Outcomes of hepatic artery infusion therapy for hepatic metastases from colorectal carcinoma after radiological placement of infusion catheters.

AIM: The aim of this study is to evaluate the safety and efficacy of hepatic artery infusion (HAI) of 5-fluorouracil (5FU) for patients with liver metastases from colorectal carcinoma after radiological placement of infusion catheters. METHODS: Forty-two patients with liver metastases from colorectal carcinoma received radiological placement of infusion catheters using the distal fixation method. They received continuous HAI of 5FU 1,000-1,500mg for 5h weekly or biweekly. Tumor status was assessed by chest-abdominal computed tomography (CT) scan after every 10 infusions. Hepatic perfusion was checked by CT arteriography via the infusion port after every 10 infusions. RESULTS: Radiological placements of catheters were performed successfully in all cases. Each patient received an average of 36 treatments (range: 10-98). Catheter failure was found in 3 patients (7.1%). Nine incidents of grade 1 toxicity were observed in 8 patients (19.0%). There was a complete response in 6 patients, partial remission in 18, stable disease in 9, and progression of disease in 9 (response rate: 57.1%). Overall median survival time was 29.1 months. Using Cox's proportional hazard model, lymph node metastases in primary colorectal carcinoma and pre-treatment serum CEA affected overall survival (P=0.011, P=0.005). CONCLUSIONS: HAI after radiological placement of infusion catheters is a safe and effective treatment particularly for patients with no lymph node metastasis in primary carcinoma or with a low pre-treatment serum CEA level.

Apoptotic wing degeneration and formation of an altruism-regulating glandular appendage (gemma) in the ponerine ant Diacamma sp. from Japan (Hymenoptera, Formicidae, Ponerinae).

We here show an example of morphological novelties, which have evolved from insect wings into the specific structures controlling social behaviour in an ant species. Most ant colonies consist of winged queen(s) and wingless workers. In the queenless ponerine ant Diacamma sp. from Japan, however, all female workers have a pair of small thoracic appendages, called "gemmae", which are homologous to the forewings and acts as an organ regulating altruism expression. Most workers, whose gemmae are clipped off by other colony members, become nonreproductive helpers, while only a single individual with complete gemmae becomes functionally reproductive. We examined histologically the development of gemmae, and compared it with that of functional wings in males. Female larvae had well-developed wing discs for both fore- and hindwings. At pupation, however, the wing discs started to evaginate and later degenerate. The hindwing discs completely degenerated, while the degeneration of forewing discs was incomplete, leading to the formation of gemmae. The degeneration process involved apoptotic cell death as confirmed by TUNEL assay. In addition, glandular cells differentiated from the epithelial cells of the forewing buds after completion of pupation. The mechanism of developmental transition from wing to gemma can be regarded as an evolutionary gain of new function, which can be seen in insect appendages and vertebrate limbs.

[Post-genome challenges against inflammatory bowel diseases].

Advancement of genome analysis might give great impact to the treatment of inflammatory bowel diseases(IBD). IBD patients are treated by sulfadrugs, steroids and anti-immune drugs. For difficult cases, leukocytapheresis, beclomethasone dipropionate, anti-TNF therapy, anti-LTB4 therapy and other new methods are applied. Developing epoch-making drugs will be achieved by finding new molecular targets. Histologic identification of dysplasia is important in the surveillance of long-standing ulcerative colitis. The molecular diagnosis is required for the distinction of dysplasia from the regenerative inflammatory changes. P53 immunostaining have been proved useful. Various molecular targets will be taken into discussion as additional procedures. Recent genome analysis have revealed some genetic factors contribute to pathogenesis of IBD, which are HLA, IL4, MUC3, IBD1 locus, IBD2 locus and so on. More information about genes concerning IBD will be provided by analyzing dense SNP map using DNA tip. They will open the way to the tailored therapy.

Correlation of the therapeutic effect of activated tumor-draining lymph node cells with specific interferon-gamma production in vitro.

It has been established that lymphocytes obtained from tumor-draining lymph nodes (DLN) are sensitized to the tumor antigen in vivo. Moreover, after being activated in vitro, these cells can be utilized for adoptive immunotherapy. In the present study, DLN cells, obtained from C57BL/6 mice with fibrosarcoma (MC-1), were activated and expanded with anti-CD3 monoclonal antibody followed by culture with recombinant interleukin-2 (rIL-2). These CD4- CD8+ CD25+ CD44+ T-cells showed specific antitumor efficacy to the pulmonary micrometastases of an autologous tumor, against which lymphokine-activated killer cells were ineffective; however, they did not show cytolytic activity in vitro. The supernatant, obtained by coculturing the activated DLN cells with MC-1 cells, exhibited the specific production of interferon-gamma (IFN-gamma) which was enhanced by rIL-2. The therapeutic effect of the activated DLN cells correlated with the specific IFN-gamma production better than with the cytolytic activity.

Overexpression of p53 protein and histologic grades of dysplasia in colorectal adenomas.

PURPOSE: To clarify the relation between tumor-suppressor gene p53 expression and histologic grades of dysplasia in colorectal adenomas, we performed immunohistochemical analysis in a series of 59 colorectal polyps and 40 advanced carcinomas. METHODS: Adenomatous polyps were stained by hematoxylin and eosin and classified into mild, moderate, and severe dysplasia (intramucosal carcinoma), according to the World Health Organization's classification. RESULTS: p53 was positive in 7.1 percent (2/28) of mild, 29.4 percent (5/17) of moderate, and 62.5 percent (5/8) of severe dysplasia. In submucosal and advanced carcinomas, positivity rates were 75 percent (3/4) and 47.5 percent (19/40), respectively. Different staining patterns were found, according to grades of dysplasia. In the adenomas with mild or moderate dysplasia, a few focal crypts showed localized p53-positive staining. Adenomas with severe dysplasia had two different staining types. One was a focal staining type as shown in mild or moderate dysplasia; the other was a diffuse staining type, in which glands with mild or moderate dysplasia, surrounding severe dysplasia area, were also stained. Submucosal and advanced carcinomas showed a strong positive staining in cancer cells only. CONCLUSIONS: Overexpression of p53 protein in adenomas with mild or moderate dysplasia and existence of two types of expression in adenomas with severe dysplasia were observed. These facts suggested the possible existence of different pathways in the adenoma to carcinoma progression.

[Feasibility of DNA analysis for prognostic evaluations of colorectal cancer using touch preparations and image cytometry].

The purpose of this study is to demonstrate the applicability of DNA ploidy analysis by using touch preparations obtained from fresh and frozen tissues on the prognostic evaluations of colorectal cancer, especially the development of hepatic metastases. The specimens obtained from surgically resected colorectal carcinomas (32), and hepatic metastases (4), were lightly touched with the slide glasses. Among the 32 patients with colorectal cancers, 7 had synchronous liver metastases, and 5 metastases developed metachronously. After formalin-fixation and Feulgen staining, the DNA analysis was performed by image cytometer (ICM, CAS200R). The data were expressed as the ploidy patterns and DNA indices (p-DNAI: peak DNA index, m-DNAI: mean DNA index), and were correlated very well with those obtained from cytophotometry. The DNA ploidy pattern among the 32 colorectal cancer specimens were Aneuploid(A) in 16, Polyploid (P) in 7, Diploid (D) in 4 and D+P in 5. The cases with synchronous or metachronous liver metastases had a higher m-DNAI (1.74 +/- 0.28) and were Aneuploid in 8, P in 3, and D+P in 1 case. Aneuploidy or Polyploidy predominated among the cases with metachronous liver metastases (4 in 5 cases), with m-DNAI higher than 1.5. Thus, "m-DNA > 1.5" could be a useful prognostic indicator of the high risk group of liver metastases. The liver metastases specimens had Aneuploid and Polyploid patterns in 2 cases each, with m-DNAI ranging from 1.88 to 2.31. DNA ploidy pattern analysis using touch preparations with image cytometry may be useful in determining the prognosis for colorectal cancer.

A case report of celiac axis compression and implications in regional chemotherapy for liver metastasis.

Regional chemotherapy through a catheter placed in the hepatic artery is routinely used for treatment of unresectable liver metastasis from colon carcinoma. With some frequency, anatomical variations of the hepatic artery, including compression of the celiac axis, are found, and must be recognized preoperatively for appropriate management and placement of the catheter. We report a case of a colon cancer patient with multiple liver metastases and compression of the celiac axis, who received decompression of the celiac axis and catheterization of the hepatic artery.

[Growth type of colorectal cancer invasion of the proper muscle in relation to DNA ploidy and distribution of PCNA].

In order to elucidate the biological characteristics of colorectal cancer invading the proper muscle, we analyzed DNA ploidy and PCNA labeling index. The growth patterns were divided into three types; those accompanied by intramucosal polypoid growth (PG+), those with non-polypoid growth (PG-), and those ranging between PG+ and PG- (PG+/-). The relationship of DNA ploidy to lymphatic vessel permeation and recurrence was also discussed. The results were as follows: 1) Growth types bore no relation to DNA ploidy and distribution of PCNA. 2) In aneuploidy cancer, it showed a high incidence of lymphatic vessel permeation. A trend of lymphatic metastasis was also observed. Aneuploidy cancer showed a poor prognosis compared with diploidy cancer.

[Continuous intra-arterial infusion chemotherapy in colorectal cancer patients with nonresectable metastatic liver cancer].

Five colorectal cancer patients with nonresectable metastatic liver cancer underwent continuous intraarterial chemotherapy in our institute from January to December 1991. Patients included four rectal cancers and one colonic cancer. 5-fluorouracil (5-FU) was infused continuously through an Infuse-A-Port; 360 mg/m2/day for one week after operation, and 180 mg/m2/day for the following three weeks. Since the fifth week after operation, two weeks without infusion and two weeks of infusion (180 mg/m2/day) were alternated as long as possible. Total periods of 5-FU infusion therapy were from one to 11 months and total doses of 5-FU ranged from 8,750 mg to 25,650 mg. Three patients showed partial response (PR) and two patients progressive disease (PD) (response rate; 60%). In three cases of PR, lengths of infusion therapy and total doses of 5-FU before PR was first observed was 8 weeks, 10,750 mg, 6 weeks, 9,250 mg, and 4 weeks, 8,750 mg, respectively. Four patients presented nausea, appetite loss or abdominal pain, which were considered to be side effects of 5-FU. In one of these four patients, infusion could not be continued because symptoms were so severe. However, catheter troubles were not noticed among all cases.

Calpain in rat cornea.

This study was conducted to provide a description of calpain proteolytic enzyme (EC 3.4.22.17) in normal rat cornea and to document immunohistochemical changes in calpain distribution during maturation. Corneal soluble proteins were fractionated by diethylaminoethyl chromatography on high-performance liquid chromatography. Fractions were analyzed for calpain by enzyme-linked immunosorbent assay, immunoblotting, and caseinolytic enzyme activity with fluorescein isothiocyanate-labeled casein. Calpain II from the soluble fraction of 2-week-old and 3-month-old rat corneas eluted at a similar NaCl concentration (220-240 mmol/l) as calpain II from other tissues, was inhibited by E64, contained an 80-kilodalton subunit in immunoblots, and was present at specific activity of 473 units per gram of protein in 3-month-old rats and 801 units per gram of protein in 2-week-old rats. Calpain antigen also was present in the ethylenediaminetetraacetic acid and EGTA washed insoluble fraction of cornea. Calpain was found (by immunohistochemical analysis) in all layers of the epithelium but not in the stroma. Enzyme-linked immunsorbent assay, immunoblots, and immunohistochemical analysis showed that calpain in the whole cornea did not change with corneal maturation. It was hypothesized that calpain in the cornea may be involved in the turnover of epithelial cells during normal maturation.

Acquired ptosis associated with a conjunctival cyst.

A 44-year-old woman with a history of previous ptosis surgery presented with a moderate ptosis of the left upper eyelid and a large cystic mass extending over the length of that lid. The mass was excised completely and histologically found to be a conjunctival ductal cyst. The levator aponeurosis was disrupted by the cyst and required reconstruction. This case demonstrates an acquired ptosis associated with a large conjunctival cyst as a late complication of ptosis surgery.

Assessment of bowel control with anorectal manometry after surgery for anorectal malformation.

Bowel function after surgery for anorectal malformation was assessed by Kelly's score in 101 children over 3 years of age. Seventy-two were examined using anorectal manometry. In the "good" group, resting pressure of the anal canal was as high as in the normal children, and the frequency of contraction waves in the anal canal was the same as in the normal children. Recto-anal reflex was recognized in about three fourths of the "good" group. On the other hand, in the "poor" group resting pressure was low, in only one were contraction waves evident and in none was there a recto-anal reflex. The findings of the anorectal manometry placed the "fair" group between the "good" and the "poor" groups. The clear contraction waves of the anal canal or the clear recto-anal reflex related to a resting pressure in the anal canal of over 20 cmH2O. This high pressure in the anal canal is important for good and continence, and depends on a precise pull-through of the rectum into the puborectalis muscle.

[Formation of secondary focus in amygdala Kindling phenomenon of the rabbit: a study by the coherence method].

Formation of the secondary focus in the rabbit amygdala Kindling (K) phenomenon was analysed by the coherence method. This method is capable of showing the degree of correlation between two signals (EEG) at each frequency. Mature male rabbits were used and a train stimulation using a biphasic square wave of 60 Hz was applied to the amygdala for two second once a day until the completion of K-phenomenon. The results obtained were as follows. 1) The coherence values between the amygdaloid K-region and opposite amygdala were usually much higher than those of the cerebral cortex (motor and optic areas) with a frequency of 6 to 7 Hz before and after completion of the K-phenomenon. 2) The speed of the secondary focus formation was observed to be parallel with the coherence value. 3) The secondary focus formation induced by the K of amygdala in a rabbit has much to do with the 6 Hz nerve circuit which links between the primary focus and secondary focus. That is, if the coherence value appears high around 6 Hz, the secondary focus is easily formed in case of a rabbit. 4) Application of this method enabled us to see the degree of functional correlation between the primary focus and secondary focus at each frequency. With all these, it is suggested that the theta frequency ranges of power spectra between above region play a vital role in producing secondary focus formation of the amygdaloid Kindling in rabbits.