[A Case of Spindle Cell Tumor in the Gastric Mucosa Treated with Laparoscopic Local Gastrectomy].

The patient was a 43-year-old man. An upper gastrointestinal endoscopic examination revealed a gastric submucosal tumor(SMT)-like, elevated 8-mm lesion in the greater curvature of the upper body of the stomach. It was diagnosed as spindle cell tumor on the basis of biopsy findings, and a gastrointestinal stromal tumor(GIST)was suspected. Various immunohistochemical staining techniques were used; however, a definitive diagnosis could not be achieved. There was no evidence of distant metastasis even on thoracoabdominal computed tomography imaging; thus, the patient was referred to our department for definitive diagnosis and surgical treatment. Laparoscopic local gastrectomy with concomitant intraoperative gastroscopy was performed. Pathological examination of the resected specimen showed a type Ⅱc-like lesion with a maximum diameter of 6 mm in the mucosal layer along with spindle cell proliferation. Immunostaining was negative for c- kit, DOG1, CD34, S-100, SMA, WT-1, desmin(N), EMA, and keratin(pan)and positive for ß-catenin, Bcl-2, and vimentin; furthermore, low Ki-67(MIB-1)expression was detected. Therefore, GIST, solitary fibrous tumor, leiomyoma, leiomyosarcoma, desmoid tumor, spindle cell carcinoma, and synovial sarcoma were excluded, and an unclassifiable spindle cell tumor arising from the gastric mucosa was diagnosed. The patient has remained recurrence-free for 1 year and 8 months post-operatively and is currently under careful outpatient follow-up.

[A Case of Large Cell Neuroendocrine Carcinoma of the Ampulla of Vater].

An 80-year-old women admitted to our hospital with jaundice. Abdominal contrast-enhanced CT scan revealed an enhanced tumor, measuring 10 mm, at the duodenal ampulla. Upper endoscopy showed a submucosal tumor-like lesion at the duodenal ampulla. Immunohistochemical findings showed positive for chromogranin A and synaptophysin, and neuroendocrine carcinoma was diagnosed. Subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection was performed. The final diagnosis was large cell neuroendocrine carcinoma(LCNEC). Multiple metastases of liver, lung and bone were occurred 14 months after the surgery, and she died 21 months after the surgery. LCNEC of the duodenal ampulla is very rare, and its prognosis is poor.

[A Case of Omental Desmoid Tumor after a Small Bowel Resection for Gastrointestinal Stromal Tumor].

An intra-abdominaldesmoid tumor, especially omentaldesmoid tumor, is rare. Here, we report a case of omentaldesmoid tumor after a smallbowelresection for gastrointestinalstromaltumor (GIST). A 73-year-old man underwent a partial resection of smallbowelfor GIST. He received adjuvant therapy with imatinib due to high risk of recurrence. After 2.5 years of treatment, a follow-up CT showed a 15mm nodule in the omentum near the splenic flexure. We considered the possibility of recurrence and imatinib failure, and laparoscopic tumor resection was performed for differential diagnosis. Immunohistochemicalstaining showed negative for c-kit, CD34, desmin, and S100. However, it was diagnosed as desmoid tumor because of positive b-catenin. Intra-abdominal desmoid tumor should be a differential diagnosis for a new single lesion in patients with GIST.

[A Case of Stage IV Breast Cancer with Extensive Metastasis Successfully Treated with S-1 plus Anastrozole Therapy].

We report the case of a patient in which S-1 plus anastrozole was administered as first-line chemotherapy for Stage IV breast cancer with skin invasion, multiple lymph node metastasis, and lymphangitis carcinomatosis. A 77-year-old woman had a mass destroyed immediately outside the axilla with dry coughs. An 11mm unpalpable mass in the right breast and an axillary mass were confirmed to be scirrhous carcinoma(Luminal type B), respectively, by core needle biopsy. In one course, S- 1(100mg/day)therapy involves taking 2 courses of 14 days of administration and 7 days off the drug. Anastrozole(1mg/ day)was administered daily. After completion of one course, marked shrinkage of the axillary tumor and supraclavicular lymph node, and lightness of coughing was observed. The metastatic lymph nodes and pulmonary metastatic lesions reduced in size by over 30%, as revealed using CT. The adverse event was only grade 1 pigmentation and lacrimation. Ten months later, the self-destructed skin was completely scarred, and metastatic lesions had maintained their reduction in size. According to the results of the SELECT BC study, S-1 as primary chemotherapy for breast cancer is an evidence-based drug that can reduce the decrease in QOL, such as hair loss, and it can be positively selected.

[Long-Term Disease-Free Survival by Curative Resection in a Case of Remnant Gastric Cancer with Peritoneal Recurrence].

The patient was 69-year-old man. For the remnant gastric cancer, partial resection of the remnant stomach with combined resection of mesentery of transverse colon was performed. Pathological diagnosis was adenocarcinoma(tub2>tub1), M, B- 50-AJ, type 3, pT4b(mesentery of transverse colon), pN0, CY0. A CT scan of 6 months after the surgery showed a tumor on the left side abdomen and diagnosed as peritoneal recurrence. Chemotherapy consisted of 1 course of TS-1(100mg/body) plus cisplatin(70mg/body), 4 courses(2 weeks administration and 1 week break)of TS-1(100mg/body), 8 courses of docetaxel(80mg/body). Tumor shrinkage and internal necrosis were observed. Peritoneal tumor was resected 19 months after the first surgery, and partial resection of the invaded transverse colon and jejunum was performed. Pathological diagnosis was metastasis of remnant gastric cancer. After that, it is 61 months since the first surgery and 42 months from the recurrence surgery without relapse.

[A Case of Perforation Peritonitis with Multiple Duodenal and Intestinal Malignant Lymphomas].

Malignant lymphomas of the duodenum and small intestine are relatively rare, but are clinically important, as they may result in perforation peritonitis. Here, we report a case of perforation peritonitis caused by multiple duodenal and small intestinal malignant lymphomas. An 84-year-old man was diagnosed with malignant lymphoma of the duodenum. Although chemotherapy was planned, emergency surgery was performed to treat perforation peritonitis. Laparoscopic observation revealed that the perforation was not in the duodenum, but in the ileum. In addition, numerous lymphoma lesions were revealed throughout the small intestine. Partial resection of the small intestine including the perforation was performed. Primary gastrointestinal malignant lymphoma may exist over multiple digestive tracts and it is necessary to carefully diagnose and treat, even in emergency surgery.

Interaction of Cx43 with Hsc70 regulates G1/S transition through CDK inhibitor p27.

Connexin 43 (Cx43) functions as a cell growth suppressor. We have demonstrated that Cx43 interacts with heat shock cognate protein 70 (Hsc70) for regulating cell proliferation. Hsc70 interacts with CDK inhibitor p27, which regulates the assembly and subcellular localization of cyclin D1-CDK4-p27 complex. However, the involvement of p27 with Cx43-mediated cell cycle suppression is still poorly understood. Here, we report that nuclear accumulation of p27 is reduced by overexpression of Cx43, and that this reduction is restored by co-overexpression with Hsc70. We found that Cx43 competes with p27 for binding to Hsc70, and as a result, decreases the level of Hsc70 in cyclin D1-CDK4-p27 complex, leading to prevention of the nuclear translocation of the complex and the G1/S transition. Collectively, our findings suggest that, in Cx43 up-regulation, which is most likely an emergency measure, Cx43-Hsc70 interaction regulates cell cycle G1/S progression through a novel mechanism by which Cx43-Hsc70 interaction prevents the nuclear accumulation of p27 through controlling the nuclear translocation of cyclin D1-CDK4-p27 complex.

[Two Cases of Colorectal Cancer with Tumor Thrombus in the Inferior Mesenteric Vein].

In colorectal cancer, progression with an intravenous tumor thrombus is very rare. Here, we report 2 cases of colorectal cancer which showed a tumor thrombus in the inferior mesenteric vein (IMV). Case 1: A 69-year-old woman was admitted for the treatment of advanced rectal cancer, and underwent a low anterior resection. Six months of post-operative therapy was carried out with mFOLFOX6, but a metachronous lung metastasis was detected and a lung partial resection was performed. Case 2: A 67-year-old man was admitted for the treatment of advanced sigmoid colon cancer with simultaneous liver metastasis, and underwent a laparoscopic high anterior resection. Four courses of mFOLFOX6+bevacizumab chemotherapy were carried out after surgery, and subsequently he underwent a partial hepatectomy. In both cases IMV tumor thrombus was suspected from abdominal contrast-enhanced computed tomography (CT). Tumor thrombus filling the lumen of the IMV was confirmed on histopathological examination. Colorectal cancer with IMV tumor thrombus is a form of advanced cancer with advanced vascular invasion, and there is a high risk of simultaneous or metachronous hematogenous metastasis. Combined modality therapy should therefore be given to improve the prognosis.

[The Clinical Efficacy of Neoadjuvant Chemotherapy for Borderline Resectable Pancreatic Carcinoma--Report of Two Cases Treated by Curative Pancreatectomy with Portal Vein Resection after Neoadjuvant Chemotherapy].

We report 2 cases of curative resection of pancreatic cancer after neoadjuvant chemotherapy. A 60-year-old woman was diagnosed as having borderline resectable pancreatic ductal adenocarcinoma with invasion of the nerve plexus covering the superior mesenteric artery. The preoperative chemotherapy, 4 courses of gemcitabine and S-1, reduced the volume of tumor; pancreaticoduodenectomy with portal vein resection after chemotherapy resulted in R0 resection. Pathological examination of the resected specimen showed fibroid tissue with myxoid degeneration and mucinous lake surrounded by differentiated adenocarcinoma. A 40-year-old woman was diagnosed as having borderline resectable pancreatic ductal adenocarcinoma with invasion of the common hepatic artery and splenic artery. The preoperative chemotherapy, 4 courses of gemcitabine and S-1, reduced the tumor volume; distal pancreatectomy with portal vein resection after chemotherapy obtained R0 resection. Pathological examination of the resected specimen revealed that the majority of the tumor was fibrotic and necrotic tissue, and few cancer cells remained viable. Neoadjuvant chemotherapy has a potential to increase the rate of R0 resection. Furthermore, preoperative chemotherapy can help avoid unnecessary surgery by allowing time for potential metastasis to become obvious.

Laparoscopic resection for colorectal cancer improves short-term outcomes in very elderly colorectal cancer patients.

BACKGROUND: Laparoscopic-assisted colectomy (LAC) for colorectal cancer has been shown to improve short-term outcomes compared with open colectomy (OC) in colorectal cancer patients. However, there are a few reports that describe the efficacy of LAC in the very elderly population. We investigated whether LAC improves short-term outcomes in elderly patients, especially those 80 years of age or older. METHOD: Eighty-two consecutive elderly (80 years of age or older) patients who underwent either OC or LAC for colorectal cancer were reviewed. Continuous variables were analyzed by the Mann-Whitney U test. Categorical variables were compared by χ tests. RESULTS: Of the 82 elderly patients with colorectal cancer, 34 patients underwent OC and 48 patients had LAC. There were no significant differences in postoperative complications between the 2 groups. LAC demonstrated less blood loss, fewer days on a liquid diet, and a shorter postoperative stay in the hospital than OC. CONCLUSIONS: LAC improved short-term outcomes even in very elderly patients.

Connexin43 functions as a novel interacting partner of heat shock cognate protein 70.

Regulation of connexin43 (Cx43) expression affects cell proliferation, differentiation and apoptosis in a gap junctional intercellular communication (GJIC)-independent manner. However, the underlying mechanisms of Cx43-mediated cell cycle suppression are still poorly understood. To elucidate the molecular mechanism of Cx43-mediated cell cycle suppression, we searched for Cx43 interacting proteins by using a proteomics approach. Here, we have identified a Cx43-interacting protein, heat shock cognate protein 70 (Hsc70). We confirmed that Hsc70 directly binds to the C-terminus of Cx43, whereas Hsc54, a splice variant of Hsc70, does not, that Cx43 competes with cyclin D1 for binding to Hsc70, and that the nuclear accumulation of cyclin D1 is reduced by overexpression of Cx43 in a GJIC-independent manner, which is restored by co-overexpression with Hsc70. As a result, the cell proliferation is regulated by Cx43. Our results suggest that Cx43-Hsc70 interaction probably plays a critical role during G1/S progression.

TGF-ß Signaling Regulates Pancreatic ß-Cell Proliferation through Control of Cell Cycle Regulator p27 Expression.

Proliferation of pancreatic ß-cells is an important mechanism underlying ß-cell mass adaptation to metabolic demands. Increasing ß-cell mass by regeneration may ameliorate or correct both type 1 and type 2 diabetes, which both result from inadequate production of insulin by ß-cells of the pancreatic islet. Transforming growth factor ß (TGF-ß) signaling is essential for fetal development and growth of pancreatic islets. In this study, we exposed HIT-T15, a clonal pancreatic ß-cell line, to TGF-ß signaling. We found that inhibition of TGF-ß signaling promotes proliferation of the cells significantly, while TGF-ß signaling stimulation inhibits proliferation of the cells remarkably. We confirmed that this proliferative regulation by TGF-ß signaling is due to the changed expression of the cell cycle regulator p27. Furthermore, we demonstrated that there is no observed effect on transcriptional activity of p27 by TGF-ß signaling. Our data show that TGF-ß signaling mediates the cell-cycle progression of pancreatic ß-cells by regulating the nuclear localization of CDK inhibitor, p27. Inhibition of TGF-ß signaling reduces the nuclear accumulation of p27, and as a result this inhibition promotes proliferation of ß-cells.

Efficacy of 5-aminolevulinic acid-mediated photodynamic therapy using light-emitting diodes in human colon cancer cells.

5-Aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) (ALA-PDT) is a highly selective treatment for malignant cells. ALA-PDT has the potential to develop into a novel therapeutic strategy for various types of cancer. Recently, light-emitting diodes (LEDs), which are inexpensive, stable and easier to handle compared to lasers, have been used in PDT as a light source. However, in colorectal cancer (CRC), the efficacy of ALA-PDT in combination with LEDs has not been fully assessed. Therefore, in this study, we evaluated the antitumor effect of ALA-PDT using various LEDs in colon cancer cells. The HT-29 human colon cancer cell line was used both in vitro and in vivo. HT-29 cells were seeded in 96-well plates. Following 5-ALA administration, cells were irradiated using LEDs at different wavelengths. Three types of LEDs, blue (peak wavelength, 456 nm), white (broad-band) and red (635 nm) were used. Twenty-four hours after irradiation, the cytotoxic effects of ALA-PDT were measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In order to evaluate the antitumor effect of ALA-PDT in vivo, nude mice were inoculated with HT-29 cells. Xenograft mice were injected intraperitoneally with 5-ALA and irradiated with 3 types of LEDs at a measured fluence rate of 96 mW/cm2 and fluence of 32 J/cm2. Each group comprised 6 mice. ALA-PDT was repeated 3 times at weekly intervals. Tumor weights were measured. Compared to the controls, ALA-PDT using LEDs showed significant antitumor effects in vitro and in vivo. The blue and white LEDs demonstrated greater antitumor effects compared to the red LEDs in vitro and in vivo. In particular, tumor inhibition rates in the blue and white LED groups were approximately 88% to those of the control group in the mouse models. In conclusion, ALA-PDT using LEDs is effective and useful in the treatment of CRC cells. This method could be a novel treatment modality for CRC.

A case of a superficial carcinoma of the esophagus with isolated lymph node metastasis around the abdominal aorta.

Superficial carcinoma of the esophagus with isolated para-aortic lymph node metastasis is quite rare. A 56-year-old female demonstrated a type 0-IIa+IIb lesion in the middle thoracic esophagus on endoscopic examination. Enhanced computed tomography and positron emission tomography demonstrated two swollen lymph nodes on the right side of the inferior vena cava, but did not demonstrate either a primary lesion or regional lymph node metastasis. A retroperitoneal videoscopic lymph node biopsy was thus performed, and the histopathological diagnosis was metastasis of squamous cell carcinoma. Induction chemotherapy was administered with cisplatin/5-FU, and followed by definitive chemoradiotherapy with cisplatin/5-FU plus 60 Gy radiation. The patient showed satisfactory responses in both the primary and metastatic lesions. This is the first case report describing superficial carcinoma of the esophagus with isolated lymph node metastasis around the abdominal aorta. A precise histological diagnosis of the lymph node is quite important in such cases, and an adequate curative effect can be expected.

Secondary torsion of vermiform appendix with mucinous cystadenoma.

Torsion of the vermiform appendix is a rare disorder, which causes abdominal symptoms indistinguishable from acute appendicitis. We report a case (a 34-year-old male) of secondary torsion of the vermiform appendix with mucinous cystadenoma. This case was characterized by mild inflammatory responses, pentazocine-resistant abdominal pain, and appendiceal tumor, which was not enhanced by the contrast medium on computed tomography presumably because of reduced blood flow by the torsion. These findings may be helpful for the preoperative diagnosis of secondary appendiceal torsion.