The gut microbiota in adults with cystic fibrosis compared to colorectal cancer.

BACKGROUND: Gut dysbiosis is implicated in colorectal cancer (CRC) pathogenesis. Cystic fibrosis (CF) is associated with both gut dysbiosis and increased CRC risk. We therefore compared the faecal microbiota from individuals with CF to CRC and screening samples. We also assessed changes in CRC-associated taxa before and after triple CF transmembrane conductance regulator (CFTR) modulator therapy. METHODS: Bacterial DNA amplification comprising V4 16S rRNA analysis was conducted on 84 baseline and 53 matched follow-up stool samples from adults with CF. These data were compared to an existing cohort of 430 CRC and 491 control gFOBT samples from the NHS Bowel Cancer Screening Programme. Data were also compared to 26 previously identified CRC-associated taxa from a published meta-analysis. RESULTS: Faecal CF samples had a lower alpha diversity and clustered distinctly from both CRC and control samples, with no clear clinical variables explaining the variation. Compared to controls, CF samples had an increased relative abundance in 6 of the 20 enriched CRC-associated taxa and depletion of 2 of the 6 taxa which have been reported as reduced in CRC. Commencing triple modulator therapy had subtle influence on the relative abundance of CRC-associated microbiota (n = 23 paired CF samples). CONCLUSIONS: CF stool samples were clearly dysbiotic, clustering distinctly from both CRC and control samples. Several bacterial shifts in CF samples resembled those observed in CRC. Studies assessing the impact of dietary or other interventions and the longer-term use of CFTR modulators on reducing this potentially pro-oncogenic milieu are needed.

The utility of staging in canine mast cell tumours.

Current staging of canine mast cell tumours (MCTs) practiced by many veterinarians involves a minimum of lymph node (LN) assessment, abdominal ultrasound and thoracic radiography. Historically, some have advocated buffy coat and bone marrow evaluation. Two hundred and twenty dogs with MCT seen at a referral clinic were staged using LN palpation/cytology, thoracic radiography and abdominal ultrasound. The utility of each method was evaluated by considering prevalence of spread and future behaviour. At presentation, 30.9% of dogs had metastases to the local LN; 6.8% of all the dogs also had distant metastases. No dog had or developed distant metastasis in the absence of LN metastasis. No dog had convincing evidence of pulmonary metastasis. In this series, the local LN was sentinel to metastasis and in the absence of local LN metastasis, the utility of further staging was low. Thoracic radiography was not useful in the staging of canine MCT.

COX-2 expression in canine anal sac adenocarcinomas and in non-neoplastic canine anal sacs.

Anal sac adenocarcinoma (ASAC) is a clinically significant canine neoplasm characterized by early lymphatic invasion. Up-regulation of cyclooxygenase isoform 2 (COX-2) has been confirmed in several animal and human neoplastic tissues. The aim of the current study was primarily to evaluate COX-2 expression in canine ASAC and compare it to COX-2 expression in non-neoplastic canine anal sac tissue using immunohistochemistry with scoring for percentage positivity and intensity. Twenty-five ASAC samples and 22 normal anal sacs were available for evaluation. All canine ASAC samples and the normal anal sac tissues stained positively for COX-2. However, while normal anal sac tissue showed strong staining of the ductal epithelial cells, ASAC samples showed staining of the neoplastic glandular epithelial cells, with varying percentage positivity and intensity between ASAC samples. COX-2 immunoreactivity of ASAC samples was of low intensity in 52% and high in 12% of the cases; the remaining samples were of intermediate intensity. Seventy-six per cent of the ASAC had over 50% of the neoplastic glandular cells staining positive. These results confirm that COX-2 is expressed in the neoplastic glandular epithelial cells in canine ASAC and suggest a potential role for COX-2 inhibitors in the management of ASAC. Furthermore, the results indicate that COX-2 is expressed in ductal epithelial cells of the normal anal sac.

A novel approach to treatment of lymphangiosarcoma in a boxer dog.

A five-year-old female boxer presented with a swelling in the area of the caudal mammary gland. The mass was surgically excised and histopathological examination revealed a poorly demarcated lesion, extending into mammary tissue and infiltrating the sinuses of adjacent lymph nodes. The diagnosis was lymphangiosarcoma. Full blood work, thoracic radiographs, abdominal and scar ultrasound were unremarkable, apart from possible inflammatory reactions in the latter and reactive/metastatic changes in inguinal lymph nodes. Doxorubicin treatment resulted in a 6-month recurrence free interval. At relapse, the dog was treated with metronomic chemotherapy using chlorambucil and meloxicam, which failed to adequately control the disease. Toceranib phosphate was introduced and resulted in almost complete regression of the mass, leaving just a skin plaque. To the authors' knowledge this is the first report describing the use of two novel therapeutic approaches to treat canine lymphangiosarcoma that resulted in a higher than previously described survival time.

Peri-articular histiocytic sarcoma and previous joint disease in Bernese Mountain Dogs.

BACKGROUND: Peri-articular histiocytic sarcoma (PAHS) occurs in dogs, including Bernese Mountain Dogs (BMD). An etiologic relationship with previous joint disease has not been documented. HYPOTHESIS: Peri-articular histiocytic sarcoma in BMD will be more frequently encountered around previously diseased joints compared with normal joints. ANIMALS: 920 European BMD. METHODS: A retrospective study, in which data were obtained through an Internet questionnaire and from 2 veterinary pathology laboratories. Archived samples of hematoxylin-eosin (H&E) staining diagnosed PAHS and synovial cell sarcoma (SCS) were immunolabeled with CD18 and pancytokeratin. Descriptive, comparative, and actuarial statistics comprise the data analysis. RESULTS: All primary synovial tumors were identified as PAHS based on their morphology, positive CD18, and negative pancytokeratin labeling. Joint disease was diagnosed in 226 BMD, of which 15 developed PAHS in a previously diseased joint and 3 in a nondiseased joint. Of the remaining 694 BMD without joint disease, 9 developed PAHS. The odds ratio for a dog with previous joint disease developing PAHS is calculated as 5.4 (95% CI: 2.3-12.5; P < .0001) compared with no previous joint problem. A significant association between previous joint disease and PAHS in the same joint was demonstrated for the left elbow (P = .016), right elbow (P = .006), right shoulder (P = .047), left and right stifle (P < .001), and left carpal joint (P = .010). CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study suggest a relation between previous joint disease and the development of PAHS in the same joint of European BMD. Owners of BMD should monitor dogs for peri-articular swellings, particularly around previously diseased joints.

Intentional marginal excision of canine limb soft tissue sarcomas followed by radiotherapy.

OBJECTIVES: To evaluate the outcome in a group of dogs treated with postoperative radiotherapy following intentional marginal excision of soft tissue sarcomas from their limbs and to assess parameters for prognostic significance. METHOD: Patients that had had intentional marginal excision of limb soft tissue sarcomas followed by radiotherapy were selected. A coarse fractionated protocol of four once weekly 8 to 9 Gy by 4 MV x-rays was used. The time to local recurrence was determined. Tumour grade, size, site, number of surgeries, surgeon and time from last surgery to radiotherapy were evaluated as potential prognostic indicators. RESULTS: Fifty-six cases were included. Minor surgical complications occurred in four patients (7%). Tumour recurred locally in 10 dogs (18%). Fourteen dogs died from tumour-related causes (25%). From Cox proportional hazard analysis time from surgery to radiotherapy was the only predictor of tumour recurrence (P=0·039); hazard ratio 8·63. Delaying radiotherapy beyond 4 weeks was associated with improved outcomes. Three dogs developed serious but non-life-threatening local complications; wound dehiscence, self-trauma and osteonecrosis of underlying bone. CLINICAL SIGNIFICANCE: Intentional marginal excision followed by hypofractionated radiotherapy is a viable option for canine limb soft tissue sarcomas, providing good long-term clinical outcomes and low morbidity.

COX-2 expression and outcome in canine nasal carcinomas treated with hypofractionated radiotherapy.

The expression of cyclooxygenase isoform 2 (COX-2) in canine nasal carcinomas has been well documented. COX-2 expression has proven to be a prognostic factor in several human tumours. The aims of this study were to assess the correlation between immunohistochemical COX-2 expression and prognosis using rhinoscopic biopsies from 42 dogs with nasal carcinomas treated with hypofractionated radiotherapy, and to establish a replicable COX-2 scoring system. Ninety per cent of sections evaluated were COX-2 positive with a mean score of 6.6 (median 8.0; range 0-12). Neither COX-2 expression nor tumour type had a significant correlation with survival. There are likely to be many as yet unidentified variants which contribute to length of survival in dogs with nasal carcinomas. Immunohistochemical COX-2 expression appears unlikely to be of prognostic significance for canine nasal carcinoma.

Impact of primary tumour stage on survival in dogs with solitary lung tumours.

OBJECTIVES: The objective of this study was to determine simple prognostic criteria for differentiation of canine solitary lung tumour cases into those that will and will not benefit from thoracic surgery. METHODS: This was a retrospective study using the records of cases presented to Davies Veterinary Specialists, Hitchin, UK, from December 1998 to December 2005. Survival analyses were performed using the Kaplan-Meier and logrank methods. Potentially significant variables were evaluated by multivariate Cox analysis. RESULTS: Forty-two patients met the inclusion criteria. Primary tumour stage T1, absence of neoplastic lymph nodes and metastases, and papillary tumour type were statistically significant favourable prognostic indicators on univariate analysis. Multivariate analysis attributed significance to primary tumour stage T1 and papillary type only. Median survival times were 555 days for T1N0M0 tumours of papillary type and 72 days for the remainder. CLINICAL SIGNIFICANCE: Survival time following surgery in dogs with primary lung tumours was poor except in clinical stage T1N0M0 cases. These data support use of clinical techniques to dichotomise cases as T1N0M0 or other, improving decision making in thoracic surgery. These data validate initiation of prospective studies examining the role of chemotherapy in the management of advanced cases.

Improved survival in a retrospective cohort of 28 dogs with insulinoma.

OBJECTIVES: To determine the survival times for a cohort of dogs with insulinoma and to describe the impact of medical therapy both in non-surgical cases and in surgical cases following relapse. METHODS: A retrospective study of dogs with insulinoma is presented. The Kaplan-Meier method is used to evaluate the survival characteristics of this population. RESULTS: Twenty-eight dogs were included in the study. The median survival time for all dogs was 547 days. Nineteen patients underwent partial pancreatectomy. The median survival time for this group was 785 days and for those subsequently receiving prednisolone therapy on relapse it was 1316 days. Perioperative complications are discussed. CLINICAL SIGNIFICANCE: Survival times in this study exceed those in other studies published previously. In part, this is explained by an improved remission duration following surgery compared with previous reports. More striking though is the longevity of patients following institution of medical therapy. These data give strong objective support to the role of medical therapy in the management of canine insulinoma, including following relapse after surgically induced remission.

Expression of E-cadherin in canine anal sac gland carcinoma and its association with survival.

The objective of this study was to determine whether an association could be demonstrated between survival and the expression of the adhesion molecule E-cadherin by the neoplastic cells in a group of dogs with anal sac gland carcinomas (ASGCs). Archived formalin-fixed, paraffin wax-embedded primary tumour specimens were obtained for 36 cases of canine ASGC with known clinical management and survival data. Immunohistochemical methods were used to evaluate E-cadherin expression by the neoplastic cells and data were evaluated for an association between E-cadherin expression and survival. On univariate analysis, the median survival time for cases with tumours expressing E-cadherin in more than 75% of cells was significantly greater than that for cases with tumours expressing E-cadherin in fewer than 75% of cells (1168 versus 448 days, P = 0.0246). Both E-cadherin expression and presence or absence of distant metastases were significantly associated with survival on multivariate analysis. This study demonstrates that expression of E-cadherin at the cytoplasmic membrane in canine ASGCs is variable and potentially predictive of survival.

Resolution of diabetes mellitus but not acromegaly in a cat with a pituitary macroadenoma treated with hypofractionated radiation.

The use of insulin-like growth factor 1 assays in the diagnosis and subsequent monitoring after radiotherapy of an acromegalic cat with a secretory pituitary adenoma and secondary insulin-resistant diabetes mellitus is described. Diabetes resolved, and exogenous insulin was no longer required for the maintenance of normoglycaemia 10 months after completion of a course of hypofractionated radiotherapy. However, insulin-like growth factor 1 remained elevated, and the cat's size and appetite continued to increase. It is suggested that radiotherapy may decrease growth hormone concentration to a level such that diabetogenic effects are no longer evident but not to a level required to decrease insulin-like growth factor 1 secretion.

Role of carboplatin in multi-modality treatment of canine tonsillar squamous cell carcinoma--a case series of five dogs.

Canine tonsillar squamous cell carcinoma is an aggressive disease with a poor prognosis. A retrospective study was undertaken of all dogs that were presented between January 1999 and January 2004 to the Animal Health Trust for the treatment of tonsillar squamous cell carcinoma. Five cases were identified, and their median survival time was 211 days (95 per cent confidence interval 80 to 352) with two of the five dogs remaining alive at the end of the study, 826 and 1628 days from diagnosis with no clinical signs of disease. The protocol was well tolerated with only one of the five dogs showing toxicity associated with carboplatin and all dogs that started radiotherapy completing it. Compared with results of previous studies, these cases suggest that surgical cytoreduction followed by coarse fractionated radiotherapy together with carboplatin may be a useful way to treat this tumour. Carboplatin alone caused partial remission in the two cases where it was used as neo-adjunctive therapy.

Effects of stage and number of tumours on prognosis of dogs with cutaneous mast cell tumours.

Between 1997 and 1999, 280 dogs with mast cell tumours were identified, of which 59 (21 per cent) had multiple tumours. Follow-up data for survival analysis were available for 145 dogs with single tumours and 50 dogs with multiple tumours. There was no significant difference between the survival times of the two groups; the survival rates after 12 and 24 months were 88 per cent and 83 per cent, respectively, for the dogs with single tumours, and 86 per cent at both intervals for the dogs with multiple tumours. Eight of the dogs with single tumours had lymph node metastases (stage II disease) and these dogs had a median survival time of 431 days, whereas the 50 dogs with multiple tumours (classified as stage III disease) and the dogs with single tumours (classified as stage I disease) had not reached their median survival times. Golden retrievers appeared to be predisposed to developing multiple tumours in the population studied, with an odds ratio of 3.8. This study found no evidence that dogs with multiple tumours had different survival times than those with single tumours, although there was evidence that the presence of lymph node metastasis generally carried a poorer prognosis.

Coarse fractionated radiation therapy for pituitary tumours in cats: a retrospective study of 12 cases.

This retrospective study describes the clinical progression of 12 cats with pituitary tumours treated with a coarse fractionated radiation protocol delivering a total dose of 37 Gy in five once weekly fractions. A pituitary macrotumour was identified in all 12 cats: 4 with neurological signs only and 8 with insulin-resistant diabetes mellitus secondary to acromegaly. One of the cats with central neurological signs died before completing the radiotherapy course; the remaining three had partial or complete remissions of their central neurological signs. Of the cats with unstable diabetes mellitus, five no longer required insulin therapy, one required less insulin and two became stable. The overall median survival time was 72.6 weeks; four cats died from related causes, two from unrelated problems and six remain alive. Radiation therapy is confirmed as an effective treatment for feline pituitary tumours, giving prolonged survival and control of both paraneoplastic and mass effect signs.

Relationships between the histological grade of cutaneous mast cell tumours in dogs, their survival and the efficacy of surgical resection.

The histological grade of 340 cutaneous mast cell tumours derived from 280 dogs was determined by an established histological grading system; 87 of the tumours (26 per cent) were well differentiated, 199 (59 per cent) were intermediately differentiated and 54 (16 per cent) were poorly differentiated. The one-year survival rates for the dogs with tumours of these three grades were significantly different (P = 0.0001), being 100 per cent, 92 per cent and 46 per cent, respectively. The median survival time for the dogs with poorly differentiated tumours was 278 days, significantly shorter than that for the dogs with either intermediately or well-differentiated tumours, which were both over 1300 days. Regrowth of the tumours was identified in 10 (19 per cent) of the dogs with poorly differentiated tumours, 12 (6 per cent) of the dogs with intermediately differentiated tumours and one of the dogs with well-differentiated tumours; only three of the tumours which regrew had initially had complete margins. The results suggest that wide surgical margins are not a prerequisite for a successful long-term outcome in dogs with well-differentiated cutaneous mast cell tumours.

Hypertrophic osteopathy secondary to pulmonary sarcoma in a cat.

A case of hypertrophic osteopathy secondary to a pulmonary spindle cell sarcoma is described. The 9-year-old male cat presented with a 1-month history of decreased appetite, decreased activity and progressive lameness with swelling and pain of all four limbs. Thoracic radiographs showed a soft tissue opaque mass in the left caudal lung lobe. Radiographs of all limbs showed extensive periosteal new bone formation of uniform opacity demonstrating a 'palisading' pattern. The lung mass was removed at exploratory thoracotomy; histopathological examination diagnosed a low-grade spindle cell sarcoma. Prior to surgery, the cat had a non-specific conjunctivitis that resolved spontaneously following lobectomy raising the possibility of a paraneoplastic association. The lameness also resolved; six months after surgery, the periosteal palisading of new bone on the long bones had remodelled, and there was no evidence of pulmonary metastases.

Synovial myxoma: magnetic resonance imaging in the assessment of an unusual canine soft tissue tumour.

Magnetic resonance imaging (MRI) of the hindlimb of a 10-year-old Labrador retriever was performed preoperatively to define the limits and invasive nature of a synovial myxoma. This unusual tumour in dogs has also only rarely been reported in humans, although the use of advanced imaging techniques has been more widely reported in the assessment of soft tissue tumours in people. MRI was an invaluable aid in the delineation of the extensive pathological changes associated with this tumour and consequently its surgical treatment. Amputation was performed and the dog remained disease-free 18 months after surgery.