Basic evaluation of a novel 4D target and human body phantom.

Stereotactic body radiation therapy (SBRT) is usually verified with a dynamic phantom or solid phantom, but there is a demand for phantoms that can accurately simulate tumor dynamics within an individual that would allow customized validation in every patient. We developed a new 4D dynamic target phantom (multi-cell 4D phantom) that allows simulation of tumor movement in patients. The basic quality and dynamic reproducibility of this new phantom was verified in this investigation. The newly developed multi-cell 4D phantom comprises four main components: soft tissue, bones, lungs, and tumor (target). The phantom structure was based on computed tomography (CT) data of a male. In this study, we investigated the basic performance of a multi-cell 4D phantom. All the CT numbers of the phantom were very close to those of human data. The geometric maximum amplitudes were 4.57 mm in the lateral direction, 4.59 mm in the ventrodorsal direction, and 3.68 mm in the cranio-caudal direction. Geometric errors were 0.84, 0.58, and 0.40 mm, respectively. Movements of the abdominal surface were stable for 60 s. Repeated measurements show no actual differences in target movements between multiple measurements and indicated high reproducibility (r > 0.97). End-to-end tests using Gafchromic film revealed a gamma pass rate of 98% or above (2 mm/3%). Although our phantom performed limited reproducibility in the movement of the patient tumor at present, a satisfactory level of precision was confirmed in general. This is a very promising device for use in the verification of radiation therapy for moving targets.

Ultrasound biomicroscopic analysis of posterior chamber intraocular lenses with transscleral sulcus suture.

OBJECTIVE: To investigate the postoperative problems of intraocular lenses (IOLs) with transscleral sulcus suture. DESIGN: Retrospective observational case series. PARTICIPANTS: Forty-one subjects (43 eyes) were included. INTERVENTION: All eyes had undergone transscleral sulcus suture of IOLs. Surgeries were all performed by surgeons in our clinic using the same technique. MAIN OUTCOME MEASURES: Ultrasound biomicroscopy of the suture sites, their surrounding structures, and central anterior chamber depth. Other parameters studied included visual acuity, aqueous flare, and routine ophthalmic examinations. RESULTS: Thirty-two of 86 haptics were sutured at the ciliary sulcus (CS) region and 29 at the ciliary process region, which was the space between CS and pars plicata, and 25 posterior to pars plicata. We designated the cases with at least one haptic located in the CS region as the anterior group, and the other cases as the posterior group. In the anterior group, anterior chamber depth was significantly more shallow than in the fellow eye in which IOLs were fixed in the bag (P = 0.049). There was a statistically greater incidence of IOL iris contact in the anterior group than in the posterior group (P = 0.00057). Pigment dispersion was seen in seven cases, all of which were classified as anterior group. Eyes in the posterior group had more aqueous flare than their fellow eyes (P = 0.014). Two cases, in which more than two lines of postoperative best-corrected visual acuity was lost because of macular degeneration after cystoid macular edema, showed marked elevation of aqueous flare in the sutured eyes compared with their fellow eyes. Forty-one of 86 haptics had vitreous incarceration. CONCLUSIONS: This technique has many limitations: the difficulty of suturing precisely at the ciliary sulcus, IOL iris contact, pigment dispersion, high aqueous flare, and vitreous incarceration. These induce two major postoperative complications: chronic inflammation and influence on the adjacent vitreous such as vitreous incarceration. The suturing technique and instruments need to be improved to diminish such complications.

Long-term results of out-of-the-bag intraocular lens implantation.

PURPOSE: To evaluate long-term results of out-of-the-bag intraocular lens (IOL) implantation. SETTING: Department of Ophthalmology, Tenri Yorozu Hospital, Nara, Japan. METHODS: This study comprised 22 patients, 13 women and 9 men, who had cataract surgery by phacoemulsification and out-of-the-bag IOL implantation because of a posterior lens capsule rupture. Sixteen patients had in-the-bag IOL implantation in the fellow eye, and these eyes were used as a control group. The IOL's position was determined by ultrasound biomicroscopy (UBM). Anterior chamber flare counts were measured by a laser flare meter. The corneal endothelium was observed by specular microscopy. RESULTS: Mean follow-up after cataract surgery was 35 months +/- 22 (SD). The UBM revealed that in the 19 eyes with sulcus-to-sulcus IOL fixation, the optics touched the iris. In 3 eyes, 1 haptic was fixated at the sulcus and the other at the ciliary body. In 2 of these eyes, the optics did not touch the iris. Anterior chamber flare counts in eyes with sulcus-to-sulcus IOL fixation were significantly higher than in eyes with in-the-bag or sulcus-to-ciliary-body fixation (P < .05). There were no statistical differences in corneal endothelial cell counts based on haptic placement. CONCLUSION: Rubbing between the IOL optic and iris seems to contribute to the high flare counts in eyes with a sulcus-to-sulcus IOL fixation. A larger haptic angle may be needed to prevent contact between the iris and IOL optic in such cases.

Distribution of plasmalemmal Ca(2+)-pump and caveolin in the corneal epithelium during the wound healing process.

PURPOSE: Caveolae are small plasmalemmal invaginations which are assumed to play various physiological functions. In the present study, distribution of two caveolae-specific proteins, the plasmalemmal Ca(2+)-pump and caveolin, was examined in the corneal epithelium in the normal state and after artificial wounding. METHODS: A central epithelial ablation was made in the mouse cornea by a razor blade. After various intervals, the corneas were excised, fixed, and rapidly frozen. The specimens were subjected to immunofluorescence microscopy and immunoelectron microscopy, using antibodies against the plasmalemmal Ca(2+)-pump or caveolin. RESULTS: In the normal corneal epithelium, both plasmalemmal Ca(2+)-pump and caveolin were observed along the cell surface by immunofluorescence microscopy, and were localized to caveolae by immunogold electron microscopy. In the regenerating epithelium, 12-18 h after injury, plasmalemmal Ca(2+)-pump was seen as many dots in the cytoplasm by immunofluorescence microscopy; in contrast, caveolin persisted along the cell surface. Immunoelectron microscopy revealed that the labeling for the plasmalemmal Ca(2+)-pump was located around membranous structures in the cytoplasm and was scarce along the plasma membrane, while caveolin remained in caveolae. The Ca(2+)-pump regained normal distribution when the wound was closed. By quantitation in electron micrographs, the number of caveolae per unit plasma membrane length was found to be decreased in the wounded corneal epithelium. CONCLUSIONS: The present results indicate that caveolae undergo compositional modification during the wound healing process of the corneal epithelium. Considering putative caveolar functions, the phenomenon may be related to possible fluctuations of the intracellular Ca(2+)-concentration in the regenerating epithelium.

Mucus escape reaction that involves the mandible: a case report and diagnostic imaging considerations.

We present a case of mucus escape reaction in which we encountered difficulty in interpreting the images acquired by plain radiography, computed tomography, and magnetic resonance imaging. The 48-year-old male Japanese patient was referred for evaluation of a gradual swelling subjacent to the inferior border of the left mandible. At the early imaging examinations, magnetic resonance imaging provided information crucial to resolving the issue of whether the lesion consisted of a central malignant disease process or a malignant disease in the submandibular space or both of these two separate disease entities. Magnetic resonance imaging demonstrated no evidence of tumorous lesion, but rather showed a fluid-containing cavity that was also confirmed by the subsequent intrasurgical inspection. On further consideration of these imaging findings, we concluded that the entity was mucus escape reaction with simultaneous occurrence of an intraconnective tissue hemorrhage adjacent to the left submandibular gland, concomitant extensive bony defect of the left mandible and lingual cortical defect, and chronic sialoadenitis of the left submandibular gland.

Tyrosine phosphorylation in desmosomes and hemidesmosomes of the corneal epithelium.

We examined the localization of phosphotyrosine (p-Tyr)-modified proteins in the normal corneal epithelium using affinity-purified rabbit anti-p-Tyr antibody. Normal rat cornea was fixed and semi-thin and ultra-thin frozen sections were prepared. Immunofluorescence microscopy showed that p-Tyr was distributed along the cell membrane of the corneal epithelium. Immunogold electron microscopy revealed that the labeling is exclusively localized in the desmosomes and hemidesmosomes. A fraction enriched with desmosomes was extracted from the bovine corneal epithelium and examined by Western blotting. Immunoblotting for p-Tyr showed eight prominent bands (290, 200, 190, 115, 85, 62, 50, and 47 kD) in the desmosomal fraction. The enrichment of p-Tyr in desmosomes and hemidesmosomes of the corneal epithelium suggests that these cell-to-cell and cell-to-substrate junctions are involved in signal transduction.

Malignant transformation of leukoplakia three times in period of 11-years--case report.

Leukoplakia is a commonly occurring precancerous lesion. The following case report describes a patient who had multiple leukoplakia in this mouth. He had three sites of leukoplakia, the left hard palate, the gum of the right maxilla and the gum of the left mandible, all of which underwent malignant transformation during the period of 11-years after diagnosis.

Redistribution of fodrin in an in vitro wound healing model of the corneal epithelium.

We previously observed the redistribution of a membrane skeletal protein, fodrin, after wounding in the corneal epithelium in vivo. In this study, we made an in vitro wound healing model using cultured corneal epithelial cells to investigate the redistribution mechanism of fodrin in the corneal epithelial cells. The distributional change of fodrin from the plasmalemma to the cytoplasm was observed soon after wounding by indirect immunofluorescence microscopy and laser scanning confocal microscopy. A similar change was caused by treating intact cells with phorbol-12-myristate-13-acetate (PMA), but not with calcium ionophore, A23187. The redistribution occurred even in cells pretreated with 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetomethyl ester (BAPTA-AM) before wounding. The redistribution caused by wounding or by PMA was inhibited by pretreating the cells with protein kinase C inhibitors, H-7 or calphostin C. Moreover, the reagents were found to slow down the migration of corneal epithelial cells after wounding. These results suggest that the redistribution of fodrin in the wounded corneal epithelium is caused through the activation of protein kinase C and might be related to the ensuing cell migration.

Immunobiological activities of chemically defined lipid A from lipopolysaccharides of Porphyromonas gingivalis.

Immunobiological activities of chemically defined lipid A from lipopolysaccharides (LPS) of Porphyromonas gingivalis strain 381, which possesses beta-(1-->6)-linked glucosamine disaccharide 1-monophosphate, with 3-hydroxy-15-methylhexadecanoyl and 3-hexadecanoyloxy-15-methylhexadecanoyl groups at the 2- and 2'-positions, respectively, were compared with those of synthetic Escherichia coli-type lipid A (compound 506) and Salmonella-type lipid A (compound 516). P. gingivalis lipid A and its LPS induced stronger or comparable production of the cytokines interleukin-1 receptor antagonist (IL-1ra), IL-6, IL-8, granulocyte-macrophage colony-stimulating factor and interferon-gamma as compared with compounds 506 and 516 in the culture supernatants of human peripheral blood monocytes or mononuclear cells. However, the P. gingivalis preparations showed low activity in inducing the production of IL-1 beta and tumour necrosis factor-alpha. Clear antagonistic effects of P. gingivalis lipid A and its LPS against IL-1 beta production induced by E. coli LPS or compound 506 were seen. Furthermore, P. gingivalis lipid A and its LPS had marked immunopharmacological activities, i.e. antitumour, natural killer cell and antiviral activities. Its monophosphorylation pattern and the presence and position of fatty acids possessing acyl chains of considerable length are unique to P. gingivalis lipid A, differing from enterobacterial lipid As. Its good balance between agonistic and antagonistic effects, making it a possible candidate for use as an immunomodulatory drug, may be attributable to these unique features.

[Decision analysis in therapeutic strategies for small bowel obstructions].

Clinical decision analysis was applied in therapeutic decision-making regarding small bowel obstructions. For strangulation obstruction, the three strategies of immediate surgery, observation of clinical course, and decision according to ultrasonographic findings were analyzed. When mortality rate, morbidity rate, or duration of hospital stay was used as the utility value, decision on the basis of ultrasonographic findings was selected as the most effective strategy, while the strategy of immediate surgery was selected when the rate of intestinal necrosis was used as the utility value. For adhesive obstructions, the three strategies of immediate surgery, conservative treatment with long tube decompression, and long tube decompression with enteroclysis (infusion contrast radiography) were analyzed. The strategy of enteroclysis was selected when morbidity rate and duration of hospital stay were used as utility values, while immediate surgery was selected when recurrence rate of adhesive obstruction was used as the utility value. For obstruction caused by intraabdominal recurrent cancer, operative treatment and conservative treatment were analyzed. The strategy of surgery was selected when rate of obstruction resolved and number of months of survival were used as utility values. Clinical decision analysis is valuable in quantitatively assessing individual variables affecting therapeutic decision-making.

Midline cervical cleft. A case report.

A case of incomplete midline cervical cleft of the upper neck is reported. It showed histological resemblance to a mature teratoma with three different germ-cell components, including cartilage, striated muscles, small salivary glands, and nerves.

Retinoblastoma in dizygotic twins born as extremely low birth weight infants.

A case of bilateral retinoblastoma affecting both of a pair of dizygotic twins was reported. To our knowledge, there has been only one previous report of dizygotic twins, both affected, with this disease. The present twins had no family history of retinoblastoma. They were born prematurely as extremely low birth weight infants after 26 weeks and 4 days of gestation, and 3 of the 4 tumors were detected at 33 weeks after conception. Using LINAC external radiation therapy followed by xenon photocoagulation when necessary, the tumors were successfully treated. These cases show that retinoblastoma can develop in the pre-term period, indicating that the second mutation involved in tumorigenesis can occur in the fetus.

[Problems with topical therapies for extensive squamous cell carcinoma of the buttocks].

In patients in whom cancer originating from a bed-sore has advanced to a stage where radical treatment is impossible, topical treatment with ointment, or systemic anti-cancer chemotherapy, is usually applied. We recently attempted treatment of extensive squamous cell carcinoma of the buttocks, for which radical treatment was impossible, by chemotherapy using a reservoir for intraarterial injection. This therapy involved intraarterial injection of bleomycin and 5-FU, together with topical treatment with 5-FU ointment. We describe the problems encountered with this therapy, e.g., measures against fever after intraarterial injection, management of the affected area, evacuation, possibility and limits of radiation therapy, and assessment of its efficacy.

Nationwide investigations of intestinal obstruction in Japan.

Two nationwide questionnaire surveys of intestinal obstruction in Japan were undertaken, covering two two-year periods, from January, 1975 to December, 1976 and from January, 1985 to December, 1986, respectively. The findings of a comparative review of these two surveys indicated that although the overall mortality of intestinal obstruction had not changed between 1975/76 and 1985/86, being 6.8 per cent and 6.5 per cent, respectively, simple adhesive obstruction had decreased from 3.2 per cent in 1975/76 to 2.0 per cent in 1985/86. The main cause of adhesion was laparotomy and in cases of both simple adhesive obstruction and strangulation adhesive obstruction, the rate of adhesion secondary to laparotomy of the upper gastrointestinal tract and colon and rectum had increased between 1975/76 and 1985/76. Obstructions caused by neoplasms had increased from 8.2 per cent in 1975/76 to 10.0 per cent in 1985/86, while those caused by adhesions had increased further still, from 42.5 per cent in 1975/76 to 60.8 per cent in 1985/86. Among the latter group, non-operatively treated cases had increased, which may be accounted for by the fact that facilities which adopt non-operative treatment using intestinal decompression as the first choice for simple adhesive obstruction cases have increased. In both surveys, the mortality of cases receiving nonoperative treatment was lower than that of operative cases.

[Evaluation of reservoir inserted for the prevention of liver metastasis of colorectal cancer].

The subjects were 22 patients who had undergone intra-arterial chemotherapy using reservoirs for prevention of postoperative liver metastasis during the period from January 1986 to September 1989, 3 with non-resected liver metastasis, 1 with resected liver metastasis with intra-arterial chemotherapy, and patients with systemic chemotherapy. None of the 7 patients with macroscopic stage II disease, who had undergone intra-arterial therapy for the prevention of liver metastasis survived (maximum duration, 25 months), had liver metastasis. Two of 8 patients with stage III disease died, and liver metastasis was observed. Two of 7 patients with stage IV disease died, one of whom them had liver metastasis. Four of 12 patients with stage II disease treated by systemic chemotherapy died, and 2 of them had liver metastasis. Four of 18 patients with stage III disease treated by systemic chemotherapy died, and one of them had liver metastasis. One of 11 patients with stage IV disease systemic chemotherapy died, and liver metastasis was noted in another. None of the patients who had undergone intra-arterial chemotherapy for the prevention of liver metastasis had liver metastasis within a period of one year. At present there is no difference in survival period between the group given intra-arterial chemotherapy for the prevention of liver metastasis and the group given systemic chemotherapy.

[Effects of intra-arterial infusion chemotherapy in local recurrence of anal cancer].

At present, there is no effective local therapy for skin metastasis after radical operation for anorectal cancer. Most local recurrent lesions of this type are not indications for surgery. However, successful control of the local lesion can enhance the quality of life because the general condition is good. We performed intra-arterial infusion chemotherapy for skin metastasis after Miles operation for anorectal cancer and observed marked effects. A 62-year-old female with anal cancer underwent Miles operation in November, 1987. About July, 1988, an indurated mass appeared in the perineal region but was left untreated. However, urinary disturbance due to the mass developed, and she was admitted in September. A catheter for Intra-arterial infusion chemotherapy was inserted via the lateral deep femoral artery, and 5-FU, BLM, and MMC were administered. Local bleeding was stopped, and the mass began to be reduced about 16 days after the administration. After about 1 month, no secretion from the mass was observed, and the urinary disturbance improved due to a reduction in the mass.

[Bolus and maintenance infusion of high-dose methotrexate].

For 17 patients with bone and soft tissue sarcoma, 32 bolus and maintenance infusions of high-dose methotrexate (MTX) were performed to induce rapid elevation of plasma MTX concentration and to maintain it. At the doses of 200-300 mg/kg, plasma MTX concentrations were measured by enzyme assay. It needed four hours to reach the steady state by five hours' constant rate infusion, with the plasma plateau concentration at about 1 X 10(-3) M/L. On the other hand, bolus infusion of MTX needed only one hour to reach over 5 X 10(-4) M/L, and the plateau concentration lasted during the maintenance infusion period. By the constant rate infusion as well as bolus infusion, it was possible to maintain the plasma concentration over 1 X 10(-4) M/L for 12 hours, but both infusions can not maintain 1 X 10(-3) M/L for a long time. From these results, clinical effects of high dose MTX against sarcomas seemed to be evaluated by the plasma MTX plateau concentration and the maintenance time.

[Preoperative radiotherapy of bone and soft tissue sarcomas].

UNLABELLED: The role of preoperative radiotherapy was evaluated in 16 cases with soft tissue sarcoma and 13 cases with osteosarcoma. Nine osteosarcoma cases underwent radiotherapy of whole lesion, and 4 cases had radiotherapy only of the surgically incurable portion. There were no local recurrences in M0 cases, but skin necrosis occurred in the whole radiation group. As for the soft tissue sarcomas, local recurrence was not seen in virgin cases, but two cases which had received previous treatment showed local recurrence. There were no cases with severe side effects. CONCLUSION: 1. Partial radiotherapy was effective as preoperative treatment for osteosarcoma. 2. preoperative radiotherapy is better than postoperative radiotherapy from many standpoints.

[Evaluation method of surgical margin in musculoskeletal sarcoma].

The evaluation of surgical margin is useful in determining the curability of surgical treatment of musculoskeletal sarcoma and the degree of possibility to reduce later surgery as part of preoperative therapy. However, at present there has been no worthwhile evaluation method developed for these purposes. In this paper we propose a new evaluation system for surgical margin as drafted by the Bone and Soft Tissue Tumor Committee of JOA. This system was applied in 197 cases at the Cancer Institute Hospital to determine the clinical significance in the treatment of musculoskeletal sarcoma. In this method, surgical margin was classified into four types according to the distance between the surgical margin and the reactive zone of the tumor. The types of surgical margins (in order of surgical extent) are curative margin, wide margin, marginal margin, and intralesional margin. Surgical margin is said to be curative if the margin is more than 5cm outside the reactive zone. It is referred to as wide if the margin is less than 5cm and marginal if the margin is at the reactive zone. In our evaluation, a thin barrier is estimated as a 2cm thickness of normal tissue, a thick barrier as a 3cm thickness of normal tissue, and joint cartilage as 5cm thickness. Moreover, in all cases the surgical margin is considered to be curative if the margin is outside a barrier and there is normal tissue between the barrier and the reactive zone of the tumor. The results of the study were as follows.(ABSTRACT TRUNCATED AT 250 WORDS)

[Urinary beta 2-microglobulin as an indicator for impaired excretion of methotrexate].

Twenty cases treated with high-dose methotrexate (MTX) infusions were studied to determine whether urinary beta 2-Microglobulin (beta 2-M) is a reliable indicator to predict impaired excretion of methotrexate. Before and after MTX infusions, the levels of urinary beta 2-M were measured along with serum creatinine, uric nitrogen, and creatinine clearance. MTX clearance was found to be impaired in four of the 20 infusions, although concentrations of serum creatinine and uric nitrogen, and creatinine clearance were normal prior to the infusions. In the four cases that resulted in impaired excretion, a significant increase of beta 2-M levels was noted before and after the high-dose MTX infusion (p less than 0.01). Although one of the four cases showed a normal level of beta 2-M before the infusion, the post-infusion level of beta 2-M extremely high. This raised level of beta 2-M was thought to be caused by impaired excretion due to decreased amounts of urine. We conclude that urinary beta 2-M is a sensitive indicator of impaired excretion of high-dose MTX infusion, and especially when levels of more than 250 ng/ml of urinary beta 2-M are found to exist, it seems to difficult to clear the drug following high-dose MTX treatment.