his lower abdomen. His condition was recognized as an aggravation of the cancer pain and his opioid dose was increased. He presented with intense abdominal pain 6 days after admission, and we diagnosed gastrointestinal perforations from an abdominal CT scan. Therefore, we undertook an emergency operation. Multiple perforations were seen on the transverse and descending colon; an extensive colectomy and a colostomy were performed. Histopathological findings showed that multiple ulcer perforations and normal mucosa coexisted throughout the resected specimen. Bevacizumab-induced ischemic changes were the suspected cause. When pain control becomes variable during opioid use, conditions such as bevacizumab-related gastrointestinal perforations should be considered, in addition to progression of the cancer pain itself, and the appropriate treatment should be administered.

[A Case of Liver and Pulmonary Metastases from Adamantinoma, a Bone Tumor].

This case involved a 28-year-old man who had undergone surgery and perioperative chemotherapy for an adamantinoma of the right tibia with multiple lung metastases. Sixteen months after the initial diagnosis, CT revealed an 8 cm diameter liver metastasis and right pneumothorax with little change in the lung metastases. Liver resection and partial pneumonectomy were performed. Pathologic findings confirmed that both liver and lung specimens had metastases from the adamantinoma. Dissimilar from the primary lesion with much interstitial tissue and spindle-shaped cells, the liver metastasis had very dense cell proliferation without interstitial tissue and dominant epithelial parts, suggesting a higher malignant potential. If other lesions are under good control, resection of the newly appearing metastasis, which has a higher malignant potential, might improve prognosis. Further accumulation of cases and detailed studies is required.

[Examination of outcomes after conversion surgery for Stage IVGastric cancer in our hospital].

PURPOSE: We examined the outcomes of conversion surgery (CS) for Stage IV gastric cancer performed in our hospital. OBJECTIVE AND METHOD: We retrospectively examined the outcomes of 5 Stage IV gastric cancer patients, for whom surgical excision was possible and CS was performed after induction chemotherapy between January 2010 and December 2013. RESULTS: The median age of the patients who underwent CS was 62 years, and non-recovering factors were as follows: M1 (LYM) for 3 patients, H1 for 1 patient, and P1 for 1 patient. For all patients, the induction chemotherapy regimen consisted only of TS-1+cisplatin (CDDP). Using diagnostic imaging to determine treatment effect, we found that 2 patients showed a partial response(PR)as a result of the induction chemotherapy. As a result of CS, R0 surgery could be enforced to 3 cases and postoperative complications accepted neither. Ef-grade which of the histopathological judging of the chemotherapy were 1a: 4 cases, 2: 1 case. After adjuvant chemotherapy treatment in 3 patients, the median survival time (MST) of the CS patients was 22.5 months. In contrast, the MST of non-CS patients, who received treatments other than CS, was 4 months. These results indicate that the MST for CS patients was substantially longer compared to patients who did not receive CS (p=0.046). CONCLUSION: Although CS in response to Stage IV gastric cancer fully needed to examine selection of a case, the timing of operation introduction, etc. to be successful, a possibility of contributing to a prognosis improvement in a multidisciplinary treatment was suggested.

Clinical features of patients with pancreatic ductal adenocarcinoma with a history of other primary malignancies: A retrospective analysis.

Patients with pancreatic ductal adenocarcinoma (PDAC) that have a history of other primary malignancies are not well documented. The current study therefore aimed to evaluate the clinicopathological characteristics of patients with PDAC with or without a history of other primary malignancies. A total of 102 patients with surgically treated PDAC that presented with or without a history of other primary malignancies were retrospectively analyzed. A total of 25 patients (24.5%) had a history of other primary malignancies (age, with history of other primary malignancy vs. without, 74.2 vs. 68.9 years; P=0.005) and the reason for consultation (P<0.001) differed significantly between the groups with a history of other primary malignancies [HoM(+)] and without a history of other primary malignancies [HoM(-)]. Incidental indications during malignancy follow-up was the most common reason for the diagnosis of PDAC in the HoM(+) group. Conversely, there were no significant differences in the resectability (P=0.645), complete resection rate (P=0.774) and final stage (P=0.474) between the two groups. Disease-free survival was also not significantly different between the two groups (P=0.184). However, overall survival was significantly poorer in the HoM(+) group compared with the HoM(-) group (P=0.003). A history of other primary malignancies was also an independent predictor of poor overall survival (hazard ratio, 2.416; 95% confidence interval, 1.324-4.406; P=0.004). In conclusion, patients with PDAC and a history of other primary malignancies had significantly poorer overall survival than their counterparts, despite no differences in disease-free survival.

NHE5 regulates growth factor signaling, integrin trafficking, and degradation in glioma cells.

Na+/H+ exchanger 5 (NHE5) is enriched in neurons and cycles between recycling endosomes and plasma membranes and transports protons to the endosomal lumen as well as to the extracellular space. Although NHE5 expression is undetectable in normal astrocytes, C6 glioma cells express NHE5 at an elevated level. Using C6 cells as a model, here we demonstrate that NHE5 has an important role in tumor growth and tumor cell proliferation and invasion. Glioma xenografts originating from NHE5-knockdown cells exhibited significantly slower growth than those from NHE1-knockdown cells and control cells. Histological characterization of the migration front of NHE5-knockdown tumors revealed a less invasive and less proliferative appearance than NHE1-knockdown and control tumors. NHE5-knockdown but not NHE1-knockdown led to downregulation of fetal bovine serum (FBS)-induced MET and EGFR signaling. Moreover, depletion of NHE5 but not NHE1 reduced the ability of cells to spread on collagen. We found that NHE5 depletion greatly abrogated endocytic recycling and the protein stability of ß1-integrin, which in part accounted for the defective cell adhesion, spreading, and invasion of NHE5-knockdown cells.

Low-dose eribulin mesylate exerts antitumor effects in gastric cancer by inhibiting fibrosis via the suppression of epithelial-mesenchymal transition and acts synergistically with 5-fluorouracil.

BACKGROUND: Characterized by aggressive proliferation, extensive stromal fibrosis, and resulting drug resistance, peritoneal dissemination in gastric cancer remains associated with poor prognosis. Interaction between cancer and stromal cells accelerates tumor progression via epithelial-mesenchymal transition (EMT), which is one of the major causes of tissue fibrosis, and human peritoneal mesothelial cells (HPMCs) play important roles as cancer stroma in peritoneal dissemination. Transforming growth factor-ß (TGF-ß) has a pivotal function in the progression of EMT, and Smad proteins play an important role in the TGF-ß signaling pathway. Eribulin mesylate (eribulin), a nontaxane microtubule dynamics inhibitor used for the treatment of advanced breast cancer, inhibits EMT changes in triple-negative breast cancer cells. We examined its ability to inhibit tumor progression and EMT changes resulting from the interaction between gastric cancer cells and HPMCs and to act synergistically with 5-fluorouracil (5-FU), a key drug for gastric cancer. MATERIALS AND METHODS: Proliferation of gastric cancer cells and HPMCs isolated from healthy omentum was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Following gastric cancer cell/HPMC coculture, EMT markers were detected by immunofluorescence, immunohistochemistry, and Western blotting; invasion assays were performed; and TGF-ß and Smad phosphorylation were assessed by Western blotting and enzyme-linked immunosorbent assay. A mouse fibrotic tumor xenograft model was established using gastric cancer cell/HPMC cocultures. The effect of eribulin and/or 5-FU was tested in each case. RESULTS: Eribulin significantly suppressed gastric cancer cell proliferation and EMT changes in MKN-45 gastric cancer cells and HPMCs induced by their interaction in vitro. Eribulin inhibited EMT at much lower concentrations (≥0.5 nM for MKN-45 and ≥0.1 nM for HPMCs) than its half maximal inhibitory concentrations (2.2 nM for MKN-45 and 8.1 nM for HPMCs), and this resulted, at least partly, from the downregulation of TGF-ß/Smad signaling. Eribulin administration of ≥0.1 mg/kg suppressed tumor progression (0.1 mg/kg, p=0.02), and fibrosis was inhibited by lower dose (0.05 mg/kg, p=0.008) in the xenograft model. Furthermore, 0.05 mg/kg administration with 5-FU brought about synergistic antitumor effects (p=0.006). CONCLUSION: Low-dose eribulin combined with 5-FU might be a promising therapy for peritoneal dissemination in gastric cancer.