Ichiro Nakada

Prognostic Significance of Immunohistochemically Detected Blood and Lymphatic Vessel Invasion in Colorectal Carcinoma: Its Impact on Prognosis

BackgroundThe prognostic significance of blood vessel invasion (BVI) and lymphatic vessel invasion (LVI) is unclear. Because of the absence of specific markers for venous and lymphatic vessels, earlier studies could not reliably distinguish between BVI and LVI.MethodsBy immunostaining for podoplanin and CD34 antigen, we retrospectively investigated LVI and BVI in 419 tissue specimens of colorectal carcinoma. We performed univariate and multivariate analysis of the clinicopathologic features, frequency of recurrence, and outcome of patients with or without LVI and BVI.ResultsThe use of hematoxylin and eosin (H&E) staining to identify BVI and LVI yielded a false positive rate of 9.1% and false negative rate of 12.6%. The incidence of BVI was significantly higher among tumors with LVI than tumors without LVI (P <.001). In logistic multivariate analysis, only LVI (P < .001) was associated with lymph node metastasis and BVI (P = .015) was associated with distant recurrence. Calculating the prognostic relevance, both two invasion types correlated with decreased survival in univariate analysis (both P <.001). In multivariate analysis, BVI (P =.024), lymph node status (P =.003) and tumor stage (P <.001) remained statistically significant factors for survival.ConclusionsOur results suggest that immunohistologic evaluation of BVI and LVI could be useful in colorectal carcinoma indicating the risk of lymph node metastasis and recurrence, thereby contributing to prognostic evaluation.

Diverticular disease of the colon at a regional general hospital in Japan

PURPOSE: X-ray film registry records were reviewed to better understand the changing nature of diverticular disease (DD) of the colon in Japan. RESULTS: Among 6,849 patients undergoing barium enema examination during a eight-year period from 1985 to 1992, this condition was found in 1,074 patients (15.7 percent), including 702 males (65.4 percent) and 372 females (34.6 percent). During this eight-year period there was an increase in frequency from 10.7 percent in 1985 to 17.8 percent in 1992. The proportion of patients with right-sided, bilateral, and left-sided DD was 69.2 percent, 17.5 percent, and 13.3 percent, respectively. The right-sided DD was more common in the younger age group and was predominant in male patients, whereas the left-sided DD increased with age, especially in female patients. Of the 1,074 patients, 11 (1.0 percent) underwent surgery in the same period. Regarding the rightsided DD, only 2 of 743 patients received surgery (0.3 percent). On the other hand, of the 143 patients with left-sided DD, 9 patients (6.3 percent) received some form of surgery. CONCLUSION: Right-sided diverticular disease of the colon is still common in Japan. It does not appear that this tendency will change in the future. Nearly all patients diagnosed as having diverticula had either no symptoms or only mild symptoms, and only about 1 percent required surgery. Right-sided diverticular disease of the colon seems to have had no serious clinical problems compared with left-sided DD.

Increased density and diameter of Lymphatic microvessels correlate with lymph node metastasis in early stage invasive colorectal carcinoma

To determine whether lymphangiogenesis was associated with the development of colorectal carcinoma and whether the mean maximal diameter of lymphatic microvessels (LMMMD) or lymphatic microvessel density (LMVD) is associated with lymph node metastasis in early stage invasive colorectal carcinoma (T1 carcinoma), we used immunohistochemical staining with podoplanin to measure LMMMD and LMVD in intratumoral (LMMMDit, LMVDit) and peritumoral areas (LMMMDpt, LMVDpt) of T1 carcinomas (n=87). By comparing the LMMMD and LMVD in normal large intestine (n=10), adenoma (n=15), and Tis carcinoma (n=15), we found out that the LMVDpt in T1 carcinoma with lymphatic vessel invasion (LVI) was significantly high (P<0.001), and there was a significant decrease in LMMMDpt in T1 carcinoma (P=0.031). Both LMMMDpt and LMVDpt were significantly increased in the T1 carcinomas, with LVI compared with the T1 carcinomas without LVI (P=0.018, P=0.003). Multivariate analysis revealed that LVI and combined greater LMMMDpt and greater LMVDpt were associated with lymph node metastases (P=0.005, P=0.036). These results indicate that lymphangiogenesis might be induced in the surrounding tumor areas of the T1 colorectal carcinoma with LVI; thus, evaluation of the diameter and density of lymphatic microvessels is important in T1 colorectal carcinoma to predict lymph node metastases.

Desmoplastic response in biopsy specimens of early colorectal carcinoma is predictive of deep submucosal invasion

PURPOSE: The aim of this study was to evaluate the role of histopathology of biopsy specimens in predicting depth of infiltration in early colorectal carcinomas before treatment. METHODS: Early colorectal carcinomas that had been resected surgically or endoscopically between 1984 and 1995 were analyzed. Histopathologic findings, including differentiation of adenocarcinoma and a desmoplastic response were investigated. RESULTS: One hundred nine early colorectal carcinomas consisted of 73 lesions of carcinomain situ, 13 submucosal carcinomas with minimum invasion, 8 lesions with moderate invasion, and 15 lesions with deep invasion. Of 73 carcinomain situ lesions, 72 (approximately 99 percent) showed well-differentiated adenocarcinomas and no desmoplastic response. Twelve (92 percent) of 13 submucosal carcinomas with minimum invasion also revealed well-differentiated adenocarcinoma without a desmoplastic response. Sixty-three percent (5/8)of lesions with moderate invasion revealed well-differentiated adenocarcinoma. None of the lesions had a desmoplastic response. Among lesions with deep invasion, 73 percent (11/15) demonstrated moderately differentiated adenocarcinoma, and 11 lesions had a prominent desmoplastic response (73 percent;P<0.01). CONCLUSIONS: These results suggest that if histopathologic findings of biopsy specimens taken from them before treatment demonstrated adenocarcinoma associated with a desmoplastic response, the lesions had at least deep invasion carcinomas. These lesions should be resected surgically. Submucosal carcinomas with minimum invasion, which have no desmoplastic response, could be treated endoscopically.

The granulocyte/lymphocyte ratio as an independent predictor of tumour growth, metastasis and progression : its clinical applications

Several investigators have suggested that the granulocyte/lymphocyte (G/L) ratio is a good indicator for the evaluation of the condition of a tumour-bearing host, although its prognotic significance is unclear. To further investigate the clinical applications of the G/L ratio, we injected 1x105 and 1x106 Lewis lung carcinoma cells (3LLc) into the feet of 4-week-old C57BL/6 mice separated into groups A, B, C and D (1x105 cells) and E, F, G and H (1x106 cells). For the observation of tumour metastasis and G/L ratio, the mice in groups A-D were sacrificed on days 11, 14, 17 and 21 after inoculation with the 3LLc cells, and the mice in groups E-H on days 7, 11, 14 and 17. The results suggest that in mice the number of granulocytes increases with time after 3LLc cell injection (P<0.05). We also retrospectively investigated the correlation between G/L ratio, clinicopathologic features and prognosis in 62 patients with gastric carcinoma. There was a significant correlation between the G/L ratio and tumour weight (r=0.746, P<0.05), as well as a significant difference between the G/L ratio and the extent of metastases (P<0.05). Additionally, the G/L ratio was significantly associated with lymph node metastasis and higher tumour stage, tumour progression (P=0.017) and 5-year survival (P=0.013). In conclusion, the G/L ratio is associated with tumour progression and shorter survival. The close correlation between G/L ratio and tumour stage or lymph node status suggests that it could be used to predict tumour metastasis, prognosis and overall survival in patients with gastric carcinoma before they undergo surgical treatment.

Prednisolone therapy for intra-abdominal desmoid tumors in a patient with familial adenomatous polyposis

The management of intra-abdominal desmoid tumors in patients with familial adenomatous polyposis (FAP) is very difficult. Non-steroidal anti-inflammatory drugs (NSAIDs), anti-estrogenic agents, and steroids are most commonly used, because surgical removal of these tumors may result in severe morbidity, with local recurrence being common. We report a patient with FAP and intra-abdominal desmoid tumors that regressed markedly after prednisolone therapy. The patient, a 38-year-old woman, had undergone total colectomy and ileorectal anastomosis with a diagnosis of FAP with colon cancer. Approximately 17 months after the surgery, she noticed an elastic firm lump in the abdominal wall. She also experienced lower abdominal distension. Computed tomography (CT) of the lower abdomen showed an invasive heterogenous low-density mass occupying the intra-abdominal space. She was treated with sulindac, NSAID, at 300 mg/day, the diagnosis being intra-abdominal desmoid tumors. She exhibited an intestinal obstruction about 9 months after the initiation of sulindac therapy. We changed the treatment and began prednisolone (initial dose, 40 mg/day). This treatment was continued for two years; subsequently the lesions regressed markedly. She is currently well, more than 3 years after the withdrawal of prednisolone.

Intra-abdominal bronchogenic cyst with gastric attachment: Report of a case

We report a rare case of an intra-abdominal bronchogenic cyst. An abnormal lesion was detected on an ultrasonogram, done as part of a physical checkup, in an 81-year-old woman. Computed tomography and magnetic resonance imaging showed a cystic mass attached to the lesser curvature of the stomach. Initially, we suspected a congenital cyst without malignant components; however, as the patient wished to have the lesion removed, we performed a minilaparotomy. The cystic lesion was firmly attached to the lesser curvature by fibrous tissue. Microscopic examination subsequently revealed the 26-mm mass to be a benign bronchogenic cyst with a bronchial element. We compared our findings with those of 50 previously reported cases of intraabdominal bronchogenic cysts. None of these patients was older than ours, and lesions attached to the esophagus or stomach were extremely unusual. Bronchogenic cysts are difficult to diagnose preoperatively based on imaging findings, but surgery may be indicated if malignant components are suspected, or if the lesion is enlarging or causing symptoms.

Abdominal stapled side-to-end anastomosis (Baker type) in low and high anterior resection: experiences and results in 69 consecutive patients at a regional general hospital in Japan

Objective  The technique of transanally introducing a circular stapled device to accomplish colorectal anastomoses has been widely used. However, the widespread popularity of this technique may have created the potential of anal sphincter injury during transanal insertion of the anastomosing stapler. Thus, to avoid the risk of anal sphincter injury during anal manipulation, we have been performing an abdominal approach, namely abdominal stapled side‐to‐end anastomosis (ASSEA) using a Purstring and premium curved EEA stapler in low and high anterior resection. This study will present our experience and results of consecutive resections.

The Use of Autologous Fibrin Glue for the Treatment of Postoperative Fecal Fistula Following an Appendectomy: Report of a Case

We herein report a case of postoperative fecal fistula following an appendectomy which was successfully treated by the use of autologous fibrin glue. An 82-year-old man had acute appendicitis and underwent an appendectomy. Later, a fecal fistula developed and he underwent drainage treatment twice. After 4 weeks of drainage and during the third recurrence, the remaining fistula was successfully treated using autologous fibrin glue, instead of surgery, due to potential complications and the risks of associated with advanced age. No recurrence has been observed for 5 months. In conclusion, autologous fibrin gluing for fecal fistula was found to be a safe, economical, and effective treatment. A search of Medline from 1980 until 2002 revealed no other report of this treatment for postoperative fecal fistula following an appendectomy.

Significance of Preoperative Evaluations of Tumor Necrosis Factor-Alpha, the Granulocyte/Lymphocyte Ratio and Their Correlation with Regard to Outcome in Gastric Cancer Patients

Aim: In order to clarify the anti-cancer effects of tumor necrosis factor-α (TNFα), we examined the relationship between the preoperative evaluations of TNFα and the granulocyte/lymphocyte ratio (G/L ratio) in relation to outcome in gastric cancer patients. Materials and Methods: Peripheral blood samples were taken within 1 week before curative gastrectomy for measurement of TNFα and the G/L ratio. Five-year survival was determined in 71 operative gastric cancer cases. Results: The 5-year survival of the high TNFα group (≧8,000 pg/ml ) was 64.1%, 29.0% for the low TNFα group (<8,000 pg/ml) and 13.3 and 73.1% for those of the high (≧4.0) and low (<4.0) G/L ratio groups, respectively. The comparisons of these 5-year survival rates showed statistically significant differences. Moreover, there was a negative linear correlation between TNFα and the G/L ratio regarding outcome. Conclusions: Preoperative evaluations with TNFα and the G/L ratio may be important prognostic indicators, and their correlation may be a good indicator of the degree of effectiveness in activating anti-cancer immunity in gastric cancer patients.