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[Change of reactive small round cell infiltration in the stroma after pre-operative 8 Gy irradiation using treatment to maxillary sinus carcinoma with Kitasato method and prognosis according to the change].

PURPOSE: In this paper, we report the results of studying the degree of reactive small round cell infiltration in the stroma as a prognostic indicator of maxillary sinus carcinoma treated with the Kitasato method and the effect of preoperative irradiation at 8 Gy on infiltration in the stroma. SUBJECTS: Out of 74 patients who had been treated with this method in the 27 years from 1976 to 2002, the following patients were enrolled in this study: (1) 17 patients from whom tissue specimens could be obtained with biopsies or probe antrotomies before preoperative irradiation, and (2) 40 patients from whom tissue specimens could be obtained after preoperative irradiation including those who survived five years and who died of a specific cause. METHOD: We classified the pattern of distribution of small round cell infiltration in the stroma into three degrees. (1) Stromal infiltration was compared before and after the operation to recognize the prognosis for each patient based on the pattern of distribution of small round cell infiltration in the stroma. (2) The correlation between the degree of stromal infiltration and prognosis was studied statistically. RESULTS: (1) Both the patients with increased stromal infiltration and those postoperatively preserving a preoperative score of 2+ with irradiation at 8 Gy had a good prognosis. (2) The five-year survival rate for patients was significantly higher in those with a score of 2+ for their tissue specimens. CONCLUSION: The Kitasato treatment method is effective and improves the QOL of patients with maxillary sinus carcinoma. The prognosis was good in the patients with increased or preserved stromal infiltration. The low-dose irradiation and chemotherapy used in combination seemed to be biological response modifiers.

Adult↗

Detection of dendritic cells in the non-obese diabetic (NOD) mouse islet pancreas infiltrate is correlated with Th2-cytokine production.

We investigate the role played by dendritic cells (DCs) in the non-obese diabetic (NOD) mouse pancreas. The early peri-islet, nondestructive infiltration phase, and intra-islet, destructive infiltration phase, which immediately precedes overt diabetes, are studied. Results show that infiltrating cells are Ia-b, ICAM-1, and, mainly, MIDC-8 immunoreactive (ir). These data from silica-treated animals and ultrastructural observations strongly support the hypothesis that DCs are both Ia-b-ir and ICAM-1-ir and that they exert a pivotal role during the period of early infiltration. This is a novel finding for NOD mice and increases the interest for this protective cell type during the rather complex islet infiltration process. Moreover, the cytokine profile demonstrates that Th2 protective cytokines are specific for peri-islet infiltrate. Disappearance of DCs from the infiltrate is concomitant with both the formation of intra-islet infiltration and the increase in proinflammatory Th1 cytokine levels. This further supports the hypothesis that DCs may exert a protective role against diabetes development.

Age Factors↗

[Study on the permeability of the infiltration glass of GI- I slip casting aluminous ceramic core].

In order to explore the infiltration condition of GI- I slip casting aluminous ceramic core glass material to aluminous ceramic substratum and provide reference for clinical use, the linear change relationship between the minimal infiltration depth and infiltration time was determined by measuring the minimal depth of glass material infiltrated to aluminous ceramic substratum from one to six hours. The result showed: there is a high linear relationship between the minimal infiltration depth for GI- I infiltration glass and the infiltration time. For clinical use, the minimal infiltration time for GI- I slip casting aluminous ceramic core at least 2.5 hrs and 5 hrs for bridge framework.

Crowns↗

Quantitative imaging and microlocalization of boron-10 in brain tumors and infiltrating tumor cells by SIMS ion microscopy: relevance to neutron capture therapy.

Boron neutron capture therapy (BNCT) is dependent on the selective accumulation of boron-10 in tumor cells relative to the contiguous normal cells. Ion microscopy was used to evaluate the microdistribution of boron-10 from p-boronophenylalanine (BPA) in the 9L rat gliosarcoma and the F98 rat glioma brain tumor models. Four routes of BPA administration were used: i.p. injection, intracarotid (i.c.) injection [with and without blood-brain barrier disruption (BBB-D)], and continuous timed i.v. infusions. i.p. injection of BPA in the 9L gliosarcoma resulted in a tumor-to-brain (T:Br) boron-10 concentration ratio of 3.7:1 when measured at the tumor-normal brain interface. In the F98 glioma, i.c injection of BPA resulted in a T:Br ratio of 2.9:1, and this increased to 5.4:1 when BBB-D was performed. The increased tumor boron uptake would potentially enhance the therapeutic ratio of BNCT by >25%. At present, ion microscopy is the only technique to provide a direct measurement of the T:Br boron-10 concentration ratio for tumor cells infiltrating normal brain. In the 9L gliosarcoma, this ratio was 2.9:1 after i.p. administration. In the F98 glioma, i.c injection resulted in a ratio of 2.2:1, and this increased to 3.0:1 after BBB-D. Ion microscopy revealed a consistent pattern of boron-10 microdistribution for both rat brain tumor models. The boron-10 concentration in the main tumor mass (MTM) was approximately twice that of the infiltrating tumor cells. One hour after a 2-h i.v. infusion of BPA in rats with the 9L gliosarcoma, tumor boron-10 concentrations were 2.7 times higher than that of infiltrating tumor cells [83 +/- 23 microg/g tissue versus 31 +/- 12 microg/g tissue (mean +/- SD)]. Continuous 3- and 6-h i.v. infusions of BPA in the 9L gliosarcoma resulted in similar high boron-10 concentrations in the MTM. The boron-10 concentration in infiltrating tumor cells was two times lower than the MTM after a 3-h infusion. After 6 h, the boron-10 concentration in infiltrating tumor cells had increased nearly 90% relative to the 2- and 3-h infusions. A 24-h i.v. infusion resulted in similar boron-10 levels between the MTM and the infiltrating tumor cells. Boron concentrations in the normal brain were similar for all four infusion times (approximately 20 microg/g tissue). These results are important for BNCT, because clinical protocols using a 2-h infusion have been performed with the assumption that infiltrating tumor cells contain equivalent amounts of boron-10 as the MTM. The results reported here suggest that this is not the case and that a 6-h or longer infusion of BPA may be necessary to raise boron-10 levels in infiltrating tumor cells to that in the MTM.

Animals↗

Clinical factors influencing the eosinophil infiltration of nasal polyps.

AIMS AND METHODS: Our study, based on a retrospective chart analysis, was aimed 1) to describe the varying degree of eosinophil infiltration in a series of 263 adult patients operated on diffuse and bilateral nasal polyposis (NPS) after failure of medical treatment, in 15 cystic fibrosis patients with bilateral nasal polyps, and in 31 patients with chronic sinusitis without polyps (18 bilateral, 13 unilateral) 2) to search for clinical factors that might influence the degree of eosinophil infiltration. Eosinophil infiltration was expressed semi-quantativity as a percentage of inflammatory cells. RESULTS: Our study confirms that eosinophil infiltration is a striking feature of nasal polyposis. All patients with chronic sinusitis showed less than 10% eosinophils (mean +/- SEM = 2 +/- 2%) whereas 88% of patients with NPS showed more than 10% eosinophils (50 +/- 2%). Cystic fibrosis lied in between with 40% of patients showing more than 10% eosinophils. In idiopathic bilateral NPS the number of eosinophils was increased in patients with asthma (58 +/- 3%) and even more in Widal's triad (75 +/- 4%). Atopic patients did not have more eosinophils (52 +/- 5%). Patients treated with systemic steroids within two months before surgery showed decreased eosinophil infiltration (22 +/- 3% vs 50 +/- 2 for treated versus untreated) whereas patients treated with topical steroids did not (47 +/- 2%). CONCLUSIONS: Thus, a link might exist between clinical presentation and eosinophil infiltration. Chronic sinusitis and nasal polyps are probably not the same disease. Eosinophils appear as a link between nasal polyps, asthma and aspirin intolerance. Atopic status does not modify eosinophil infiltration of nasal polyps. Systemic steroids appear significantly more effective to reduce the eosinophil infiltrate than topical steroids in our selected group of operated patients.

Adolescent↗

[Determination of shrinkage and bending strength of GI-II infiltrated ceramic].

OBJECTIVE: To determine the shrinkage and strength of GI-II Infiltrated Ceramic for providing scientific basis of its clinical use. METHODS: The adobes by slip-casting alumina powder of GI-II Infiltrated Ceramic were sintered at 1125 degrees C for 2 hours. The sintered alumina bodies were then divided into two groups and infiltrated by melt glass at 1125 degrees C and 1100 degrees C respectively for 6 hours. The length of the infiltrated ceramic specimens before and after fabrication was determined to calculate shrinkage. Their strength values were obtained by 3-point bending test. RESULTS: The infiltrated ceramic infiltrated at 1125 degrees C was 0.289 +/- 0.155% in shrinkage, 367.7 +/- 76.1 MPa in strength, and 4.79 in Weibull modulus; that infiltrated at 1100 degrees C was 0.253 +/- 0.043%, 377.5 +/- 64.4 MPa, and 5.52, respectively. There was no statistically significant difference between those two groups. But their strength values were statistically high, compared with 300 MPa. CONCLUSION: The shrinkage of GI-II Infiltrated Ceramic could be compensated by brushing spacer on dies and expansion of die stone. Its strength satisfied the requirement for clinical use of all-ceramic bridge materials. This kind of high-strength and low-shrinkage ceramic could be used for fabricating all ceramic crown and bridge core.

Aluminum Oxide↗

Tumor-associated macrophage (TAM) infiltration in gastric cancer.

BACKGROUND: Tumor-associated macrophages (TAMs) are defined as macrophages that migrate into the tumor stroma. TAMs are known to directly or indirectly affect immune suppression. TAMs have not previously been reported in gastric cancer. MATERIALS AND METHODS: Using anti-CD68 antibodies, we immunohistochemically evaluated TAM infiltration in 97 gastric cancer patients who underwent tumor resection. Furthermore, CD3-zeta chain expression of tumor infiltrating lymphocytes (TILs) from the same section was also examined. According to the degree of TAM infiltration, 97 patients were divided into two groups (high TAM group, more than 200 positive cells; low TAM group, less than 200 positive cells). Clarification of the clinicopathological features of TAM-positive gastric cancer was attempted. RESULTS: TAM infiltration in the tumor nest ranged from 0 to 621 cells (average 187). The degree of infiltration positively correlated with depth of invasion, nodal status and clinical stage. Patients in the high TAM group had lower CD3-zeta expression by TILs than patients in the low TAM group. CD3-zeta expression by TILs negatively correlated with infiltration of TAMs (p < 0.01). Patients with a high TAM count had poorer surgical outcomes than those with a low TAM count. CONCLUSION: From the results of the current study, TAM infiltration may be used as a prognostic marker in gastric cancer. Negative correlation between TAM infiltration and CD3-zeta expression by TILs suggests that TAMs may be responsible for the immunological inactivity of T cells in gastric cancer.

Adult↗

[Nasal polyposis: quantification of the eosinophil and granulocyte infiltrates. Anatomo-clinical correlations].

OBJECTIVE: Prospective study designed to count the number of granulocytic cells and eosinophils in nasal polyp tissue removed during ethmoidectomy and to look for anatomical correlations. METHODS: Bilateral ethmoidectomy with a postoperative local steroid treatment was performed in 40 patients with nasal polyposis. Immunolabeling of the operative specimen using common leukocyte antigen (CD 45) and granulocytes associated antigen (CD 15) and quantification of the granulocyte infiltrate by image and manual counting of eosinophils with the mean of micro-reticule, were performed. The results were compared to those of 10 healthy subjects. An endoscopy of the postoperative cavities was performed one year after surgery to assess the local results. RESULTS: The granulocyte and eosinophil infiltrates were significantly more important in the operated patients compared to the healthy population (p<10(- 4)). A "moderate" granulocytic infiltration (G -) was found in 11 patients out of 40 (27.5%). Among them, 9 patients showed less than 30% eosinophils (mean 16.2% +/- 2%). "Severe" granulocytic infiltrate (G +) was found in 29 patients out of 40 (72.5%). Among them, 25 patients showed more than 30% eosinophils (mean 48.8% +/- 2%). Most of the patients with G + type infiltrate suffered from asthma or Widal disease. One year after surgery, 17 out of 29 G + patients had no nasal polyposis recurrence, 12 out of 29 G + patients had a recurrence. However, 12 out of 15 patients with recurrent polyposis had G + type infiltrate. CONCLUSIONS: Granulocyte and eosinophil infiltration cannot be considered as a prognostic factor for recurrence at the time of surgery. A severe granulocyte and eosinophil infiltration is a typical feature of nasal polyposis, particularly in patients with asthma and/or in the aspirin triad.

Adolescent↗

[Infiltration of DCs and CD4+ T cells in muscle after DNA immunization].

OBJECTIVE: In order to get a better understanding of the mechanism of DNA initiating specific cytotoxicity T lymphocyte (CTL) immune response, we observed the local infiltration in injection site at different time after DNA immunization and further studied the characters of infiltration cells. METHODS: The local infiltration in injection sites was observed by HE staining at 6 h, 12 h and 1-6 days after DNA immunization. Infiltration cells were further studied with the mice dendritic cells marker CD205, T lymphocyte marker CD4 and CD8 by immunohistological methods. RESULTS: phAFP injection into mouse muscle led to a local infiltration. Infiltrates reached peak at 3-6 days after injection and appeared in several discrete clusters within the muscles. The predominant cell types found in infiltrates were macrophage-like cells and lymphocytes. Immunohistological staining revealed CD205+ and CD4+ cells. CD4+ cells could be detected in any of the injected muscles. CD205+ cells were only seen at 24 h to day 3, appearing later and disappearing earlier than CD4+ cells. However, CD8+ immunostaining positivity could not be found. CONCLUSION: Our findings indicate that the character of local infiltration after DNA immunization is different from the inflammation of injection. The recruitment of CD205+ to the injection site suggests that DCs and Th cells play an important role in DNA immunization.

Animals↗

Lymphoid infiltrates of the stomach. Evaluation of histologic criteria for the diagnosis of low-grade gastric lymphoma on endoscopic biopsy specimens.

Low-grade gastric lymphomas may be difficult to distinguish from benign inflammatory infiltrates on endoscopic biopsy specimens. Recent reports have suggested that so-called lymphoepithelial lesions (infiltration of lymphocytes into glandular epithelium) are characteristic of primary gastric lymphomas. We evaluated the presence and prominence of lymphoepithelial lesions and other histologic criteria in 25 low-grade gastric lymphomas (21 primary) and 58 benign inflammatory infiltrates to evaluate their utility in distinguishing benign from malignant gastric lymphoid infiltrates. The following features were associated only with lymphomas: (a) prominent (2-3 +) lymphoepithelial lesions (eight of 24 versus none of 58; p less than .0001); (b) Dutcher bodies (three of 25 versus none of 58, p = .05); and (c) moderate cytologic atypia (nine of 25 versus none of 58, p less than .0001). One or more of these features was seen in 18 of 25 gastric lymphomas (72%). Features more often associated with, but not limited to, lymphomas were dense (2-3 +) lymphoid infiltrates (25 of 25 versus five of 58, p less than .0001), rare or questionable lymphoepithelial lesions (11 of 24 versus 17 of 58, p = .01), muscularis mucosae invasion (20 of 20 versus 20 of 47, p less than .0001), ulceration (12 of 24 versus five of 58, p less than .0001), and mild cytologic atypia (eight of 25 versus six of 58, p less than .005). Germinal centers, crypt abscesses, and reactive epithelial atypia were seen with equal frequency in both types of infiltrate. Acute inflammation (2-3 +) was associated more often with inflammatory infiltrates (two of 25 versus 27 of 58, p less than .001). Our results suggest that dense lymphoid infiltrates with either prominent lymphoepithelial lesions, moderate cytologic atypia, or Dutcher bodies are highly suggestive and may be diagnostic of lymphoma. This constellation of findings is present in about 70% of endoscopic biopsy specimens of low-grade gastric lymphoma. In addition, the majority of cases of primary low-grade gastric lymphoma have morphologic, immunophenotypic, and clinical features that justify their inclusion in the category of low-grade lymphomas of mucosa-associated lymphoid tissue, whereas a minority are examples of lymphomatous polyposis of the gastrointestinal tract (centrocytic lymphoma).

Adult↗

Duplicitous growth of infiltrative basal cell carcinoma: Analysis of clinically undetected tumor extent in a paired case-control study.

BACKGROUND: Many clinicians believe infiltrative basal cell carcinoma (BCC) is a more difficult tumor to eradicate than nodular BCC because the growth of infiltrative BCC is not easy to detect clinically. However, data supporting this observation are largely anecdotal. OBJECTIVE: Our purpose was to show that infiltrative BCC have wider and deeper tumor extensions than nodular BCC of similar clinical size. METHODS: In this retrospective study, 139 cases of infiltrative BCC excised by Mohs micrographic surgery (MMS) were matched to a control group of 139 cases of nodular BCC similarly excised. They were paired by site, size, number of recurrences, age, gender, and previous treatment type. The cases were selected and paired by computer from 1197 consecutive BCC (primary and recurrent) referred for MMS over a 5-year period. MMS technique allowed us to quantitate the extent of tumor spread using three measurements: the number of surgical stages required for complete removal of tumor, the width of tissue required to remove subclinical extension of tumor, and the depth of defect at completion of MMS. RESULTS: Analysis showed the infiltrative BCC was more difficult to detect and to eradicate than the nodular BCC. The number of surgical stages required for complete removal of tumor, the width of tissue required to remove subclinical extension of tumor, and the depth of defect at completion of MMS were all greater with infiltrative BCC when compared with nodular BCC regardless of whether cases were primary or recurrent. These differences were all statistically significant. CONCLUSION: Infiltrative BCC can be significantly more destructive than nodular BCC because tumor extension is difficult to detect clinically. Clinicians should treat infiltrative BCC with its potential for convert invasion in mind.

Adult↗

The clinical presentation, prevalence, and risk factors of focal corneal infiltrates in soft contact lens wearers.

PURPOSE: We evaluated the clinical presentation, prevalence, and associated risk factors for focal corneal infiltrates with overlying fluorescein staining in a population of soft contact lens wearers. METHODS: We measured the prevalence of focal stromal infiltrates with overlying fluorescein staining among contact lens wearers in a large cross-sectional, masked, multicenter study. RESULTS: The practice-based occurrence of infiltrates with overlying staining was 1.6%, or 38 of 2,324 patients examined. The events were milder than those reported in studies conducted in specialty eye care centers; were usually noted during unscheduled office visits; and were accompanied by symptoms of redness, photophobia, pain, and foreign body sensation. The infiltrates were located in all corneal zones, with 44.7% of the infiltrates involving the central zone, none of which caused significant loss of acuity at follow-up. The risk factors of overnight wear, lens modality (e.g., conventional, disposable), and smoking have been confirmed. Overnight wear showed a prevalence ratio of 1.88 compared with daily wear (P < 0.055, chi-square); lens modality showed an increased risk for disposables compared with conventional lenses of 2.1 (P = 0.036, chi-square). Smoking was associated with an increased prevalence of events; 1.2% of "never" and 2.2% and 2.4% of "former" and "current" smokers, respectively, experienced an infiltrate, for a prevalence ratio of 2.0 (P < 0.04). Smoking and lens modality also interacted positively with extended wear, amplifying the risk associated with those factors. CONCLUSIONS: We found a 1.6% practice-based prevalence and a wide range of clinical presentation of focal infiltrates in soft contact lens wearers, and we measured the relative risks of extended wear, lens modality, and smoking in a general practice population. In these cases, there was no distinct pattern in location or severity of corneal infiltrates, and visual acuity following the events was not compromised.

Adult↗

Intratumoral administration of sizofiran activates Langerhans cell and T-cell infiltration in cervical cancer.

In order to ascertain a correlation between infiltration of Langerhans cells (LCs) or T-cells in tumor tissues and the intratumoral administration of a biological response modifier, Sizofiran (SPG) was analyzed in cancer of the uterine cervix. Cancer specimens of 45 patients with stage II-III invasive cervical cancers were analyzed. SPG was administered to the cervical tumor at high and low concentrations (Strong SPG and weak SPG) as well as by intramuscular injection twice a week. LC and T-cell infiltrations to tumor tissues of the uterine cervix were studied immunohistochemically and electron microscopically. Of 10 patients with systemic but no local immunization, 1 (10.0%) showed an increase in LC infiltration and 2 (20.0%) showed a decrease. Of 15 patients with strong SPG immunization, 2 (13%) showed an increase and 5 (33%) showed a decrease. In contrast, of 20 patients with weak SPG immunization, the incidence of increase in LC infiltration was 55% (11 patients), significantly greater than the above-mentioned groups and none showed a decrease. Of the 20 patients with weak SPG administration, 3 (15%) showed T-cell infiltration before SPG administration, and 12 (60%) showed an increase in T-cell infiltration after SPG was given. Up on electron microscopy, Birbeck granules in the cytoplasm of LC significantly increased after SPG immunization, indicating activation of LC. In conclusion, the present study suggested that the LC and T-cell infiltrations in cancer tissues were augmented by intratumoral SPG administration at a certain concentration. Intratumoral administration of SPG may be applied to improve the prognosis after multidisciplinary treatment of advanced cervical cancer.

Adjuvants, Immunologic↗

Expression of MAGE antigens and analysis of the inflammatory T-cell infiltrate in human seminoma.

The MAGE gene family encodes antigens that are recognized by cytotoxic T-cells. The expression of MAGE antigens has been linked to tumor stage, and MAGE peptides are under investigation as possible vaccines. Seminomas are tumors that are typically accompanied by a heavy inflammatory infiltrate, but have not been studied with regard to their MAGE antigen expression and its correlation with the inflammatory infiltrate. We investigated, therefore, MAGE protein expression, the amount of cytotoxic T-cells, clonality of the lymphocytic infiltrate, apoptotic activity and occurrence of necrosis. Specimens of 27 patients with classical seminoma were examined by immunohistochemistry for CD4, CD8, CD56, CD45R0, beta2-microglobulin and HLA-DR. MAGE expression was detected with the monoclonal antibody 57B, reactive with MAGE-1, -3, -4, -6 and -12. Clonality of the inflammatory infiltrate was examined by multiplex polymerase chain reaction (PCR) analysis of the T-cell receptor rearrangement. Apoptotic cells were detected by DNA nick-end labeling of fragmented DNA, and the apoptotic index was determined semi-quantitatively. Expression of 57B was found in 19 (70%) of 27 seminomas. In all cases, more than 70% of T-cells expressed CD45R0. In four cases, a predominant infiltration of CD8-positive cytotoxic T-cells (CD4/CD8 ratio < 1) was present. However, 15 seminomas showed a CD4/CD8 ratio > 1. In all cases, infiltration of CD56-positive natural killer cells was only focal. HLA-DR expression was not detectable in tumor tissue; beta2-microglobulin was only focal in three cases. Analysis of the T-cell clonality revealed a polyclonal population. The apoptotic index was not significantly different in 57B-positive seminomas (4.15%) compared with 57B negative seminomas (3.80%). Also, no correlation between the 57B expression and the occurrence of necrosis was found. MAGE antigens are homogeneously expressed in most seminomas, but their presence does not appear to represent a dominant epitope responsible for the lymphocytic infiltrate.

Adult↗

CT findings of leukemic pulmonary infiltration with pathologic correlation.

The aim of this study was to demonstrate the characteristic CT findings of leukemic pulmonary infiltration based on the pathologic findings. The CT findings of 11 leukemic patients with leukemic pulmonary infiltration were compared with those of 22 leukemic patients with other diseases as a control group. Evaluated pulmonary parenchymal CT findings included thickening of bronchovascular bundles and interlobular septa, prominence of peripheral pulmonary arteries, ground-glass opacities, air-space consolidation, and nodules. The CT-pathologic correlations for leukemic infiltration were evaluated in 7 patients. Frequent parenchymal CT findings were thickening of bronchovascular bundles (81.8%), prominence of peripheral pulmonary arteries (81.8%), and non-lobular and non-segmental ground-glass opacities (90.9%). The first two findings were significantly more frequently observed in leukemic infiltration than in the control group, had good interobserver agreement, and corresponded pathologically to leukemic cell infiltration around the pulmonary arteries, bronchi, or bronchioles. Non-lobular and non-segmental ground-glass opacity corresponded to leukemic cell infiltration within alveolar spaces and septa adjacent to the pulmonary arteries or bronchi and also corresponded to hemorrhage, edema, or diffuse alveolar damage. Thickening of bronchovascular bundles and prominence of peripheral pulmonary arteries are CT findings suggestive for leukemic infiltration and correspond to peribronchovascular tumor extension.

Adult↗

Neutrophil infiltration into human gliomas.

Human gliomas were analysed for the infiltration of neutrophils using immunohistochemistry by staining sections for CD15-positive and myeloperoxidase-positive cells. Over 70% of all glioma samples analysed (n = 105) had significant neutrophil infiltration, but there was a marked and significant correlation between tumour grade and the extent of the neutrophil infiltration. In the low grade tumours only 40-50% had significant infiltration, while in glioblastoma multiforme over 85% of the samples analysed had significant infiltration. Numbers of neutrophils infiltrating glioblastoma multiforme tumours were also greater than in the other tumour groups. Circulating white blood cell counts were elevated above the normal range in all glioma patients, but this elevation was entirely due to increased numbers of circulating neutrophils. Again, the highest numbers of circulating neutrophils were seen in the glioblastoma multiforme patients. These experiments indicate that glioma-derived factors may directly or indirectly affect the number of circulating neutrophils and influence their infiltration into the tumours.

Bone Marrow↗

Effect of pre-operative short course famotidine on tumor infiltrating lymphocytes in colorectal cancer: a double blind, placebo controlled, prospective randomized study.

BACKGROUND: Pilot studies have shown that histamine H2 receptor antagonists augment the natural immunity against cancer in colorectal and gastric cancer by enhancing lymphocytic infiltration in the tumors. However, a study of adjuvant ranitidine failed to show a significant benefit in colorectal cancer, possibly because of the immunosuppression exerted by blood transfusion and post-operative infections. The pre-operative use of H2 receptor antagonists may therefore be of greater benefit. Except for a pilot study using cimetidine, there are no trials that have evaluated the effect of pre-operative H2 receptor antagonists on tumor infiltrating lymphocytes in colorectal cancer. OBJECTIVE: To evaluate the efficacy of famotidine in augmenting tumor infiltrating lymphocytes in colorectal cancer. STUDY DESIGN: Double blind, placebo controlled, prospective randomized study. METHODS: Twenty-three patients with resectable colorectal cancer were randomized to receive famotidine (n = 11) or placebo (n = 12). Famotidine was given for 1 week pre-operatively in a dose of 40 mg per day p.o. After resection, the specimens were analyzed histologically for lymphocytic infiltration by a pathologist blinded to the two groups. Lymphocytic infiltration more than 50 cells per high power field, involving more than 50% of the tumor-normal tissue interface was considered significant. RESULTS: The two groups were comparable for age, gender, pre-operative carcino embryonic antigen (CEA) levels and pathological stage. Significant lymphocytic infiltration was seen in 63.6% (7 of 11) patients in the study group compared to only 8.5% (1 of 12) patients in the placebo group (P = 0.005). Despite fewer recurrences and a longer survival in the study group, the difference was not significant. CONCLUSION: This study shows that pre-operative famotidine may significantly enhance lymphocytic infiltration in colorectal cancer and may have potential for use as an anticancer agent in colorectal cancer.

Adult↗

Interleukin-2 expanded tumor-infiltrating lymphocytes and their response to preoperative alpha-interferon in patients with renal cell carcinoma.

To determine whether interferon-alpha could augment antitumorigenic effect of the tumor-infiltrating lymphocytes expanded with interleukin-2, we evaluated the properties of interleukin-2 expanded tumor-infiltrating lymphocytes in 24 patients with renal cell carcinoma with or without treatment with interferon-alpha. Tumor-infiltrating lymphocytes containing tumor cells were separated from nephrectomy specimens by enzymatic digestion and Percoll gradient centrifugation, and were cultured in the serum-free medium containing interleukin-2. The number of lymphocytes increased by 10 to 1,000-fold by day 28 of culture. There was no difference in the proliferation of tumor-infiltrating lymphocytes between interferon-alpha treated patients and controls. On day 14 tumor-infiltrating lymphocytes in the treated patients contained significantly more activated cells (HLA-DR+) and suppressor T cells (CD8+11+) than those in the controls. No significant difference was noted, however, in the cytotoxicity of tumor-infiltrating lymphocytes against autologous and allogenic renal cell carcinoma, K-562 or Daudi cells between the experimental and control groups on day 14 or 28. No specific effects on the major histocompatibility antigens, such as modulation of the expression attributable to the preoperative treatment with interferon-alpha, were observed on renal cell carcinoma tissue when determined by immunohistochemical staining. These findings suggest that interferon-alpha does not consistently produce a beneficial effect on interleukin-2 expanded tumor-infiltrating lymphocytes in patients with renal cell carcinoma.

Adult↗