[A Case of Stage â £ Gastric Cancer with Multiple Liver Metastases, Resected Primary Tumor after Chemotherapy, and Alive for 3.5 Years without Recurrence].

A 67-year-old man visited our hospital for epigastric pain. Esophagogastroduodenoscopy(EGD)revealed type 2 gastric cancer from the cardia to the gastric angle, and histopathological examination revealed papillary adenocarcinoma(pap), HER2-positive. Contrast-enhanced CT showed wall thickening mainly in the posterior wall of the gastric body, enlarged lymph nodes that were lumped together with the main lesion, and 8 low-absorption areas with ring shaped contrast effects in both lobes of the liver. The patient was diagnosed as gastric cancer cT4aN(+)M1[HEP], clinical Stage ⅣB. Six courses of capecitabine plus cisplatin plus trastuzumab(XP plus Tmab)therapy and 17 courses of capecitabine plus trastuzumab(X plus Tmab)therapy were performed. After chemotherapy, liver and lymph node metastases disappeared on CT and MRI. EGD showed residual gastric cancer, and the policy was to resect the primary tumor. Laparoscopic total gastrectomy with D2 lymph node dissection was performed. Pathological results showed T1b(SM)depth, no lymph node metastasis, and histologic response was Grade 2a. Six courses of X plus Tmab were administered as postoperative adjuvant chemotherapy, but were discontinued at the patient's request. Currently, 5 years have passed since the first chemotherapy and 3.5 years have passed since the surgery, and the patient is alive without recurrence, suggesting that the conversion surgery may have contributed to the prolonged survival.

[A Case of Postoperative Peritoneal Dissemination Recurrence of CY1 Gastric Cancer with cCR after Nab-PTX Therapy].

A 72-year-old man visited his local doctor for gastric discomfort. Esophagogastroduodenoscopy revealed a type 3 tumor on the gastric antrum, and histopathological examination revealed a moderately differentiated adenocarcinoma(tub2). The patient was referred to our hospital and CT scan revealed wall thickening with contrast effect in the gastric angle but no enlarged lymph nodes in the region. The patient was diagnosed as cT3N0M0, Stage ⅡB gastric cancer and underwent open distal gastrectomy and D2 lymph node dissection. No peritoneal dissemination was observed, but intraoperative laparoscopic cytology showed Class Ⅴ. The patient was diagnosed as CY1 Stage Ⅳ gastric cancer, and treated with S-1 plus Tmab therapy starting 1 month after surgery. One year postoperative follow-up CT revealed recurrence of peritoneal disseminations, and the patient was treated with nab-PTX as a second-line therapy. Tumor shrinkage was achieved steadily, and the peritoneal disseminations disappeared at the CT after 12 courses, resulting in cCR. Thereafter, cCR continued and treatment was terminated at the 17th course. Seven years have passed since the end of chemotherapy, and the patient is still alive without recurrence.

[A Case of Postoperative Recurrence of Liver Metastasis after Gastrectomy for Gastric Cancer-No Recurrence for Five Years after Twice Liver Resections].

The patient was an 89-year-old man. He underwent laparoscopic distal gastrectomy for gastric cancer and was diagnosed as T1bN1M0, Stage ⅠB. Eight months after surgery, a CT scan showed an 18 mm-sized hypodense mass in S6 of the liver, and the patient was diagnosed with recurrent liver metastasis. He was treated with 3 courses of CapeOX therapy, and the response was judged as partial response(PR). Laparoscopic partial hepatic S6 resection was performed for the single liver metastasis. The pathological results showed liver metastasis of gastric cancer. Capecitabine was started as adjuvant chemotherapy. Nine months after surgery for liver metastasis, CT scan showed a 12 mm-sized single tumor in S5 and the patient was diagnosed with recurrent liver metastasis. The patient underwent laparoscopic partial hepatectomy after 3 courses of weekly paclitaxel plus ramucirumab therapy. The pathological result showed liver metastasis of gastric cancer. After the surgery, adjuvant chemotherapy was not administered according to the patient's request. Seven years have passed since the resection of the gastric cancer, and 5 years have passed since the resection of the second liver metastasis, and the patient has not had any recurrence.

Metachronous colorectal liver metastasis that occurred 10 years after laparoscopic colectomy: a case report.

BACKGROUND: Delayed onset of colorectal liver metastasis (CRLM) > 5 years after primary colorectal surgery is rare. Herein, we report a case of delayed-onset CRLM that occurred 10 years after primary surgery, for which laparoscopic hepatectomy was performed. CASE PRESENTATION: A 68-year-old man was admitted to the hospital. His medical history revealed double colon cancer detected 10 years ago, for which laparoscopic colectomy was performed. The pathological tumor-node-metastasis stages were stages I and II. Thereafter, oral floor cancer occurred 7 years after the primary surgery and was curatively resected. The annual follow-up with positron emission tomography-computed tomography (CT) identified a tumor at segment 7/8 (S7/8) of the liver with an abnormal accumulation of fluorodeoxyglucose. Dynamic CT showed a 23-mm tumor, with ring enhancement in the early phase. Magnetic resonance imaging with gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid demonstrated that the tumor had high intensity in T2 weighted sequences and low intensity in the hepatobiliary phase. With a preoperative diagnosis of intrahepatic cholangiocarcinoma or delayed liver metastasis, laparoscopic S7/8 partial resection was performed. The operative time was 324 min, and the intraoperative bleeding volume was 35 mL. The patient was discharged on day 15 without any postoperative complications. Upon histopathological examination, the final diagnosis was CRLM. The patient has survived for 1 year without any recurrence. CONCLUSIONS: It is important to pay attention to the occurrence of delayed-metachronous CRLM.

Nonocclusive mesenteric ischemia during treatment for ketoacidosis associated with acute-onset type 1 diabetes mellitus: A case report.

This case report describes a patient with nonocclusive mesenteric ischemia that developed due to diabetic ketoacidosis. We believe that early diagnosis and intervention may improve the prognosis of nonocclusive mesenteric ischemia that has low vascular risk, with the major risk factor being dehydration due to diabetic ketoacidosis.

Efficacy of upfront hepatectomy without neoadjuvant chemotherapy for resectable colorectal liver metastasis.

BACKGROUND: Hepatectomy for resectable colorectal liver metastasis (CRLM) is recommended. However, the efficacy of upfront hepatectomy without neoadjuvant chemotherapy (NAC) is unclear due to the uncertainty of perioperative systemic chemotherapy. Moreover, it is crucial to predict the prognosis when considering perioperative chemotherapy. This study evaluated the impact of neoadjuvant chemotherapy on the prognosis of patients with resectable CRLM and assessed the usefulness of Beppu's nomogram for predicting prognosis. METHODS: This retrospective study identified 88 consecutive inpatients who underwent primary hepatic resection for CRLM; 58 received neoadjuvant chemotherapy and 30 underwent upfront surgery. Factors associated with recurrence-free survival were identified via univariate and multivariate analysis. Furthermore, propensity score analysis using inverse probability of treatment weighting (IPTW) was performed. RESULTS: On univariate analysis, poor recurrence-free survival was associated with multiple tumors, advanced primary tumor stage, vascular invasion by the primary tumor, a Beppu's nomogram score ≥ 6, and neoadjuvant chemotherapy. On multivariate analysis, a Beppu's nomogram score ≥ 6 and neoadjuvant chemotherapy were independent risk factors for recurrence. Neoadjuvant chemotherapy recipients had a higher incidence of lymph node metastasis and vascular invasion than non-recipients. Propensity score analysis revealed no significant difference in the recurrence-free survival rate between these groups. CONCLUSIONS: Our results show that upfront hepatectomy without neoadjuvant chemotherapy can be considered for resectable CRLM treatment. Beppu's nomogram score can be a tool for predicting the prognosis of patients with CRLM.

[A Case of Rectal Neuroendocrine Carcinoma Treated with Multidisciplinary Therapy but with a Poor Prognosis].

A 70-year-old man presented to our hospital with weight loss. A colonoscopy revealed advanced cancer in the lower rectum. Computed tomography showed a tumor larger than 5 cm in the lower rectum with metastasis to the right lateral lymph node. The patient was diagnosed with advanced locally rectal cancer, and chemoradiotherapy(35 Gy plus S-1)was added after 6 courses of mFOLFOX6, and laparoscopic abdominal perineal resection and right lateral lymph nodes dissection were performed. Histopathological examination revealed endocrine cell carcinoma(pT3[A], pN0, M0, pStage Ⅱa). Four months after the operation, recurrence was found in the pelvis, lymph nodes, and lungs, and he died 9 months after the operation. Neuroendocrine carcinoma is relatively rare, so the further accumulation of cases and establishment of treatment methods are desired.

A multi-institutional feasibility study of S-1/oxaliplatin plus bevacizumab in patients with advanced/metastatic colorectal cancer: the HiSCO-02 prospective phase II study.

PURPOSE: FOLFOX is a standard combination chemotherapy regimen for metastatic colorectal cancer (CRC). 5-Fluorouracil (5-FU) is infused continuously through a pump for 46 h; therefore, replacement of infused 5-FU with oral S-1 would be more convenient for patients. We investigated the efficacy and safety of S-1/oxaliplatin (SOX) plus bevacizumab regimen in a community setting. METHODS: We conducted a phase II clinical study in Hiroshima, Japan. We enrolled individuals aged 20-80 years who had metastatic CRC, an Eastern Cooperative Oncology Group performance status of 0 or 1, assessable lesions, and not received previous chemotherapy. Eligible patients were administered SOX plus bevacizumab (S-1 80 mg/m2/day, day 1-14 orally; and oxaliplatin 130 mg/m2 day 1 i.v., bevacizumab 7.5 mg/kg, day 1 i.v. q3w). The primary endpoint was response rate (RR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Between May 2011 and January 2014, 55 patients (mean age 64 years) were enrolled at 12 institutions. Median follow up duration was 20.2 months (range 1.3-47.1 months). RR was 47.1 % [95 % confidence interval (CI) 33.7-60.6 %]. Median PFS and OS was 9.2 months (95 % CI 7.6-10.8) and 22.5 months (95 % CI 19.4-25.9), respectively. Major adverse events (grade 3/4) were neutropenia (9.3 %), thrombocytopenia (5.6 %), anorexia (18.5 %), and sensory neuropathy (16.7 %). CONCLUSION: These data suggested that SOX plus bevacizumab is effective and capable of being managed in metastatic CRC patients in our community clinical practice.

[A case of advanced gastric cancer effectively treated with weekly paclitaxel as neoadjuvant chemotherapy].

We report a patient with advanced gastric cancer responding remarkably to neoadjuvant chemotherapy consisting of weekly paclitaxel. The patient was a 50-year-old male who had large advanced gastric cancer, suspected of invasion to the duodenum and pancreas and severe lymph node metastasis [cT4 (pancreas), cN2, cH0, cP0, cM0, cStage IV]. He was treated with weekly paclitaxel as neoadjuvant chemotherapy. According to gastroscope and CT findings, a significant tumor reduction was obtained after 3 courses. Therefore, distal gastrectomy with D2 nodal dissection were performed. The histological diagnosis was pT2, pN2, pStage IIIA, and the histological effect of the main tumor was judged to be Grade 2. The patient has now been in good health without recurrence for 3 years after surgery. This case suggests that neoadjuvant chemotherapy with weekly paclitaxel is a potentially effective regimen for advanced gastric cancer.

Post-translational palmitoylation and glycosylation of Wnt-5a are necessary for its signalling.

Wnt-5a is a representative ligand that activates a beta-catenin-independent pathway in Wnt signalling. In the present paper, the roles of the post-translational modifications in the actions of Wnt-5a were investigated. We found that Wnt-5a is modified with palmitate at Cys104 and glycans at Asn114, Asn120, Asn311 and Asn325. The palmitoylation was not essential for the secretion of Wnt-5a, but was necessary for its ability to suppress Wnt-3a-dependent T-cell factor transcriptional activity and to stimulate cell migration. Wnt-5a activated focal adhesion kinase and this activation also required palmitoylation. Wild-type Wnt-5a induced the internalization of Fz (Frizzled) 5, but a Wnt-5a mutant that lacks the palmitoylation site did not. Furthermore, the binding of Wnt-5a to the extracellular domain of Fz5 required palmitoylation of Wnt-5a. These results indicate that palmitoylation of Wnt-5a is important for the triggering of signalling at the cell surface level and, therefore, that the lipid-unmodified form of Wnt-5a cannot activate intracellular signal cascades. In contrast, glycosylation was necessary for the secretion of Wnt-5a, but not essential for the actions of Wnt-5a. Thus the post-translational palmitoylation and glycosylation of Wnt-5a are important for the actions and secretion of Wnt-5a.

Expression of Wnt-5a is correlated with aggressiveness of gastric cancer by stimulating cell migration and invasion.

Wnt-5a is a representative ligand that activates a beta-catenin-independent pathway in the Wnt signaling. Although abnormal activation of beta-catenin-dependent pathway is often observed in human cancer, the relationship between beta-catenin-independent pathway and tumorigenesis is not clear. We sought to clarify how Wnt-5a is involved in aggressiveness of gastric cancer. Abnormal expression of Wnt-5a was observed in 71 of 237 gastric cancer cases by means of immunohistochemistry. The positivity of Wnt-5a expression was correlated with advanced stages and poor prognosis of gastric cancer. Wnt-5a had the abilities to stimulate cell migration and invasion in gastric cancer cells. Wnt-5a activated focal adhesion kinase and small GTP-binding protein Rac, both of which are known to play a role in cell migration. Cell migration, membrane ruffling, and turnover of paxillin were suppressed in Wnt-5a knockdown cells. Furthermore, anti-Wnt-5a antibody suppressed gastric cancer cell migration. These results suggest that Wnt-5a stimulates cell migration by regulating focal adhesion complexes and that Wnt-5a is not only a prognostic factor but also a good therapeutic target for gastric cancer.