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Generally, a colon lesion is evaluated by endoscopy. In many cases, total colonoscopy is often difficult to perform due to postsurgical adhesion. Here, we described a case of a colon tumor that could not be recognized by colonoscopy and palpation under laparotomy. Nonetheless, this tumor could be observed by laparoscopy from the appendix root after appendectomy. Eventually, this tumor was locally resected. The patient was a 79-year-old male who had PET-CT examination to explore distant metastasis before the rectal cancer surgery. In this examination, the ascending-colon lesion was suspected as a malignant tumor. This tumor could not be observed by colonoscopy because of the adhesion from the past history of right pneumonectomy and open cholecystectomy. Nevertheless, the contrast enema at the hepatic flexure of the colon was normal. We then suspected an early colon carcinoma and subsequently performed laparotomy. However, the tumor was not detected by palpation at the ascending colon. Thus, we observed the colon tumor by laparoscopy from the appendix root after appendectomy, followed by local excision of the colon tumor. Therefore, observation by laparoscopy from the appendix root was useful for the diagnosis and treatment of the ascending-colon lesion that could not be recognized by colonoscopy and palpation under laparotomy.

Transient elevation of antiphospholipid antibody (APLA) is commonly observed in cases of viral infection; however, it is generally not associated with clinical thromboembolic events. In this report, we present a rare case of superior mesenteric artery (SMA) thrombosis associated with a transient elevation of APLA and discuss its relationship with fibromuscular dysplasia and adenomyosis of the uterus. Furthermore, we discuss the use of anticoagulant therapy in cases with transient elevation of APLA. In this case, a 46-year-old woman with no significant medical history was diagnosed with intestinal stenosis after SMA thrombosis that had been resolved with anticoagulant therapy. Laboratory examination showed elevated levels of anticardiolipin antibody. Resection of the stenosed ileum and hysterectomy for huge adenomyosis were performed. Anticardiolipin antibody level normalized 4 months after the operation. Anticoagulant therapy was withdrawn after anticardiolipin antibody normalized, and the patient has been free from thromboembolic events ever since. Transient elevation of APLA should be kept in mind in all patients with thromboembolic events, including those with no medical history of collagen diseases or infection. In the present case, association with fibromuscular dysplasia and adenomyosis of the uterus is suspected, but further investigation is required. Once the APLA level normalizes with the resolved thrombus, decision of withdrawing the anticoagulant therapy can be considered.

A number of previous studies have reported that 30-50% of patients with colorectal cancer (CRC) harbor Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, which is a major predictive biomarker of resistance to epidermal growth factor (EGFR)-targeted therapy. Treatment with an anti-EGFR inhibitor is recommended for patients with KRAS wild-type metastatic colorectal cancer (mCRC). A recent retrospective study of cetuximab reported that patients with KRAS p.G13D mutations had better outcomes compared with those with other mutations. The aim of this retrospective study was to assess the prevalence of KRAS p.G13D mutations and evaluate the effectiveness of cetuximab in mCRC patients with KRAS p.G13D or other KRAS mutations. We reviewed the clinical records of 98 mCRC patients with KRAS mutations who were treated between August, 2004 and January, 2011 in four hospitals located in Tokyo and Kyushu Island. We also investigated KRAS mutation subtypes and patient characteristics. In the patients who received cetuximab, univariate and multivariate analyses were performed to assess the effect of KRAS p.G13D mutations on progression-free survival (PFS) and overall survival (OS). Of the 98 patients, 23 (23.5%) had KRAS p.G13D-mutated tumors, whereas 75 (76.5%) had tumors harboring other mutations. Of the 31 patients who received cetuximab, 9 (29.0%) had KRAS p.G13D mutations and 22 (71.0%) had other mutations. There were no significant differences in age, gender, primary site, pathological type, history of chemotherapy, or the combined use of irinotecan between either of the patient subgroups. The univariate analysis revealed no significant difference in PFS or OS between the patients with KRAS p.G13D mutations and those with other mutations (median PFS, 4.5 vs. 2.8 months, respectively; P=0.65; and median OS, 15.3 vs. 8.9 months, respectively; P=0.51). However, the multivariate analysis revealed a trend toward better PFS among patients harboring p.G13D mutations (PFS: HR=0.29; 95% CI: 0.08-1.10; P=0.07; OS: HR=0.23; 95% CI: 0.04-1.54; P=0.13). In conclusion, treatment with cetuximab may be more clinically beneficial in mCRC patients with a KRAS p.G13D mutation, compared with those harboring other mutations. However, further investigation is required to clearly determine the benefits of cetuximab treatment in patients with KRAS p.G13D mutation-positive mCRC.

Background Isolated cancer cells of non-solid type poorly differentiated adenocarcinoma (por2) or signet-ring cell carcinoma (sig) are frequently seen in scirrhous gastric cancers with a very poor prognosis. These cells are often scattered in granulation tissue or desmoplastic fibrotic tissue and tend to be overlooked in routine pathological examination. We aimed to raise a novel antibody that can identify the isolated cancer cells easily. Methods Because the MUC1 cytoplasmic tail domain (CTD) has many biological roles including tumor progression and cell adhesion disturbance and is expected to be expressed in isolated cancer cells, we raised a novel monoclonal antibody (MAb) MUC1-014E against an intracellular nonrepeating 19-amino-acid sequence (RYVPPSSTDRSPYEKVSAG: N-1217-1235-C) of the MUC1 CTD, using a synthetic peptide including the 7-amino-acid epitope (STDRSPY: N-1223-1229-C). Results In the immunohistochemical staining of 107 gastrectomy specimens including 48 por2 and 31 sig lesions, the MAb MUC1-014E showed high rates of positive staining (≥5% of carcinoma cells stained) for por2 (100%) and sig (97%), and of the highest intensity staining (4+, ≥75% of carcinoma cells stained) for por2 (100%) and sig (90%). In the 89 biopsy specimens including 82 por2 and 38 sig lesions, the MAb MUC1-014E showed high rates of positive staining for por2 (100%) and sig (100%) and of 4+ staining for por2 (87%) and sig (84%). All the rates were significantly higher than those with cytokeratins (AE1/AE3 or CAM5.2). Conclusions The MAb MUC1-014E is very useful for accurate detection of isolated cancer cells in scirrhous gastric cancers.

Objective The clinicopathological significance of four morphological types of intraductal papillary mucinous neoplasms of the pancreas (IPMNs; gastric, intestinal, pancreatobiliary and oncocytic) was assessed. Design Retrospective multicentre analysis of 283 surgically resected IPMNs. Results Of the 283 IPMNs, 139 were of the gastric type, 101 were intestinal, 19 were pancreatobiliary and 24 were oncocytic. These types were significantly associated with clinicopathological factors including sex (p=0.0032), age (p=0.00924), ectatic duct size (p=0.0245), detection of mural nodules (p=4.09×10 −6 ), histological grade (p −16 ), macroscopic types with differential involvement of the pancreatic duct system (p=3.91×10 −5 ), invasive phenotypes (p=3.34×10 −12 ), stage (p −16 ) and recurrence (p=0.00574). Kaplan–Meier analysis showed significant differences in patient survival by morphological type (p=5.24×10 −6 ). Survival rates at 5 and 10 years, respectively, were 0.937 (95% CI 0.892 to 0.984) for patients with gastric-type IPMNs; 0.886 (95% CI 0.813 to 0.965) and 0.685 (95% CI 0.553 to 0.849) for those with intestinal-type IPMNs; 0.839 (95% CI 0.684 to 1.000) and 0.734 (95% CI 0.526 to 1.000) for those with oncocytic-type IPMNs; and 0.520 (95% CI 0.298 to 0.909) and undetermined for those with pancreatobiliary-type IPMNs. Analysis by the Cox proportional hazards model comparing prognostic risks determined by stage and the morphological and macroscopic types indicated that staging was the most significant predictor of survival (p=3.68×10 −8 ) followed by the morphological type (p=0.0435). Furthermore, the morphological type remained a significant predictor in a subcohort of invasive cases (p=0.0089). Conclusion In this multicentre retrospective analysis, the morphological type of IPMN appears to be an independent predictor of patient prognosis.

非閉塞性腸管虚血症17例の臨床像,診断,治療成績について検討した.年齢は56歳から90歳,平均73歳であった.基礎疾患として心血管疾患13例,糖尿病3例,慢性腎不全2例,誘因としてdigitalis・利尿剤投与5例,手術侵襲3例,敗血症2例,血液透析2例,血液濃縮2例などを認めた. 11例が術前ショックを呈した.造影CTを施行した12例に腸間膜動脈閉塞を伴わない腸管虚血所見を認めた.血管拡張剤の動注療法は術前,術後に1例ずつ施行した.虚血・壊死範囲は小腸から結腸9例,小腸6例,全腸管2例であった.在院死亡率は56%で,術前ショック,交感神経作動薬投与,広範囲腸管壊死は予後不良であった.周術期のprostaglandin E1の投与例は予後良好であった.動脈硬化関連疾患を有する高齢者に全身の灌流低下が生じ,腹部症状が出現したら, CTで上腸間膜動脈の閉塞と虚血腸管の有無を検索する.本症と診断したら血管拡張剤の投与と必要最小限の腸切除を行う.

Background Mucins are implicated in survival in various cancers, but there have been no report addressed on survival in appendiceal carcinoma, an uncommon disease with different clinical and pathological features from those of other colon cancers. We aimed to investigate the clinical implications of expression of mucins in appendiceal carcinoma. Methods Expression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6, MUC16 and MUC17 in cancer tissue were examined by immunohistochemistry in 108 cases of surgically resected appendiceal carcinoma. Results The following relationships of mucins with clinicopathologic factors were identified: MUC1 with positive lymphatic invasion (p = 0.036); MUC2 with histological type (mucinous carcinoma, p

Previously it has been found that the MUC2 gene for intestinal type secretory mucin is highly expressed in intraductal papillary mucinous tumors (IPMT), which are characterized by non-invasive growth and a favorable outcome. In contrast, MUC2 mRNA is rarely expressed in invasive ductal carcinomas (IDC), which have poor outcomes. The gastric type secretory mucin, MUC5AC, is strongly expressed in the surface mucous cells of gastric mucosa. As both MUC2 and MUC5AC mucins share the characteristics of forming highly viscous gels, it is expected that not only MUC2 mucin expression but also MUC5AC mucin expression may be associated with a favorable prognosis in patients with pancreatic tumors. MUC5AC mucin gene expression was examined in 24 cases of IPMT and 38 cases of IDC by in situ hybridization using a digoxigenin-labeled oligonucleotide. The results were compared with MUC2 mucin gene expression. Neither MUC5AC mRNA nor MUC2 mRNA was detected in normal pancreatic tissues. MUC5AC mRNA was expressed in 20 of 24 cases of IPMT (83%) and in five of 38 cases of IDC (13%). In contrast, MUC2 mRNA was expressed in 14 of 24 cases of IPMT (58%) and in none of the 38 cases of IDC (0%). The expression rates of MUC5AC mRNA and MUC2 mRNA in IPMT were significantly higher than those in IDC (P < 0.001, respectively). Intraductal papillary mucinous tumors are characterized by three histological types: (i) villous dark cell type; (ii) papillary clear cell type; and (iii) compact cell type. The villous dark cell type generally expressed both MUC5AC+ and MUC2+ genes. Alternatively, the papillary clear cell type and the compact cell type usually showed MUC5AC+ and MUC2− expression. Patients with MUC5AC mRNA expression had a significantly better survival prognosis than those with no MUC5AC mRNA expression (P < 0.005). In conclusion, MUC5AC gene expression occurs in a majority of IPMT cases, even in those with no MUC2 production. MUC5AC expression can be correlated with tumors that demonstrate an expansive growth pattern and lower levels of invasion and metastasis.

The expression of MUC-1 mucin (membrane-associated mucin) and MUC-2 mucin (secretory mucin) were immunohistochemically examined in 46 invasive ductal carcinomas (IDC) and 16 intraductal papillary mucinous tumors (IPMT) of the pancreas. Intraductal papillary mucinous tumors usually reveal expansive growth. However, of the 16 IPMT examined in the present study, three showed an invasive growth pattern, which was similar to 'mucinous carcinoma', around the non-invasive growth areas. Of 46 IDC, MUC-1 mucin detected by monoclonal antibodies, DF3 and MY.1E12, was expressed in 44 cases (96%) and in 45 cases (98%), respectively, whereas MUC-2 mucin detected by polyclonal antibody, anti-MRP, was not expressed in any of the cases (0%). In contrast, in the non-invasive growth areas of the 16 IPMT, MUC-1 mucin detected by DF3 and MY.1E12 was expressed in four cases (25%) and in six cases (38%), respectively, whereas MUC-2 mucin detected by anti-MRP was expressed in 13 cases (81%). The invasive growth areas of the three IPMT showed positive expression of MUC-1 mucins detected by DF3 and MY.1E12, although the non-invasive growth areas showed negative expression of MUC-1 mucins, except for their focal positive expression in one of the three cases. These findings indicate that the invasive growth areas of IPMT acquire a characteristic of MUC-1 mucin expression that is usually seen in IDC.

Our previous studies of pancreatic and intrahepatic bile-duct tumors revealed that MUC2 mucin (“secretory mucin”, detected by a polyclonal antibody, anti-MRP) was highly expressed in intraductal papillary-mucinous tumors of the pancreas (IPMTs) and bile duct cystadenocarcinomas of the liver (BDCs) with expansive growth pattern and favorable prognosis, whereas it was rarely or not expressed in invasive ductal carcinomas of the pancreas (IDCs) and cholangiocarcinomas of the liver (CCs) with invasive growth pattern and poor prognosis. In contrast, MUC1 mucin (“membrane-bound mucin” detected by the monoclonal antibody, DF3) was rarely or not expressed in IPMTs and BDCs, but was always expressed in IDCs and CCs (Cancer 71:2191–2199, 1993;Int J Cancer 55:82–91, 1993). The results of these studies suggest that the difference in the expression of MUC1 and MUC2 mucins is a useful indicator of malignant potential in neoplasms of the pancreas and intrahepatic bile duct. This article is a review of our previous studies described above. In addition, we present longer-term follow-up data for the cases reported in our previous studies as well as demonstrating pathological prognostic factors, such as lymph node status, lymphatic infiltration, and perineural invasion. We also examined several additional cases of IPMTs and analyzed the same prognostic factors. We could confirmed the findings of our previous studies, and found that most IPMTs and BDCs with a MUC1(−) and MUC2(+) expression pattern showed less aggressive pathological factors than most IDCs and CCS with a MUC1(+) and MUC2(−) expression pattern.

A unique anomaly of the direct union between the cystic duct and the main pancreatic duct is presented. A 19-year-old man with a history of repeated epigastralgia underwent endoscopic retrograde cholangiopancreaticography that showed a direct union between the cystic duct and the main pancreatic duct. No pancreaticobiliary maljunction was noticed. Cholecystectomy accompanied by resection of the long cystic duct was performed. The excised gallbladder showed cholesterolosis, chronic cholecystitis, and hyperplasia of the pseudopyloric glands microscopically. The patient has been well for 3 years since surgery.

This study aimed to examine expression profile of MUC4 in intraductal papillary mucinous neoplasm of the pancreas (IPMN).We performed immunohistochemistry (IHC) of MUC4 in 142 IPMNs, with evaluation of the specificity of 2 anti-MUC4 monoclonal antibodies, 8G7 and 1G8, in cancer cell lines.Monoclonal antibody 8G7 showed a clear immunoreactivity, whereas MAb 1G8 did not show any immunoreactivity, in the Western blotting and IHC for human pancreatic carcinoma cell lines expressing MUC4 messenger RNA. However, IHC signals detected by both monoclonal antibodies were observed in the tissue specimens. The expression rates of MUC4/8G7 detected by MAb 8G7 and MUC4/1G8 detected by MAb 1G8 in the intestinal-type IPMNs were significantly higher than those in the gastric-type IPMNs. In the intestinal-type IPMNs, MUC4/8G7 was expressed mainly in the cytoplasm of the neoplastic cells, whereas MUC4/1G8 was expressed mainly at the cell apexes. Even in the gastric-type IPMNs with rare MUC4 expression in the low-grade dysplasia, both MUC4 expression rates increased when dysplasia advanced.A significantly higher expression of MUC4 in intestinal-type IPMNs than in gastric-type IPMNs will be one of the biomarkers to discriminate between the intestinal-type IPMNs with high malignancy potential from gastric-type IPMNs with low malignancy potential.

We have previously reported that MUC4 expression is a poor prognostic factor in various carcinomas. Our previous study also showed that MUC1 expression in gastric cancers, including the early and advanced stages is a poor prognostic factor. In the present study, the expression profiles of MUC4 and MUC1 were examined by immunohistochemistry (IHC) using two anti-MUC4 monoclonal antibodies (MAbs), 8G7 and 1G8, and anti-MUC1 MAb DF3 in 104 gastrectomy specimens of early gastric adenocarcinoma with submucosal invasion (pT1b2), including 197 histological subtype lesions. Before the IHC study of the human specimens, we evaluated the specificity of the two MAbs by Western blotting and IHC of two MUC4 mRNA expressing gastric cancer cell lines. MAb 8G7 reacted clearly, whereas MAb 1G8 did not show any reactivity, in either Western blotting or IHC. In the IHC of the gastric cancers, the expression rates of MUC4/8G7 detected by MAb 8G7, MUC4/1G8 detected by MAb 1G8 and MUC1/DF3 detected by MAb DF3 in well differentiated types (70%, 38/54; 67%, 36/54; 52%, 28/54) were significantly higher than those in poorly differentiated types (18%, 10/55; 36%, 20/55; 13%, 7/55) (P

Background. Pancreatic cancer has a poor prognosis, and early diagnosis of carcinoma and discrimination between malignant and benign conditions are difficult. Many pancreatic cancer-associated antigens, such as CA 19-9, DU-PAN-2, YPan-1, and SPan-1, have been studied. However, expression of Tn, sialosyl-Tn, and T antigens in tissues of different types of pancreatic neoplasms has not been investigated systematically. Moreover, little is known about the distribution of different types of apomucins in the pancreas. Methods. The expression of Tn, sialosyl-Tn, and T antigens and DF3 (mammary type apomucin) and intestinal MRP (intestinal type apomucin) was examined immunohistochemically in 47 pancreatic tumors: 36 invasive ductal carcinomas, 5 intraductal papillary tumors, and 6 adenomas. Results. In normal pancreatic tissues, neither Tn nor sialosyl-Tn antigen was expressed. In contrast, expression of both Tn and sialosyl-Tn antigens was observed in all the invasive ductal carcinomas and intraductal papillary tumors. None of the adenomas expressed both Tn and sialosyl-Tn. DF3 antigen was expressed in all invasive ductal carcinomas but not in intraductal papillary tumors, whereas intestinal MRP was expressed in all the intraductal papillary tumors but not in the invasive ductal carcinomas. Conclusions. The results from this study suggest that the expression of the mucin core protein and mucin carbohydrate antigens is correlated with the biologic behavior of pancreatic tumors. In particular, the expression of mammary type mucin core protein and intestinal type mucin core protein showed a striking contrast between invasive ductal carcinomas with a poor prognosis and intraductal papillary tumors with a favorable prognosis.

Many patients with invasive ductal carcinoma of the pancreas (IDC) have a poor outcome. MUC4 expression has been implicated as a marker for diagnosis and progression of IDC, but there are no studies of the relation between MUC4 expression and patient prognosis in IDC.To investigate the prognostic significance of MUC4 expression in IDC.The expression profiles of MUC4, ErbB2, p27, and MUC1 were investigated in IDC tissues from 135 patients by means of immunohistochemistry.MUC4 was expressed in 43 of the 135 patients with IDC (31.9%). The survival of 21 patients with high MUC4 expression (20% of neoplastic cells stained) was significantly worse than that of the 114 patients with low MUC4 expression (20% of neoplastic cells stained) (p = 0.0043). Univariate analysis showed that high MUC4 expression (p = 0.0061), large primary tumour status (T2) (p = 0.0436), distant metastasis (p = 0.0383), lymphatic invasion (p = 0.0243), and surgical margins (p = 0.0333) were significant risk factors affecting the outcome of patients with IDC. Backward stepwise multivariate analysis showed that MUC4 expression (p = 0.0121), lymph node metastasis (p = 0.0245), and lymphatic invasion (p = 0.0239) were significant independent risk factors. ErbB2, p27, and MUC1 were not independent risk factors.This study shows that MUC4 expression in IDC is a new independent factor for poor prognosis and predicts the outcome of patients with IDC.