[Pulmonary pleomorphic carcinoma; report of 2 cases].

The 1st case was a 74-year-old male diagnosed as femoral neck fracture. Biopsy of the bone revealed metastatic adenocarcinoma. Chest computed tomography (CT) showed a mass lesion located in the right lower lobe. With a diagnosis of primary lung cancer (cT2N1M1), two-staged operation was performed. Pathological diagnosis was pleomorphic carcinoma [pT2N1M1 (OSS), stage IV]. He died 8 months after surgery due to metastasis to the thoracic spine. The 2nd case was a 80-year-old female who complained of lateral chest pain. Chest CT revealed a tumor in the right hilar region, which was diagnosed as adenocarcinoma by transbronchial lung biopsy. Only thoracic drainage was performed since metastases to the brain and the rib were demonstrated. She died 2 months after admission. Autopsy revealed pleomorphic carcinoma of the lung with metastasis to the brain, costa and mediastinal lymph nodes.

A non-surgical rat model of foreign body-associated urinary tract infection with Pseudomonas aeruginosa.

This study established a rat model of foreign body-associated urinary tract infection. A spiral polyethylene tube (PT) was placed transurethrally into the bladder without surgical manipulation, followed by transurethral inoculation with Pseudomonas aeruginosa. The persistence of P. aeruginosa in the kidneys and bladder was significantly enhanced by placement of the PT, whereas the bacteria were eliminated rapidly from the urinary tract in the animals without the PT. Scanning electron microscopy revealed a thick biofilm on the surface of the PT from the early stage of infection. Histopathologically, acute pyelonephritis was followed by chronic renal inflammation as well as continuous and sporadic polymorphonuclear leukocyte accumulation and hemorrhage in the pelvis and adjacent tissues, suggesting continuous ascending introduction of the bacteria from the biofilm adhering to the PT. We believe our model simulates the pathophysiology of foreign body-associated urinary tract infection characterized by biofilm formation on the surface of a foreign body.

Therapeutic effect of oral levofloxacin, ciprofloxacin, and ampicillin on experimental murine pneumonia caused by penicillin intermediate Streptococcus pneumoniae for which the minimum inhibitory concentrations of the quinolones are similar.

The therapeutic efficacy of oral treatment with levofloxacin, ciprofloxacin, and ampicillin on an experimental pneumonia caused by the penicillin-intermediate Streptococcus pneumoniae for which the minimum inhibitory concentrations (MICs) of the quinolones are similar was assessed in immunocompetent CBA/J mice. Levofloxacin exhibited a dose-dependent therapeutic effect, and achieved complete eradication of S. pneumoniae from the lungs at 120 mg/kg/day, whereas ciprofloxacin and ampicillin were hardly effective at all. A pharmacokinetic study in infected mice revealed good oral absorption and lung tissue penetration of levofloxacin (peak lung concentration: 5.95 microg/g of lung), low oral absorption of ciprofloxacin in spite of a good penetration into lung tissue (1.10 microg/g of lung), and low lung tissue penetration of ampicillin despite rather good oral absorption (1.71 microg/g of lung). In an in vitro time-kill study that simulated the peak concentration of drugs in the lungs of infected animals, the killing activity of levofloxacin was found to be greater than that of ciprofloxacin and ampicillin. These data suggest that the therapeutic efficacy of levofloxacin in this model is attributable to both its potent bactericidal activity and excellent pharmacokinetic profile.

In vitro and in vivo activities of levofloxacin against biofilm-producing Pseudomonas aeruginosa.

Interactions between biofilm cells of Pseudomonas aeruginosa and levofloxacin were studied. P. aeruginosa incubated for 6 days with Teflon sheets formed a biofilm on its surface. Against the biofilm bacteria, levofloxacin at an MIC determined by the standard method for the strain was highly bactericidal whereas gentamicin, ceftazidime, and ciprofloxacin showed no significant killing activity. Levofloxacin, ciprofloxacin, and gentamicin, but not ceftazidime, exhibited killing activity against nongrowing cells of the strain incubated in phosphate buffer. In addition, levofloxacin, ciprofloxacin, and ceftazidime, but not gentamicin, showed the ability to penetrate an agar containing alginate. These findings may explain the efficacy of levofloxacin and the ineffectiveness of gentamicin and ceftazidime against biofilm bacteria; however, the cause of the ineffectiveness of ciprofloxacin still remains to be determined. In experimental pneumonia in guinea pigs, in which the biofilm mode of growth of the strain was observed in the lung, only levofloxacin exhibited substantial therapeutic efficacy. These findings suggest the significant role of levofloxacin in therapy of biofilm bacterium-associated infectious diseases.

Case report: portal-systemic encephalopathy due to a congenital extrahepatic portosystemic shunt.

We present a case of portal-systemic encephalopathy due to a congenital splenorenal shunt. A 69 year old woman was admitted to hospital because of recurrent episodes of disturbed consciousness. The present episode had begun 3 months prior to admission. Although the patient demonstrated mildly slurred speech, the remainder of her neurological examination was unremarkable. She showed no clinical signs of portal hypertension and her liver function, except for a serum hepaplastin test of 58% and an ICG retention rate of 28% at 15 min, was normal. Her serum ammonium level was 210 micrograms/dL. The venous phase of a superior mesenteric arteriogram revealed a splenorenal shunt and narrowing of the portal vein, which was 4 mm in diameter. The histological findings, demonstrated by a needle liver biopsy specimen, were consistent with mild fibrosis and lymphocytic infiltration. Following the diagnosis of a splenorenal shunt in the absence of liver cirrhosis, ligature of the shunt was performed with a splenectomy. The portal vein pressure after ligature of the shunt rose from 12.5 to 18.8 mmHg. This shunt was thought to be of congenital origin. The high preoperative serum ammonia concentration decreased to the normal range postoperatively and the serum hepaplastin test and ICG retention rate similarly improved postoperatively. A follow-up superior mesenteric arteriogram was performed during the venous phase, demonstrating resolution of the shunt and decreased portal vein narrowing. The patient has suffered no further episodes of disturbed consciousness postoperatively.

[Effect of chemotherapy using irinotecan (CPT-11) against recurrent colorectal cancer].

Irinotecan (CPT-11) is a camptothecine derivative with antitumor activity and inhibitor of DNA topoisomerase I. CPT-11 showed a excellent and broad anticancer activity against several malignant tumors. In this study, as in the Japanese phase II study, CPT-11 was administered at 100 mg/m2 weekly by intravenous infusion against 10 patients with recurrent colorectal cancer. Median total dose was 513 mg. Partial responses were obtained in 4/10 patient (40%). Lung metastases showed a 33.3% response and lymphnode metastases showed a 60% response. However, liver metastases showed no response. The median duration to the onset of partial response was 20 days and the median overall response duration was 89 days. Adverse effects were leukopenia (40%), nausea, vomiting and diarrhea (80%), fever (20%), and general malaise (30%). These were generally well tolerated and reversible. From these results, CPT-11 seemed to become an effective drug for recurrent colorectal cancer. Further trials of combination chemotherapy utilizing CPT-11 seem to be warranted.

[Two cases of hepatic metastasis of colorectal cancer treated effectively by intrahepatic arterial infusion immunotherapy using OK-432, rIL-2, MMC and 5-FU].

Two cases of hepatic metastasis of colorectal cancer were treated effectively by intrahepatic-arterial infusion immunotherapy using OK-432 (2 KE/week or 2 weeks), recombinant IL-2 (35 x 10(4) JRU or 40 x 10(4) JRU/week or 2 weeks), MMC (4 mg/week or 2 weeks) and 5-FU (250 mg/day during admission, 250 mg/week or 2 weeks during outpatient treatment). The levels of CEA were decreased from 17.2 ng/ml to 2.4 ng/ml after 8 weeks in the first case (50 y. o. male) and from 521 ng/ml to 66 ng/ml after 8 weeks in the second case (36 y. o. female), respectively. Abdominal CT revealed a partial response for 11 months in the first case and 6.5 months in the second case.

Assisted circulation using cardiomyoplasty together with aortomyoplasty.

Both dynamic cardiomyoplasty and counterpulsation by the synchronous paced contraction of skeletal muscles in aortomyoplasty can improve ventricular function. The goal of this study was to clarify the effect of cardiomyoplasty combined with aortomyoplasty on cardiac dysfunction in dogs. The percentage of increase in various hemodynamic parameters was calculated during assisted and unassisted cardiac cycles and was compared for three groups: cardiomyoplasty only (Group A), aortomyoplasty only (Group B), and both methods combined (Group C). In Group A, the left ventricular pressure (LVP), systolic aortic pressure (systolic AoP), and dp/dt of LVP (LV dp/dt) increased significantly; the diastolic aortic pressure (diastolic AoP) did not change; and the endocardial viability ration (EVR) decreased during assisted cardiac cycles. In Group B, the diastolic AoP and EVR were improved significantly, but the LVP, LV dp/dt, and systolic AoP were unchanged during assisted cardiac cycles. In contrast to Groups A and B, all parameters were improved in Group C during assisted cardiac cycles. Cardiac assistance using cardiomyoplasty together with aortomyoplasty was more effective than either procedure used alone.

p53 immunoreaction in endoscopic biopsy specimens of colorectal cancer, and its prognostic significance.

The expression of p53 protein was immunohistochemically studied in formalin-fixed paraffin-embedded biopsy specimens of 203 colorectal carcinomas by use of a monoclonal antibody specific for the p53 protein. PAb1801. p53 protein expression with its reactivity localised in nuclei was found in 121 (59.6%) of the cancers. There was no correlation of p53 immunoreactivity with histological classification, wall invasion, lymphatic invasion, venous invasion, lymph node metastases, or peritoneal metastases. p53-positive cancers were more frequently associated with liver metastasis than p53-negative ones. Patients with p53-positive tumours had significantly poorer prognoses than those with p53-negative tumours. The 5 year survival rate was 58.1% for patients with p53-positive tumours, and 76.3% for those with p53-negative tumours. In Dukes' stage C tumours, an especially good correlation was found between p53 immunoreactivity and prognosis. In addition, patients with p53-positive tumours had higher recurrence rates. The results indicate that p53 immunoreactivity may be a useful prognostic marker of colorectal cancers.

Prognostic value of nucleolar organizer regions in endoscopically biopsied tissues of colorectal cancers.

We studied the proliferative activity in endoscopically biopsied tumors by means of argyrophil-protein nucleolar organizer region (AgNOR) scores. AgNOR scores of 109 colorectal cancers ranged from 2.48 to 6.72 (mean: 3.27 +/- 0.52). The 109 tumors were divided into two groups by the median value of AgNOR counts. There was no significant correlation between the AgNOR scores and the histologic type, invasion of bowel wall, lymph node metastases or peritoneal metastases. There was a significant association between the AgNOR scores and lymphatic invasion or liver metastases. Patients with higher AgNOR score tumors had significantly poorer prognoses than those with lower AgNOR score tumors. In Dukes' stage C, especially, the survival rate for patients with higher AgNOR score tumors was significantly lower than for those with lower AgNOR score tumors. Recurrence was found in 8.7% of the tumors with lower AgNOR scores and 19.4% of the tumors with higher scores. Aneuploid tumors had higher AgNOR scores than tumors with the diploid pattern. The results suggest that the AgNOR scores may possibly be a useful prognostic marker of colorectal cancer.

Analysis of hepatic recurrence of colorectal cancer after resection of hepatic metastases.

Forty patients with history of resected hepatic metastases of colorectal cancer were examined for pattern of recurrence. The 5-year survival rate was 41.3% for 40 patients. Recurrences of the malignancy were seen in 25 of the patients, with hepatic recurrence in 42.5% of them. The hepatic recurrence rate did not correlate with the lobar distribution of metastases or surgical methods. The pathological margins of less than 1 cm, 3 or more liver metastatic lesions, and the metastatic lesions of greater than 5 cm were at increased risk of hepatic recurrence. The recurrence rate was high, or 56% for aneuploid tumors, while it was 18.5% for diploid tumors.

Expression of p53 protein in colorectal cancer and its relationship to short-term prognosis.

BACKGROUND AND METHODS: The expression of p53 protein in 100 large bowel cancers was studied immunohistochemically by use of a monoclonal antibody (PAb1801). RESULTS: Immunoreactivity was found in 61.0% of specimens from 100 patients with colorectal cancer. The pattern of p53 expression was mainly detected in the nuclei of the cancer cells. There was no significant correlation between the expression of p53 and the histologic grade, tumor size, serosal invasion, lymphatic invasion, venous invasion, lymph node metastasis, or liver metastasis. However, patients with p53-positive tumors had a greater relative risk of death compared with those with p53-negative tumors. The p53 negative-tumors showed a recurrence rate of 5.9%; for the p53 positive-tumors, a recurrence rate of 23.8% was recorded. The 3-year survival rate was 96.7% of 39 patients with p53-negative carcinomas and 61.8% for the patients with p53-positive tumors; there was a significant difference in the rate between the two groups of patients (P < 0.05). The growth fraction of p53-positive tumors determined with a monoclonal antibody against DNA polymerase alpha (49.0%) was significantly higher than that of p53-negative tumors (40.7%, P < 0.01). CONCLUSIONS: These results suggest that the immunoreactivity of p53 may be a biologic marker of prognostic significance.

[Immunohistochemical detection of p53 in colorectal cancer and its relationship to prognosis].

The expression of p53 in colorectal tumors was studied immunohistochemically by monoclonal antibody (PAb1801). No nuclear staining was evident in the tumor cells of colorectal adenomas. p53 immunoreactivity was found in 59 (61.5%) of 96 colorectal cancers. There was no significant correlation between the p53 immunoreactivity and histologic type, tumor size, invasion of bowel wall, lymphatic invasion, venous invasion, lymph node metastasis, peritoneal dissemination, or liver metastasis. However, the p53 negative tumors showed a recurrence rate of 3.3%, while for the p53 positive tumors a recurrence rate of 20.9%. p53 negative tumors were associated with favorable prognosis, whereas those with p53 positive tumors were related to poor prognosis. DNA polymerase alpha positive cells rate in p53 positive tumors was significantly higher than in p53 negative tumors. The results suggested that p53 immunoreactivity might possibly be a useful prognostic marker of colorectal cancers.

Intraperitoneal hyperthermic treatment for peritoneal dissemination of colorectal cancers.

Continuous hyperthermic peritoneal perfusion (CHPP) combined with administration of anticancer drugs was performed in eight colorectal cancer patients with peritoneal dissemination. An overall response rate of 50 percent was achieved in the eight patients. Two of three complete responders are long, recurrence-free survivors for 15 and 30 months. The two-year survival has been achieved in 18.8 percent of the patients receiving CHPP, and this rate is significantly higher than the rates in P2 and P3 patients who did not receive CHPP. The complications of CHPP with administration of anticancer drugs were mild bone marrow suppression in two (25 percent) of the eight patients and also a mild grade of renal dysfunction in one (12.5 percent), though not lethal. The results suggest that the combination of CHPP with the administration of anticancer drugs is a safe and effective therapy for peritoneal dissemination of colorectal cancers.

[Aortic arch and descending aortic replacement under deep hypothermia and circulatory arrest through left thoracotomy--case report].

Graft replacement of the transverse aortic arch and the descending thoracic aorta was done for two cases with Stanford type B aortic dissection involving the aortic arch. Cardiopulmonary bypass was established with left atrium and femoral vein for venous line and femoral artery for arterial line. Patients were cooled until their EEG activity had disappeared, then the bypass was discontinued. Lesser curvature of the transverse aortic arch was resected and graft was sutured by beveled fashion. After reinstitution of the bypass, intercostal arteries (Th8-10) were reattached to the graft and distal anastomosis was made above the diaphragma. Postoperative recovery was uneventful in both cases.

Autonomic nerve endings in the odontoblast/predentin border and predentin of the canine teeth of dogs.

Autonomic nerve endings in the odontoblast/predentin border and the predentin were observed by electron microscopy in the canine teeth of dogs. Adrenergic nerve endings with a number of very electron-dense granular vesicles and a minority of agranular vesicles of different sizes were clearly observed, but seen rarely, at the odontoblast/predentin border, in the predentin adjacent to the odontoblast processes, and as free endings in the middle part of the predentin. Cholinergic nerve endings were also observed with a number of agranular vesicles of different sizes without any visible exocytosis, in the odontoblast/predentin border, and in the predentin. Near the areas of collagen formation, extensive exocytosis of granular vesicles of different sizes was observed in adrenergic nerve endings located as free nerve endings in the predentin.

DNA polymerase alpha positive-cell rate in colorectal cancer and its relationship to prognosis.

A total of 63 patients with colorectal cancer were studied for proliferative activity by an immunohistochemical technique using a monoclonal antibody against DNA polymerase alpha. The DNA polymerase alpha positive cell rates ranged from 24.0% to 74.6%. There was a correlation between the DNA polymerase alpha positive cell rates of biopsies and resected specimens. There was no significant correlation between DNA polymerase alpha positive cell rates and histological type, tumour size, invasion of bowel wall, lymphatic invasion, venous invasion, lymph node metastasis or peritoneal metastasis. Tumours with a high growth fraction (a DNA polymerase alpha positive cell rate greater than or equal to 42%) were more frequently associated with liver metastasis than those with a low growth fraction (a DNA polymerase alpha positive cell rate less than 42%). Patients with high growth fraction tumours had significantly poorer prognoses than those with low growth fraction tumours. The results of multivariate analysis using the proportional hazard model of Cox indicated that the DNA polymerase alpha positive cell rates, liver metastasis, and peritoneal metastasis were independent prognostic factors. The results indicate that the DNA polymerase alpha positive cell rate may be a useful prognostic marker of colorectal cancers.

[Serum sialyl-Tn antigen in colorectal cancer and its relationship to prognosis].

Serum sialyl-Tn antigen level was studied in 117 cases of colorectal cancer. The positive rates for serum sialyl-Tn antigen were 23.1% in primary colorectal cancer. There is a significant correlation between the positive rates of serum sialyl-Tn antigen and liver metastases, peritoneal dissemination, or lymph node metastases. The survival rate for patients with sialyl-Tn antigen positive sera was lower than those with sialyl-Tn antigen negative. Among patients who underwent curative operation, patients with sialyl-Tn positive sera gave a recurrence rate of 35.7%, while those with sialyl-Tn negative sera recorded a recurrence rate of 14.7%. There is no correlation between the positive rates of serum sialyl-Tn antigen and DNA ploidy pattern. Serum sialyl-Tn antigen levels may be a useful indicator in projecting the prognosis of colorectal cancer.

[Study on correlation of hematogenous metastasis in advanced colorectal cancer with the morphological mode of tumor invasion in the pm layer].

We studied the influence of the morphological mode of tumor invasion in muscularis propria (pm) layer, in 177 patients who received resection for colorectal carcinoma that invaded beyond the pm layer. Tapering Index (TI = A/B) defined from the ratio between the length of tumor invasion on upper pm layer (A) and that on lower pm layer (B), TI value was significantly lower in cases with hematogenous metastasis than that in cases without hematogenous metastasis. Cases in which TI values were under 1.3 in colon cancer and 1.9 in rectal cancer had higher possibility of synchronous or metachronous hematogenous metastasis and poorer prognosis. Therefore, we suspected that TI value would be an important factor in prediction of hematogenous metastasis.

Clinical significance of tumor marker NCC-ST 439 in large bowel cancers.

We examined serum NCC-ST 439 for its significance as a tumor marker of large bowel cancer in 121 patients with primary and 36 with recurrent large bowel cancer. Serum NCC-ST 439 was positive in 27.3 percent of the former and 66.7 percent of the latter. It was false-positive in only 5.6 percent of patients with benign diseases. Positive serum NCC-ST 439 correlated with lymph node and liver metastases. The combination assay for NCC-ST 439, CEA, and CA19-9 was positive in 49.6 percent of the patients with primary tumors and 88.9 percent of those with recurrent tumors; in other words, the diagnostic accuracy improved. The results demonstrated that the determination of serum NCC-ST 439 in large bowel cancer might be useful in cancer staging and that NCC-ST 439, if used in combination with CEA, is particularly useful in diagnosing recurrences because of its improved diagnostic accuracy.