[A Resected Case of Long-Term Survival of Pancreatic Cancer with Simultaneous Multiple Lung Metastasis with Systemic Chemotherapy].

The patient was a 78-year-old man with resection of distal pancreatectomy for pancreatic cancer with simultaneous multiple lung metastasis. They were papillary and tubular adenocarcinoma, Pt, TS3, infiltrative type, ly0, v0, pT3, CH0, DU0, S1, RP1, PV0, A1(Asp), PL0, OO0 and pN0, M1(PUL), pStage IV. He was received gemcitabine after the surgery. S-1 was added because of lung metastasis progression. Chemotherapy was continued for about 10 years from resection, and intra-abdominal recurrence was not observed and good performance status was maintained. 5-year survival rate of pancreatic cancer is as low as about 6.5%in Stage IV. There are cases where lung resection to isolated lung metastasis are performed after resection of pancreas and long-term-survival are obtained. A resected case of long-term-survival of pancreatic cancer with simultaneous multiple lung metastasis is rare, so we will report with a few literature considerations.

[Unresectable combined hepatocellular-cholangiocellular carcinoma treated with transcatheter arterial chemoembolization and gemcitabine: a case study].

A 76-year-old female was referred to our hospital because of liver dysfunction. Abdominal contrasted computed tomography (CT) revealed a tumor of 7.5cm in the hepatic hilar area. Based on the biopsy, the tumor was diagnosed by as combined hepatocellular-cholangiocellular carcinoma (with stem-cell features). The tumor was considered unresectable;hence, the patient underwent transcatheter arterial chemoembolization (TACE). However, a CT scan revealed the treatment to be ineffective. Subsequently, systemic gemcitabine (GEM) chemotherapy was administered and tumor shrinkage was observed with reperfusion of the umbilical portion of the left portal vein. The patient's condition is currently stable 17 months after diagnosis, with no tumor regrowth on account of repeated TACE and GEM therapy. The present case of unresectable combined hepatocellular-cholangiocellular carcinoma was successfully treated using TACE and systemic GEM chemotherapy.

Re-evaluation of Phenotypic Expression in Differentiated-type Early Adenocarcinoma of the Stomach.

A total of 313 cases of differentiated-type early gastric adenocarcinomas, including 113 cases of small-sized carcinoma (5< × ≤10 mm) and 121 cases of microcarcinoma (0< × ≤5 mm), were examined immunohistochemically to clarify the phenotypic expressions. They were classified into four categories (gastric phenotype (G-type), intestinal phenotype, gastrointestinal phenotype, and null phenotype) by a two-step process: the phenotype based on an immunoprofile of mucin core proteins (MUCs) with CDX2 (w/.CDX2-assessment); and the phenotype of MUCs only (w/o.CDX2-assessment). CDX2 expression was observed in 89.1% (279/313); it was highly expressed in 87.6% (106/121) of microcarcinomas. MUC2 expression increased as tumor size increased (P < 0.05). Compared with w/o.CDX2-assessment, w/.CDX2-assessment showed significantly fewer G-type carcinomas (P < 0.05). Each phenotype marker was less expressed in the submucosal part than in the mucosal part. In conclusion, CDX2 was a sensitive marker for assessing intestinal phenotype. A large portion of the early differentiated-type adenocarcinomas expressed CDX2 from the very early stage of carcinogenesis, and the proportion of G-type was unexpectedly low. Lower expression of each phenotype marker was considered the cause of phenotype alteration during submucosal invasion.

[Three Cases of Long-Term Survival in Colon Cancer with Postoperative Peritoneal Recurrence].

Case 1 is a 57-year-old man with pelvic recurrence 1 year 8 months after surgery for ascending colon cancer.We performed a Hartmann's operation.He has been relapse-free for 11 years.Case 2 is a 67-year-old man with intraperitoneal small intestinal relapse 4 years after surgery for cecum cancer.We performed resection.He has brain metastases recurrence in 2 years 6 months after surgery, died after 2 years 9 months.Case 3 is a 53-year-old man with recurrence in the bladder rectal fossa 5 years after sigmoidectomy.We performed resection.He has been relapse-free survival at 1 year 2 months.

Mucin phenotype expression of gastric neuroendocrine neoplasms: analysis of histopathology and carcinogenesis.

BACKGROUND: Gastric neuroendocrine neoplasia has been classified as neuroendocrine tumor (NET), a less-malignant type, and neuroendocrine carcinoma (NEC), a more-malignant type. We investigated phenotypic expression profiles to clarify the differences between NET and NEC in terms of histopathology and carcinogenesis. METHODS: We assayed 86 cases of gastric neuroendocrine neoplasms (NET G1, n = 25; NET G2, n = 9; NEC, n = 52), using six exocrine markers (MUC5AC, human gastric mucin, MUC6, M-GGMC-1, MUC2, and CDX2). RESULTS: NEC frequently coexisted with adenocarcinomatous components (75 %; 39 of 52) and the majority (71.8 %; 28 of 39) showed intraglandular endocrine cell hyperplasia, although no cases of NET showed adenocarcinomatous components. Mucin phenotype significantly differed between NET and NEC; none of NET cases expressed any exocrine markers other than CDX2, although the majority of NEC (86.5 %; 45 of 52) expressed at least one or more exocrine markers with various positive rates for each marker (range, 8.2-74.0 %). Each NEC component showed only the phenotype expressed in the adenocarcinomatous component in the same tumor. Furthermore, double immunohistochemistry revealed dual expression of CDX2 and chromogranin A in half the NEC cases (23 of 46). CONCLUSIONS: These data suggest that gastric NETs (G1 and G2) and NECs have different processes of carcinogenesis, and gastric NECs may be generated from preceding adenocarcinomas.

Surgery for non-Meckel's small-bowel diverticular perforation: two case reports and a literature review.

BACKGROUND: Similar to colonic diverticula, small-intestinal diverticula are often asymptomatic, but may cause life-threatening acute complications. Non-Meckel's small-bowel diverticular perforation is rare, and the rate of mortality is high. However, there is currently no consensus regarding its therapeutic management. CASE PRESENTATION: Case 1: A 73-year-old Japanese man with localized lower abdominal pain was referred to our hospital. Enhanced computed tomography (CT) revealed diverticulitis of the small intestine, which was managed conservatively. Four days after admission, abdominal pain worsened, and repeat CT revealed extraintestinal gas. Emergency surgery was performed for the segmental resection of the perforated jejunum with anastomosis. Case 2: A 73-year-old Japanese woman was transferred to our hospital with small-bowel perforation. CT revealed scattered diverticula in the small intestine and extraintestinal gas around the small-intestinal diverticula. Emergency surgery was performed for the segmental resection of the perforated jejunum with anastomosis. CONCLUSIONS: Conservative treatment for small-bowel diverticular perforation may be attempted in mild cases; however, surgical intervention should not be delayed. Segmental resection of the affected intestinal tract with an anastomosis is the standard treatment. Residual diverticula should be documented because of the possibility of diverticulosis recurrence.

Re-evaluation of phenotypic expression in undifferentiated-type early gastric adenocarcinomas using mucin core protein and CDX2.

BACKGROUND: Undifferentiated-type early gastric adenocarcinomas are generally classified into two groups: pure undifferentiated-type adenocarcinomas, which naturally develop as undifferentiated-type without a glandular component; and mixed differentiated/undifferentiated-type adenocarcinomas, which are associated with some vestigial glandular component and presumably develop from differentiated-type adenocarcinoma. The differences in phenotypic expression between these two groups were examined using mucin core protein and CDX2. METHODS: A total of 210 lesions of undifferentiated-type early gastric adenocarcinoma less than 25 mm in diameter were classified into four categories (gastric type, gastrointestinal type, intestinal type, and null type) based on their MUC5AC, MUC6, MUC2, and CDX2 immunoprofiles. RESULTS: Gastric type was significantly (p < 0.01) decreased and gastrointestinal type was significantly (p < 0.01) increased both in pure undifferentiated-type adenocarcinomas and in mixed differentiated/undifferentiated-type adenocarcinomas when CDX2 was applied to mucin core protein. In the pure undifferentiated-type adenocarcinomas, gastric type decreased and gastrointestinal type increased as tumor size increased (p < 0.05). In contrast, in the mixed differentiated/undifferentiated-type adenocarcinomas, gastrointestinal type was most common even in small-sized (≤10 mm) carcinomas and was generally stable regardless of tumor size. In submucosal carcinomas, gastrointestinal type decreased and gastric type and intestinal type increased during carcinoma invasion from the intramucosal to submucosal parts (p < 0.05). The positivity rates for all phenotypic markers, especially gastric markers, tended to decrease during submucosal invasion. CONCLUSIONS: CDX2 is a sensitive marker for assessing intestinal phenotypic expression, and it is likely that there are two different pathways of tumor progression in undifferentiated-type adenocarcinoma of the stomach, according to phenotypic expression.

Hemorrhagic Gastric Metastasis from Hepatocellular Carcinoma Successfully Treated Using Coil Embolization of the Left Gastric Artery.

A 62-year-old man initially underwent transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma (HCC). One year after the initial treatment, he developed anemia. Upper gastrointestinal endoscopy revealed irregularly elevated tumors in the lower anterior gastric body, which were diagnosed to be metastasis from HCC. Left gastric artery coil embolization was performed to prevent sustained bleeding, and his anemia partially improved. In addition to direct invasion, hematogenous metastasis to the stomach from HCC is possible and therefore should be considered during treatment. Transcatheter arterial embolization for gastric metastasis is an effective treatment method which achieves a good degree of hemostasis in patients without any surgical indications.

Genetic changes of p53, K-ras, and microsatellite instability in gallbladder carcinoma in high-incidence areas of Japan and Hungary.

AIM: To disclose geographic differences in genetic changes involved in gallbladder carcinogenesis between two distinct high-incidence areas of Japan and Hungary. METHODS: We examined 42 cases of gallbladder carcinoma: 22 Japanese and 20 Hungarian cases. p53 mutations at exons 5 to 8 and K-ras mutations at codon 12 were tested by direct sequencing. Microsatellite instability was determined from fluorescent dye-labeled PCR amplifications of five-microsatellite markers (BAT-25, BAT-26, D2S123, D5S346, and D17S250). RESULTS: Mutations of p53 were detected in 11 of 22 Japanese cases and 6 of 18 Hungarian cases (11/22 vs 6/18, P = 0.348). Transition at CpG sites was found in none of 11 Japanese cases and 2 of 6 Hungarian cases; the difference was marginally significant (0/11 vs 2/6, P = 0.110). K-ras mutations were detected in only one of the Hungarian cases. Eight of 19 (42.1%) Japanese cases were MSI-high (presence of novel peaks in more than one of the five loci analyzed), whereas only 1 of 15 (6.7%) Hungarian cases was MSI-high (P = 0.047). CONCLUSION: It appears that the p53 mutations and MSI differ in patients with gallbladder carcinoma between two distinct high-incidence areas. Geographic variation might exist in the process of gallbladder carcinogenesis.

Effect of loss of heterozygosity of the c-kit gene on prognosis after hepatectomy for metastatic liver gastrointestinal stromal tumors.

The authors have previously reported that loss of heterozygosity (LOH) of the c-kit gene could be responsible for the gain in high proliferative activity in some gastrointestinal stromal tumors (GIST), resulting in enhanced metastatic potential. In the present study, an attempt was made to identify the factors that might predict the postoperative prognosis of patients with metastatic liver GIST. The clinicopathologic or genetic features of resected liver GIST in 14 patients who had undergone a hepatectomy for metachronous liver metastases and who had not received adjuvant imatinib treatment were examined. LOH of the c-kit gene was observed in seven of 12 metastatic liver GIST (58.3%), of which DNA suitable for testing could be extracted. Ten patients had recurrence after hepatectomy and four had none. The median post-recurrent disease-free survival (PRDFS) after hepatectomy was 27.5 months (range 8-104). The tumor-specific PRDFS was examined using clinicopathologic features, c-kit mutation and LOH of the c-kit gene. No single clinicopathologic or genetic finding was significantly associated with PRDFS. However, patients with 'Ki67 labeling index <5% and LOH(-)' had a significantly longer PRDFS than those with 'Ki67 >/=5% or LOH(+)' (P = 0.032), and there was no correlation between the presence of LOH of the c-kit gene and the Ki67 labeling index. LOH of the c-kit gene in metastatic liver seems to be a common event, and LOH of the c-kit gene in resected liver GIST may be a helpful factor in the prediction of the post-recurrent prognosis of patients with liver metastasis.

Co-expression of gastric and biliary phenotype in pyloric-gland type adenoma of the gallbladder: immunohistochemical analysis of mucin profile and CD10.

Pyloric-gland type adenoma of the gallbladder is formed by proliferation of glands resembling pyloric glands, morphologically. No previous report has described the cellular phenotype and differentiation of pyloric-gland type adenoma of the gallbladder, using CD10 as a marker of proper biliary phenotype. Immunostainings were performed for mucin markers such as MUC5AC, human gastric mucin (HGM) for gastric foveolar type epithelium, MUC6, M-GGMC-1 for pyloric-gland type and MUC2 for intestinal goblet-cell type, and for CD10 as a proper biliary type marker on 58 pyloric-gland type adenomas of the gallbladder, as well as for p53, Ki-67 and CDX2. The percentage (X) of reactive cells in relation to the total number of tumor cells was estimated semi-quantitatively, and divided into four categories: X=0% (negative), 0%or=30%. CDX2 expression was considered to be positive when the percentage of positively stained cells was >or=10%. Out of the 58 pyloric-gland type adenomas, >or=30% of adenoma cells were positive for MUC5AC in 22 (38%) tumors, HGM in 29 (50%), MUC6 in 58 (100%), M-GGMC-1 in 54 (93%), MUC2 in none (0%), and CD10 in 20 (34%). MUC6 (P<0.001) and M-GGMC-1 (P<0.001) mucins were detected more frequently in pyloric-gland type adenomas, and CD10 expression was significantly decreased, compared with normal gallbladder epithelium (P=0.006). P53 overexpression was not found in any of the 58 tumors, including two adenomas with carcinomatous foci. The mean number of Ki-67-positive cells was 10.3+/-5.8%. CDX2 expression was judged as negative in all 58 pyloric-gland type adenomas. In pyloric-gland type adenomas of the gallbladder, expression of pyloric-gland type mucins was observed with a high frequency, whereas intestinal goblet-cell mucins were rarely seen. In addition, co-expression of gastric foveolar type mucins and CD10 was also demonstrated. Pyloric-gland type adenomas of the gallbladder show a differentiation toward pyloric glands in terms of immunohistochemistry, as well as morphology, accompanied by co-expression of gastric foveolar and native biliary phenotypes.

Two cases of gastrointestinal stromal tumor of the stomach with lymph node metastasis.

Lymph node metastasis from gastrointestinal stromal tumor (GIST) is quite rare. We report two cases of gastric GIST with nodal metastases and results of their mutation analyses. In the first case (78-year-old male), a mass 4.0 cm in size was located at the gastric cardia. Proximal gastrectomy was performed. In the other case (40-year-old female), the gastric tumor was 2.5 cm in size. Computed tomography scan revealed a hepatic metastasis. Imatinib mesylate was administered as primary treatment, at the patient's preference, but the tumors exhibited no response. Wedge resection of the stomach and partial hepatectomy were performed. In both cases, histological examination revealed that the tumors consisted of spindle cells. In the former case, there was an isolated lymph node metastasis at the right cardia. In the latter, three of 5 sampled nodes adjacent to the tumor were positive. In both cases, immunohistochemical analyses showed that primary and metastatic tumors were diffusely positive for CD117 and CD34 and negative for desmin and S100-protein. In the former case, there was a deletion mutation in CD117 exon 11, the most common genotype in GIST. In the latter, there were no detectable mutations in CD117 or platelet-derived growth factor receptor alpha.

A case of biatrial multiple myxomas with glandular structure.

A 45-year-old male, who had been indicated by brain magnetic resonance imaging to have cerebral infarctions, was found by echocardiography to have a tumor in the left atrium. He had experienced several of the constitutional disturbances associated with myxoma. At the ages of 19 and 35 he had had two episodes associated with embolisms, and at the later one he was diagnosed as having multiple cerebral aneurysms. He received an urgent operation in which three left atrial tumors and one right atrial tumor were resected. Histologically, the tumors were myxomas, and the left atrial main tumor had glandular structure. In view of his clinical history, this patient seems to have had cardiac myxomas for a long period. The multiple growths that occurred in this case may be a good argument for allowing this condition to last for so long. To our knowledge, the present case was the first report of cardiac myxoma with glandular structure in Japan.

Living-related liver transplantation for multiple liver metastases from rectal carcinoid tumor: a case report.

A 42-year-old woman was admitted to our hospital because of multiple liver tumors detected by ultrasonography. Colonoscopy revealed submucosal tumor in the rectum, which was considered the primary lesion. Endoscopic mucosal resection followed by histopathological examination revealed that the tumor was carcinoid. The resected margin of the tumor was positive for malignant cells. Two courses to transcatheter arterial chemotherapy for liver metastasis were ineffective. Accordingly, the rectal tumor and metastatic lymph nodes were surgically resected. One month after the operation, she received liver transplantation (left lateral segment and caudate lobe) from her son. No recurrent lesion has been observed at two years after the liver transplantation. Liver transplantation should be considered as a treatment option even in advanced case of carcinoid metastasis to the liver. We also discuss the literature on liver transplantation for metastatic carcinoid tumor.

Histopathological differences in the development of small intestinal metaplasia between antrum and body of stomach.

This study used mucin immunohistochemistry to investigate differences in the properties of intestinal metaplasia between the antrum and body of the stomach in 28 resected specimens. Intestinal metaplasia was classified as: (1) small intestinal metaplasia (SIM) with a tubule, including CD10-positive brush border on a background of MUC5AC-/ HGM-negative cells; or (2) goblet cell metaplasia (GCM) with MUC2-positive and CD10-negative cells. In the antrum, frequencies of SIM and GCM were nearly equal irrespective of metaplasia grade. Frequency and length of remnant pyloric gland for SIM were significantly greater in the antrum than in the body. In the proliferative zone, there existed a lower level in SIM than in non-intestinalized tubules. These findings suggest that the proliferative zone shifts from the neck zone toward the bottom of the tubule during the SIM process in the antrum. In the body, however, the grade of SIM grade was significantly higher than that of GCM. The proliferative zone was located higher in the fundic gland, pseudopyloric gland and SIM, in that order. Almost all remnant pyloric glands for SIM were negative for pepsinogen I. These facts indicate that SIM in the body originates in a proliferative zone that shifted downward to an area near the bottom of the tubule, with atrophic pyloric glands originating from pseudopyloric gland metaplasia.

[Pathomorphology of ulcerative colitis].

Microscopic and macroscopic appearances of ulcerative colitis (UC) by its phase of inflammation were summarized. The most characteristic microscopic findings of active phase UC is diffuse lymphoplasmacytic infiltration, essentially associated with basal plasmacytosis. Although inflammation of UC is basically limited to the mucosa, active inflammation extends into the submucosa in some instance, and acute ischemic change is overlapped to cause toxic megacolon. In remission phase, inflammation is reduced and goblet cell mucus is fully recovered but evidences of the past inflammation such as irregular shape and disarrangement of crypts, Paneth cell metaplasia, thickening of the muscularis mucosae and discrepancy between the crypt base and the muscularis mucosae are usually demonstrated. Macroscopic appearances of UC reflect its microscopic findings such as degree of inflammation, whether inflammation is (was) limited to the mucosa or extend(ed) into the submucosa. Active phase is classified into erythematous, spongy, granular, pseudopolyp, ulcerative, and fulminant (toxic megacolon) type. In the former two types, inflammation is limited in the mucosa, and the latter two types are associated with ischemic change. In remission phase, erythematous and spongy types recover to the almost normal looking mucosa or fine granular mucosa with preservation of mucosal folds, granular type recovers to granular, fine granular or flat atrophic mucosa without preservation of mucosal folds, and pseudopolyp type recovers to mucosa with inflammatory polyposis.

Therapeutic role of pericardiocentesis for acute necrotizing eosinophilic myocarditis with cardiac tamponade.

We describe a patient with acute necrotizing eosinophilic myocarditis who recovered rapidly after pericardial drainage and without corticosteroid therapy. The 25-year- old man was referred to our hospital with suspected acute myocardial infarction on the basis of severe epigastralgia, abnormal Q waves and ST elevation on electrocardiography, and an increase in cardiac enzymes. Echocardiography disclosed pericardial effusion that compressed the right ventricle, left ventricular dysfunction in conjunction with posterolateral hypokinesis, and a thickened ventricular wall but no mural thrombus. The eosinophil count in the peripheral blood was slightly increased. Coronary angiography showed normal arteries and thus prompted an endomyocardial biopsy. The patient was transferred to the intensive care unit with a clinical diagnosis of myocarditis associated with cardiac tamponade. Emergency pericardiocentesis relieved symptoms immediately. The cells in the pericardial effusion were mainly eosinophils; interleukin 5 and interleukin 13 levels were predominantly elevated, and the effusion was drained for 5 days. The biopsy specimen revealed necrotizing eosinophilic myocarditis. Left ventricular function recovered within a week without corticosteroid therapy. No relapse was observed as of 8 months after diagnosis.

Risk factors for nodal micrometastasis of submucosal gastric carcinoma: assessment of indications for endoscopic treatment.

BACKGROUND: Despite the widespread use of endoscopic mucosal resection (EMR) for intramucosal gastric carcinoma, there is no standardized therapy for those patients in whom the carcinoma is found, after EMR, to have invaded the submucosa.Our aim in this study was to examine the relationship between the clinicopathological features of submucosal invasive carcinomas and their incidence of nodal micrometastasis, as detected by anti-human cytokeratin immunohistochemistry, in order to assess the curative potential of submucosal carcinoma by EMR.METHODS: Fifty surgically resected submucosal gastric carcinomas which would have satisfied the absolute indications for EMR, except for the criterion of submucosal invasion, were examined. The extent of submucosal invasion was determined by measuring its vertical and horizontal spread. Immunohistochemical analysis was performed with anti-human cytokeratin antibody (CAM5.2).RESULTS: Three of 50 cases (6.0%) were positive for nodal metastasis by routine H&E examination. Nodal micrometastases were detected in 11 of 47 cases (23.4%). Statistical analysis revealed that both the depth and the width of carcinoma in the submucosa were significantly larger in cases with than in those without micrometastasis ( P = 0.019 and P = 0.006, respectively). The group with lymphatic invasion showed more frequent micrometastasis than the group without ( P = 0.014). There were no micrometastases in submucosal carcinomas whose submucosal invasion was less than 200 &mgr;m vertically and less than 320 &mgr;m horizontally.CONCLUSIONS: The present study indicates that differentiated gastric adenocarcinoma with minimal submucosal invasion (less than 200 &mgr;m vertically and less than 320 &mgr;m horizontally) and not accompanied by peptic ulcer or other risk factors, such as lymphatic invasion, can be considered as having high curative potential by EMR alone, without the necessity for further radical surgery.

[Diagnosis and treatment of carcinoid tumors in the gastrointestinal tract].

Histopathologically and biologically, endocrine cell tumors in the gastrointestinal tract are divided into two groups: 1) carcinoid, a low-grade malignancy, and 2) endocrine cell carcinoma (synonymous with small cell carcinoma), a high-grade malignancy. Atypical carcinoid, which has increased histological atypia and proliferative activity, shows more aggressive biological behavior than classical carcinoid. As a rule, endocrine cell carcinoma should be resected surgically with dissection of lymph nodes and adjuvant therapy if needed, while carcinoid should be treated by endoscopic resection or localized resection without lymph node dissection. Classical carcinoid of more than 2.0 cm in size and atypical carcinoid should be treated more carefully because of the increased risk of vascular permeation or distant metastasis.