Findings in cattle consigned to Victorian knackeries between 2009 and 2018.

OBJECTIVE: To describe the causes of death or culling in cattle in Victoria, Australia, through surveillance at knackeries. METHODS: Data were collected from 2797 adult cattle consigned to four Victorian knackeries over a 10-year period (2009-2018, inclusive). Cattle were sampled either at the point of collection or at a knackery. A single best-fit diagnosis was assigned to each case to describe the cause of loss. RESULTS: Sampled cattle were predominantly female dairy cattle originating from the three main dairying regions in Victoria. The most commonly diagnosed conditions were calving paralysis (6.8%), followed by mastitis (6.4%), hypocalcaemia (6.4%) and dystocia (5.9%). "Unknown" accounted for 24.2% of the cattle examined. CONCLUSION: This study provides a unique insight into the causes of death and culling in cattle consigned to Victorian knackeries. The periparturient period was identified as a high risk period for knackery consignment in adult female cattle.

First-in-human phase I study of copanlisib (BAY 80-6946), an intravenous pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors and non-Hodgkin's lymphomas.

BACKGROUND: To evaluate the safety, tolerability, pharmacokinetics, and maximum tolerated dose (MTD) of copanlisib, a phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors or non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Phase I dose-escalation study including patients with advanced solid tumors or NHL, and a cohort of patients with type 2 diabetes mellitus. Patients received three weekly intravenous infusions of copanlisib per 28-day cycle over the dose range 0.1-1.2 mg/kg. Plasma copanlisib levels were analyzed for pharmacokinetics. Biomarker analysis included PIK3CA, KRAS, BRAF, and PTEN mutational status and PTEN immunohistochemistry. Whole-body [(18)F]-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) was carried out at baseline and following the first dose to assess early pharmacodynamic effects. Plasma glucose and insulin levels were evaluated serially. RESULTS: Fifty-seven patients received treatment. The MTD was 0.8 mg/kg copanlisib. The most frequent treatment-related adverse events were nausea and transient hyperglycemia. Copanlisib exposure was dose-proportional with no accumulation; peak exposure positively correlated with transient hyperglycemia post-infusion. Sixteen of 20 patients treated at the MTD had reduced (18)FDG-PET uptake; 7 (33%) had a reduction >25%. One patient achieved a complete response (CR; endometrial carcinoma exhibiting both PIK3CA and PTEN mutations and complete PTEN loss) and two had a partial response (PR; both metastatic breast cancer). Among the nine NHL patients, all six with follicular lymphoma (FL) responded (one CR and five PRs) and one patient with diffuse large B-cell lymphoma had a PR by investigator assessment; two patients with FL who achieved CR (per post hoc independent radiologic review) were on treatment >3 years. CONCLUSION: Copanlisib, dosed intermittently on days 1, 8, and 15 of a 28-day cycle, was well tolerated and the MTD was determined to be 0.8 mg/kg. Copanlisib exhibited dose-proportional pharmacokinetics and promising anti-tumor activity, particularly in patients with NHL. CLINICALTRIALSGOV: NCT00962611; https://clinicaltrials.gov/ct2/show/NCT00962611.

Burkitt leukaemia/lymphoma: R-CODOX-M/R-IVAC remains gold standard treatment in BL.

BACKGROUND: Sporadic Burkitt lymphoma (BL), characterised by translocation-associated C-MYC upregulation is a rare, aggressive lymphoma with a cure rate up to 90 % using the R-CODOX-M/R-IVAC (RCRI) protocol. RCRI is active in HIV-associated BL in combination with HAART. The WHO classification system defines lymphomas intermediate between DLBCL and BL, in which lymphomas with t(14;18)(q32;q21) and C-MYC-carrying translocation, i.e. 'double-hit' are included (BL-DH), and these patients are conventionally treated with RCRI. RESULT: We describe the SJH experience of 25 patients with BL, BL + HIV and BL-DH treated with RCRI between 2002 and 2011. Twelve BL patients (8M/4F), median age 49.1 years (range 20-73 years); of whom 9 had extensive disease, including 8 with marrow and 2 with CNS involvement. Eleven patients remain in remission at 80.5 months (range 37-147 months) from completion of treatment and one died of progressive BL giving an OS of 91.6 % at 1 year with no late relapses. Eight patients with BL + HIV were treated (6M/2F) with a median age 40.25 years (range 24-64). Five remain in complete remission (CR) at 65 months (range 13-109 months), three patients died, two of progressive disease and one of treatment-associated hepatotoxicity in CR. Five patients with BL-DH were included; (3M/2F), age 47.8 years (range 42-55 years); and all patients died of progressive disease, 4 on RCRI therapy and a further patient despite an allogeneic transplantation. CONCLUSION: These results confirm that RCRI is an effective treatment in adults with BL and BL + HIV and remains the gold standard against which other regimens should be compared. We confirm the poor prognosis found in BL-DH, indicating new treatment approaches are needed for this sub-group which should be identified at diagnosis by FISH analysis.

Image assessment of cervical dimensions after LLETZ: a prospective observational study.

OBJECTIVE: To assess the impact of large loop excision of the transformation zone (LLETZ) for cervical intraepithelial neoplasia (CIN) on cervical morphology as assessed by three-dimensional ultrasound. DESIGN: Prospective observational study. SETTING: University Hospital in Dublin. POPULATION: Women with CIN who underwent an LLETZ procedure. METHODS: All 106 participants had a three-dimensional transvaginal ultrasound scan (3DTVS) performed immediately before and 6 months after LLETZ. The excised LLETZ specimen dimensions were also recorded. Blind analysis of the images was performed. The volume of the uterus and cervix was documented. MAIN OUTCOME MEASURES: The relationship between the extirpated LLETZ dimensions and subsequent cervical and uterine biometry, as assessed by 3DTVS. RESULTS: LLETZ induced a statistically significant reduction in both the length (mean, -0.46 cm; P < 0.001) and the volume (-6.12 cm(3) ; P < 0.001) of the uterus, and in the volume of the cervix (-1.60 cm(3) ; P < 0.001). The volume of the excised specimen had a significant impact on the reduction of the length of the uterus (ß, -0.038; P = 0.012), the volume of the uterus (ß, -0.791; P = 0.036) and the volume of the cervix (ß, -0.121; P = 0.046). The circumference of the excised specimen appeared to have a significant impact on the length (ß, -0.016; 95% CI, -0.028 to -0.003; P = 0.013) and volume (ß, -0.413; 95% CI, -0.719 to -0.107; P = 0.009) of the uterus 6 months after LLETZ. CONCLUSIONS: The volume of tissue removed at LLETZ is related to the subsequent cervical volume, as well as the uterine length and volume, 6 months after the procedure.

Regorafenib (BAY 73-4506) in advanced colorectal cancer: a phase I study.

BACKGROUND: In a phase I dose-escalation study, regorafenib demonstrated tolerability and antitumour activity in solid tumour patients. The study was expanded to focus on patients with metastatic colorectal cancer (CRC). METHODS: Patients received oral regorafenib 60-220 mg daily (160 mg daily in the extension cohort) in cycles of 21 days on, 7 days off treatment. Assessments included toxicity, response, pharmacokinetics and pharmacodynamics. RESULTS: Thirty-eight patients with heavily pretreated CRC (median 4 prior lines of therapy, range 0-7) were enrolled in the dose-escalation and extension phases; 26 patients received regorafenib 160 mg daily. Median treatment duration was 53 days (range 7-280 days). The most common treatment-related toxicities included hand-foot skin reaction, fatigue, voice change and rash. Twenty-seven patients were evaluable for response: 1 achieved partial response and 19 had stable disease. Median progression-free survival was 107 days (95% CI, 66-161). At steady state, regorafenib and its active metabolites had similar systemic exposure. Pharmacodynamic assessment indicated decreased tumour perfusion in most patients. CONCLUSION: Regorafenib showed tolerability and antitumour activity in patients with metastatic CRC. This expanded-cohort phase I study provided the foundation for further clinical trials of regorafenib in this patient population.

Complete clinical response to neoadjuvant chemotherapy in a 54-year-old male with Askin tumor.

Askin tumor is a tumor of the thoracopulmonary region that most commonly affects children and adolescents. These rare tumors are a form of primitive neuroectodermal tumor and typically carry a poor prognosis. Treatment is multimodal and consists of a combination of neoadjuvant chemotherapy, radical resection, and adjuvant chemo- and radiotherapy or all of the above. Surgery is advocated in most cases. We report a case of Askin tumor in a 54-year-old male who showed rapid and complete response to neoadjuvant chemotherapy. This allowed potentially radical surgery to be avoided. At one-year follow-up he remains disease-free.

Rapid assessment breast clinics--evolution through audit.

This observational, cohort study aimed to examine the potential utility of Rapid Assessment Breast Clinics (RABC) beyond cancer detection at presentation. One thousand four hundred and twenty nine women were studied over an 18 month period. 154 (10.7%) had breast cancer - 87.7% of whom were seen expediently with 92.9% being diagnosed at one attendance. One hundred and forty three (10%) of those with a benign diagnosis were found by routine questioning to have significant familial risk separate to their reason for referral. Despite careful triage, considerable contamination of appointment allotment occurred with many who were correctly triaged as non-urgent being seen 'urgently'. One hundred and seventy six attendees (12.3%) had neither the symptom that triggered referral, nor breast lump, nipple discharge nor family history of breast cancer, while 283 (19.8%) had no objective clinical or radiological abnormality. Although RABC reliably categorise malignant versus non-malignant diagnoses despite cluttering by low risk women, a significant proportion of non-cancer patients still require address of future risk rather than reassurance of their present status alone.

Unusual presentation of an appendiceal malignancy.

Primary malignant epithelial tumors of the appendix are uncommon. The most common presentation of appendiceal malignancy is right lower abdominal pain suggestive of acute appendicitis. Presentation caused by loco-regional spread with involvement of neighboring organs is rare. We present the case of a 48-year-old woman with an appendiceal malignancy who presented with symptoms and signs suggestive of complicated diverticular disease with an enterovaginal fistula. From a review of the literature, this is the first report of an appendiceal malignancy presenting in this manner.

Primary abdominal wall clear cell carcinoma arising in a Caesarean section scar endometriosis.

BACKGROUND: Endometriosis occurring in a surgical scar is well recognized and occurs mainly in patients with a history of hysterectomy or Caesarean section. Scar endometriosis, as well as endometriosis at other sites, can undergo malignant change. Endometrioid carcinoma is the most common malignant tumour arising in endometriosis. However, clear cell carcinoma can also occur but is unusual. AIM: To discuss the diagnosis and management of such a case. METHODS: We report a case of primary clear cell carcinoma in endometriosis of a Caesarean section scar and review the literature. RESULTS: The patient presented with a large right lower quadrant abdominal wall mass within a Caesarean section scar. Histological examination revealed a clear cell carcinoma. The patient had a prior history of pelvic endometriosis. According to the Irish National Cancer Registry, this is the first reported case of a primary abdominal wall clear cell carcinoma developing within a Caesarean section scar in Ireland. CONCLUSION: Any lesion occurring in a Caesarean section scar with a history of previous endometriosis cannot be underestimated and warrants careful clinical follow-up and histological evaluation as appropriate.

Auditing a new lung cancer service.

The Adelaide and Meath Hospital (AMNCH) is a new hospital, with the respiratory service established in 1999. We report on our experience with lung cancer in this short time. We conducted a retrospective chart audit, identifying patients from the Oncology Nurse patient list, of lung cancer cases diagnosed in 2001-2002. In 2001, 47 cases were diagnosed, with 71 cases diagnosed in 2002. Time to tissue diagnosis was 14.8, 2-46 (mean, range, one subject skewing the data) days. Diagnosis by tissue type was as follows: non-small cell carcinoma (NSCLC) n=92 (77.9%), small cell lung carcinoma (SCLC) n=17 (14.4%), mesothelioma n=2 (17%), carcinoid n=1 (0.8%) and no tissue diagnosis n=6 (5.1%). Staging of NSCLC: stage 1a n=3 (3.2%), stage 1b n=6 (6.5%), stage 2a n=5 (5.4%), stage 2b n=2 (2.2%), stage 3a n=10 (10.9%), stage 3b n=22 (23.9%) and stage 4 n=44 (47.8%). Staging of SCLC: limited stage n=5 (29.4%), extensive stage n=12 (70.6%). Positive emission tomography (PET) was employed in the staging of 22 patients. In these patients PET up-staged the disease in 8 patients, and management was unchanged in 8 patients. We conclude that 1. the relatively new respiratory service in AMNCH is handling increasing numbers of lung cancer cases, 2. cases are diagnosed within an acceptable time-frame, 3. rate of tissue diagnosis is comparable to national figures, 4. most patients present with advanced disease and 5. PET is a useful imaging modality for detection of cancer spread in selected patients.

Endometrioid carcinoma of the urinary bladder complicating vesical Mullerianosis: a case report and review of the literature.

Endometriosis of the urinary bladder is uncommon, and malignant transformation within vesical endometriosis is extremely rare. Vesical endometriosis and Mullerianosis can cause problems in differential diagnosis with vesical neoplasm, and, conversely, primary vesical neoplasm arising in endometriosis can be difficult to distinguish from secondary vesical involvement. Mullerianosis has rarely been described in the urinary bladder. A case of endometrioid adenocarcinoma of the urinary bladder is reported, which illustrates the difficulties in diagnosis and the importance of morphology and ancillary studies in establishing the correct diagnosis.

Technical report. Intra-operative ultrasound-guided needle localization for impalpable testicular lesions.

AIMS: To describe a new technique of intra-operative ultrasound-guided needle localization of impalpable intratesticular lesions. MATERIALS AND METHODS: Three patients with impalpable testicular lesions identified on ultrasound underwent needle localization under ultrasound guidance. The procedure was performed in the operating theatre under general anaesthetic using a 7.5-8 MHz linear array probe and a portable ultrasound machine. Under direct guidance, a 21 G needle was placed through the centre of the lesion allowing resection and immediate frozen section analysis. RESULTS: In two patients malignancy was confirmed and an orchidectomy was performed. In one patient a benign lesion was detected obviating the need for orchidectomy. CONCLUSION: Patients presenting with impalpable testicular lesions can pose a diagnostic dilemma and orchidectomy is often performed. We describe an ultrasound-guided intra-operative localization technique enabling direct pathological examination so surgical approach can be re-evaluated in the presence of a benign lesion. This is particularly important in the case of a solitary testicle in order to preserve testicular function.

Granulomatous appendicitis.

Granulomatous inflammation of the appendix is uncommon. It can be caused by a variety of conditions, including systemic disorders such as Crohn's disease and sarcoidosis, and infections such as mycobacterium tuberculosis, yersinia pseudotuberculosis, parasites and fungi. Granulomatous appendicitis as an isolated pathological entity unassociated with systemic disease is rare. Isolated granulomatous inflammation of the appendix of unknown aetiology, otherwise known as idiopathic granulomatous appendicitis is extremely rare. Patients with this condition present with the typical signs and symptoms of acute appendicitis. We present a series of patients with isolated granulomatous inflammation of the appendix, and discuss the difficulties encountered in the management of this condition.

An immunohistochemical study of p21 and p53 expression in primary node-positive breast carcinoma.

AIMS: p21, an inhibitor of cyclin-dependent kinase, is involved in the p53 pathway of growth control. Its expression has been linked to cellular differentiation. It has been implicated in p53-mediated growth arrest following DNA damage and in terminally differentiated cells. This study analysed p21 and p53 expression, in a series of node-positive patients with breast carcinoma and examined histopathological parameters of the tumour and the prognostic implications of p21 and p53 expression. METHODS: One hundred and five consecutive patients with node-positive disease and at least 3 years follow-up were identified. Sections were stained for p53 and p21 using monoclonal antibodies. Results were expressed as percentage positive cells, and over 20% considered positive for p53 and over 10% considered for p21. RESULTS: p21 was overexpressed (>10% of cells positive) in 65% of patients and p53 was overexpressed (>20% of cells positive in 68%. The mean (SEM) level of p21 staining was 5.7(0.8)% and was 54.9(4.0)% for p53. There was no correlation between p21 and p53 expression (r=0.071 P=0.5). There were no significant differences in demographic criteria between patients that were p21 positive or negative and p53 positive or negative. There were no significant differences in tumour type, grade or stage between the groups. p21 expression did not have prognostic significance; however, p53 positivity was associated with a worse prognosis, which remained when controlled for stage. CONCLUSIONS: This study demonstrated p21 overexpression in 65% of patients with node-positive breast carcinoma. Levels did not correlate with p53 status and unlike p53 failed to have prognostic significance.