Clinicopathological characteristics of skipping lymph node metastases in patients with colorectal cancer

We evaluated the optic disc in 77 eyes of 77 normal volunteers using a scanning laser tomograph (Heidelberg Retina Tomograph: HRT, version 1.11). Particular attention was paid to age, refractive error, and disc size. The topographic parameters included: cup area, C/D area ratio, rim area, cup volume, rim volume, mean cup depth, maximum cup depth, cup shape measure, height variation contour, mean RNFL thickness, and RNFL cross section area. There was a significant decline in mean RNFL thickness and RNFL cross section area with increase in age (p < 0.05). The mean and maximum cup depths were significantly deeper in myopic eyes (p < 0.05). Large discs had large values of cup area, C/D area ratio, rim area, cup volume, mean cup depth, cup shape measure (p < 0.01), and maximum cup depth (p < 0.05). Large discs had small values of mean RNFL thickness and RNFL cross section area. Rim volume was independent of age, refractive error, or disc area.     

Brain-specific angiogenesis inhibitor 1 expression is inversely correlated with vascularity and distant metastasis of colorectal cancer

Brain-specific angiogenesis inhibitor (BAI) 1 was recently isolated as a novel p53 inducible gene. BAI1 has been suggested to play a significant role in angiostasis. We studied the expression of BAI1 in 49 colorectal cancer specimens by RT-PCR. BAI1 expression was significantly reduced in colorectal cancers as compared to the extraneoplastic tissues (X(2) test, p=0.041). BAI1 expression was inversely correlated with vascular invasion and metastasis (Fisher's exact test, p 0.045). Moreover, vascularity in the colorectal cancer was inversely correlated with BAI1 gene expression (Mann-Whitney U-test, p=0.0003). These observations suggested that BAI1 expression might inhibit angiogenesis and metastasis of colorectal cancer.     

Microcirculation of the lymph node with metastases

Microangiographic and histologic examination of the popliteal lymph node was performed on 49 rabbits 3 to 55 days after V2 tumor implantation into the hind paw. Control animals received subcutaneous tissue extract from normal rabbit donors. During the first 10 days after the tumor implant from an allogeneic animal donor, the draining lymph node exhibited a hypervascular response which after 2 weeks gradually subsided. Subsequently, during the early stages of lymph node metastasis there was still hypervascularity adjacent to the metastatic deposit. In about 4 weeks the metastases became more established and surrounded by layers of plasma cells. The hypervascular changes of the surrounding lymph node subsided by this time. In lymph node metastases the microvasculature could be an indicator of the immunologic activity of the host.     

NM23 gene product expression does not predict lymph node metastases or survival in young patients with colorectal cancer

PURPOSE: To develop a hepatic artery embolization protocol and investigate its efficacy in a prospective study treating patients with hereditary hemorrhagic telangiectasia and predominant hepatic involvement. MATERIALS AND METHODS: One man and four women with hereditary hemorrhagic telangiectasia presented with symptoms of high-output heart failure, abdominal angina, or severe portal hypertension. The hepatic arteries were embolized in stages in three to five sessions at 1- to 15-week intervals. After peripheral embolization with polyvinyl alcohol particles, proximal arteries were embolized with coils. Computed tomography and assessment of cardiac output were performed before and after therapy and at the end of follow-up (median, 25 months; range, 12-55 months). RESULTS: After embolization, analgesics and antiemetics were necessary for a median of 5 and 2 days, respectively. Other than ischemic cholangitis (one patient), no complications were observed. The mean cardiac output decreased significantly (P < .05) from 14.2 L/min to 8.0 L/min. Symptoms of high-output heart failure, abdominal angina, and portal hypertension resolved in all patients. Seven months after embolization, one patient died of postoperative sepsis after an unsuccessful surgical attempt to create a portacaval shunt. Delayed recurrence of symptoms was not noted in the other patients. CONCLUSION: In symptomatic patients with hereditary hemorrhagic telangiectasia and predominant hepatic involvement, embolization of the hepatic arteries in stages is well tolerated by the patients and results in good clinical improvement at midterm follow-up.     

Significance of CT in the detection of regional lymph node metastases in colorectal carcinoma

PURPOSE: For preoperative staging of colorectal cancer a CT scan is frequently performed. This report examines the sensitivity of CT for regional lymph node metastasis of colorectal cancer using different criteria. MATERIALS AND METHODS: Preoperative CT scans of 153 patients with colorectal cancer were analyzed using different criteria for N1. The results were then compared to the postoperative histological findings. RESULTS: For N1 = lymph nodes (LN) > 1 cm the sensitivity was 47%. For N1 = LN > 1 cm or an increased number of LN < 1 cm the sensitivity was 71%. In patients with a primary tumor seen on CT, sensitivity rose to 87%. DISCUSSION: Evidence of regional nodal metastatic disease is only relevant for rectal cancer, colon polyps, and for locally excised tumors when considering present surgical concepts for the treatment of colorectal cancer. In these cases CT analysis using the broadened criteria for N1 proposes a valuable argument regarding possible preoperative radiotherapy or an operative revision.     

Human AP endonuclease 1 (HAP1) protein expression in breast cancer correlates with lymph node status and angiogenesis

Human AP endonuclease (HAP1) plays a major role in the repair of apurinic/apyrimidinic (AP) sites in cellular DNA. We used immunohistochemistry to examine the expression of HAP1 in normal breast and in 102 primary breast carcinomas. In normal breast epithelium, HAP1 had a uniformly nuclear localization. However, in lactating glandular epithelium, the expression of HAP1 was predominantly cytoplasmic. In carcinomas, both nuclear and cytoplasmic (44%), cytoplasmic (28%) or nuclear staining (24%) were observed. In four cases (4%), no HAP1 expression was detected. All patterns of expression for HAP1 were demonstrated for ductal carcinomas in situ (DCIS), although comedo-type DCIS were usually accompanied by mostly cytoplasmic staining. Similarly, the HAP1 expression in regions of invasive tumour necrosis was cytoplasmic. Pure nuclear HAP1 expression was significantly correlated with low angiogenesis (P = 0.007) and negative lymph node status (P = 0.001). In contrast, cases with cytoplasmic as well as nuclear staining were associated with poor prognostic factors, such as high angiogenesis (P = 0.03) and node positivity (P = 0.03). The pure nuclear staining may be related to better differentiation, as in normal breast, and hence better prognostic features, and cytoplasmic staining to a more metabolically active phenotype with high protein synthesis, as in lactating breast.     

Apoptosis loss and bcl-2 expression: key determinants of lymph node metastases in T1 breast cancer

The Bcl-2 proto-oncogene extends cell survival but does not confer any proliferative advantage to cells that express it. Thus, the loss of apoptosis may have a role in progression allowing the acquisition of additional mutations. To determine whether apoptosis loss at diagnosis is associated with the metastatic advantage of ductal breast carcinomas and to examine the relationship between Bcl-2 expression, p53, and tumor cell death status, we examined tumor samples from 116 patients diagnosed with T1 (2 cm or less) breast cancer with (n = 49) or without (n = 67) lymph node metastases. Apoptosis loss in histological sections was considered when <1% of tumor nuclei were stained with terminal deoxynucleotidyl transferase labeled with biotin. We studied the expression of Bcl-2 and p53 by immunohistochemistry and in 37 p53 mutations by single-strand conformational polymorphism analysis and cycle sequencing. Multivariate logistic regression modeling was used to estimate prevalence odds ratios (pORs) for apoptosis loss and presence of lymph node metastases. Patients with marked apoptosis loss in their tumor cells were about 5 times more likely to present lymph node metastases than those with no apoptosis loss in their tumor cells (adjusted pOR, 4.7; 95% confidence interval, 1.4-15.6; trend test, P = 0.008). Bcl-2 expression was strongly associated with both apoptosis loss (pOR, 6.9; trend test, P < 0.0001) and presence of lymph node metastases (pOR, 5.7; trend test, P = 0.002). These associations were more evident in histological grade I and II tumors than in poorly differentiated histological grade III tumors and in p53-negative tumors than in p53-positive tumors. This study demonstrates for the first time that the lymphatic progression of T1 human breast cancer is strongly related to apoptosis loss.     

Results of resection of gastric cancer with distant metastases

BACKGROUND/AIMS: The present study was carried out in order to examine the outcome of resection in cases of gastric cancer with distant metastases. METHODOLOGY: The survival rates of two hundred and eighty-one patients who had undergone resection for primary carcinomas of the stomach, and who had distant metastases according to the TNM classification, were studied. RESULTS: The 5-year survival rates for patients with metastasis to the peritoneum or group 3 nodes were 8.9% and 15.3% respectively and were significantly higher than the survival rates for patients with metastasis to the liver (0%), to group 4 nodes (2.2%) or to more than one site among the liver, lymph nodes and peritoneum (3.5%). Moreover, the 5-year survival rates for patients with metastasis to the peritoneum and N3 nodes increased significantly to 29.4% and 24.2%, respectively, when curative surgery was performed. CONCLUSIONS: The findings of the present study suggests that metastases to the adjacent peritoneum or group 3 nodes have a greater chance of being cured using radical surgery, and that gastrectomy with extended lymphadenectomy (D2-D3) may be used for advanced gastric cancer if there is no gross evidence of metastasis to the distant peritoneum, liver or group 4 nodes.     

Reduced expression of tissue inhibitor of metalloproteinase in nodal metastasis of stomach cancer

The abuse of zipeprol, an antitussive agent, was found to be most prevalent among young people in Korea. Because abusers take large doses of this drug for its hallucinogenic effects, fatalities from zipeprol overdose abuse have been on the rise since 1991. Since 1991, a total of 69 zipeprol-related deaths have occurred throughout the nation. A demographic study shows that in ninety six percent of cases involving ziperol alone, the victims were in their teens and twenties. The male/female ratio in zipeprol related death was 3.5:1. Most of these zipeprol-associated deaths occurred in the larger cities of Seoul and Inchon. The blood concentration of zipeprol ranged from 0.8 to 38.3 micrograms/mL in single drug involved deaths, while zipeprol varied from 0.1 to 35.3 micrograms/mL in zipeprol and dextromethorphan victims.     

Risk of internal mammary lymph node metastases and its prognostic value in breast cancer patients

Metabolic control analysis (MCA) has provided the language and framework for quantitative study of control over flux, or over metabolites, by individual enzymes of a pathway. By contrast, top-down control analysis (TDCA) yields an immediate overview of the control structure of the whole system of interest, giving information about the control exercised by large sections of complex pathways. Unlike MCA, TDCA does not rely on the use of specific inhibitors or genetic manipulation to determine control coefficients. The method and an application of TDCA to ketogenesis are described.     

Controversy about treatment of colorectal cancer in view of surgeon--lymph node dissection for colorectal surgery (lateral lymph node dissection and TME)]

Lateral lymph node dissection is technique for reducing local recurrence rate after resection of rectal cancer. In this study, we will report a decade experience for lateral lymph node dissection of rectal cancer in 491 cases. Lateral lymph node metastases occurred in 15.4% of rectal cancer which was below peritoneal reflection and through muscularis propria into non-peritoneal. It is a problem that it has never been well designed study of lateral lymph node dissection for rectal cancer. On the other hand, TME has also contributed reducing local recurrence rate. But, distant margin for resection of rectal cancer is controversial.     

Treatment of breast cancer with ipsilateral supraclavicular node metastases

During 1954-1977, among 2803 cases of breast cancer 99 (3.5%) had ipsilateral supraclavicular node mestastases. The results of treatment are reported, based on follow-up for more than 10 years. According to the treatment modality, the patients were divided into 4 groups: I. surgery with postoperative adjuvant chemotherapy and radiation therapy; II. radiation and chemotherapy; III. chemotherapy; IV. no treatment. In group I, surgical procedures consisted of segmental mastectomy in 6; simple mastectomy in 7; modified radical mastectomy in 16; standard radical mastectomy in 12, and extended radical mastectomy in 3. The over-all five-year survival rate was 9%. It was 18% (8/44) in group I, but only 5% (1/21) in group II. None survived for 5 years in group III and group IV. The results seem to indicate that more aggressive multi-modality treatment of breast cancer with ipsilateral supraclavicular lymph node metastases is indicated to expect better survival.     

Preoperative natural killer cell activity: correlation with distant metastases in curatively research colorectal carcinomas

A new technique for collecting blood from conscious and unrestrained rats is reported. Plasma arginine vasopressin (AVP) concentration has been known to be influenced by various procedures used for blood collection (e.g., manual contact and anesthesia). In the study reported here, the improvement of the routine jugular vein cannula method was undertaken by extending the connection tubing to allow use of a swivel mechanism. Plasma AVP, glucose, and corticosterone concentrations in virgin rats were measured in blood samples collected by use of the new method and of two generally accepted methods (decapitation and routine jugular vein cannula methods). All values of the three parameters obtained were the lowest when the new method was used, suggesting that this new swivel method induced the least stress in the rats.     

Therapeutic effect of the matrix metalloproteinase inhibitor, batimastat, in a human colorectal cancer ascites model

The matrix metalloproteinase inhibitor batimastat was administered to a human colorectal cancer ascites model, which was initiated by injection of C170HM2 cells into the peritoneal cavity of SCID mice and resulted in solid tumour deposits and ascites formation. The cell line expressed both the 72 and 92 kDa forms of gelatinase by zymography. Batimastat administered from day 0 (40 mg kg-1) reduced the volume of ascites to 21% of control in mice treated from day 0 (P < 0.002) but not day 10. Formation of solid peritoneal deposits was significantly reduced to 77% of vehicle control when batimastat was administered from day 0 (P < 0.01) and 69% of control when administered from day 10 (P < 0.05). Thus, batimastat has the ability to reduce the volume of ascites forming in SCID mice injected intraperitoneally with the human colorectal cell line, C170HM2, when administered from day 0 but not from day 10. Solid peritoneal tumour deposits were significantly reduced in both treatment groups, highlighting the therapeutic potential of batimastat in this clinical condition.     

Factors affecting prognosis of papillary thyroid carcinoma with bilateral cervical lymph node metastases

One hundred thirty nine cases of papillary thyroid carcinoma with bilateral lymph node metastases were reviewed. They were surgically treated at the Cancer Hospital of Shanghai Medical University in the years from 1956 through 1990. There were 73 men and 66 women with a median age of 35 (range 11-70) years. The median follow-up period was 11 years. Kaplan-Meier survival curves were calculated for the population. The overall survival rate was 94.7% at 5 years, 85.9% at 10 years, and 82.3% at 15 years. In univariate analysis, factors influencing prognosis are age at diagnosis, tumor size, extrathyroidal invasion, residual tumor and thoroughness of excision. When Cox proportional risk model was applied to analyze the survival data, factors of survival significance are the age at diagnosis and thoroughness of excision.     

Influence of surgery on metachronous distant metastases and survival in rectal cancer

PURPOSE: Total mesorectal excision (TME) and other technical surgical factors reduce local recurrence rate in rectal cancer. Scientific evidence of the positive effect of optimal surgery on survival is locking. Whether a reduction in the incidence of distant metastases can be achieved with optimal surgery is uncertain. We examine the effects of the quality of surgery, as reflected by local recurrence rate, on survival and the incidence of initial distant metastases. PATIENTS AND METHODS: Between 1974 and 1991, 1,581 consecutive patients who underwent curative resection (RO) for rectal carcinoma were monitored for recurrence and survival. TME was introduced in 1985. No patient received adjuvant radiotherapy or chemotherapy. The median follow-up time was greater than 13 years. RESULTS: The local recurrence rate decreased from 39.4% to 9.8% during the study period (P < .0001). The observed 5-year survival rate improved from 50% to 71% (P < .0001). Three hundred six patients with local recurrence had a significantly lower observed 5-year survival rate (P < .0001). A total of 1,285 patients had no local recurrence, but 275 of them developed distant metastases (International Union Against Cancer [UICC] stage I, 8%; stage II, 16%; stage III, 40%). Better-quality surgery had no effect on the incidence of initial distant metastases, which remained constant (P = .44). CONCLUSION: Quality of surgery is an independent prognostic factor for survival in rectal cancer, but has no influence on initial occurrence of distant metastases. Local recurrence cannot be considered an outcome criterion of adjuvant treatment without consideration of the surgeon as a risk factor.