[A case of extensive digestive tract metastasis from invasive lobular carcinoma of the breast].

A 59-year-old female patient underwent surgery for invasive lobular carcinoma of the right breast 12 years ago. The final diagnosis was invasive lobular carcinoma (T4N1M0 stage IIIB). She underwent chemotherapy, radiotherapy, and hormonal therapy after surgery. She had abdominal bloating and vomiting 12 years after surgery. Contrast-enhanced computed tomography (CECT) and esophagogastroduodenoscopy showed edematous thickening from the stomach to the duodenum and moderate amounts of ascites. Lymph node metastasis was not observed. Biopsy specimens of the stomach revealed signet ring cell carcinoma. Immunochemical studies (ER, GCDFP-15, MUC1, MUC5AC, and MUC6) confirmed gastroduodenal metastasis of invasive lobular carcinoma. Ascites disappeared after she underwent chemotherapy with paclitaxel and bevacizumab; however, wall thickening had spread from the lower esophagus to the stomach, small intestine, colon, and rectum on the CECT. She died 7 months after the diagnosis of gastroduodenal metastasis. Herein, we report a case of invasive lobular carcinoma of the breast with extensive digestive tract metastasis.

[A Case of Jejunal Ectopic Pancreatic Cancer with Intestinal Perforation].

This patient was a 96-year-old woman. She was referred to our hospital with abdominal pain and vomiting. The levels of the tumor markers CEA and CA19-9 were elevated, at 39.47 ng/mL and 918.5 U/mL, respectively. She was diagnosed with peritonitis with digestive tract perforation by abdominal CT and an emergency operation was performed. At laparotomy, dirty ascites was observed in the peritoneal cavity. A perforation, 1 cm in diameter was found in the jejunum 15 cm from the Treitz ligament, and a mass, 2 cm in diameter was also palpated on the mesentery side. We performed jejunectomy including the tumor. The submucosal tumor was 2 cm in size and the mucosal surface of the perforation was ulcerated. Pathohistological inspection of the extracted sample revealed no heteromorphism in the small intestine mucosal plane. A moderately differentiated adenocarcinoma was diagnosed in the submucosal layer of the heterotopic pancreas of Heinrich typeⅡ. No tumor cells were found in the perforation. Thirteen previous cases of ectopic pancreatic cancer have been reported and this was the 14th case.

[Risk factors for tumor recurrence after curative resection in patients with Stage IIIa colon and rectosigmoid cancer].

PURPOSE: The aim of this study was to elucidate the risk factors for recurrence of Stage IIIa colon and rectosigmoid cancer. PATIENTS AND METHODS: The subjects were 93 patients with Stage IIIa colon and rectosigmoid cancer who underwent radical colectomy in this department between 2001 and 2011. Various risk factors for recurrence were examined. RESULTS: The overall recurrence rate was 18% (17/93 cases). Univariate analysis identified a risk factor for recurrence: depth of tumor invasion( ≥serosa exposed[ SE])(hazard ratio[ HR] 10.04, 95% confidence interva[l CI] 3.26-30.89, p<0.0001). The rate of 1, 2, and 3-year relapse-free survival of patients with respect to the depth of tumor invasion( ≥SE) were 76%, 61%, and 56%, respectively. CONCLUSION: Tumor depth SE or serosa infiltrating( SI) was a risk factor for the recurrence of Stage IIIa colon and rectosigmoid cancer.

[A case of lethal interstitial pneumonia after neoadjuvant chemotherapy for advanced gastric cancer].

We report a case of lethal interstitial pneumonia that occurred after neoadjuvant chemotherapy for advanced gastric cancer. A 76-year-old man with no history of interstitial pneumonia received 2 courses of S-1 (100 mg/body) following 1 course of S-1 plus cisplatin( CDDP) from June 2012. He complained of dyspnea on exertion 6 days after completion of the treatment. Chest radiography and computed tomography (CT) revealed diffuse interstitial lesions in bilateral lung fields. Bronchoalveolar lavage( BAL) revealed an increased number of lymphocytes and leukocytes. Transbronchial lung biopsy (TBLB) revealed interstitial pneumonia with fibrous thickening in the alveolar septum. The drug lymphocyte stimulation test (DLST) was positive for S-1 and negative for CDDP. These results suggested that S-1 had induced interstitial pneumonia. Steroid therapy( 40 mg/day prednisolone following 500 mg methylprednisolone pulse therapy) and an antibiotic agent were administered but were ineffective. He rapidly developed respiratory failure and required tracheal intubation and mechanical ventilation on hospital day 24, and died on hospital day 38.

The Evaluation of Lipoma Arborescens with Intermittent Knee Joint Effusion Based on an Analysis of Serum Cytokine Levels and an Immunohistological Examination: A Case Report.

We herein report a 27-year-old woman who presented with recurrent knee pain. Laboratory findings revealed minimal inflammation. Arthrography revealed structures resembling adipose tissues. Magnetic resonance imaging showed a high signal intensity of these structures, leading to the diagnosis of lipoma arborescens (LA). Synovectomy was performed. Pathology revealed adipocyte proliferation and B-cell clusters but no T-cell infiltration. A serum cytokine analysis revealed low levels of interleukin-6 and tumor necrosis factor-α compared with patients with rheumatoid arthritis. The pathogenesis of LA remains unclear, but immunostaining and serum cytokine levels may provide valuable data for future investigations.

A case of arteriovenous malformation in the inferior mesenteric artery region resected surgically under intraoperative indocyanine green fluorescence imaging.

INTRODUCTION AND IMPORTANCE: An arteriovenous malformation (AVM) is defined as a vascular malformation with a short, non-capillary communication between the arteries and veins. Most gastrointestinal AVMs are solitary, occurring predominantly in the stomach, small intestine and right colon, and rarely in the inferior mesenteric artery (IMA) region. CASE PRESENTATION: A 70-year-old man was first diagnosed with ischemic enteritis two years earlier, and was hospitalized several times with the same diagnosis. He visited our hospital because of left lower abdominal pain and melena. Colonoscopy showed findings suggestive of ischemic enteritis, and contrast-enhanced computed tomography (CT) and IMA angiography showed hyperplasia and dilation of blood vessels from the sigmoid-descending colon junction to the upper rectum. We performed conventional laparoscopic low anterior resection using intraoperative intravenous injection of indocyanine green (ICG). The final diagnosis was arteriovenous malformation in the IMA region. The patient had an uneventful postoperative course and was discharged on the 13th day after the operation. CLINICAL DISCUSSION: Cases of AVM in the IMA region are relatively rare. This is the first reported case of AVM in the IMA region that was resected under intraoperative ICG fluorescence imaging (FI), which provided useful information on the extent of intestinal resection and mesenteric dissection required, and confirmed the adequacy of intestinal blood flow during and after mesenteric dissection and anastomosis. CONCLUSION: It is advisable to use ICG FI intraoperatively during resection of AVMs in the IMA region, as with colorectal cancer surgery.

Interaction between adipose tissue stromal cells and gastric cancer cells in vitro.

Adipose tissue exists in the gastric submucosa and subserosa. Thus, adipose tissue stromal cells (ATSCs), which include mesenchymal stem cells (MSCs), seem critical for the progression of gastric cancer but their interaction with the cancer cells is unknown. We demonstrated an interaction between these cells, using immunohistochemistry, Western blot and the collagen gel invasion assay system, in which the adenocarcinoma cells (well and poorly differentiated types, MKN28 and MKN45, respectively) were cultured on a ATSC-embedded or ATSC-non-embedded gel. ATSCs promoted the expression of the growth marker, proliferation cell nuclear antigen but inhibited that of the apoptosis marker, single-stranded DNA, in the cancer cell types. ATSCs accelerated the invasion of only MKN28 into the gel and promoted the expression of mitogen-activated protein kinase (MAPK, pERK-1/2) but decreased that of the molecularly targeted protein, HER2, in the cancer cells. ATSCs did not affect the expression of the prostaglandin biosynthetic enzyme cyclooxgenase-2 (COX-2) in the cancer cells. The COX-2 inhibitor celecoxib did not affect the morphology or invasion of the cancer cells. The cancer cell types in turn promoted the display of the myofibroblast marker, α-smooth muscle actin, whereas they decreased that of some MSC markers, e.g., CD44 and CD105, in ATSCs. The data suggest that (1) ATSCs influence the progression of gastric cancer by increasing their growth/invasion and decreasing their apoptosis through MAPK activation in a COX-2-independent way; (2) ATSCs adversely affect HER2-targeted therapy; (3) the cancer cells induce the cancer-associated myofibroblast phenotype in ATSCs.

The air liquid-interface, a skin microenvironment, promotes growth of melanoma cells, but not their apoptosis and invasion, through activation of mitogen-activated protein kinase.

The air-liquid interface (ALI) is a common microenvironment of the skin, but it is unknown whether the ALI affects melanoma cell behaviors. Using a collagen gel invasion assay, immunohistochemistry, and Western blots, here we show that melanoma cell proliferation in cultures with an ALI is higher than melanoma cell proliferation in submerged cultures. Bromodeoxyuridine (BrdU) uptake, an indicator of cell proliferation, of melanoma cells at the ALI was about 3 times that of submerged cells, while ALI and submerged melanoma cells had similar levels of single-stranded DNA (a marker of apoptosis). The ALI enhanced the expression of Raf-1, MEK-1 and pERK-1/2 components of the mitogen-activated protein kinase (MAPK) cascade, in cells more than the submerged condition did. The increases in BrdU uptake and pERK-1/2 expression promoted by ALI was abolished by the MEK inhibitor, PD-98059. ALI-treated and submerged melanoma cells did not infiltrate into the collagen gel, and they showed no significant difference in the expression of the invasion- and motility-related molecules, matrix metalloproteinase-1 and -9, laminin 5, and filamin A. Our data indicate that the ALI, a skin microenvironment, accelerates the growth, but not the apoptosis or invasion, of melanoma cells through MAPK activation.

[A case of radiation therapy successfully treated liver and lung tumors arising from postoperative cecum cancer].

The patient was an 85-year-old man who underwent a rt-hemicolectomy, cholecystectomy and choledocholithotomy for cecum cancer and bile duct stone. The tumor was a well differentiated adenocarcinoma, type 2 in the Japanese classification of colorectal carcinoma. The tumor was considered to be in stage II (ss, ly2, v0, n (-), P0, H0, M (-)). He did not receive any adjuvant chemotherapy. After 2 years and 3 months from the surgery, an abdominal MRI and an abdominal CT scan revealed a 30 mm hepatic nodule lesion. We diagnosed with liver metastasis of the cecum cancer. The patient refused both surgery and radio-frequency ablation therapy. We chose radiotherapy for liver metastasis. He was given a total dose of 50 Gy/25 fractions. After 3 months from the radiotherapy, the tumor was reduced gradually and tumor marker (CEA) was normalized. The disease was diagnosed as CR because no tumors were detected. There has been no liver recurrence. But after 4 years and 6 months from the surgery, 20 mm lung nodules in rt-lower lung were revealed by chest X-ray. Once more, we chose radiotherapy for lung tumor. He was given a total dose of 66 Gy/33 fractions. At present, the tumor was reduced gradually. There has been no recurrence since his irradiation. If the case was made a good choice, radiation therapy appears to be effective for liver and lung tumors from the colorectal cancer.

[A case of unresectable type 4 gastric cancer which has kept a long-term partial response with adjuvant systemic chemotherapy].

A 69-year-old woman was admitted to our hospital with complaint of epigastric discomfort in February 2006. The detailed examination had revealed type 4 advanced gastric cancer. An exploratory laparotomy was performed for the unresectable case due to peritonitis cartinomatoza. Postoperative S-1 monotherapy (100 mg/body, 4 weeks on, 2 weeks off) was started as an outpatient in April 2006. After 3-course, partial response (PR) was observed for the primary lesion by gastrointestinal endoscopy. In April 2007, the regimen was changed to S-1 (100 mg/body, 3 weeks on, 2 weeks off)+CDDP (60 mg/m2, days 8) combined chemotherapy, then the primary lesion showed a slight increase. Thereafter, the regimen was changed to S-1 monotherapy in March 2008, and S-1+CDDP combined therapy in July 2008 again. PR was kept observed for three years successfully after the exploratory laparotomy. A case of type 4 unresectable gastric cancer was reported that the postoperative chemotherapy of S-1 was effective.

[Two cases of advanced gastric cancer with postoperative severe complications after neo-adjuvant chemotherapy].

We report two cases of advanced gastric cancer with severe postoperative complications after neo-adjuvant chemotherapy (NAC). The first case is a 60-year-old man who was diagnosed as a type 2 advanced gastric cancer with paraaortic lymph node metastases and the elevation of serum CA19-9 level. NAC was started, but no reductions were noted after 3 courses. Palliative total gastrectomy with distal pancreatectomy, splenectomy, cholecystectomy, and partial hepatectomy for T4 gastric cancer exhibiting obstruction were performed in June 2007. On postoperative day 10, abdominal CT scan revealed left subphrenic abscess, then CT-guided percutaneous drainage was performed. A culture of the abscess yielded Candida albicans and Candida glabrata. The second case is a 58-year-old man who was diagnosed as a type 2 advanced gastric cancer with multiple lymph node metastases and the elevation of serum CA19-9 level. NAC were performed, but no reductions were noted. A distal gastrectomy was performed in January 2008. On the first postoperative day, a severe abdominal distension was appeared suddenly and increasingly. An emergency laparotomy was undergone, but no findings of the bowel obstruction were observed. On postoperative day 2, a rise of serum beta-D-glucan level was recognized. Both cases were improved by an antifungal drug therapy.

Seizures and syncope due to complete atrioventricular block in a patient with acute myocarditis with a normal left ventricular systolic function.

A 43-year-old man was admitted to our hospital presenting with seizures and syncope. He had a history of a cold with a fever of 39°C occurring three days earlier. Electrocardiography (ECG) showed complete atrioventricular block (AV block) with a maximum pause of 32 seconds, for which temporary pacing was performed. Echocardiography showed mild hypertrophy of the left ventricle (LV) with a normal ejection fraction of 61%. Coronary angiography showed normal coronary arteries. Then, an endomyocardial biopsy was performed, the results of which indicated a diagnosis of acute myocarditis. After admission, the complete atrioventricular block disappeared together with normalization of the LV wall thickness.

Adipose tissue-organotypic culture system as a promising model for studying adipose tissue biology and regeneration.

Adipose tissue consists of mature adipocytes, preadipocytes and mesenchymal stem cells (MSCs), but a culture system for analyzing their cell types within the tissue has not been established. We have recently developed "adipose tissue-organotypic culture system" that maintains unilocular structure, proliferative ability and functions of mature adipocytes for a long term, using three-dimensional collagen gel culture of the tissue fragments. In this system, both preadipocytes and MSCs regenerate actively at the peripheral zone of the fragments. Our method will open up a new way for studying both multiple cell types within adipose tissue and the cell-based mechanisms of obesity and metabolic syndrome. Thus, it seems to be a promising model for investigating adipose tissue biology and regeneration. In this article, we introduce adipose tissue-organotypic culture, and propose two theories regarding the mechanism of tissue regeneration that occurs specifically at peripheral zone of tissue fragments in vitro.

Effects of extracellular matrices on F9 teratocarcinoma stem cells: a crucial role of type IV collagen in the early stage of differentiation of F9 stem cells.

F9 teratocarcinoma stem cells treated with retinoic acid (RA) differentiate into visceral endoderm, and this process affects the expression of some extracellular matrix (ECM) proteins. As the direct influence of ECM molecules on the differentiation of F9 stem cells has not been studied, we investigated the effects of various ECM proteins on the early differentiation of these cells. Monolayers of F9 stem cells were cultured on dishes coated with various ECM, such as type I or IV collagen, fibronectin, or laminin. They aggregated and formed spheroid bodies in the absence of RA only on type IV collagen. The outer layer cells of the spheroid bodies exhibited numerous microvilli, junctional complexes and mature cell organelles. Alpha-fetoprotein was positive in the outer layer cells. A small amount of laminin was detected in the matrix of the spheroid bodies. These data suggest that type IV collagen promoted the early stage of the differentiation of F9 stem cells without RA. The other ECM molecules failed to induce them to form spheroid bodies. The reversibility of the structure of the spheroid bodies to a monolayer was also examined. When the spheroid bodies were reseeded only on fibronectin- or laminin-coated culture dishes, they broke down and the cells spread to the surface in the absence of RA. The differentiation of F9 stem cells induced by type IV collagen seemed to be reversible and to take place at an early stage of their morphogenesis. These findings suggest that type IV collagen plays an important role in early embryogenesis.

Case of postradiation osteosarcoma with a short latency period of 3 years.

Osteosarcoma is one of the neoplasms that may occur following exposure to radiation. A case of osteosarcoma arising in the craniofacial bone with a short latency period of 3 years after radiotherapy for maxillary squamous cell carcinoma is described. A 64-year-old-man underwent right partial maxillectomy and chemoradiotherapy due to squamous cell carcinoma of his right maxillary sinus. Histologically, the tumor was composed of moderately differentiated squamous cell carcinoma with a component of spindle cell carcinoma. Three years later, osteosarcoma developed in the craniofacial bone within the irradiation field of the first tumor. Detailed histological examination demonstrated that there was no component of osteosarcoma in the first tumor or squamous cell carcinoma in the second tumor. Radiation-induced osteosarcoma usually occurs after a long latency period of more than 10 years after the radiotherapy. In this case, osteosarcoma was possibly a radiation-induced osteosarcoma with a short latency period of 3 years.