Shingo Noura

Comparative Detection of Lymph Node Micrometastases of Stage II Colorectal Cancer by Reverse Transcriptase Polymerase Chain Reaction and Immunohistochemistry

PURPOSE Inconsistent conclusions have been drawn about the clinical significance of micrometastases in lymph nodes (LNs) of node-negative colorectal cancer (CRC) patients. We performed a comparative study of detection of micrometastases using immunohistochemistry (IHC) by anti-cytokeratin antibody and carcinoembryonic antigen (CEA)-specific reverse-transcriptase polymerase chain reaction (RT-PCR) in the same patients, in an attempt to move closer to their clinical application. PATIENTS AND METHODS Sixty-four CRC patients, with RNA of good quality available from paraffin-embedded LN specimens, were selected from 84 stage II patients who underwent curative surgery between 1988 and 1996. We investigated associations between the presence of micrometastases by each method and prognosis. RESULTS Micrometastases were detected in 19 (29.6%) of 64 patients by RT-PCR and in 35 (54.7%) of 64 patients by IHC. By RT-PCR analysis, patients exhibiting a positive band for CEA mRNA had a significantly worse prognosis than those who were RT-PCR-negative, with respect to both disease-free and overall survival (P =.027 and.015, respectively). By IHC analysis, the presence of micrometastasis did not predict patient outcome in terms of either disease-free or overall survival. Infiltrating pattern of tumor growth characteristic was significantly associated with shorter disease-free survival among various clinical or pathologic factors. By multivariate Cox regression analysis, micrometastasis detected by RT-PCR and the Crohns-like lymphoid reaction were both independent prognostic factors. CONCLUSION Micrometastases detected by RT-PCR, but not IHC, may be of clinical value in identifying patients who may be at high risk for recurrence of CRC and who are therefore likely to benefit from systemic adjuvant therapy.

Feasibility of a Lateral Region Sentinel Node Biopsy of Lower Rectal Cancer Guided by Indocyanine Green Using a Near-Infrared Camera System

A lateral pelvic lymph node dissection (LPLD) for lower rectal cancer may be beneficial for a limited number of patients. If sentinel node (SN) navigation surgery could be applied to lower rectal cancer, then unnecessary LPLDs could be avoided. The aim of this study was to investigate the feasibility of lateral region SN biopsy by means of indocyanine green (ICG) visualized with a near-infrared camera system (Photodynamic Eye, PDE). This study investigated the existence of a lateral region SN in 25 patients with lower rectal cancer. ICG was injected around the tumor, and the lateral pelvic region was observed with PDE. With PDE, the lymph nodes and lymph vessels that received ICG appeared as shining fluorescent spots and streams in the fluorescence image. This allowed the detection of not only tumor-negative SNs but also tumor-positive SNs as shining spots. The lateral SNs were detected in 6 of 6 T1 and T2 diseases and 17 of 19 T3 diseases. The lateral SNs were successfully identified in 23 (92%) of the 25 patients. The mean number of lateral SNs per patients was 2.1. Of the 23 patients, 6 patients underwent LPLD. Of the 3 patients who had a tumor-negative SN, all dissected lateral non-SNs were negative in all 3 cases. We could detect the lateral SNs, not only in T1 and T2 disease, but also in T3 disease. Although this is only a preliminary study, the detection of lateral SNs in lower rectal cancer by means of the ICG fluorescence imaging system is considered to be a promising technique that may be used for determining the indications for performing LPLD.BackgroundA lateral pelvic lymph node dissection (LPLD) for lower rectal cancer may be beneficial for a limited number of patients. If sentinel node (SN) navigation surgery could be applied to lower rectal cancer, then unnecessary LPLDs could be avoided. The aim of this study was to investigate the feasibility of lateral region SN biopsy by means of indocyanine green (ICG) visualized with a near-infrared camera system (Photodynamic Eye, PDE).MethodsThis study investigated the existence of a lateral region SN in 25 patients with lower rectal cancer. ICG was injected around the tumor, and the lateral pelvic region was observed with PDE.ResultsWith PDE, the lymph nodes and lymph vessels that received ICG appeared as shining fluorescent spots and streams in the fluorescence image. This allowed the detection of not only tumor-negative SNs but also tumor-positive SNs as shining spots. The lateral SNs were detected in 6 of 6 T1 and T2 diseases and 17 of 19 T3 diseases. The lateral SNs were successfully identified in 23 (92%) of the 25 patients. The mean number of lateral SNs per patients was 2.1. Of the 23 patients, 6 patients underwent LPLD. Of the 3 patients who had a tumor-negative SN, all dissected lateral non-SNs were negative in all 3 cases.ConclusionsWe could detect the lateral SNs, not only in T1 and T2 disease, but also in T3 disease. Although this is only a preliminary study, the detection of lateral SNs in lower rectal cancer by means of the ICG fluorescence imaging system is considered to be a promising technique that may be used for determining the indications for performing LPLD.

Comprehensive Clinico-Glycomic Study of 16 Colorectal Cancer Specimens: Elucidation of Aberrant Glycosylation and Its Mechanistic Causes in Colorectal Cancer Cells

The structures of neutral and acidic glycosphingolipids from both normal colorectal epithelial cells and colorectal cancer cells, which were highly purified with the epithelial cell marker CD326, have been analyzed. The analysis was performed on samples from 16 patients. The carbohydrate moieties from glycosphingolipids were released by endoglycoceramidase II, labeled by pyridylamination, and identified using two-dimensional mapping and mass spectrometry. The structures from normal colorectal epithelial cells are characterized by dominant expression of neutral type-1 chain oligosaccharides. Three specific alterations were observed in malignant transformation; increased ratios of type-2 oligosaccharides, increased alpha2-3 and/or alpha2-6 sialylation and increased alpha1-2 fucosylation. Although the degree of alteration varies case to case, we found that two characteristic alterations tend to be associated with clinical features. One is a shift from type-1 dominant normal colorectal epithelial cells to type-2 dominant colorectal cancer cells. This shift was found in 5 patients having hepatic metastasis. The other is specific elevation of alpha2-3 sialylation observed in 2 cases exhibiting high serum levels of CA19-9. Examination of the activities of the related glycosyltransferases revealed that while some alterations could be accounted for by changes in the activities of related glycosyltransferases others could not. Although the number of cases analyzed is small, these findings provide valuable information which will help in the elucidation of the mechanism of synthesis of aberrant glycosylation and its involvement in cancer malignancy.

Association of the Primary Tumor Location with the Site of Tumor Recurrence after Curative Resection of Thoracic Esophageal Carcinoma

The site of surgical failure in cases of thoracic esophageal cancer (TEC) may be affected by the vertical location of the cancer in this longitudinal organ, suggesting the need to select the mode of adjuvant therapy based on location. We classified 501 TECs (92% squamous cell carcinomas) that underwent curative surgery without preoperative treatment as 13% upper thoracic (Ut), 51% middle thoracic (Mt), and 36% lower thoracic (Lt) lesions. Recurrent disease was discovered in 180 (36%) of the patients during a postoperative survey, most frequently in the cervical nodes (19%), liver (18%), abdominal paraaortic nodes (17%), and upper mediastinal nodes (17%). Although postoperative survival rates were similar (5-year survival: Ut 51%, Mt 55%, Lt 54%), the tumor recurrence site was significantly affected by the TEC vertical location, with recurrence in the cervical and upper mediastinal nodes being most frequent for Ut and Mt cases and in the liver and abdominal paraaortic nodes for Lt cases. Insufficient surgical lymph node clearance could be assessed by the recurrence index (RI), defined as the frequency of metastasis at recurrence divided by that at surgery. The RI was significantly lower for the upper abdominal nodes (4%, 8/184) than the lower mediastinal nodes (15%, 19/123) or the upper mediastinal nodes (19%, 30/154). These findings indicated that regional tumor recurrence, corresponding to the surgical field, was more frequent in the Ut and Mt cases (53% and 51%) than the Lt cases (18%); and distant recurrence was more frequent in the Lt cases (62%) than in Ut or Mt cases (25% and 36%). Thus the vertical location of the thoracic esophageal cancer can be said to affected strongly the site of tumor recurrence after curative surgery. Regional radiotherapy might be expected to have an adjuvant effect on Ut/Mt tumors and systemic chemotherapy on Lt tumors.

Long-term Prognostic Value of Conventional Peritoneal Lavage Cytology in Patients Undergoing Curative Colorectal Cancer Resection

PURPOSE: Free malignant cells in the peritoneal cavity might play a role in the metastasis process. However, this phenomenon needs further elucidation. The aims of this study were to investigate the frequency of free cancer cells detected on cytologic examination of lavage fluid after peritoneal washing in patients undergoing curative surgery for colorectal cancer, to explore risk factors for exfoliation of cancer cells into the peritoneal cavity, and to evaluate the influence peritoneal lavage cytology as a prognostic tool. METHODS: Peritoneal lavage was performed in 697 patients undergoing curative resection of colorectal cancer. Before the manipulation of the tumor, 100 mL of physiologic saline solution was administered into the abdominal cavity and the fluid was collected for cytologic examination. Specimens were classified as positive if at least one cancer cell was detected. RESULTS: The mean follow-up period was 90.5 months. Overall, 15 (2.2%) of the 697 patients had positive results. Four characteristics were identified as risk factors for exfoliation of cancer cells into the peritoneal cavity: 1) depth of invasion, 2) regional lymph nodes, 3) lymphatic invasion, and 4) venous invasion. In univariate analyses of all 697 patients and the subgroup of 374 patients with pT3 or T4 tumors, patients with positive cytology findings had significantly worse disease-free and cancer-specific survival than patients with negative cytology findings (P < 0.001). On multivariate analysis, peritoneal cytology remained an independent predictor of cancer-specific survival in all patients and in patients with pT3 or pT4 tumors. Only peritoneal cytology was a significant prognostic factor for peritoneal recurrence (P < 0.0001). CONCLUSION: Conventional peritoneal cytology is a useful prognostic tool in patients undergoing curative surgery for colorectal cancer and may be helpful in making decisions whether to select intraperitoneal or systemic chemotherapy.

Preoperative chemoradiation reduces the risk of pancreatic fistula after distal pancreatectomy for pancreatic adenocarcinoma

BACKGROUND Pancreatic fistula (PF) is a common complication after pancreatectomy. Previous reports indicate that preoperative irradiation decreases the risk of PF after pancreatoduodenectomy. In this context, the impact of preoperative chemoradiation therapy (CRT) on PF formation after distal pancreatectomy is of interest. METHODS Fifty-eight patients with pancreatic adenocarcinoma who underwent distal pancreatectomy, including 28 patients with preoperative gemcitabine-based CRT and 30 patients without preoperative treatment, were assessed in this study. The incidence and severity of postoperative PF, assessed according to the definition of the International Study Group on Pancreatic Fistula, were compared between the 2 groups. RESULTS In the CRT group, 86% of patients did not develop PF, whereas grades A and B PF were observed in 1 and 3 patients, respectively. In the non-CRT group, 33% of patients did not develop a PF, whereas grades A and B PF were observed in 9 and 11 patients, respectively. The incidence of clinically significant PF, defined as either grade B or grade C PF, was less in the CRT group (P = .031). The amylase activities in the draining fluid on postoperative days 1 and 3 were both less in the CRT group (P = .003 and P = .006, respectively). CONCLUSION Preoperative CRT significantly decreases the incidence of PF after distal pancreatectomy, which potentially provides another benefit to patients in addition to its original advantages (ie, locoregional effect and patient selection effect), allowing more opportunities for the immediate initiation of postoperative adjuvant treatment.

Postoperative Cytology for Drained Fluid from the Pancreatic Bed After “Curative” Resection of Pancreatic Cancers: Does It Predict Both the Patient’s Prognosis and the Site of Cancer Recurrence?

Objective To evaluate the postoperative cytology of drained fluid from the pancreatic bed as a predictive indicator of local recurrence after curative (R0) resection of pancreatic cancer. Summary Background Data The pancreatic bed offers a common site of cancer recurrence (local recurrence), even after curative (R0) resection is performed for pancreatic cancer. If local recurrence is thereby predicted precisely, soon after surgery, we have a chance to treat it by adding radiation or some other locoregional therapy before it can grow or spread beyond the pancreatic bed. However, there have been no previous reports of cytology performed on the drained fluid after pancreatectomy. Methods This study includes 94 patients who had shown negative results in the peritoneal washing cytology before resection and subsequently received pancreatectomies for pancreatic tumors. They consisted of 12 benign tumors, 17 noninvasive or minimally invasive carcinomas and 65 invasive ductal carcinomas (R0 = 58; R1/2 = 7). Postoperatively, the drained fluid from the pancreatic bed was collected for 24 hours and used for cytologic examination. The cytologic results were examined in association with the histopathology of the resected tumor, patients survival, and mode of cancer recurrence, including local recurrence. Results Patients with benign tumors or noninvasive/minimally invasive carcinomas had negative result in cytology, and none of them have died of local recurrence (limited to the pancreatic bed) to date. However, patients with invasive ductal carcinoma revealed higher cytology-positive rates: 28% (16/58) in curative (R0) resection; and 71% (5/7) in noncurative (R1/2) resection. Among 58 patients with R0 resection, the 3-year survival rate was 14% in 16 cytology-positive patients and 55% in 42 cytology-negative patients (P < 0.05). The 3-year cumulative rate of local recurrence was 85% and 23%, respectively (P < 0.05). Compared with other histopathologic parameters obtained from the resected specimens, the drain cytology was more specific in predicting the subsequent development of local recurrence. Conclusions Drain-cytology was a quick examination that enabled us to specifically indicate both minute residual cancer and subsequent development of local recurrence even after R0 resection of pancreatic cancer.

Staging laparoscopy using ALA‐mediated photodynamic diagnosis improves the detection of peritoneal metastases in advanced gastric cancer

This study evaluated the usefulness of photodynamic diagnosis (PDD) using oral 5‐aminolevulinic acid (ALA) for the detection of peritoneal metastases in advanced gastric cancer.

Brain metastasis from colorectal cancer: prognostic factors and survival.

Colorectal cancer (CRC) rarely metastasizes to the brain, and the incidence rate has been reported to be 1–2%. Unfortunately, the median survival for patients with brain metastasis (BM) from CRC is short. In this study, we retrospectively investigated the BM from CRC and examined the prognostic factors.

Outcome of surgical resection for recurrent pulmonary metastasis from colorectal carcinoma.

BACKGROUND The outcomes after repeat pulmonary resection for colorectal cancer (CRC) and the factors associated with the prognosis of these patients remain uncharacterized. METHODS Data on 156 patients who underwent curative resection of pulmonary metastasis from CRC were reviewed. Repeat pulmonary resection was performed in 25 patients; the present study examined the outcomes and factors associated with prognosis after repeat pulmonary resection. RESULTS The 5-year survival rate after the first pulmonary resection was 56.2%. A multivariate analysis identified a histological type other than well-differentiated adenocarcinoma, a high prethoracotomy serum carcinoembryonic antigen (CEA) level, and the presence of hilar or mediastinal lymph node metastasis as poor prognostic factors for the first pulmonary resection. The 5-year survival rate after repeat pulmonary resection was 42.1%. Hilar or mediastinal lymph node metastasis at the time of the repeat resection was significantly associated with poor survival. CONCLUSIONS Repeat pulmonary resection for metastatic CRC provides satisfactory outcomes. Hilar or mediastinal lymph node involvement is consistently associated with a poor prognosis after the first and repeat pulmonary resections.