Outcomes of patients with cancer and sarcoid-like granulomatosis associated with immune checkpoint inhibitors: A case-control study.

PURPOSE: Sarcoid-like granulomatosis (SLG) reaction caused by immunotherapy remains poorly understood. This study aims to investigate the outcome of patients with cancer and SLG associated with immunotherapy. PATIENTS AND METHODS: Between April 2016 and June 2020, 434 patients with immunological adverse events were screened from the ImmunoTOX assessment board of Gustave Roussy, an academic cancer centre in France. Among them, 28 patients had SLG associated with immunotherapy (SLG cohort) and 406 patients had other immunological adverse events (control cohort). Clinical characteristics and outcome of patients were compared from SLG and control cohort. RESULTS: The SLG cohort consisted of 28 patients, 14 women and 14 men, with the median (range) age of 56.5 (28.7-75.3) years. Patients in the SLG cohort with sarcoidosis were asymptomatic (only radiographical finding) in 13 (46.4%) cases; otherwise, the most frequent symptoms were dyspnoea in 8 (28.6%) patients and cough in 5 (17.8%) patients. The computerised tomography scan found sarcoidosis localisations in mediastinal or peri-hilar thoracic lymph nodes in 26 (92.9%) patients, and lung parenchymal involvement was found in 14 (50.0%) patients. The radiographic Scadding stages for sarcoidosis classification were distributed in stages 0, I, II, III and IV in 2 patients (7.1%), 13 patients (46.4%), 11 patients (39.3%), 1 patient (3.6%) and 1 patient (3.6%), respectively. Compared with patients with other immunological toxicities (cohort control), patients with sarcoidosis presented most frequently with melanoma (75.0% versus 21.9% of patients; p < 0.001) and more often received combined therapies of anti-programmed cell death 1 plus anti-cytotoxic T-lymphocyte antigen 4 protein (46.4% versus 12.6% of patients; p = 0.002). Patients with sarcoidosis had an improved overall survival (OS); the median OS was not reached in the SLG cohort and 40.4 months in the control cohort, hazard ratio = 0.232 (95% confidence interval: 0.086-0.630) (p = 0.002). CONCLUSION: Sarcoidosis-like reactions in patients receiving immunotherapy were reported as non-severe immunological reactions in most cases and were correlated with improved OS. SLG should not be misdiagnosed as tumour progression in patients receiving immunotherapy treatment for cancer.

Clinicopathologic Features of Tissue Granulomas in Transplant Recipients: A Single Center Study in a Nontuberculosis Endemic Region.

CONTEXT.­: There is a paucity of literature about tissue granulomas in transplant patients. OBJECTIVE.­: To characterize the clinicopathologic features of granulomas in this population and develop a clinically judicious approach to their evaluation. DESIGN.­: We performed chart reviews of solid organ and allogeneic hematopoietic stem cell transplant recipients at Yale New Haven Hospital to identify patients with granulomas on biopsy obtained pathologic specimens. Pretransplant and posttransplant specimens were included. Data points included demographics, clinical presentation, epidemiologic risk factors, biopsy indication, location and timing, immunosuppression, histopathology, microbiology, and associated clinical diagnosis. Granuloma-related readmissions and mortality were recorded at 1, 3, and 12 months. RESULTS.­: Biopsy proven granulomas were identified in 56 of 2139 (2.6%) patients. Of 56, 16 (29%) were infectious. Common infectious etiologies were bartonellosis (n = 3) and cytomegalovirus hepatitis (n = 3). Tuberculosis was not identified. Clinical symptoms prompted tissue biopsy in 27 of 56 (48.2%) cases while biopsies were obtained for evaluation of incidental findings or routine disease surveillance in 29 of 56 (51.8%). Presence of symptoms was significantly associated with infectious etiologies; 11 of 27 (40.7%) symptomatic patients compared with 5 of 29 (17.2%) asymptomatic patients had infectious causes. One death from granulomatous cryptogenic organizing pneumonia occurred. In pretransplant asymptomatic patients, no episodes of symptomatic disease occurred posttransplantation. CONCLUSIONS.­: Granulomas were uncommon in a large transplant population; most were noninfectious but presence of symptoms was associated with infectious etiologies. Granulomas discovered pretransplant without clear infectious etiology likely do not require prolonged surveillance after transplantation. Symptomatology and epidemiologic risks factors should guide extent of microbiologic evaluation.

Mandibular Osteolytic Lesion Associated with Exuberant Hyaline Ring Granuloma Reaction.

OBJECTIVE: To report an unusual case of oral hyaline ring granuloma (HRG) that caused an extensive osteolytic lesion. CLINICAL PRESENTATION AND INTERVENTION: A 22-year-old female was referred to our hospital with a large expansile cystic lesion in the left mandibular ramus associated with a clinically visible, partially erupted third molar. A diagnosis of paradental cyst was made. After marsupialization of the lesion, histopathological analysis of the surgical specimen showed an unusual exuberant HRG reaction supported by scarce fibrous stroma. CONCLUSION: This was a case of exuberant HRG reaction that caused extensive bone destruction.

Mediastinal Granulomatous Inflammation and Overall Survival in Patients with a History of Malignancy.

RATIONALE: Investigators have postulated that mediastinal granulomatous inflammation is associated with prolonged overall survival in patients with cancer. OBJECTIVES: We sought to determine whether mediastinal granulomatous inflammation affects overall survival in patients with a history of treated cancer. METHODS: Patients with a history of treated cancer who underwent endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) for evaluation of mediastinal or hilar lymphadenopathy were grouped based on whether they had mediastinal granulomatous inflammation or benign mediastinal lymphadenopathy without granulomas. Overall survival from the date of EBUS-TBNA to cancer-related death or to last follow-up in patient groups was compared. MEASUREMENTS AND MAIN RESULTS: We reviewed the records of 106 patients (44 with mediastinal granulomatous inflammation and 62 with benign mediastinal lymphadenopathy). The 3-year survival rate was 90% overall and 93 and 88% in patients with mediastinal granulomatous inflammation and benign mediastinal lymphadenopathy, respectively (P=0.40). After multivariate adjustment, whether patients had mediastinal granulomatous inflammation or benign mediastinal lymphadenopathy did not significantly affect the risk of cancer death (mediastinal granulomatous inflammation to benign mediastinal lymphadenopathy hazard ratio, 1.27; P=0.76). CONCLUSIONS: These results suggest that patients who develop mediastinal granulomatous inflammation after cancer treatment do not have an increased overall survival when compared with patients who develop benign mediastinal lymphadenopathy. EBUS-TBNA is warranted for patients with treated cancer who develop mediastinal and/or hilar lymphadenopathy to avoid erroneous upstaging or misdiagnosis of cancer recurrence that would lead to suboptimal management.

Visceral granulomas in farmed large yellow croaker, Larimichthys crocea (Richardson), caused by a bacterial pathogen, Pseudomonas plecoglossicida.

An enzootic disease characterized by granulomas in internal organs occurred in cage-farmed large yellow croaker, Larimichthys crocea (Richardson), in April and November 2010, in Ningbo, Zhejiang Province. One bacterial strain, named XSDHY-P, was isolated from the diseased fish and identified by biochemical characterization, fatty acid methyl ester (FAME) analysis and multilocus sequence analysis (MLSA). According to the results obtained from the biochemical tests, FAME analysis and phylogenetic analysis derived from 16S ribosomal RNA, gyrB, oprF, oprI, oprL and rpoD gene sequencing, the bacterial isolate, XSDHY-P, was identified as Pseudomonas plecoglossicida. Moreover, lethal dose, 50% trials were carried out to demonstrate the virulence of XSDHY-P in large yellow croaker when administered at 2.13 9 105 colony-forming units per fish. Visceral granulomas were found in the experimentally infected fish as well as in the naturally infected fish, indicating that P. plecoglossicida is another bacterial pathogen that causes granulomatosis in L. crocea.

Mycobacterial bone marrow infections at a medical centre in Taiwan, 2001-2009.

Mycobacterial bone marrow (BM) infection is the most common diagnosis established by BM examinations for fever of unknown origin. In this study, clinical features and outcomes of patients who fulfilled the criteria for BM infection due to Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacteria (NTM) at a medical centre in Taiwan from 2001 to 2009 were investigated. The BM histopathological findings were also analysed. A total of 24 patients (16 men, eight women) with mycobacterial BM infections were found. Of these, nine (38%) were positive for human immunodeficiency virus (HIV) and six (25%) had no pre-existing immunocompromised conditions. MTB isolates were obtained from 11 (46%) patients and NTM species were isolated from 10 (42%) patients, including M. avium complex (MAC, n = 7) and M. kansasii (n = 3). Patients with MTB infections were significantly older than those with NTM infections (60·5 vs. 47·7 years, P = 0·043) and were less likely to have a positive BM culture (45% vs. 100%, P = 0·012). The 90-day survival rates for MTB and NTM BM infections were 68% and 60%, respectively (P = 0·61). In addition, the presence of BM granulomas was significantly more common in patients with MTB BM infections than in those with NTM infections (82% vs. 30%, P = 0·030). In Taiwan, the importance of NTM was not inferior to MTB and besides MAC, M. kansasii might be an important pathogen in non-HIV-infected patients. The presence of BM granulomas and caseation provides valuable information regarding early treatment pending culture results.

Granulomatous myocarditis in severe heart failure patients undergoing implantation of a left ventricular assist device.

BACKGROUND: Granulomatous myocarditis may develop into cardiomyopathy and severe congestive heart failure that requires implantation of a left ventricular assist device (LVAD). METHODS: Left ventricular (LV) core samples were collected from 177 patients with severe heart failure at the time of LVAD implantation, and samples were histologically examined and graded for severity of hypertrophy and fibrosis. Granulomatous myocarditis incidentally seen in a subset of samples was characterized by staining and culturing for mycobacteria and fungi. Various clinical parameters in these patients were analyzed. RESULTS: Of the 177 LV core samples examined, 6 (3.4%) showed nonnecrotizing granulomatous inflammation in the myocardial wall. Stains and cultures for mycobacteria and fungi were negative. All six patients [three women, three men; five African American, one Asian; mean age, 52±9 years (range, 41-61 years)] had arrhythmias and required an automatic implantable cardioverter defibrillator. Before LVAD implantation, the patients' mean cardiac index was 1.8±0.4 l/min/m(2); cardiac output, 2.9±0.6 l/min; and ejection fraction, 20±2%. One year after LVAD implantation, one patient had undergone heart transplantation. At 2 years, a second patient was transplanted, and one died. At 3 years, a third patient was transplanted and died postoperatively; two patients remained on support. No clinical evidence indicated involvement of other organs or recurrence in the transplanted patients. CONCLUSION: The incidental diagnosis of granulomatous myocarditis in our patients indicates that histological study of LV core samples in patients who undergo LVAD implantation may contribute to the diagnosis and be a consideration in the management of the underlying cause of heart failure.

Granulomatous disease in common variable immunodeficiency.

Granulomatous disease occurs in 8-22% of patients with common variable immunodeficiency (CVID). We examined the clinical and immunologic information of all 37 of 455 (8.1%) CVID subjects with this complication. The median age at diagnosis of CVID was 26 (2-59). 14 had granulomas 1-18 years before diagnosis of CVID. In 6 detection of granulomas coincided with this diagnosis; for 17, granulomas were documented later. 54% had lung granulomas, 43% in lymph nodes and 32% in liver. 54% of the group had had autoimmune diseases, mostly immune thrombocytopenia and hemolytic anemia. 24% had had a splenectomy. Nineteen (51.3%) required steroid treatment for granulomas; other immune suppressants were used in some. Over 25 years 28.5% died (median age 37.5), but not significantly more when compared to our CVID patients without granulomas (19.8%). Those with lung granulomas had similar mortality to those with granulomas in other tissues.

A regulatory effect of the balance between TNF-alpha and IL-6 in the granulomatous and inflammatory response to Rhodococcus aurantiacus infection in mice.

After i.v. inoculation with Rhodococcus aurantiacus, wild-type (WT) mice develop nonnecrotic, epithelioid granulomas. Because a high level of TNF-alpha is observed during the initial phase postinfection, we examined the extent to which TNF-alpha contributes to granulomatous inflammation using TNF-alpha gene-deficient (TNF-alpha(-/-)) mice. Despite a lack of R. aurantiacus proliferation, TNF-alpha(-/-) mice displayed high mortality rates within 5 days postinfection, as well as a high level of IL-6 in their spleens. Histological examination showed an absence of granuloma formation in TNF-alpha(-/-) mice. Pretreatment of TNF-alpha(-/-) mice with rTNF-alpha failed to restore this granuloma formation but accelerated bacterial removal and cellular recruitment. This rTNF-alpha administration also attenuated IL-6 production, resulting in increased survival rates of TNF-alpha(-/-) mice. Heat-killed R. aurantiacus induced in vitro enhanced mRNA expression and production of IL-6 in macrophages and DCs from TNF-alpha(-/-) mice when compared with WT controls, and treatment of TNF-alpha(-/-) mouse cells with rTNF-alpha decreased the IL-6 secretion. Moreover, anti-TNF-alpha or anti-IL-6 treatment increased IL-6 or TNF-alpha production by WT mouse cells, respectively. These data suggest that the production of TNF-alpha and IL-6 can be negatively regulated by each other. Administration of rIFN-gamma to TNF-alpha(-/-) mice caused immature granulomas in livers, and treatment with both rTNF-alpha and rIFN-gamma led to the formation of mature granulomas. Overall, TNF-alpha appears crucial for bacterial clearance, cellular recruitment, and granuloma formation. The balance between TNF-alpha and IL-6 during the early phase of infection controls the development of the inflammatory response to R. aurantiacus infection.

Cytokines, chemokines and other biomolecular markers in sarcoidosis.

In recent years our knowledge in terms of the network of interactions between immunocompetent cells that set the stage for the pathogenesis of sarcoidosis has continuously improved. Remarkable advances have been made in understanding general immunological and molecular aspects of the mechanisms leading to granuloma formation. In this manuscript we will review the current concepts on cellular interactions which define regulatory networks ultimately contributing to the granuloma formation at sites of disease activity in sarcoidosis. The biological effects of Th1 and Th2 cytokines in sarcoid lung will be taken into account and the importance of the local production of those chemokines and cytokines whose release has been recently demonstrated within the lung of patients with sarcoidosis will be emphasized.

Interventional bronchoscopy for the management of airway complications following lung transplantation.

STUDY OBJECTIVES: To assess the efficacy and complications of different interventional bronchoscopic techniques used to treat airway complications after lung transplantation. DESIGN: Retrospective study. SETTING: Heart-lung transplant unit of a university hospital. PATIENTS: From November 1986 to January 2000, interventional bronchoscopy was performed in 41 of 312 lung transplant recipients (13.1%) for tracheobronchial stenosis, bronchomalacia, granuloma formation, and dehiscence. INTERVENTIONS: Dilatation, stent placement, laser or forceps excision. MEASUREMENTS AND RESULTS: Mean (+/- SE) improvement in FEV(1) in 26 patients undergoing dilatation for a stenotic or a combined lesion was 93 +/- 334 mL or 8 +/- 21%. In seven of these patients not proceeding to stent placement, mean improvement in FEV(1) was 361 +/- 179 mL or 21 +/- 9%. Patients needing stent placement after dilatation had a mean change in FEV(1) after dilatation of - 5 +/- 325 mL or 3 +/- 23%, and an improvement of 625 +/- 480 mL or 52 +/- 43% after stent insertion. Mean improvement in FEV(1) for patients treated with stent insertion for bronchomalacia was 673 +/- 30 mL or 81 +/- 24%. Complications of airway stents were migration (27%), mucous plugging (27%), granuloma formation (36%), stent fracture (3%), and formation of a false passage (6%). Mortality associated with interventional bronchoscopy was 2.4% (1 of 41 patients). For patients with airway complications successfully undergoing interventional bronchoscopy, the overall 1-year, 3-year, and 5-year survival rates were 79%, 45%, and 32%, respectively, vs 87%, 69%, and 56% for those without airway complications (p < 0.05). CONCLUSION: Only a small number of patients with airway stenosis after lung transplantation will respond to bronchial dilatation alone. Patients with airway complications after lung transplantation have a higher mortality than patients without airway complications.

Lethal granuloma disintegration in mycobacteria-infected TNFRp55-/- mice is dependent on T cells and IL-12.

Genetically susceptible, TNFRp55 gene-deficient (TNFRp55-/-) mice succumb to infection with Mycobacterium avium. Before their death, M. avium-infected TNFRp55-/- mice develop granulomatous lesions that, in contrast to granulomas in wild-type syngeneic mice, undergo acute disintegration. To determine the factors involved in these events, we depleted T cell subsets or neutralized the inflammatory cytokines IFN-gamma, IL-12, or TNF in TNFRp55-/- mice infected i.v. with M. avium. Infected TNFRp55-/- mice treated with a control mAb became moribund between days 26 and 34 postinfection, showing widespread inflammatory cell apoptosis within disintegrating granulomas. In contrast, TNFRp55-/- mice depleted of either CD4+ or CD8+ cells after granuloma initiation stayed healthy until at least day 38 postinfection and showed no signs of granuloma destruction. Neutralization of IL-12, but not of IFN-gamma or TNF, also protected M. avium-infected TNFRp55-/- mice from granuloma decomposition and from premature death. Treatment with dexamethasone or with a specific inhibitor of inducible NO synthase did not prevent granuloma dissolution or death of TNFRp55-/- mice. In conclusion, granuloma disintegration in TNFRp55-/- mice is a lethal event that is dependent on IL-12 and that is mediated by an excess of T cells.

Necrobiotic xanthogranuloma: long-term outcome of ocular and systemic involvement.

PURPOSE: To report long-term outcomes of patients with necrobiotic xanthogranuloma, to investigate the propriety of therapeutic surgical excision or debulking, and to study tissue specimens by immunoperoxidase staining and in situ hybridization. METHODS: Medical records of all patients at the Mayo Clinic, Rochester, Minnesota, with necrobiotic xanthogranuloma between 1980 and 1997 were reviewed. A follow-up letter was sent to each patient inquiring about the current status of the lesions, the treatment regimen, and associated systemic diseases. RESULTS: The average age (+/- standard deviation) of the 15 men and 11 women was 56.8 +/- 14.8 years. Of the 26 patients, 21 (81%) had lesions of the ocular adnexa. Ulceration of the lesions occurred in 11 patients (42%). The lesions recurred after surgical removal in 11 patients (42%) and on prior incision sites from unrelated operations in three patients (12%). The average duration of follow-up from the appearance of characteristic skin lesions was 10 +/- 6.1 years. Four patients had multiple myeloma, five had a plasma cell dyscrasia, and one had a lymphoproliferative disorder during this period. Time to development of associated malignancy ranged from 8 years before the skin lesions to 11 years after the skin lesions. Overall survival was 100% at 10 years and 90% at 15 years (95% confidence limit, 0.73 to 1.00). Immunoperoxidase stains demonstrated that most histiocytes are not of Langerhans cell lineage. Monoclonal immune globulins were not identified in tissue specimens. CONCLUSION: Care of patients with necrobiotic xanthogranuloma should include avoidance of surgical removal, if possible, and lifelong follow-up to detect the development of associated malignancy.

Prognostic factors for dogs with granulomatous meningoencephalomyelitis: 42 cases (1982-1996).

OBJECTIVE: To assess signalment, clinical signs, results of CSF analysis, treatment, and survival times in dogs with granulomatous meningoencephalomyelitis (GME) and to identify factors associated with survival. DESIGN: Retrospective study. SAMPLE POPULATION: Medical records of 42 dogs with GME. PROCEDURE: Information on signalment, neurolocalization, presence of focal or multifocal signs, results of CSF analysis, method of treatment, and time from onset of clinical signs to death was retrieved from medical records of each dog. Kaplan-Meier survival analysis was used to assess survival times. The Cox proportional hazards method was used to identify predictors of survival. RESULTS: Females and toy and terrier breeds were predisposed to GME. Half of the dogs had focal neurologic signs, and half had multifocal involvement. Clinical signs referable to the forebrain were most common with focal involvement, whereas signs referable to the forebrain and brainstem were most commonly seen with multifocal involvement. Cerebrospinal fluid analysis commonly revealed a mononuclear pleocytosis. Survival times ranged from 1 to > 1,215 days. Significant differences in survival times were demonstrated for the following factors: focal versus multifocal clinical signs, neurolocalization of focal signs, and treatment with radiation. Radiation was the only independent predictor of survival. CLINICAL IMPLICATIONS: Dogs with signs suggesting focal involvement of GME tend to survive longer than those with multifocal involvement. Radiation is an effective treatment for dogs with GME, particularly those with clinical signs suggesting focal involvement.

Pathogen-free granulomatous diseases of the central nervous system.

Pathogen-free granulomatous diseases (PFGD) of the central nervous system (CNS) are a group of disorders with protean clinical and pathological findings. Failure to identify a causative organism leads to considerable diagnostic difficulty. The neuropathology records between 1985 and 1995 were retrospectively reviewed, and the medical records of all patients in whom a diagnosis of PFGD of the CNS was made were retrieved. Patients in whom an infective agent was shown either by culture, special staining techniques, or by immunohistochemical methods were excluded. We identified 11 patients (eight male, three female) who fulfilled the pathological criteria for this condition. Average age at diagnosis was 38.7 years (range, 17 to 78). Neurological symptoms were the presenting feature in nine patients. Neuroimaging findings included hydrocephalus (54.5%), meningeal enhancement (45.5%), and mass lesions (45.5%). Seven patients had antemortem CNS biopsies (brain/meninges [n = 6], spinal [n = 1]), which showed noncaseating granulomas. Eight patients died (mortality rate: 72.7%). Postmortem examination showed granulomatous involvement of the leptomeninges and cerebral parenchyma in all cases with systemic involvement in 50%, chiefly in the form of noncaseating granulomas of the hilar nodes. Six patients fulfilled the clinical, radiological, and pathological diagnostic criteria for neurosarcoidosis. The remaining five patients had an unclassifiable pathogen-free granulomatous disease of the CNS. PFGD of the CNS are associated with a poor prognosis. Although neurosarcoidosis may account for some of the cases, there remains an unclassifiable subgroup that continues to be a diagnostic and management challenge.

Intracranial fungal granuloma.

BACKGROUND: Intracranial fungal granulomas are uncommon and their pathogenesis, clinical picture, and effectiveness of therapy remains unclear. METHODS: Thirty-two cases were studied retrospectively in two groups: (1) Rhinocerebral group (22 cases) had a chronic paranasal sinus (PNS) disease with secondary involvement of skull base, cranial nerves, and/or brain. The granulomas were adherent to dura, firm, avascular, and tough, requiring a knife to cut. (2) Primary intracranial group (10 cases) had no detectable PNS lesion at initial presentation. The granulomas were soft, suckable, and contained pus or necrotic material. RESULTS: Postoperative and overall mortality were 37.5% and 50%, respectively. Meningoencephalitis was the most common cause of death. Altered sensorium, pus in the granuloma, and/or severe brain edema were poor prognostic factors. All survivors except four have symptomatic residual or recurrent lesions. CONCLUSION: Early diagnosis with MRI or stereotactic biopsy, radical surgery, and high dose and chronic suppressive chemotherapy may improve overall results in these cases.

Mycobacterium marinum causes both long-term subclinical infection and acute disease in the leopard frog (Rana pipiens).

Mycobacterium marinum grows at an optimal temperature of 33 degrees C, far lower than that for M. tuberculosis. Consequently, M. marinum infection of mammals is restricted largely to the cooler surfaces of the body, such as the extremities, but it causes a systemic infection in a large number of poikilothermic animals. Here, we describe a laboratory animal model for M. marinum disease in the leopard frog (Rana pipiens), a natural host species. M. marinum causes a chronic granulomatous, nonlethal disease in immunocompetent frogs. Immunosuppression of the frogs with hydrocortisone results in an acute, fulminant, lethal disease. This animal model, in which a spectrum of tuberculosis-like disease can be produced, will be useful for the dissection of the genetic basis of mycobacterial pathogenesis.

Granulomatous inflammation of the oropharyngeal cavity as a possible cause for unexpected high mortality in a Fischer 344 rat carcinogenicity study.

An unexpected, high, test-substance-unrelated mortality has been found predominantly in female Fischer 344 rats of a 2-year gavage carcinogenicity study, which is still in the active phase. Most of the dead animals (53%) had an impacted food or bedding bolus in the oropharyngeal cavity. Histologic evaluation of this area revealed a calcified, granulomatous inflammation of the sero-mucinous glands (60%), frequently accompanied by papillary projections (50%) into the lumen. Additionally, decentral islet formation of the tracheal cartilage was evident in all animals examined. We assume that the partial blockage of the oropharyngeal lumina was the cause of death, because other possible factors were ruled out. To detect a possible strain-related predisposition, Fischer 344 and Sprague Dawley rats that had been used for technician gavage training were studied. Granulomas and papillary projections, as well as the decentral islet formation in the tracheal cartilage, however, were found in gavaged Fischer 344 but not Sprague Dawley rats. We consider the high mortality to be related to three factors: a predisposition of the Fischer 344 rat strain, an unphysiological pH of the solvent (pH 10), and chronic irritation due to an inflexible, metallic gavage tube.

Radiation therapy of canine brain masses.

This article evaluates the responses of 14 dogs with brain masses using orthovoltage irradiation for definitive treatment. Dogs were anesthetized for computed tomography (CT) examination, formation of head immobilization and positioning devices, radiation treatment simulation, and treatments. Total doses of 39 Gy (9 dogs) or 45 Gy (5 dogs) to the tumor were administered over 25 to 41 days. Two or three portals (parallel opposed lateral with or without a dorsal field) were used. Treatment volumes included the tumor and peritumoral edema, as determined by CT scan, and a 1-cm margin. Histopathologic diagnoses were available in 9 of 14 dogs. There were 4 meningiomas, 1 lymphosarcoma, 1 pituitary adenoma, 1 metastatic anaplastic carcinoma, 1 anaplastic oligodendroglioma and 1 dog with granulomatous meningoencephalitis. At the end of radiation therapy, 10 dogs could be evaluated for progression of clinical signs: 3 dogs deteriorated or failed to improve, and 7 dogs improved. At the time of analysis, all dogs were dead. Mean and median survival times, measured from the beginning of radiation, were 345 and 489 days, respectively. This was compared with mean survival times of 30 to 81 days reported in the literature for dogs with brain tumors that did not receive treatment. The median survival time of 9 dogs treated with 39 Gy was 153 days, versus 519 days for 5 dogs that received 45 Gy. It appears that radiation therapy prolongs survival times for dogs with brain masses. Although megavoltage therapy would be optimal, orthovoltage radiation can be applied in total doses of 45 Gy in 3.75 Gy fractions over 28 days without adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)