Intranodal antitumor immunocyte infiltration in node-negative gastric cancers.

The status and role of immunocytes and dendritic cells in regional lymph nodes in patients with gastric cancer are examined in this study. Forty-nine patients with gastric cancer who underwent curative resection were enrolled in the present study. These patients had no lymph node metastases according to a histological examination. The infiltration of natural killer (NK) cells, dendritic cells, and MIB-1-positive immunocytes was investigated. Based on the Japanese Classification of Gastric Carcinoma, regional lymph nodes were divided into three compartments: (a) compartment 1 (lymph node station numbers 1-6); (b) compartment 2 (lymph node station numbers 7-12); and (c) compartment 3 (lymph node station numbers 14 and 16). Dendritic cells and MIB-1-positive immunocytes infiltrated compartment 1 lymph nodes in increased numbers compared with the lymph nodes of compartments 2 or 3 (P < 0.05). Conversely, intranodal NK cell infiltration did not differ significantly among the three compartments. The incidence of intranodal dendritic and MIB-1-positive cell infiltration in patients with submucosal gastric cancer was significantly higher than in patients with tumors that invaded beyond the muscularis propria. The decreased expression of these immunological markers correlated well with recurrent disease, regardless of tumor depth. The immunocyte level is higher in lymph nodes near the primary tumor (compartment 1) than in those that are distant from the tumor (compartments 2 and 3). This pertains to all three markers, i.e., NK, dendritic, and MIB-1-positive cells. Unlike dendritic and MIB-1-positive cells, intratumoral infiltration of NK cells did not correlate well with either lymph node compartment or the depth of tumor invasion. The degree of NK cell infiltration may be directly associated with antitumor effects, especially in compartment 1. A decrease in all three markers is associated with tumor recurrence.

Impairment of cefdinir absorption by iron ion.

The effect of iron ion on the absorption of cefdinir, a new oral cephalosporin derivative, was evaluated in healthy male volunteers in a randomized three-way crossover study. The subjects received 200 mg cefdinir alone, 200 mg cefdinir and two tablets of iron ion concomitantly, and two tablets of iron ion preparation 3 hours after 200 mg cefdinir administration. The area under the concentration curve [AUC(0-12)] of cefdinir with concurrent iron was significantly smaller than that with cefdinir alone (mean +/- SD, 0.78 +/- 0.38 versus 10.3 +/- 1.35 micrograms.hr/ml). While there were no differences in AUC(0-3) between drug alone and drug with iron 3 hours later, the AUC(3-12) with delayed iron was significantly smaller than that of cefdinir alone (4.60 +/- 1.54 versus 8.03 +/- 1.72 micrograms.hr/ml). These findings suggest that the mechanism of interaction between cefdinir and iron ion preparation is the formation of a chelation complex and that this complex probably restricts gastrointestinal absorption.

Invariant chain expression in gastric cancer.

Invariant chain (Ii) is a chaperone molecule that inhibits the binding of endogenous antigens to HLA class II. The tumor cell with overexpressed Ii chain is thought to escape attacking cytotoxic lymphocytes by suppressing the host immune. However, the relationship between Ii expression by the tumor and clinicopathological factors in gastric cancer remains unclear. We studied 126 patients with gastric cancer who had undergone curative gastrectomy at Kagoshima University Hospital between 1988 and 1997. In order to detect Ii and HLA-DR expression by tumor cells, immunohistochemical staining with anti-CD74 and anti-HLA-DR antibodies were performed by avidin-biotin peroxidase complex method. The 126 patients studied were divided into two groups based on Ii expression. Ii and HLA-DR were expressed both on the surface and in the cytoplasm of tumor cells and tumor infiltrating lymphocytes. A total of 48 patients were identified as Ii positive, while the remaining 78 patients were Ii negative. Ii expression negatively correlated with the depth of invasion of the tumor as well as the patients' clinical stage. Ii expression was negatively correlated with HLA-DR expression. Patients with Ii negative expression had significantly better surgical outcomes than those with Ii positive expression (P<0.05). Ii expression in gastric cancer affected surgical outcome and Ii expression was negatively correlated with depth of invasion and HLA-DR expression. Ii expression in gastric cancer may be a prognostic factor related to suppressive effects on host immune responses to tumor cells.

Clinical impact of intratumoral natural killer cell and dendritic cell infiltration in gastric cancer.

Intratumoral natural killer cells (NKC) and dendritic cells (DC) may affect the clinical features of various gastrointestinal cancers. However, the relationship between intratumoral NKC and DC remains unclear. We examined 169 patients with gastric cancer who underwent gastrectomy at Kagoshima University Hospital. Immunohistochemical staining of CD57 and S-100-protein was performed to evaluate NKC and DC infiltration, respectively. A total of 25 areas containing pericancerous tissue were selected for determining the number of NKC and DC under high power microscopy (x400). Patients were classified into two groups according to NKC and DC population. Intratumoral lymphocytic infiltration was also calculated in 15 areas with a high power (x400) objective. The degree of NKC and DC infiltration was gradually decreased according to the progression of nodal involvement. Patients with many NKC infiltration had a lower positivity of lymph node metastasis and lymphatic invasion than patients with little NKC infiltration. DC infiltration was also negatively correlated with depth of invasion, lymph node metastasis and curativity. DC infiltration was positively correlated with lymphocytic infiltration (P=0.01. r=0.6). The 5-year survival rates of patients with many NKC infiltration and patients with DC many infiltration were 75 and 78%, respectively, both of which were significantly better than that of patients with little NKC and DC infiltration (P<0.05). NKC may be activated without DC or intratumoral lymphocytes. Intratumoral NKC may act as an independent immunologic effector against tumor cells, unlike DC.

Strategy of gastric cancer in patients 85 years old and older.

BACKGROUND/AIMS: There is little information about the clinical and pathological features of patients with gastric cancer aged 85 years old and older. METHODOLOGY: We analyzed data of 197 gastric cancer patients aged 75 years and older. The patients were dividing into three age groups and we retrospectively studied 25 gastric cancer patients aged 85 years old and older and compared their clinical courses with those of 94 patients in their late 70s and 78 patients in their early 80s. RESULTS: The patients aged 85 years and older had a significantly higher rate of symptoms on admission such as gastric outlet obstruction and progressive anemia (64%), than did the other two age groups (p<0.05). Twenty-five percent of the oldest age group did not have surgery, and none had a D2 lymph node dissection. Perioperative complications were more frequent in the oldest group than in the youngest group (p<0.05). Survival in the oldest patients was not affected by surgical resection. CONCLUSIONS: These results indicate curative gastric surgery has a less positive impact in patients aged 85 years and older than younger patients. Treatment for gastric cancer in patients 85 years old and older should emphasize the palliation of symptoms but not curative resection.

Quantitative analysis of electromyogram interference pattern in extraocular muscle.

Turns and amplitude analysis of the electromyogram (EMG) interference pattern has been applied to the extraocular muscles for the first time in the literature, to the best of our knowledge. EMGs of 261 horizontal rectus muscles recorded during the past 18 years were retrospectively examined and divided into four categories according to the clinical diagnosis: 56 complete palsy due to neuropathy, 67 incomplete palsy due to neuropathy, 19 myopathy, and 119 normal. The number of turns per second and mean amplitude between a pair of successive turns were automatically calculated by computer. Significant differences (P < 0.05) were encountered in all data among the four clinical categories except for the number of turns between myopathy and normal. The number of turns was plotted against the amplitude in each muscle on an X-Y diagram. The data of completely paretic muscle showed less number of turns and smaller amplitude and were clearly distinguishable from the data of the other three categories on the X-Y diagram. The interference pattern of incomplete palsy and myopathy had smaller amplitude than that of normal muscle. However, most of the data overlapped on the X-Y diagram particularly between data of incomplete neuropathy and myopathy.

Botulinum toxin type A purified neurotoxin complex for the treatment of blepharospasm: a dose-response study measuring eyelid force.

The clinical efficacy of botulinum toxin type A was studied in patients with blepharospasm. Clinical symptoms were evaluated using the Jankovic rating scale. To measure dose response, we used a recently developed device to measure eyelid muscle force. The results showed significant improvement (P = 0.0000) in the Jankovic rating scale scores in all dose groups. The number of patients with marked improvement (6-point decrease or more in the total Jankovic rating scale score) increased with higher dose injections. After injections of 0.50, 1.25, or 2.50 U/site, 6 sites/eye, the eyelid muscle force decreased by 33.2 +/- 28.1%, 41.7 +/- 25.1%, or 69.6 +/- 5.0%, respectively. The decrease of eyelid muscle force showed a significant dose response (P = 0.0254). The mean duration of effect was 12.9 weeks in patients after dose injections of 1.25 U/site, which was significantly longer (P = 0.0205) than the 9.6 weeks in patients after dose injections of 0.50 U/site. No severe adverse effects were observed. We concluded that injections of botulinum toxin type A at an initial dose of 1.25 U/site are a safe and effective treatment for blepharospasm.

Measurements of active and passive force of horizontal muscles in strabismus.

A precision device was developed for quantitative measurement of the active and passive forces of the horizontal muscles in several different types of strabismus. The device consists of a tension gauge for measuring isometric muscle tension (active force) and passive length-tension (passive force), and a circular-motion guide mechanism. In normal subjects, the active force showed nearly linear changes with the eye position, as was reported in past studies. A similar relationship between the active force and the eye position was observed also in strabismus patients in our study. Normal subjects showed a stronger force in the medial than the lateral rectus muscle. Among strabismus patients, those with normal retinal correspondence (NRC)-intermittent exotropia showed a force closest to that of the normal controls. However, the force of the lateral rectus muscle was significantly greater in those with constant exotropia than in the normal controls. The active force of the medial rectus muscle was significantly smaller in those with dual retinal correspondence (DRC)-intermittent exotropia and constant exotropia. Conversely, the active force of the medial rectus muscle was significantly greater in those with esotropia, compared with the normal group. As for the passive force, there was no significant difference between the temporal passive force and the nasal passive force in the normal and esotropic groups, but the temporal passive force was significantly greater in the esotropic group. The magnitude of the force was greater in both directions when traction was applied against the muscle having the stronger active force. These results suggest that the lateral rectus muscle force is relatively stronger in patients with DRC-intermittent exotropia due to a weakness of the medial rectus muscle force, and that the absolute strength of the lateral rectus muscle force is increased in patients with constant exotropia, but in NRC-intermittent exotropia the muscle forces are almost normal. Those with esotropia are considered to have an absolute increase in the medial rectus muscle force.

Results of surgery for paralytic esotropia due to abducens palsy.

The surgical effects of three methods, transposition of the vertical rectus muscles, Jensen's procedure, and resection (advancement) of the lateral rectus muscle, were compared among 109 cases of paralytic esotropia due to abducens palsy. These procedures were combined with recession of the medial rectus muscle in about half the cases. Of the 109 cases, 22 were followed up for 4 years or longer. Results were similar, provided that the following protocols for surgery were adhered to: in cases of complete paralysis, transposition of the vertical rectus muscles was done, and in cases of incomplete paralysis, resection (advancement) of the lateral rectus muscle was performed. With both procedures, results were improved if recession of the medial rectus muscle was carried out at the same time.

Long-term results of surgery for superior oblique palsy.

The results one month after surgery in 159 cases of superior oblique palsy were compared according to the method of surgery with the results 4 years or longer after surgery. There were 141 cases of congenital palsy and 18 cases of acquired palsy, for a total of 159 cases. Our study showed that surgery on the oblique muscle provided long-lasting effects, while recession of the superior rectus muscle or recession of the contralateral inferior rectus muscle could cause late overcorrection. When performing surgery on the rectus muscle, careful attention must be paid to suturing the muscle.

[Botulinum toxin type A (BOTOX) for treatment of blepharospasm: an open label, dose-response study].

The clinical effect of Botulinum Toxin Type A (BOTOX) were studied in patients with blepharospasm. Clinical symptoms were evaluated with Jankovic's rating scale, widely used for blepharospasm. To see dose response, eyelid muscle force of the patients was measured with a device recently developed for measurement of eyelid muscle force. The results showed significant improvement (p = 0.0000) on Jankovic's rating scale in all patient groups after effective dose injections of 0.5, 1.25, and 2.5 U/site. Particularly the number of patients with marked improvement (decrease of six points or more in total score on Jankovic's rating scale) increased with higher dose injections. The eyelid muscle force also decreased by 33.2 +/- 28.1%, 41.7 +/- 25.1%, and 69.6 +/- 5.0% in patients groups after effective dose injections of 0.5, 1.25, and 2.5 U/site, respectively. The decrease of the eyelid muscle force showed significant dose response (p = 0.0254). Mean duration of effect was 12.9 weeks in patients after effective dose injections of 1.25 U/site, which was significantly longer (p = 0.0205) than that of 9.6 weeks in patients after effective dose injections of 0.5 U/site. No severe adverse effects were observed. We concluded that BOTOX injections of 1.25 U/site or more are a safe and effective treatment of blepharospasm.

[Computed tomography findings in convergent strabismus fixus].

X-ray computed tomography (CT) of the eyeball and orbit revealed the cause of eye movement disorder in convergent strabismus fixus. The findings suggest that the disease can be diagnosed and treated at an early stage. Twelve cases of progressive esotropia with high myopia and 20 cases with normal visual acuity served as subjects in this study. The CT slice was parallel to the German horizontal plane, and the lens and medial and lateral rectus muscles were scanned. The average axial length of the affected eyes was significantly longer than in normal eyes. In progressive esotropia, the characteristic CT findings are an elongated eyeball, mechanical contact between the eyeball and lateral wall of the orbit, and a downward displacement of the lateral rectus muscle. Thus, it is reasonable to conclude that eye movement disorder in convergent strabismus fixus results from weakness of the lateral rectus muscle which has been displaced downward due to compression of the eyeball against the orbital wall.

[Quantitative analysis of electromyogram interference pattern in extraocular muscle].

Quantitative analysis of electromyogram (EMG) interference pattern was performed for objective evaluation. EMGs of 261 horizontal rectus muscles had been recorded in our laboratory during the past 18 years, and they were divided according to the clinical diagnosis into four categories: 56 records due to complete neuropathy, 67 due to incomplete neuropathy, 19 due to myopathy, and 119 normal. The turns and amplitude analysis program was used for EMG analysis. A turn was one wave of the interference pattern, for which we used an amplitude of more than 15 microV. Turns meant the number of turn waves per second. Turns/second and mean amplitude/turn (A/T) were plotted against each other on an X-Y diagram, and a statistical evaluation of data was done. Complete neuropathy recordings that had lower turns and lower A/T were separated from the other three categories. Incomplete neuropathy and myopathy occurred on the lower A/T area. There was a significant difference (p < 0.05) between each pair of comparisons from all four categories except for turns evaluated between myopathy and normal. Quantitative analysis proved useful for the objective evaluation of the EMG interference pattern, particularly between cases of complete and incomplete neuropathy.

[Surgical and botulinum toxin treatment in two cases of abnormal retinal correspondence-exotropia with congenital homonymous hemianopsia].

We report 2 unusual cases of congenital occipital hemianopsia associated with abnormal retinal correspondence (ARC)-exotropia. Two Japanese males, 25 and 28 years of age, visited our hospital for surgical correction of manifest exotropia with dissociated vertical deviation and overaction of the superior oblique muscle. Visual field examination demonstrated homonymous hemianopsia with approximately 5 to 10 degrees of macular sparing. Visually evoked potential examination showed small amplitude similar to dissociated vertical deviation patients in all half-field stimulation. Electrooculogram examination demonstrated defective pursuit to the ipsilateral side. Some investigators have speculated that progressive exotropia compensates for homonymous hemianopsia and is a rare contraindication for strabismus surgery. To confirm the deterioration of motor and visual functions before surgery in these patients, we tried injections of botulinum A type toxin into the lateral rectus muscle ipsilateral to the hemianopsia. Contrary to the hypothesis, our patients had no change in their binocular visual fields and visual function. Finally, we performed recession of the lateral rectus muscle, so that both patients were satisfied with their ocular alignment, with no marked change of visual behavior.

[Preoperative prediction of the amount of surgical correction by using Botulinum A type toxin for the treatment of paralytic esotropia].

The aim of this study was to obtain the correct choice of initial surgical procedure and to predict the amount of surgical correction by using the maximum reduction rate of eye position after Botulinum A-type toxin injection for the treatment of acquired neurogenic paralytic strabismus. The subjects were 30 with sixth nerve palsy and 33 with non-paralytic esotopia with no previous surgery. The results were that if the maximum reduction rate of eye position after the first injection of 1.25 U was less than 68%, the modified Jensen procedure with recession of medial rectus muscle was necessary to achieve 100% recovery. However, if it was more than 100%, then recession-resection of the horizontal rectus muscles alone produced successful ocular alignment. Based on our data of 100 cases of sixth nerve palsy that showed spontaneous recovery, we conclude that surgical treatment should be planned, if the maximum percentage reduction of preoperative eye position after Botulinum A-type toxin treatment is under 68% (reflecting the inability of the medial rectus muscle to contract and the lengthening of the lateral rectus muscle), and if the patient has no spontaneous improvement at all within 12 weeks after onset.

[A case of local recurrence of rectal cancer successfully treated by UFT combined with two-route CDDP chemotherapy under the AT-II induced hypertension].

A case of local recurrence of rectal cancer was successfully treated by UFT combined with two-route CDDP chemotherapy under the AT-II induced hypertension. UFT (600 mg/day) was orally administered every day. CDDP (75 mg/m2) was infused into the right internal iliac artery via subcutaneously grafted Infuse-a-port under hypertensive state induced by the AT-II (3 micrograms/min). Sodium thiosulfate was intravenously given to protect the CDDP induced nephrotoxicity. The recurrence tumor palpated by digital examination and revealed by MRI disappeared after the fourth two-route CDDP chemotherapy. The serum CEA level elevated before the treatment also normalized. This combined chemotherapy was considered to be an effective measure to cure the local recurrence of rectal cancer.