Takeyasu Suda

Simultaneous detection of colorectal carcinoma liver and lung metastases does not warrant resection

BACKGROUND Recent evidence suggests that metastasectomy is efficacious for selected patients with hepatic and pulmonary metastases from a colorectal primary. The aim of this study was to identify a subgroup of patients who best benefit from hepatic and pulmonary metastasectomy among those with colorectal carcinoma metastases. STUDY DESIGN We analyzed retrospectively a total of 136 patients who underwent resection of hepatic or pulmonary metastases of colorectal origin at Niigata University Medical Hospital between 1982 and 2000. The median follow-up period was 94 months. Eighty-four patients underwent hepatectomy alone, 25 underwent pulmonary resection alone, and 27 underwent both hepatic and pulmonary resection. The 27 patients undergoing hepatic and pulmonary resection were divided into two groups: 17 patients with sequentially detected hepatic and pulmonary metastases and 10 patients with simultaneously detected metastases. Survival time was determined from the date of initial metastasectomy. Differences in cumulative survival were evaluated using the log-rank test. Sixteen factors were assessed for their influence on the survival of the 27 patients undergoing resection of hepatic and pulmonary metastases; univariate and multivariate analyses were used in this evaluation. RESULTS Patient survival after hepatic and pulmonary resection was comparable with that after hepatectomy alone (p = 0.536) and that after pulmonary resection alone (p = 0.294). Among the 27 patients undergoing hepatic and pulmonary resection, the outcomes after resection were significantly better in patients with sequentially detected metastases (cumulative 5-year survival of 44%) than in those with simultaneously detected ones (cumulative 5-year survival of 0%) (p < 0.001). On multivariate analysis sequential detection of hepatic and pulmonary metastases was the strongest independent favorable prognostic factor (p <0.001). CONCLUSIONS Patients with sequentially detected hepatic and pulmonary metastases from a colorectal primary are good candidates for aggressive metastasectomy. Simultaneous detection of these metastases does not warrant resection.

Prognostic significance of lateral lymph node micrometastases in lower rectal cancer: An immunohistochemical study with CAM5.2

PURPOSE The aims of this study were to determine the rate of lymph node micrometastases and to evaluate their prognostic value in lateral lymph nodes in lower rectal cancer at or below the peritoneal reflection. METHODS A retrospective analysis was made of 892 lymph nodes from 66 consecutive patients who had undergone radical resection with lateral lymph node dissection. These lymph nodes were examined immunohistochemically with an antibody against cytokeratins 7 and 8, CAM5.2. RESULTS Routine hematoxylin-eosin staining revealed 9 patients with positive lateral lymph nodes that were stained consistently with CAM5.2. Among 57 patients in whom lateral lymph node metastases were not detected by hematoxylin-eosin staining, cytokeratin staining was positive in 19 nodes (2.7 percent) from 11 patients (19.3 percent). These 11 patients with micrometastases in lateral nodes showed a significantly high recurrence rate (P = 0.048) and worse overall survival (P = 0.01) than the 46 patients without lateral node metastases. The recurrence rate and overall survival of patients with micrometastases did not differ significantly from those of patients with positive lateral nodes with hematoxylin-eosin staining. Local recurrence developed in 6 of 66 patients, but neither the presence nor the absence of micrometastases in lateral nodes influenced the local recurrence rate. CONCLUSION The presence of nodal micrometastases leads to a poor prognosis. The survival of patients with micrometastases was not different from that of patients with overt metastases. Therefore, patients with cytokeratin-positive cells in lateral lymph nodes should be regarded as having overt metastases.

Clinicopathologic characteristics of clinically relevant cytomegalovirus infection in inflammatory bowel disease.

BackgroundIn this study we aimed to identify clinically relevant patterns of cytomegalovirus (CMV) infection in inflammatory bowel disease.MethodsTwenty-two patients with severe ulcerative colitis (UC), 12 with moderate UC, and 16 with Crohns disease were studied retrospectively. We confirmed CMV infection immunohistochemically. The patients were classified into three groups according to the density of CMV-infected cells. Clinicopathologic features were compared between the groups.ResultsDense CMV infection was found only in five patients with severe UC. Scattered CMV infection was found in nine patients with severe UC, three with moderate UC, and one patient with Crohns disease, and in three controls (normal mucosa from early colorectal cancer specimens). For patients with severe UC, severity of CMV infection tended to correlate with older age and more rapid deterioration, including toxic megacolon and panperitonitis. The dense CMV group took significantly higher final daily doses of steroids before the operation, and showed steroid resistance. The frequency of emergency surgery was higher and postoperative hospital stay was significantly longer in the dense CMV group. No significant differences were observed in sex, disease duration, steroid administration (total amount or duration), or frequencies of other therapies among the three groups. Immunohistochemically, CMV positivity in endothelial cells around the ulcer base was a significant feature in dense CMV infection, compared with scattered CMV infection.ConclusionsOlder patients with severe steroid-resistant UC may be at particular risk for CMV infection. Dense CMV infection, especially when it occurs predominantly in endothelial cells, may be a useful marker for clinically relevant CMV infection.

Prognostic Significance of Lateral Lymph Node Micrometastases in Lower Rectal Cancer

AbstractPURPOSE: The aims of this study were to determine the rate of lymph node micrometastases and to evaluate their prognostic value in lateral lymph nodes in lower rectal cancer at or below the peritoneal reflection. METHODS: A retrospective analysis was made of 892 lymph nodes from 66 consecutive patients who had undergone radical resection with lateral lymph node dissection. These lymph nodes were examined immunohistochemically with an antibody against cytokeratins 7 and 8, CAM5.2. RESULTS: Routine hematoxylin-eosin staining revealed 9 patients with positive lateral lymph nodes that were stained consistently with CAM5.2. Among 57 patients in whom lateral lymph node metastases were not detected by hematoxylin-eosin staining, cytokeratin staining was positive in 19 nodes (2.7 percent) from 11 patients (19.3 percent). These 11 patients with micrometastases in lateral nodes showed a significantly high recurrence rate (P = 0.048) and worse overall survival (P = 0.01) than the 46 patients without lateral node metastases. The recurrence rate and overall survival of patients with micrometastases did not differ significantly from those of patients with positive lateral nodes with hematoxylin-eosin staining. Local recurrence developed in 6 of 66 patients, but neither the presence nor the absence of micrometastases in lateral nodes influenced the local recurrence rate. CONCLUSION: The presence of nodal micrometastases leads to a poor prognosis. The survival of patients with micrometastases was not different from that of patients with overt metastases. Therefore, patients with cytokeratin-positive cells in lateral lymph nodes should be regarded as having overt metastases.

Multiple Repeat Resections of Intra- and Extrahepatic Recurrencesin Patients Undergoing Initial Hepatectomy for Colorectal CarcinomaMetastases

Recent evidence suggests that single repeat metastasectomy may provide survival benefits for selected patients experiencing hepatic or pulmonary recurrences following initial hepatectomy for colorectal carcinoma metastases. The aim of this retrospective study was to clarify the efficacy of multiple repeat resections of intra- and extrahepatic recurrences following initial hepatectomy. A total of 100 patients underwent curative partial hepatectomy as the initial procedure for colorectal carcinoma metastases. Tumor relapse after initial hepatectomy was seen in 72 patients, of whom 28 underwent 45 repeat metastasectomies of various sites: 18 patients underwent a single repeat metastasectomy, and 10 underwent multiple repeat metastasectomies. The overall survival rate at 5 years after initial hepatectomy was 36.6%, while the 5-year survival rate after repeat metastasectomy in the 28 patients was 43.6%. The outcome of initial hepatectomy was comparable with that of repeat metastasectomy (p = 0.6924). Among the 28 patients undergoing repeat metastasectomy, the outcome of resection of intrahepatic recurrences in 11 patients was comparable with the outcome of resection of extrahepatic recurrences in 17 patients(p = 0.3926). The outcome of multiple repeat metastasectomies compared favorably with single repeat metastasectomy(p = 0.1803). Multivariate analysis(p < 0.0001) showed that repeat metastasectomy was the strongest prognostic factor. In conclusion, both single and multiple repeat resections of intra- and extrahepatic recurrences after initial hepatectomy are efficacious in colorectal carcinoma patients. Repeat resection should be considered for any resectable recurrences after hepatectomy.

CD161+ T (NT) cells exist predominantly in human intestinal epithelium as well as in liver

It has been reported that human CD161 (NKR‐P1A)+ T cells are counterparts of murine natural T (NT) cells and predominantly accumulate in the liver. However, NT cells in the human intestine have not been well analysed. The aim of this study was to assess the existence of NT cells in human intestinal epithelium and determine their phenotypical characterization. Intra‐epithelial lymphocytes (IEL) were isolated from surgical specimens (jejunum, ileum and colon). The surface phenotype of IEL was analysed using a FACScan and compared with that of mononuclear cells (MNC) from other organs. CD161+ T cells were abundant in human intestinal epithelium as well as the liver. The majority of CD161+ T cells in IEL were CD8+ cells. About 50% of CD161+ T cells in hepatic lymphocytes (HL) expressed CD56, whereas only 14% of CD161+ T cells in IEL expressed CD56. The jejunum showed the greatest abundance of CD161+ T cells among the intestinal regions investigated. These results suggest that CD161+ T (NT) cells predominantly exist in human intestinal epithelium and may play an important role in local immunity.

Expression of Fas ligand is an early event in colorectal carcinogenesis

Fas ligand (FasL) is expressed in many cancers and plays an important role in establishing immunologically privileged environments that allow tumors to escape the hosts immune surveillance. We investigate the expression of FasL in human colorectal cancer and colorectal adenoma and elucidate the relationship between FasL expression and the clinicopathological characteristics of colorectal cancers.

Mutations of p53 in Morphologically Non-neoplastic Mucosa of Long-standing Ulcerative Colitis

Two cases of ulcerative colitis (UC)‐associated carcinoma or dysplasia and morphologically non‐neoplastic mucosa with p53 protein overexpression (MNNM‐p53OE) were selected. DNA was extracted from the paraffin blocks of these lesions and exons 5‐8 of the p53 gene were analyzed by PCR and direct sequencing. In addition, mutations in K‐ras codon 12 were analyzed by PCR‐RFLP methods. MNNM‐p53OE was located surrounding and adjoining a coexisting carcinoma and/or dysplasia. A p53 mutation was detected in 12/22 (54.5%) MNNM‐p53OE samples, 4/8 (50%) dysplasia samples and 8/8 (100%) carcinoma samples. The/j53 mutations detected in MNNM‐p53OE were identical to those demonstrated in the adjoining carcinoma and/or dysplasia. No K‐ras codon 12 mutation was detected in any of the samples. These results indicate that MNNM‐p53OE may share an identical clonal linkage with a coexisting carcinoma and/or dysplasia, and may be an initial and submorphological form of UC‐associated neoplasia. Recognition of MNNM‐p53OE in biopsy specimens may help to identify patients with UC at risk of developing colorectal carcinoma.

Toxic megacolon associated with cytomegalovirus infection in ulcerative colitis

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Synchronous development of HCC and CCC in the same subsegment of the liver in a patient with type C liver cirrhosis

As a result of having undergone computed tomography (CT), a 75-year-old woman with type-C liver cirrhosiswas shown to have two tumors on the ventral and dorsal sides of subsegment 3 (S3). The tumor on the ventral side was diagnosed as a classic hepatocellular carcinoma (HCC), while that on the dorsal side was considered atypical for a HCC. Although the indocyanine green (ICG) findings indicated poor hepatic reserve, the prothrombin time (PT) was relatively good. An operation was performed in February 2007; however, this resulted in exploratory laparotomy. Dynamic CT performed 12 mo after the operation revealed that the tumor on the dorsal side of S3 had apparently increased. The marginal portion of the tumor was shown to be in the early and parenchymal phases, while the internal portion was found to have grown only slightly in the delayed phase. We diagnosed this tumor as a cholangiocellular carcinoma (CCC). S3 subsegmentectomy was performed in April 2008. The tumor on the ventral side was pathologically diagnosed as a moderately differentiated HCC, and that on the dorsal side was diagnosed as a CCC. We can therefore report a rare case of synchronous development of HCC and CCC in the same subsegment of the liver in a patient with type-C liver cirrhosis. We also add a literature review for all the reported cases published in Japan and around the world, and summarize the features of double cancer exhibiting both HCC and CCC.