[A Case of Early-Stage Cecal Cancer with Mesenteric Phlebosclerosis Requiring Laparoscopic Right Hemicolectomy of the Colon].

The patient was a 71-year-old woman diagnosed with mesenteric phlebosclerosis(MP)2 years earlier. CT performed to investigate her abdominal pain revealed an ascending colon obstruction. Colonoscopy(CS)revealed MP extending to the ascending colon hepatic flexure with stenosis and a cecal tumor(biopsy tub1). Although the cancerous lesion itself was potentially curable by endoscopic treatment, it was surgically resected because of the ascending colon stenosis caused by the MP that had also caused intestinal obstruction. Intraoperative findings revealed wall thickening and stiffening from the cecum to the ascending colon hepatic flexure. Postoperative pathological examination revealed cecal carcinoma pTis, N0, M0, pStage 0. The background mucosal tissue was consistent with MP, but no findings suggested a relationship between the MP and tumor. Although the relationship between MP and carcinogenesis is unknown, and no such relationship was identified in this case, we report this case because a further accumulation of cases of MP and carcinoma is necessary, considering the rarity of MP itself and the non-negligible number of cases with carcinoma.

[A Case of BRAF-Mutated Obstructive Colon Cancer with Liver Metastases Treated with Multidisciplinary Therapy].

A 39-year-old woman visited our hospital with complaints of nausea, vomiting, and lower abdominal pain for 2 weeks. Abdominal CT revealed thickening of the transverse colonic wall, dilated bowel, and a metastatic ischemic tumor in the liver (S7). We diagnosed her with obstructive colon cancer, clinical Stage Ⅳa(T, type 2, cT3, N0, M1a[liver]). At first, we placed a self-expanding metallic stent(SEMS)to decompress bowel obstructions. We planned a surgical resection of the primary tumor followed by partial resection of the liver. We performed a laparoscopic right hemicolectomy(D3)24 days after the stenting. Pathologically, we diagnosed her with BRAF-mutated colon cancer, pStage Ⅳa(pT4a, N1b[2/43], M1a[liver]). On completion of 4 courses of mFOLFOXIRI and bevacizumab, we confirmed a reduction of the S7 tumor but found a new tumor in S6. Since the tumors were potentially resectable, we performed partial liver resection(S6, S7)1 month later. A month following the hepatectomy, CT revealed a new tumor in S4. The patient has been receiving general chemotherapy (CapeOX and bevacizumab)without disease progression for 6 months. We experienced a challenging case of BRAF- mutated obstructive colon cancer with liver metastases.

[A Successful Case of Multimodal Therapy for Multiple Hypervascular Tumor of Unknown Primary Origin in the Liver].

We experienced a successful case in which the patient was treated with a combination of operation and transcatheter arterial chemoembolization for a hypervascular tumor of unknown primary origin in the liver; we report this case with a literature review. A 76-year-old man noticed an upper abdominal tumor and he visited our department for detailed examination. Enhanced CT scan showed multiple hypervascular tumors scattered across both lobes of the liver, and the pattern of contrast effect implied that the tumors were primary neuroendocrine tumors or endocrine metastases. Gastroscopy and colonoscopy showed no tumor in the intestine. TACE was performed mainly for the tumors in the right lobe. One month later, we performed left lateral segmentectomy and partial hepatectomy for segment 6. Histopathological findings showed that the tumors in the left lateral segment had neuroendocrine properties, and the tumor in segment 6 was necrosed. One year has passed since the surgery without recurrence of neuroendocrine tumors in the liver or other organs.

[A Case of Advanced Gastric Cancer with Right Gastroepiploic Vein Tumor Thrombus Treated by Preoperative S-1 plus CDDP That Resulted in Pathological Complete Response].

We report a case of advanced gastric cancer with right gastroepiploic vein tumor thrombus treated using preoperative S-1 plus cisplatin(CDDP)in which pathological complete response was achieved. A 78-year-old man was diagnosed with type 2 gastric cancer located at the greater curvature of the antrum, accompanied by right gastroepiploic vein tumor thrombus. Four courses of S-1 plus CDDP were administered as neoadjuvant chemotherapy. After 2 courses, computed tomography(CT) revealed the disappearance of the tumor in the right gastroepiploic vein thrombus. Distal gastrectomy with D2 lymphadenec- tomy was performed, and the diagnosis was pathological complete response(CR). Eight courses of S-1(100mg/day on days 1-28, followed by 2 weeks of rest)were administered as adjuvant chemotherapy. During the 1-year postoperative follow up, the patient showed no recurrence. An S-1 plus CDDP regimen can be a useful preoperative chemotherapy option for advanced gastric cancer with tumor vein thrombus.

[Intrahepatic Bile Duct Metastasis from Rectal Adenocarcinoma Eight Years after Curative Operation].

A 60-year-old male undergoing pelvic evisceration with D3 lymph node dissection for pR0 in 2006f or carcinoma of the rectum was diagnosed pathologically with moderately differentiated adenocarcinoma, fStage ⅡA(UICC pT3, pN0, M0). Follow-up CT revealed hypovascular liver tumors with intrahepatic bile duct dilation in the right lobe 8 years after the pelvic evisceration. We conducted right lobe hepatectomy. The resected specimens showed that the tumor extended predominantly along the right intrahepatic bile duct. Histological findings and an immunohistochemical examination of CK7, CK20, and CDX2 revealed metastasis of the rectum cancer. We finally diagnosed him with intrahepatic bile duct metastasis from rectal adenocarcinoma.

[A Case of Cecal Cancer with Simultaneous Liver Metastases Successfully Treated with Multidisciplinary Therapy Including Two-Stage Hepatectomy].

We report a case of colon cancer with simultaneous liver metastases successfully treated with multidisciplinary therapy including two-stage hepatectomy. This is a case of a 72-year-old woman diagnosed with type 1 cecal cancer with 2 simulta- neous liver metastases(S4/8: 98mm, S3: 63mm). At first, laparoscopic resection of the primary site was performed to prevent colon ileus. Liver metastases rapidly grew and became unresectable; fortunately, 11 courses of mFOLFOX6 and bevacizu- mab were effective and liver metastases shrunk(S4/8: 85mm, S3: 67mm). At last, two-stage hepatectomy was performed as conversion surgery, and the patient survived without recurrence for more than 2 years.

[Two Cases of Aneurysm Rupture in Advanced Colorectal Cancer Successfully Treated with Selective Trans-Catheter Arterial Embolization].

We report 2 successful cases treated with trans-catheter arterial embolization(TAE)for hemorrhagic shock due to pseudoaneurysm rupture at the primary tumor site in advanced colorectal cancer. Case 1: A 73-year-old female underwent Hartmann surgery at another hospital for rectal perforation and peritonitis. Six months later, she had a massive bloody stool and was transferred to our hospital. She was diagnosed with bleeding from advanced rectal cancer that remained following the first surgery. Contrast computed tomography(CT)showed that a branch of the superior rectal artery(SRA)developed an aneurysm at the primary tumor site, and TAE was performed to stop bleeding on hospital day 3. Case 2: A 79-year-old male with type 2 sigmoid colon cancer and simultaneous multiple liver metastases developed copious blood in the stool before primary tumor resection and was transferred to our hospital. Contrast CT showed that a branch of the SRA developed an aneurysm at the primary tumor site, and TAE was immediately performed to stop bleeding.

[A Case of Perforated Gastric MALT Lymphoma with Total Gastrectomy].

A 62-year-old man presented with complaints of acute abdominal pain. Abdominal enhanced CT showed free air in the abdominal cavity, a thickened stomach wall accompanied by deep ulcer, and enlarged lymph nodes around the stomach. Emergent surgery was conducted, and a perforation in the upper part of the stomach was found. Total gastrectomy was performed. On pathological examination, a mucosa-associated lymphoid tissue lymphoma was diagnosed. Histologic examination revealed the absence of Helicobacter pylori in the gastric mucosa. After the operation, adjuvant chemotherapy was not administered. However, he has been well for 11 months without any recurrence. Gastric MALT lymphoma with spontaneous perforation is considered extremely rare. A brief review of the literature is presented.

[A Case of Non-Functioning Pancreatic Neuroendocrine Tumor Accompanied by Stenosis of the Main Pancreatic Duct].

We experienced a rare case of pancreatic neuroendocrine tumor(pNET)in which stenosis of the main pancreatic duct occurred despite the tumor diameter being less than 1 cm; therefore, here, we report this case with some literature review.A 41-year-old woman showed dilation of the main pancreatic duct on an abdominal ultrasound as part of a health examination, and she visited our department for a more detailed examination.Enhanced CT scan showed a 7mm subtle enhancing mass in the head of the pancreas and the upstream main pancreatic duct was dilated up to 7 mm.ERCP and MRCP images also showed a dilated main pancreas duct.We suspected that her tumor was a pNET.We decided not to perform surgery immediately. After 6 months of follow-up, the tumor size increased to 10 mm; therefore, we performed subtotal stomach-preserving pancreaticoduodenectomy considering the possibility of pancreatic cancer.Histopathological findings showed that the pancreatic tumor had the property of a neuroendocrine tumor and the proliferated fibrous stroma around it caused the pancreas duct stenosis.

A three-tier classification system based on the depth of submucosal invasion and budding/sprouting can improve the treatment strategy for T1 colorectal cancer: a retrospective multicenter study.

More than 85% of patients with T1 colorectal cancer have no lymph node metastasis and can be cured by endoscopic resection. To avoid unnecessary surgery after complete endoscopic resection, accurate histologic methods for evaluating resected specimens are needed to discriminate those at high risk for lymph node metastasis. A retrospective multi-institutional, cross-sectional study of 806 T1 colorectal cancer patients was conducted. A budding/sprouting score was incorporated for predicting lymph node metastasis in addition to other parameters, including the depth of submucosal invasion, histologic grade, and lymphovascular invasion. Lymph node metastasis was detected in 97 patients. Independent predictors of lymph node metastasis by multivariate analysis were depth of submucosal invasion ≥1000 µm (odds ratio (95% confidence interval)=5.56 (2.14-19.10)) and high-grade budding/sprouting (3.14 (1.91-5.21)). Among lesions with a depth of submucosal invasion ≥1000 µm, lymph node metastasis was detected in 59 (29%) of 207 patients with high-grade budding/sprouting, and in 34 (9%) of 396 with low-grade budding/sprouting. Lymph node metastasis was detected in only 4 (2%) of 203 lesions with a depth of submucosal invasion <1000 µm. Of these four tumors, three invaded lymphatic and/or venous vessels. Thus, the risk for lymph node metastasis can be classified into three groups: high risk with a depth of submucosal invasion ≥1000 µm and high-grade budding/sprouting, intermediate-risk with a depth of submucosal invasion ≥1000 µm and low-grade budding/sprouting, and low-risk with a depth of submucosal invasion <1000 µm. These findings revealed that a depth of submucosal invasion ≥1000 µm and high-grade budding/sprouting are powerful predictive parameters for lymph node metastasis in T1 colorectal cancer. This three-tier risk classification system will facilitate the decision for additional major surgery for T1 colorectal cancer patients after successful endoscopic treatment.

Histopathological Examination of a Symptomatic Carotid Web: A Case Report.

Carotid webs cause ischemic stroke in young people and are associated with a high rate of stroke recurrence. Histopathological examination is crucial for clarifying the pathogenesis and mechanisms underlying the occurrence of carotid webs, although the mechanisms generally remain unclear. Here, we report a case of a symptomatic carotid web in a woman in her 50s who had a medical history of two ischemic strokes. She was diagnosed with a right carotid web and underwent carotid endarterectomy 18 days after the second stroke. Histopathological examination clearly revealed several phases of intimal hyperplasia. Furthermore, a thrombus attached to the carotid web showed invasion by fibroblasts and capillaries, and organization had begun. We presume that after the appearance of the carotid web, the thrombus formed by stagnant flow and became organized, causing the carotid web to grow and change in shape.

[A case of scirrhous stomach cancer with follicular lymphoma of the duodenum].

The patient was a 73-year-old woman with hematemesis, who was brought to our hospital by an ambulance. Emergency upper gastrointestinal endoscopy was performed, and a thickened wall and multiple ulcers were noted in the middle- lower region of the stomach body. The biopsy revealed gastric cancer (por), and the macroscopic depth of invasion was up to the subserosal layer. Multiple white granular protruding lesions were observed in the duodenal bulb and were diagnosed as follicular lymphoma by biopsy. As follicular lymphoma generally takes a long time to progress in many cases, the vital prognosis would be determined by the gastric cancer. Thus, total gastrectomy was performed for gastric cancer. For reconstruction, the double-tract method was used. Duodenal follicular lymphoma was continuously monitored by upper gastrointestinal endoscopy. Here, we describe the case of a patient with a complication of follicular lymphoma arising from duodenal and gastric cancer, which is very rare, and report this case along with a literature review.

[A case of intussusception caused by low-grade appendiceal mucinous neoplasm with high serum levels of carcinoembryonic antigen resected by laparoscopy-assisted colectomy].

The patient was a 43-year-old woman who visited our hospital with a primary complaint of intermittent abdominal pain. Upper gastrointestinal endoscopy revealed mild gastritis. The patient was treated with oral drugs, and the course was followed. Subsequently, the abdominal pain aggravated, and computed tomography (CT) was performed, in which right colic intussusception with a 4 cm cystic mass in the advanced portion was noted. Reduction by enema was attempted on the same day; however, a residual tumorous lesion was present in the ileocecal region. The patient was diagnosed with a cecal submucosal tumor with intussusception, and therefore, laparoscopic surgery was performed. Intussusception of the entire appendix in the ascending colon was noted, for which laparoscopic ileocecal resection was performed. In the excised specimen, a cystic lesion comprising the appendix filled with mucus was present. The postoperative recovery was favorable, and the patient was discharged on the seventh postoperative day. The lesion was histopathologically diagnosed as low-grade appendiceal mucinous neoplasm.

HSP60 may predict good pathological response to neoadjuvant chemoradiotherapy in bladder cancer.

BACKGROUND: Heat shock proteins (HSPs) play crucial roles in cellular responses to stressful conditions. Expression of HSPs in invasive or high-risk superficial bladder cancer was investigated to identify whether HSPs predict pathological response to neoadjuvant chemoradiotherapy (CRT). METHODS: Immunohistochemistry was used to assess expression levels of HSP27, HSP60, HSP70, HSP90 and p53 in 54 patients with invasive or high-risk superficial bladder cancer, prior to low-dose neoadjuvant CRT, followed by radical or partial cystectomy. Patients were classified into two groups (good or poor responders) depending on pathological response to CRT, which was defined as the proportion of morphological therapeutic changes in surgical specimens. Good responders showed morphological therapeutic changes in two-thirds or more of tumor tissues. In contrast, poor responders showed changes in less than two-thirds of tumor tissues. RESULTS: Using a multivariate analysis, positive HSP60 expression prior to CRT was found to be marginally associated with good pathological response to CRT (P = 0.0564). None of clinicopathological factors was associated with HSP60 expression level. In the good pathological responders, the 5-year cause-specific survival was 88%, which was significantly better than survival in the poor responders (51%) (P = 0.0373). CONCLUSIONS: Positive HSP60 expression prior to CRT may predict good pathological response to low-dose neoadjuvant CRT in invasive or high-risk superficial bladder cancer.

p53 Mutation analysis of low-grade dysplasia and high-grade dysplasia/carcinoma in situ of the esophagus using laser capture microdissection.

OBJECTIVES: The aim of this study was to determine the prevalence and to analyze the characteristics of p53 point mutation in esophageal intraepithelial lesions. METHODS: p53 Immunohistochemical and genetic analyses were performed on histopathologically and morphometrically diagnosed lesions. Laser capture microdissection samples were used for increased accuracy. RESULTS: Of the 70 lesions studied, 21 were high-grade dysplasia/carcinoma in situ (HGD/CIS), 21 low-grade dysplasia (LGD), 16 reactive atypical epithelia (RAE) and 12 normal epithelia (NE). Immunohistochemical staining showed p53 protein accumulation in 86% (18/21) of HGD/CIS, 81% (17/21) of LGD, and in none of RAE and NE. p53 point mutation was detected in 71% (15/21) of HGD/CIS, 67% (14/21) of LGD, but in none of RAE and NE. Of HGD/CIS and LGD with p53 protein accumulation, similar percentages had mutations: 83% (15/18) and 82% (14/17), respectively. Of lesions with mutations, 72% (21/29) had mutations at hot spots such as codons 238, 248, 273 and 282. CONCLUSIONS: p53 Point mutation prevalent in HGD/CIS was also present in a large number of LGD. This is strong evidence that LGD is a neoplastic lesion and that p53 point mutation is deeply involved in esophageal carcinogenesis.

Expression of homeodomain protein CDX2 in gallbladder carcinomas.

PURPOSE: Caudal-related homeobox protein CDX2 plays an important role in the regulation of cell proliferation and differentiation of the intestinal epithelium. CDX2 is associated with intestinal metaplasia and carcinomas of the stomach, but the role of CDX2 in gallbladder carcinogenesis remains unknown. METHODS: We analyzed the expression of CDX2 and intestinal apomucin MUC2 in gallbladder cancer cell lines at the mRNA level by the RT-PCR method. We also investigated the expression of CDX2 and MUC2 in 68 primary gallbladder carcinomas by the immunohistochemical staining method and compared the expression of CDX2 with the clinicopathological factors in the gallbladder carcinoma cases. RESULTS: Expression of CDX2 and MUC2 was found in three of four gallbladder cancer cell lines at the mRNA level. In addition, we found that CDX2 was absent in the normal gallbladder epithelium, but the CDX2 protein was expressed in 25 of the 68 (36.8%) gallbladder carcinomas. Interestingly, in the tubular type gallbladder carcinomas, the frequency of CDX2 expression was much higher in the well-differentiated type than the moderately and poorly differentiated types, the difference being statistically significant (P<0.01). CDX2 expression showed a relationship with expression of MUC2 (P<0.04) in the gallbladder carcinomas. CDX2 was expressed in intestinal metaplasia and dysplasia, which are hypothesized to be premalignant conditions. CONCLUSION: These results imply that CDX2 plays an important role in gallbladder carcinogenesis with intestinal differentiation.

Importance of thymidine phosphorylase expression in tumor stroma as a prognostic factor in patients with advanced colorectal carcinoma.

Thymidine phosphorylase (TP) is a unique enzyme involved not only in angiogenesis, but in 5-fluorouracil (5-FU) metabolism as well. TP is produced by both tumor and stromal cells. The aim of this study was to reveal the clinical implication of TP localization in tumor tissues. Advanced colorectal cancer specimens (n=97) were prepared for immunohistochemical staining using monoclonal antibodies against TP, p53, vascular endothelial growth factor (VEGF), factor VIII, CD68 and thymidylate synthase (TS). Clinicopathological factors and the clinical prognosis were examined for each indicator. High tumor TP expression and high stromal TP expression were observed in 38% (36/95 cases) and 49% (47/95 cases) of the cases, respectively. High tumor TP expression tended to correlate with microvessel density (MVD) (p=0.0511). Among patients who underwent curative resection, those with high stromal TP expression had a favorable prognosis (p=0.0127). High stromal TP status was also a strong prognostic factor in the group receiving adjuvant 5-FU derivatives (p=0.0222). TP produced by tumor cells has a stimulatory effect on tumor angiogenesis, while that produced by stromal cells plays an entirely different role. The latter may enhance the anticancer effect of 5-FU via its catalyzed function.

Propionibacterium acnes is the most common bacterium commensal in peripheral lung tissue and mediastinal lymph nodes from subjects without sarcoidosis.

BACKGROUND: In studies of the unknown etiology of sarcoidosis, Propionibacterium acnes (a possible agent) was found in the lungs and lymph nodes of many sarcoidosis patients and some control subjects. P. acnes might be commensal not only to the skin, conjunctivae, and intestine, but also to the lungs and lymph nodes of individuals without sarcoidosis. METHODS: We cultured peripheral lung tissue and various lymph nodes obtained from patients with diseases other than sarcoidosis. DNA of 45 isolates of P. acnes from these patients, 67 isolates from normal skin, conjunctiva, and intestine, and 39 isolates from sarcoid lymph nodes were compared by random amplified polymorphic DNA analysis. RESULTS: P. acnes was isolated from half of 43 lungs and 8 of 11 mediastinal lymph nodes, mostly in pure culture. P. acnes was isolated from half of 20 gastric and 3 of 12 intestinal lymph nodes; intestinal bacteria were also numerous. In general, fewer than 500 colony-forming units of P. acnes per gram tissue were isolated, but 4 lung tissue specimens, 2 of which had a few granulomas, had many more. P. acnes strains from a particular site (lung, lymph node, skin or conjunctivae, and intestine) were genetically similar, more than isolates obtained from different sites. Lymph-node isolates from subjects with and without sarcoidosis differed little. CONCLUSION: These results suggest that P. acnes normally resides in peripheral lung tissue and mediastinal lymph nodes and that the strains of P. acnes isolated from sarcoid lymph nodes were not specific to sarcoidosis.

Spontaneous " healing" of breast cancer.

BACKGROUND: Healing is a phenomenon by which the intraductal component of breast cancer disappears and is replaced by fibrous tissue. Focally localized healing often prevents confirmation of the continuity of intraductal carcinoma. OBJECTIVE: To clarify the clinicopathological characteristics of breast cancer with healing. PATIENTS AND METHODS: At our hospital, 308 patients (311 breasts) underwent breast conservation therapy without neoadjuvant chemotherapy for breast cancer in 2000. These surgical specimens were histopathologically investigated with 5 mm serial sections. We assessed the proportion and the characteristics of breast cancer with healing. RESULTS: (1) The proportion of breast cancer with healing was 7% (21/311). (2) In the 21 patients, the mean age was 59.2 years, and the mean diameter was 2.8 cm. (3) The histological type of the breast cancer varied: noninvasive ductal carcinoma in 2 cases, papillotubular carcinoma in 5, solid-tubular carcinoma in 8, scirrhous carcinoma in 5, invasive lobular carcinoma in 1, and Paget's disease in 1. However in all cases, the histologic type of the intraductal carcinoma foci was the comedo/solid type and the nuclear grade of cancer cells was high. (4) In cases with healing, areas of healing were seen in an average of 5 (1-26) blocks, compared with intraductal carcinoma foci in 13 blocks (2-40). Healing was located on the nipple side of the main lesion in 8 cases, the peripheral side in 9, and both sides in 4. In 3 cases, healing was seen at the surgical margin of the partial mastectomy specimen. CONCLUSION: The proportion of breast cancer cases with healing was 7% and these cases were intraductal carcinoma of the comedo/solid type, consisting of highly malignant cancer cells.