Tsukasa Hotta

Chemosensitivity testing of fresh human gastric cancer with highly purified tumour cells using the MTT assay.

A major problem associated with the chemosensitivity testing of fresh human tumour cells using the MTT assay is the contamination of nonmalignant cells in the tumour tissues. Highly purified fresh human gastric cancer cells could be obtained from 43 solid tumours and eight malignant ascites for the MTT assay. The success rate of the MTT assay was 87.9% (51 of the 58 cases), and the purity of tumour cells was greater than 90% after separation on Ficoll-Hypaque and Percoll discontinuous gradients in primary, or metastatic lesions, and also ascites. Cisplatin, mitomycin, and doxorubicin were more potent drugs than etoposide and 5-FU against gastric cancer cells. The chemosensitivity in differentiated cancer was equivalent to that in non-differentiated cancer. Twenty of the 51 patients with gastric cancer had evaluable lesions, and they received chemotherapy according to the results of the MTT assay using highly purified tumour cells. A clinical response was obtained in 12 of these 20 patients (response rate: 60.0%; five with complete response, seven with partial response).

Re‐expression of CEACAM1 long cytoplasmic domain isoform is associated with invasion and migration of colorectal cancer

Carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1) is known to be downregulated at the transcriptional level in adenoma and carcinoma. Recent reports have shown that CEACAM1 is overexpressed at protein level in colorectal cancer and correlated with clinical stage. The reason why colorectal cancer cells re‐expressed CEACAM1 remains unclear. The aim of our study was to clarify the implication of CEACAM1 re‐expression in colorectal cancer. Immunohistochemical analyses were conducted with CEACAM1 long (CEACAM1‐L) or short (CEACAM1‐S) cytoplasmic domain‐specific antibodies on clinical samples from 164 patients with colorectal cancer. The risk factors for metastasis and survival were calculated for clinical implication of CEACAM1 re‐expression. Invasion chamber and wound healing assays were performed for the effect of CEACAM1 expression on invasion and migration of colorectal cancer cells. CEACAM1‐L and CEACAM1‐S stained with greater intensity at the invasion front than at the luminal surface of tumors. Differences between the long and short cytoplasmic isoform expression levels were observed at the invasion front. Multivariate analysis showed that CEACAM1‐L dominance was an independent risk factor for lymph node metastasis, hematogenous metastasis and short survival. The Kaplan–Meier evaluation demonstrated that CEACAM1‐L dominance was associated with shorter survival time (p < 0.0001). In the invasion chamber and wound healing assays, CEACAM1‐L promoted invasion and migration. Re‐expression of CEACAM1 is observed at the invasion front of colorectal cancer. CEACAM1‐L dominance is associated with metastasis and shorter survival of the patients with colorectal cancer. CEACAM1‐L dominance is important for colorectal cancer cells invasion and migration.

Postoperative evaluation of pylorus-preserving procedures compared with conventional distal gastrectomy for early gastric cancer.

Abstract We evaluated postoperative function in 98 patients who underwent surgery for early gastric cancer between 1995 and 1998 to compare the results of pylorus-preserving procedures to those of conventional distal gastrectomy with Billroth I (B-I). The pylorus-preserving procedures included endoscopic mucosal resection (EMR), performed in 12 patients; local resection (Local), performed in 14 patients; segmental resection (Seg), performed in 8 patients; and pylorus-preserving gastrectomy (PPG), performed in 19 patients. B-I was performed in 45 patients. The nutritional status and serum albumin (Alb) levels after PPG, the hemoglobin (Hb) levels after EMR, Local, and PPG, and the present/preoperative body weight ratios after EMR, Local, Seg, and PPG were superior to those after B-I. The time before oral intake was recommenced after EMR and Local, the volume of oral intake tolerated after EMR, Local, Seg, and PPG, and the postoperative hospital stay after EMR were all superior to those after B-I. Moreover, significantly fewer patients suffered reflux symptoms after EMR, Local, and PPG, abdominal fullness after EMR, and early dumping syndrome after EMR, Local, and PPG than after B-I. There was also less evidence of gastritis after EMR, Local, and PPG, and of bile reflux after EMR, Local, and PPG, than after B-I. These findings indicate that pylorus-preserving procedures may result in a better postoperative quality of life for selected patients with early gastric cancer.

So-Called Carcinosarcoma of the Gallbladder; Spindle Cell Carcinoma of the Gallbladder: Report of a Case

We report a so-called carcinosarcoma of the gallbladder in a 53-year-old man. The findings of ultrasonography, computed tomography, endoscopic retrograde cholangiopancreatography, and angiography revealed a large mass of the gallbladder with a cholesterol stone. He underwent three operations, and died from liver failure with multiple liver metastasis immediately after the third operation. A pathological examination revealed neoplastic tissue composed of sarcomatous and glandular components. Hematoxylin–eosin stain proved the presence of carcinosarcoma in the gallbladder, but an immunohistochemical study proved that the sarcomatous component was stained by antivimentin and also anticytokeratin antibodies, which thus proved it to be so-called carcinosarcoma of the gallbladder. As a result, an immunohistochemical study is considered to provide valuable information regarding the identification of sarcomatous elements in such cases.

Clinical evaluation of chemosensitivity testing for patients with colorectal cancer using MTT assay

PURPOSE: Colorectal cancer is one of the tumors most refractory to treatment by chemotherapy. The chemosensitivity test should be performed to individualize the chemotherapy for patients with colorectal cancer, which is less sensitive for anticancer drugs. The present study was designed to determine the chemosensitivity in fresh human colorectal cancer, using highly purified tumor cells, and the correlation of this sensitivity with clinical response. METHODS: We determined the chemosensitivity for cisplatin, mitomycin C, adriamycin, and 5-fluorouracilin vitroin 93 fresh human colorectal cancers using the MTT assay and performed chemotherapy according to results of the MTT assay. RESULTS: Inhibition rate of tumor cells for cisplatin was higher than those for other drugs. Fifteen patients who have evaluable lesions received chemotherapy according to results of the MTT assay. Clinical responses were obtained in 5 of 15 patients, and the inhibition rate for cisplatin was higher in responders than in nonresponders. CONCLUSIONS: It is suggested that the chemotherapy according to results of the MTT assay is effective in patients with colorectal cancer.

C-Reactive protein is an independent surgical indication marker for appendicitis: a retrospective study

BackgroundThis study is an attempt to clarify the role of C-reactive protein (CRP) as a surgical indication marker for appendicitis.MethodsOne hundred and fifty patients who underwent appendectomies and had pathologically confirmed appendicitis were reviewed between May 1, 1999 and September 31, 2007. The correlation between preoperative clinical factors and the actual histological severity, and identify surgical indication markers were assessed by univariate and multivariate analyses.ResultsUnivariate analysis showed that only the CRP level significantly differ between the surgical treatment necessary group (gangrenous appendicitis) and the possible non-surgical treatment group (catarrhalis and phlegmonous appendicitis). Multivariate analysis indicated only the CRP level to be a surgical indication marker for acute appendicitis. The receiver-operating characteristic (ROC) curve indicated that the cutoff value of CRP for surgical indication of appendicitis is 4.95 mg/dl.ConclusionOnly the CRP level is consistent with the severity of appendicitis, and considered to be a surgical indication marker for acute appendicitis.

Randomized clinical trial of defaecatory function after anterior resection for rectal cancer with high versus low ligation of the inferior mesenteric artery

Defaecatory function is often poor after anterior resection. Denervation of the neorectum following high ligation of the inferior mesenteric artery (IMA) is a possible cause of impaired defaecatory function. The purpose of this randomized clinical trial was to clarify whether the level of ligation of the IMA in patients with rectal cancer affects defaecatory function.

Reconstruction of an infected recurrent ventral hernia after a mesh repair using a pedicled tensor fascia lata flap: Report of two cases

Recently, the use of prosthetic mesh has revolutionized the repair of ventral hernias. However, the occurrence of infection related with the use of this prosthesis remains an important complication, which may result in occurrence of fistula formation of the skin or intestine, sepsis, or reoccurrence of ventral hernia. This report presents two cases where a pedicled musculocutaneous flap using the tensor fascia lata (pedicled TFL flap) was effective as a treatment for an infectious large abdominal hernia, and reviews the previous literature. Two Japanese men aged 61 and 78 years old underwent a ventral hernia repair using Composix Kugel mesh. They both developed a wound infection with methicillin-resistant Staphylococcus aureus. Conservative therapy was not successful and the defect in the abdominal wall of two patients measured 12 × 21 cm and 7 × 10 cm in length, respectively. Reoperations were performed by removing the infectious mesh and then reconstructing the abdominal wall with the bilateral and left-side pedicled TFL flaps, respectively. No recurrence of the ventral hernia has been recognized for 50 months and 7 months after reoperation, respectively. A review of previous studies showed that no patients treated with a pedicled TFL flap experienced a recurrent hernia. Therefore, the pedicled TFL flap was considered to be effective for infectious large abdominal recurrent hernia.

Identification of the Molecular Mechanisms for Dedifferentiation at the Invasion Front of Colorectal Cancer by a Gene Expression Analysis

Purpose: The aim of this study is to identify gene expression signatures that accompany dedifferentiation at the cancer invasion front in colorectal cancer. Experimental Design: Two types of colorectal cancer were selected. Both types were well-differentiated adenocarcinomas at the superficial lesion. One type showed a dedifferentiated phenotype at the invasion front (type A, 13 samples); the other showed almost no dedifferentiated cancer cells at the invasion front (type B, 12 samples). Laser microdissection was combined with a cDNA microarray analysis to investigate the superficial lesions and the invasion front in colorectal cancers. Results: Eighty-three genes were differentially expressed between types A and B in the superficial lesions, and the samples of superficial lesions were divided correctly into two clusters by these genes. Interestingly, the samples of the invasion front were also divided into the two same clusters by these genes. The text mining method selected 10 genes involved in potential mechanisms causing dedifferentiation of cancer cells at the invasion front. The potential mechanisms include the networks of transforming growth factor-β, Wnt, and Hedgehog signals. The expression levels of 10 genes were calculated by quantitative reverse transcription-PCR and 8 genes were confirmed to be significantly differentially expressed between two types (P < 0.05). The gene expression profiles of 8 genes divided 12 test cases into two clusters with one misclassification. Conclusions: The molecular mechanisms constructed with 8 genes from three networks of transforming growth factor-β, Wnt, and Hedgehog signals were found to correlate with dedifferentiation at the invasion front of colorectal cancer.

Clinical impact of a macroscopically complete resection of colorectal cancer with peritoneal carcinomatosis

BACKGROUND So far, few reports have focused on the clinicopathological features and patterns of recurrence after a complete resection of peritoneal carcinomatosis (PC) of colorectal origin. The purpose of the present study was to show the clinicopathological features of a macroscopically complete resected tumor and the pattern of recurrence after the curative resection of colorectal PC. METHODS In 153 patients with colorectal PC, 31 patients who underwent a complete resection of a synchronous primary lesion of a colorectal PC between 1998 and 2007 were assessed retrospectively. RESULTS Clinicopathological differences were observed in the tumor location, presence of extraperitoneal metastases, extent of PC, and presence of lymph node metastases between a macroscopically complete resection and noncomplete resection patients (P = .045, P < .0001, P < .001, and P = .039, respectively). Tumor recurrence after the complete resection of colorectal PC was observed in 24 patients (77.4%). The 5-year survival rate after complete resection was 36.0%. The survival rate in the macroscopically complete resection group was higher than in the incomplete resection group (P < .001). The 5-year intra- and extraperitoneal recurrence survival rates were 63.9% and 33.8%, respectively. No significant clinicopathological factors affected intraperitoneal recurrence-free survival. Conversely, a univariate analysis using the log-rank test revealed that extended PC and presence of lymph node metastases were poor factors affecting extraperitoneal recurrence (P = .009 and P = .023, respectively). Eleven of 31 patients survived for 5 years after resection. Two of the 4 patients with liver metastases had received a hepatectomy. CONCLUSION Although the 5-year survival rate after a macroscopically complete resection for colorectal PC approached 36.0%, 77.4% of patients developed intra- and extraperitoneal recurrence. Extended PC and presence of lymph node metastases were poor factors affecting extraperitoneal recurrence.