[Two Cases of Long-Term Use of TAS-102 for Unresectable Colorectal Cancer].

TAS-102 has been administered to patients with unresectable colorectal cancer. We initiated TAS-102 administration in 2014 and gradually increased the number of indications. In a global, multicenter, randomized, double-blind, phase III study (RECOURSE study), TAS-102 administration improved overall survival by 1.8 months and progression-free survival by 0.3 months compared with those in the placebo group. However, there are limited clinical reports of long-term administration of TAS-102. We encountered 2 cases of continuous long-term use of the TAS-102 for over 2 years. In our cases, although the cancer had been recognized early as exhibiting slow growth during follow-up, the physical symptoms did not appear for an extended period. Although grade 3 neutropenia was pointed out several times during the follow-up term, severe digestive symptoms had not occurred. Therefore, the patients could remain motivated to receive the drug. In our cases, the adequate treatment for neutropenia enabled long-term administration of TAS-102; therefore, TAS-102 would be tolerable for patients of colorectal cancer after receiving chemotherapy for an extended period.

Table screen 360-degree three-dimensional display using a small array of high-speed projectors.

We propose a 360-degree three-dimensional display with a table screen, which consists of a small number of high-speed projectors and a rotating screen. Because each high-speed projector is located outside the rotating axis of the screen, multiple projectors can be aligned. The lens shift technique is used to superimpose multiple images generated by all projectors on the rotating screen. The screen has an off-axis lens function such that the rotation of the screen generates numerous viewing points on a circle. The use of multiple projectors enables an increase in the number of colors, an increase in the number of viewing points, and a reduction in the screen rotation speed. We develop an image synthesis technique for the proposed display system. A color display system employing three high-speed projectors is demonstrated.

Laparoscopic total gastrectomy for multiple sporadic gastric gastrointestinal stromal tumors: report of a case.

A 64-year-old man was admitted to our hospital with hematemesis. Emergency upper gastrointestinal endoscopy revealed bleeding from a submucosal tumor (SMT) in the antrum of the stomach, with two other SMTs at different sites. Based on his family history, we diagnosed familial multiple gastric gastrointestinal stromal tumors (GISTs) and performed laparoscopic total gastrectomy. Three distinct tumors were found: one in the fornix, one in the lesser curvature of the angle, and one in the antrum of the stomach. Microscopic examination of the resected specimens revealed different cytomorphologies, of the spindle and epithelioid type, as well as immunophenotypes in the tumors. Mutation analysis revealed different sites of mutation in c-kit and PDGFRA. No mutation was detected in the normal tissue of the stomach. These findings confirmed a diagnosis of multiple sporadic gastric GISTs. Thus, investigating germline mutation might assist in the preoperative diagnosis of multiple gastric GISTs.

[Advanced breast cancer in a patient achieving long-term SD after letrozole administration for liver metastasis developing during anastrozole therapy].

We report a 69-year-old woman with breast cancer who was effectively treated with letrozole as a second-line therapy after becoming resistant to anastrozole. Her chief complaint at presentation was back pain. Physical examination and imaging studies showed a left breast tumor with skin invasion, multiple intramammary lesions, enlarged left axillary lymph node, and multiple bone metastases. Needle biopsy revealed invasive ductal carcinoma(scirrhous carcinoma)that was ER+/PgR+/ HER2-. The administration of anastrozole and bisphosphonate for 13 months resulted in a 33% reduction of the longest diameters of the breast tumors, but a liver metastasis developed. The treatment was changed to letrozole administration from January 2007.T he optimal effect of letrozole as determined by measurement on CT images was long-term SD maintained for about 13 months. No significant side effects were observed, and the QOL was favorable.

Long-term outcomes of incidental gallbladder carcinoma without additional resection: A single institution experiment.

Incidental gallbladder carcinoma (IGC), defined as unexpected malignancy identified in the surgical gallbladder specimen of a cholecystectomy performed for a benign diagnosis, can be difficult to suspect preoperatively. Furthermore, there are valid clinical reasons to defer reoperation for additional resection, particularly in elderly patients. The present study aimed to determine the long-term outcomes and prognostic factors associated with recurrence in patients with IGC. The medical records of 678 patients who underwent cholecystectomy at Toyooka Hospital between September 2011 and November 2017 were reviewed. The cases identified to be IGC were retrospectively analyzed to determine patient and histopathological characteristics, surgical details, long-term outcomes and factors associated with cancer recurrence. A total of 22 patients were diagnosed with gallbladder carcinoma following cholecystectomy by histopathological examination, and 12 of these were identified to be IGC. The median age was 80 years (range 70-89 years). Although 6 of the 12 patients with IGC had stage pT2 or pT3 tumors, only 1 patient underwent additional resection. Recurrence occurred in 3 of the 8 patients who did not undergo additional resection and were available for long-term follow-up. Recurrence was not associated with the extent of tumor invasion but may be associated with other histopathological findings, preoperative treatment history and risk factors for recurrence. Furthermore, long-term survival was observed in patients with pT2 and pT3 tumors who did not undergo additional resection. Recurrence was not associated with the extent of tumor invasion but may be associated with other histopathological findings, preoperative treatment history, and risk factors for recurrence. Furthermore, long-term survival was observed in patients with pT2 and pT3 tumors who did not undergo additional resection. Even if it is a progressive IGC case, appropriate preoperative treatment or cholecystectomy without persistence of the carcinoma cell, based on a preoperative image evaluation and a postoperative histopathological examination, may greatly influence the long-term prognosis of IGC.

Extra-gastrointestinal stromal tumor with a large cyst.

Gastrointestinal stromal tumors (GISTs) arising at sites other than the alimentary tract are rare, and they are called extra-GISTs (EGISTs). We report a case of a large EGIST forming a cyst, probably arising in the mesentery of the transverse colon. A 64-year-old Japanese man presented to a hospital with an abdominal tumor forming a large cyst. Intraoperatively, the tumor was neither present in nor in contact with the alimentary tract. It was present in the mesentery of the transverse colon and was attached to the greater omentum and peritoneum, immediately anterior to the body of the pancreas. The tumor was resected with the spleen and a part of the pancreas. Histological examination of the tumor revealed that it belonged to the high-risk category of cystic EGISTs.

Progressive attenuation of myocardial vascular endothelial growth factor expression is a seminal event in diabetic cardiomyopathy: restoration of microvascular homeostasis and recovery of cardiac function in diabetic cardiomyopathy after replenishment of local vascular endothelial growth factor.

BACKGROUND: Diabetic cardiomyopathy (DCM) is characterized by microvascular pathology and interstitial fibrosis, which leads to progressive heart failure; however, the pathogenesis of DCM remains uncertain. METHODS AND RESULTS: Using the streptozotocin-induced diabetic rat model, we evaluated the natural course of DCM over a period of 1 year by serial echocardiography, Western blot analysis for vascular endothelial growth factor (VEGF), endothelial progenitor cell assays, myocardial blood flow measurements, and histopathologic analysis that included terminal dUTP nick end-labeling (TUNEL), capillary and cardiomyocyte density, and fibrosis area. Downregulation of myocardial VEGF expression preceded all other features of DCM and was followed by increased apoptosis of endothelial cells, decreased numbers of circulating endothelial progenitor cells, decreased capillary density, and impaired myocardial perfusion. Apoptosis and necrosis of cardiomyocytes ensued, along with fibrosis and progressive diastolic and then systolic dysfunction. To provide further evidence of the central role of VEGF in the pathophysiology of DCM, we replenished myocardial VEGF expression using naked DNA gene therapy via direct intramyocardial injection of plasmid DNA encoding VEGF (phVEGF165). VEGF-replenished rats showed increased capillary density, decreased endothelial cell and cardiomyocyte apoptosis, and in situ differentiation of bone marrow-derived endothelial progenitor cells into endothelial cells. These anatomic findings were accompanied by significant improvements in cardiac function. CONCLUSIONS: These findings suggest that downregulation of VEGF may compromise microvascular homeostasis in the myocardium and thereby play a central role in the pathogenesis of DCM.

Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia.

BACKGROUND: We investigated whether catheter-based, intramyocardial transplantation of autologous endothelial progenitor cells can enhance neovascularization in myocardial ischemia. METHODS AND RESULTS: Myocardial ischemia was induced by placement of an ameroid constrictor around swine left circumflex artery. Four weeks after constrictor placement, CD31+ mononuclear cells (MNCs) were freshly isolated from the peripheral blood of each animal. After overnight incubation of CD31+ MNCs in noncoated plates, nonadhesive cells (NA/CD31+ MNCs) were harvested as the endothelial progenitor cell-enriched fraction. Nonadhesive CD31- cells (NA/CD31- MNCs) were also prepared. Autologous transplantation of 10(7) NA/CD31+ MNCs, 10(7) NA/CD31- MNCs, or PBS was performed with a NOGA mapping injection catheter to target ischemic myocardium. In a parallel study, 10(5) human CD34+ MNCs, 10(5) human CD34- MNCs, or PBS was transplanted into ischemic myocardium of nude rats 10 minutes after ligation of the left anterior descending coronary artery. In the swine study, ischemic area by NOGA mapping, Rentrop grade angiographic collateral development, and echocardiographic left ventricular ejection fraction improved significantly 4 weeks after transplantation of NA/CD31+ MNCs but not after injection of NA/CD31- MNCs or PBS. Capillary density in ischemic myocardium 4 weeks after transplantation was significantly greater in the NA/CD31+ MNC group than the control groups. In the rat study, echocardiographic left ventricular systolic function and capillary density were significantly better preserved in the CD34+ MNC group than in the control groups 4 weeks after myocardial ischemia. CONCLUSIONS: These favorable outcomes encourage future clinical trials of catheter-based, intramyocardial transplantation of autologous CD34+ MNCs in the setting of chronic myocardial ischemia.

Intramuscular metastasis from gastric cancer.

Skeletal muscle is an uncommon site of hematogenous metastasis of gastric carcinoma. We report here a rare case of gastric carcinoma with multiple intramuscular metastases. Our patient had advanced gastric carcinoma and complained of left gluteal induration with tenderness. Because magnetic resonance imaging (MRI) revealed that the gluteal tumor showed iso-signal intensity on T1-weighted images and high signal intensity on T2-weighted images, with reticulated texture around the tumor, and the patient had advanced gastric carcinoma, we speculated that the tumor was an intramuscular metastatic tumor from primary gastric carcinoma. There were also multiple intramuscular metastatic lesions in both gluteal muscles on the MRI findings that were not detected by physical examination. Therefore, the patient underwent total gastrectomy with combined resection of spleen, with subsequent chemotherapy. Three months after the operation, we excised the gluteal tumor to alleviate the gluteal pain. Histological examinations confirmed that the gluteal tumor was a metastasis from primary gastric carcinoma.

Expression of cyclooxygenase-2 is associated with carcinogenesis of the lower part of thoracic esophageal squamous cell carcinoma and p53 expression.

Cyclooxygenase (COX) is a key enzyme in arachidonic acid metabolism. Two isoforms of this enzyme have been identified: constitutive COX-1 and inducible COX-2. Recently, expression of COX-2 has been found in several human carcinomas. COX-2 expression may contribute to the synthesis of prostanoids, which relate to carcinogenesis and tumor progression. We investigated the expression of COX-2 in 175 human esophageal squamous cell carcinoma tissues using immunohistochemistry and evaluated the relationship with clinicopathological findings. In addition, due to the known relevance of p53 to carcinogenesis, we evaluated the expression of COX-2 and p53. Interestingly, cancer tissues with high COX-2 expression were found significantly more often in the middle and lower esophagus than in the cervical and upper esophagus (p = 0.0014). No significant differences were observed in other clinicopathological data such as age, sex, histopathological grading, lymphatic invasion, venous invasion, TNM clinical classification and patient prognosis. p53 expression was associated with the expression of COX-2 (p = 0.0122). Our findings suggest that COX-2 may play a role in the development of squamous cell carcinoma in the lower part of the thoracic esophagus.

Expression of cyclooxygenase-2 in primary and remnant gastric carcinoma: comparing it with p53 accumulation, Helicobacter pylori infection, and vascular endothelial growth factor expression.

BACKGROUND AND OBJECTIVES: Cyclooxygenase-2 (COX-2) expression may contribute to the synthesis of prostanoids, which have been related to carcinogenesis and tumor progression. It is well known that the gastric remnant is at greater risk of the development of gastric cancer than is the whole stomach; incidence rates for gastric cardia adenocarcinoma are rising in the United States and Europe. Our objective was to determine the involvement of COX-2 in primary and remnant gastric cancer tissues as well as in adjacent noncancerous mucosa. METHODS: We investigated the expression of COX-2 in 91 human gastric cancer tissue and adjacent noncancerous mucosa samples (40 remnant gastric cancer, 37 gastric cardia cancer, and 14 gastric corpus and antrum cancer), using immunohistochemistry. In addition, p53 expression, Helicobacter pylori infection, and vascular endothelial growth factor in the tissues were evaluated by immunohistochemical staining and compared with COX-2 expression. RESULTS: There were no significant differences in clinicopathological data in the gastric cancer tissues. There was a significant relation between the expression of COX-2 and p53 in gastric cancer tissues (P = 0.0048). However, vascular endothelial growth factor expression and Helicobacter pylori infection showed no correlation with the expression of COX-2. In the case of adjacent noncancerous mucosa, the positive rate of COX-2 expression was significantly higher in the remnant gastric cancers (75.0%) than in the primary gastric cancers (25.5%) (P < 0.0001). CONCLUSIONS: This information may help in the analysis of the carcinogenesis of gastric cancer; there is also a possibility that the COX-2 selective inhibitor to the remnant gastric cancer has a chemopreventive effect.