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 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.

[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.

Potential of classification of cancer by multiple discriminant analysis for relationship between cancer and expression of human cellular phosphoprotein.

This is the first report to describe the potential for classification of cancer using anti-phosphoprotein monoclonal antibodies (PPmAbs) and multiple discriminant analysis. Over 150 hybridoma clones producing monoclonal antibodies were generated against a human phosphoprotein mixture derived from a human leukemia cell line. The expression profiles of 22 cell lines from 9 different types of cancer using PPmAbs were examined. The relationship between cancer cells and the expression of human phosphoprotein in the cells was analyzed by multiple discriminant analysis and was used to construct a diagnostic system for cancers. Multiple discriminant analysis was able to successfully classify the cell lines into the correct cancer group by using the diagnostic system for cancers. These results show that multiple discriminant analysis based on phosphoprotein expression in cells or tissues may be a potentially valuable method for assisting in the classification of several cancers.

SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kgamma Activity through Deacetylation of Specific Lysine Residues in Mammals.

BACKGROUND: SIRT1, a NAD-dependent deacetylase, has diverse roles in a variety of organs such as regulation of endocrine function and metabolism. However, it remains to be addressed how it regulates hormone release there. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that SIRT1 is abundantly expressed in pituitary thyrotropes and regulates thyroid hormone secretion. Manipulation of SIRT1 level revealed that SIRT1 positively regulated the exocytosis of TSH-containing granules. Using LC/MS-based interactomics, phosphatidylinositol-4-phosphate 5-kinase (PIP5K)gamma was identified as a SIRT1 binding partner and deacetylation substrate. SIRT1 deacetylated two specific lysine residues (K265/K268) in PIP5Kgamma and enhanced PIP5Kgamma enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5Kgamma knockdown. SIRT1 knockdown decreased the levels of deacetylated PIP5Kgamma, PI(4,5)P(2), and reduced the secretion of TSH from pituitary cells. These results were also observed in SIRT1-knockout mice. CONCLUSIONS/SIGNIFICANCE: Our findings indicated that the control of TSH release by the SIRT1-PIP5Kgamma pathway is important for regulating the metabolism of the whole body.

Histopathologic analysis of sixteen autopsy cases of chronic hypersensitivity pneumonitis and comparison with idiopathic pulmonary fibrosis/usual interstitial pneumonia.

Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by the inhalation of organic substances and certain inorganic chemicals. The histopathologic features of chronic HP (CHP) have not been studied extensively. We examined the pathologic characteristics of 16 autopsy cases of clinically confirmed CHP and compared them with 11 cases of idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP). To clarify the exact intralobular location of the fibrotic lesions, we conducted 3-dimensional reconstruction of fibrosis of CHP and IPF/UIP. Granuloma was not detected in any CHP case. Similar to IPF/UIP, honeycombing lesions were found dominantly in the lower lobes in most CHP cases; upper lobe dominance and asymmetrical distribution of honeycomb lesions were more frequent in CHP than in IPF/UIP. In all lungs affected by CHP, centrilobular fibrosis was outstanding, often connecting to the perilobular areas in the appearance of "bridging fibrosis," which was clearly demonstrated by 3-dimensional imaging. Centrilobular and bridging fibrosis were significantly more conspicuous in CHP than IPF/UIP; however, considerable overlap was found. It is important to thoroughly explore the possibility of antigen exposure in cases of lungs with UIP with centrilobular fibrosis to discriminate CHP from IPF/UIP.

Significant increase in the expression of matrix metalloproteinase 7 in primary CNS lymphoma.

The aim of this study is to compare the expression pattern of matrix metalloproteinases (MMP) in primary CNS lymphoma (PCNSL) with that of nodal lymphoma (NL). PCNSL possesses a characteristic pattern of brain infiltration, specifically, perivascular aggregation and destruction of the surrounding connective tissue. Hypotheses have been proposed that this infiltration pattern indicates the infiltration of lympoma cells from outside the CNS. However, the mechanism of this infiltration pattern has not been clearly explained. Here we performed quantitative analysis of mRNA expression of MMP1, 2, 3, 7 and 9 in lymphoma cells from 10 cases of PCNSL, all of which were diagnosed as diffuse large B-cell lymphoma (DLBCL), and 14 cases of nodal DLBCL. Immunohistochemistry was also performed for phenotyping of lymphoma cells and for examining the localization of MMPs. The expression level of MMP7 in PCNSL (median ratio to normal lymophocytes, 45.6) was significantly higher than the level in NL (median, 7.55). By contrast, the expression levels of MMP2 (median, 31.7) and MMP9 (median, 1.30) in PCNSL were significantly lower than those in NL (median, 120 and 16.5, respectively). The expression levels of MMP1 and MMP3 were very low and not different between PCNSL and NL (almost comparable to those in normal lymphocytes). Immunohistochemical phenotyping revealed that the frequency of non-germinal center type DLBCL was significantly higher in PCNSL than in NL. These results, notably the significantly increased expression of MMP7 in PCNSL, suggest the involvement of this MMP in the characteristic infiltration pattern of PCNSL. They also support the existing hypothesis that PCNSL and NL are of different origins.

Frequency and number of neuroendocrine tumor cells in prostate cancer: no difference between radical prostatectomy specimens from patients with and without neoadjuvant hormonal therapy.

BACKGROUND: Neuroendocrine tumor cells in prostate cancer are thought to increase after hormonal therapy due to neuroendocrine differentiation of tumor cells. This assumption is based on the histological analyses of limited portions of the cancerous lesions examined. METHODS: Radical prostatectomy specimens were obtained from 122 consecutive patients with prostate adenocarcinoma, 70 of whom underwent prostatectomy alone (Group A) and 52 with neoadjuvant hormonal therapy (Group B). Sections from all the 5-mm-thick slices from formalin-fixed specimens were immunostained for chromogranin-A, and the total number of choromogranin-A-positive neuroendocrine tumor cells were counted. RESULTS: No difference was found between Groups A and B in the frequency of cancer with neuroendocrine cells. The total number of neuroendocrine cells in cancer varied widely with no difference of median values in the two groups. CONCLUSIONS: These results do not support the assumption that hormonal therapy induces neuroendocrine differentiation, but suggest androgen-independent neuroendocrine cells existed before therapy.

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.