Treatment and outcomes of multidrug-resistant tuberculosis in Auckland, 1995-2018.

BACKGROUND: New Zealand has a low burden of tuberculosis; however, multidrug-resistant tuberculosis (MDR-TB) still represents a challenge for clinicians. This is the first description of clinical aspects of MDR-TB in New Zealand. AIMS: To evaluate the treatment and outcomes of patients with MDR-TB disease in Auckland. Secondary aims were to review the incidence and clinical characteristics of MDR-TB disease. METHODS: Clinical data were obtained for patients treated for MDR-TB at Auckland District Health Board (ADHB). RESULTS: There were 60 patients nationally with MDR-TB between 1989 and 2018; 41 (69%) of 60 patients received care at ADHB. Pulmonary infection was present in 36 (88%) of 41 patients, with 19 (46%) of 41 patients with smear-positive sputum (smear 1-2+ in 6/41, 15%; smear 3-4+ in 13/41, 32%). The median duration of treatment was 22 months (range 7.5-26) for 18 (44%) of 41 patients who completed MDR-TB treatment by August 2018. The median duration of amikacin treatment was 6 months (range 2-12) for the 23 (61%) of 38 patients in whom these data were available. All 38 patients who received treatment for MDR-TB experienced adverse effects, most commonly gastrointestinal (66%), neurological (50%), ototoxicity (47%) and psychiatric (37%). Complications of intravenous access were experienced by 10 (27%) of 37 patients. Of the 19 (46%) of 41 patients who completed treatment, 18 (95%) achieved cure. There was one case who had recurrence because of inadequate treatment, and one case who had spontaneous resolution without treatment. Seventeen (41%) patients left Auckland prior to completion of treatment, mostly to return to their country of origin (15/17, 88%). CONCLUSION: MDR-TB is uncommon in New Zealand. Treatment is frequently associated with adverse events; however, rates of cure for people completing treatment in New Zealand are high.

Pathological findings after primary chemotherapy in patients undergoing simultaneous orchidectomy and retroperitoneal lymph node dissection for advanced germ cell tumours.

OBJECTIVE: To determine the differential response to systemic chemotherapy in patients undergoing simultaneous orchidectomy and retroperitoneal lymph node dissection (RPLND) after chemotherapy for metastatic testicular cancer. PATIENTS AND METHODS: Patients who underwent simultaneous RPLND and orchidectomy after chemotherapy were identified from our clinical databases. Postoperative pathological findings and patient characteristics were reviewed. RESULTS: In all, 42 patients were identified. After chemotherapy, necrosis, teratoma and cancer were identified in 25 (59.5%), 14 (33.3%) and three (7.1%) RPLN specimens and 15 (35.7%), 15 (35.7%) and 12 (28.6%) orchidectomy specimens respectively. Of the 25 patients with necrotic RPLN specimens 12 (48.0%) had active disease within the orchidectomy specimen (eight invasive cancer and four mature teratoma). The overall histological discordance rate was 38.1%. Findings in the orchidectomy specimens were more aggressive than those in the RPLN specimens (i.e. cancer worse than teratoma, which is worse than necrosis) in 33.3%. CONCLUSIONS: There is significant disparity between orchidectomy and RPLND findings with viable tumour appearing frequently in the testis despite tumour-free RPLNs. These findings support completion orchidectomy as part of advanced testicular germ cell treatment.

Cardiovascular magnetic resonance imaging in assessment of intracaval and intracardiac extension of renal cell carcinoma.

OBJECTIVES: About 1 in 5 patients with renal cell carcinoma have intravascular tumoral extension at presentation. Level of tumoral extension within inferior vena cava determines surgical approach, with higher extension requiring cardiopulmonary bypass. Tumoral invasion of inferior vena caval wall is associated with poor prognosis. We evaluated accuracy of magnetic resonance imaging (MRI) in assessing level of intravascular extension of renal cell carcinoma and predicting vessel wall invasion. METHODS: MRIs and surgical database were reviewed from January 1999 to December 2008. Sixty-four patients with suspected intravascular extension of renal cell carcinoma underwent MRI. Forty-one underwent curative or palliative surgery at our institution and were included in final analysis. MRI scans were reviewed to determine intravascular extension and tumoral adherence to the vessel wall, as assessed by circumferential flow around the intravascular tumor and its mobility during different phases of cardiac cycle. MRI findings were correlated with surgical findings to assess accuracy. RESULTS: There was 87.8% agreement (P < .001; κ = 0.82) between MRI and surgical findings regarding level of intravascular extension of tumor. MRI was highly sensitive and specific (93%) in assessing supradiaphragmatic extension (negative predictive value, 96%). Depending on sign used, sensitivities and negative predictive values in assessing tumoral adherence to vessel wall ranged from 86% to 95% and 81% to 91%, respectively. CONCLUSIONS: MRI is highly accurate in staging intravascular and intracardiac extension, aiding in accurate preoperative surgical planning. MRI may help determine prognosis of renal cell carcinoma by accurately assessing tumoral adherence to the vessel wall.

The role of embolization in the management of tumour recurrence after radical nephrectomy.

This article presents the case of a 56-year-old woman who developed a tumour recurrence following radical nephrectomy. This was invading the descending colon and causing severe gastrointestinal haemorrhage. Angiography revealed neovascularization from T11 and T12 intercostal arteries, which were successfully embolized percutaneously.

Case report: malignant teratoma of the uterine corpus.

BACKGROUND: Teratomas are the commonest germ cell tumours and are most frequently found in the testes and ovary. Extragonadal teratomas are rare and mainly occur in midline structures. Uterine teratomas are extremely rare with only a few previous case reports, usually involving mature teratomas of the uterine cervix. CASE PRESENTATION: We report an 82-year-old lady presenting with post-menopausal bleeding. Initial investigations revealed a benign teratoma of the uterus which was removed. Her symptoms persisted and a recurrent, now malignant, teratoma of the uterine corpus was resected at hysterectomy. Six months after surgery she relapsed with para-aortic lymphadenopathy and was treated with a taxane, etoposide and cisplatin-containing chemotherapy regimen followed by retroperitoneal lymph node dissection. CONCLUSION: In this report we discuss the aetiology, diagnosis and management of uterine teratomas, and review previous case studies.

Integration of ERG gene mapping and gene-expression profiling identifies distinct categories of human prostate cancer.

OBJECTIVE: To integrate the mapping of ERG alterations with the collection of expression microarray (EMA) data, as previous EMA analyses have failed to consider the genetic heterogeneity and complex patterns of ERG alteration frequently found in cancerous prostates. MATERIALS AND METHODS: We determined genome-wide expression levels with GeneChip Human Exon 1.0 ST arrays (Affymetrix, Santa Clara, CA, USA) using RNA prepared from 35 specimens of prostate cancer from 28 prostates. RESULTS: The expression profiles showed clustering, in unsupervised hierarchical analyses, into two distinct prostate cancer categories, with one group strongly associated with indicators of poor clinical outcome. The two categories are not tightly linked to ERG status. By analysis of the data we identified a subgroup of cancers lacking ERG rearrangements that showed an outlier pattern of SPINK1 mRNA expression. There was a major distinction between ERG rearranged and non-rearranged cancers that involves the levels of expression of genes linked to exposure to beta-oestradiol, and to retinoic acid. CONCLUSIONS: Expression profiling of prostate cancer samples containing single patterns of ERG alterations can provide novel insights into the mechanism of prostate cancer development, and support the view that factors other than ERG status are the major determinants of poor clinical outcome.

Retroperitoneal lymph node dissection after chemotherapy in patients with elevated tumour markers: indications, histopathology and outcome.

OBJECTIVE: To evaluate the factors affecting outcome and the pathological findings in patients who had retroperitoneal lymph node dissection (pcRPLND) after chemotherapy with elevated tumour markers, as such patients have an unfavourable prognosis, with further salvage chemotherapy being the usual treatment of choice. PATIENTS AND METHODS: Information on the preoperative treatment, tumour markers, histopathology and outcome data of the patients who had pcRPLND were extracted from the hospital databases. Survival was analysed using the Kaplan-Meier method and multivariate analysis with Cox regression model. RESULTS: In all, 358 patients had pcRPLND between September 1992 and April 2006, by one surgeon. In 48 patients the tumour markers were elevated at the time of surgery, they were on a 'rising trend' in 26 (54%) and 'downward or stable' trend in 22 (46%). The overall incidence of active germ cell tumour, differentiated teratoma and necrosis in the resected specimens was 58%, 25% and 17%, respectively. The median follow-up was 51.5 months and the overall 5-year survival was 69%. The favourable prognostic factors assessed by univariate analysis were elevation of alpha-fetoprotein alone, complete resection of residual disease, histological finding of differentiated teratoma in the resected tissues and normalization of tumour markers after pcRPLND. By multivariate analysis the only statistically significant independent survival factor was the normalization of the tumour markers after pcRPLND. CONCLUSION: For selected patients with elevated tumour markers after chemotherapy, RPLND can offer a significant chance of cure with no need for further chemotherapy. The patients most likely to benefit are those with elevations of alpha-fetoprotein alone. In this group, pcRPLND can offer the prospect of long-term survival and should be considered in the management of selected patients.

Detection of TMPRSS2-ERG translocations in human prostate cancer by expression profiling using GeneChip Human Exon 1.0 ST arrays.

Translocation of TMPRSS2 to the ERG gene, found in a high proportion of human prostate cancer, results in overexpression of the 3'-ERG sequences joined to the 5'-TMPRSS2 promoter. The studies presented here were designed to test the ability of expression analysis on GeneChip Human Exon 1.0 ST arrays to detect 5'-TMPRSS2-ERG-3' hybrid transcripts encoded by this translocation. Monitoring the relative expression of each ERG exon revealed altered transcription of the ERG gene in 15 of a series of 27 prostate cancer samples. In all cases, exons 4 to 11 exhibited enhanced expression compared with exons 2 and 3. This pattern of expression indicated that the most abundant hybrid transcripts involve fusions to ERG exon 4, and RT-PCR analyses confirmed the joining of TMPRSS2 exon 1 to ERG exon 4 in all 15 cases. The exon expression patterns also indicated that TMPRSS2-ERG fusion transcripts commonly contain deletion of ERG exon 8. Analysis of gene-level data from the arrays allowed the identification of genes whose expression levels significantly correlated with the presence of the translocation. These studies demonstrate that expression analyses using exon arrays represent a valuable approach for detecting ETS gene translocation in prostate cancer, in parallel with analyses of gene expression profiles.

Repeat retroperitoneal lymph-node dissection after chemotherapy for metastatic testicular germ cell tumour.

OBJECTIVES: To examine the operative findings, histopathology and clinical outcome of patients undergoing repeat retroperitoneal lymph node dissection (RPLND) after initial chemotherapy and RPLND (PC-RPLND) for metastatic testicular germ cell tumour (GCT), as a small proportion relapse or have residual disease after incomplete resection in the lung, retrocrural or pelvic nodes, and retroperitoneum. PATIENTS AND METHODS: Between September 1992 and May 2006, 359 patients had PC-RPLND under the care of one surgeon, 54 of which were repeat procedures. We compared the long-term outcome between those having primary and those having repeat PC-RPLND. RESULTS: The median (range) time from original to repeat surgery was 2.4 (0.25-26.5) years, and the median follow-up after the repeat procedure was 5.8 (0.08-12.9) years. There was no difference in survival between patients requiring only one PC-RPLND and those having a repeat procedure (P = 0.592). The most frequent sites of recurrent disease were: behind the great vessels/para-aortic areas (38, 46%), in the suprahilar region (18, 18%), in the retrocrural area (16, 19%), in the pelvic nodes (10, 12%) and in the lung (one, 1%). The most common pathological findings in the repeat PC-RPLNDs were differentiated teratoma (19, 35%), malignant teratoma undifferentiated (nine, 17%), adenocarcinoma (eight, 15%) and necrotic tissue (five, 9.2%). CONCLUSION: Although a small proportion of patients with metastatic GCT might require repeat PC-RPLND, there is no difference in survival between this group and those having one PC-RPLND. However, to avoid cancer recurrence and reoperation, it is crucial that the first PC-RPLND is careful and complete, preferably done in a centre with expertise in this procedure.

Characteristics of incidental prostatic adenocarcinoma in contemporary radical cystoprostatectomy specimens.

OBJECTIVES: To investigate the relationship between prostate-specific antigen (PSA) level and tumour volume for incidental adenocarcinoma of the prostate found in cystoprostatectomy (CP) specimens, and to analyse the incidence of clinically significant prostate cancers in CP specimens and the biochemical recurrence of incidental prostate cancers on short-term follow up. PATIENTS AND METHODS: Complete data from 97 of 105 prostates from CP specimens were available. Prostates were thoroughly analysed and sectioned at 2 mm intervals. PSA levels and the findings at digital rectal examination before surgery were obtained prospectively. None of the patients had any evidence of prostate cancer before CP. RESULTS: Incidental prostate cancer was detected in 58 of 97 (60%) of the CP specimens; of these, 31 (53%) were significant according to the definition of Stamey et al. There was a weak correlation between tumour volume and PSA level, weighted solely by the four larger-volume cancers. The median PSA level for patients with and without prostate cancer was not significantly different (3.1 vs 1.1 ng/mL, P = 0.06). The follow-up of the 35 patients alive with prostate cancer showed four PSA recurrences (PSA >0.02 ng/mL) with one distant metastasis after a median follow-up of 3 years. None of the patients with insignificant tumours developed biochemical recurrence. CONCLUSIONS: The weak correlation between PSA level and tumour volume in these patients supports the argument that PSA is largely produced by benign prostatic hyperplasia and is therefore a poor screening tool for asymptomatic healthy men. Most incidental prostate cancers in CP specimens are significant, contrary to previous analyses, but have little practical importance in terms of oncological outcome.

Retroperitoneal anomalies in men with testicular germ cell tumours.

OBJECTIVES: To assess whether vascular and other retroperitoneal anomalies are more frequent during retroperitoneal lymph node dissection (RPLND) for metastatic testicular tumours (when retroperitoneal masses persist after chemotherapy) than would be expected, based on the initial observations from one centre with a large experience of RPLND in the UK. PATIENTS AND METHODS: A prospective series of 278 consecutive patients treated with RPLND for testicular tumours comprised the sample population. For each patient the presence or absence of four factors from the history was recorded. Each patient then underwent RPLND. During surgery, a template was constructed of the anatomy of the retroperitoneum and the information stored. Eight different retroperitoneal anatomical anomalies were identified in the sample population; the incidence of each was then compared with the largest available study of a normal population, and differences analysed statistically. RESULTS: Of the 278 patients who had RPLND, 55 had 59 anomalies (21%), found by history and as retroperitoneal vascular and urological anomalies; cryptorchidism was present in 7.6%, 9.5 times the incidence in the control population (P < 0.01). A left-sided inferior vena cava was present in 3.6% of patients, 21 times the incidence in the control population (P < 0.001); a retro-aortic left renal vein in 3.2%, four times that in the control population (P < 0.05); and ipsilateral renal agenesis had an incidence of 1% in the test population, 11 times greater than in the control population (P < 0.01). CONCLUSIONS: This prospective study of 278 RPLNDs provides evidence that some retroperitoneal anatomical anomalies are associated with testicular germ cell tumours. The link between maldescent and testicular tumours, rather than an isolated association, should be considered as part of a spectrum of retroperitoneal anomalies that occur in these men.

Adjuvant chemotherapy for non-small cell lung cancer: a New Zealand perspective.

This article reviews recent developments with the use of adjuvant chemotherapy for resected early-stage non-small cell lung cancer (NSCLC) and the implications of these developments for healthcare in New Zealand (NZ). Non-small cell lung cancer is a major cause of mortality and morbidity in NZ, and is greatly over-represented among Maori and socioeconomically deprived populations. Early-stage NSCLC is potentially curable by surgery, but long-term outcome after surgical resection is limited by disease recurrence locally or at sites distant from the primary disease. Three recent large randomised controlled phase III trials using modern platinum-based combination chemotherapy protocols have shown significant survival benefits for the use of postoperative adjuvant chemotherapy after resection of early-stage NSCLC. Cisplatin plus vinorelbine was used as the adjuvant chemotherapy regimen in two of these trials resulting in improvements in 5-year survival of 51.2% versus 42.6% (p=0.013) and 69% versus 54% (p=0.03), respectively. In NZ, adjuvant chemotherapy for NSCLC is expected to prevent up to 15 lung cancer deaths each year for relatively low drug expenditure and has the potential to benefit Maori and the economically-deprived disproportionately more than other populations. In conclusion, it is the opinion of this group of NZ lung cancer specialists that adjuvant chemotherapy with cisplatin plus vinorelbine should now be adopted as a standard of care for patients with resected stage II and III NSCLC. For this to occur, current PHARMAC policies preventing its use for these eligible patients will need to be revised.

Surgical excision of isolated renal-bed recurrence after radical nephrectomy for renal cell carcinoma.

OBJECTIVE: To present our results on managing loco-regional recurrence of renal cell carcinoma (RCC) with surgical excision, as local recurrence at the site of a previous nephrectomy is resistant to both systemic therapy and radiotherapy. PATIENTS AND METHODS: In all, 16 patients were operated on between 1994 and 2003 for local recurrence of RCC. The median (mean, range) age at the time of local recurrence was 57.9 (57.4, 28.9-71.7) years, and the median interval from primary surgery 2.22 (3.88, 0.27-14.46) years. Before surgery eight patients had been given systemic immunotherapy, with no response of their local recurrence. RESULTS: Two patients were deemed inoperable because of direct invasion of the great vessels and the liver by tumour. The remaining 14 patients had recurrence in residual adrenal tissue (two), para-aortic nodes (three), para-caval nodes (two), retrocaval nodes (one), renal bed (six), liver, spleen and stomach (one each), and diaphragm (two). Although complete macroscopic en-bloc clearance was achieved in these patients, only eight had tumour-free margins on histological examination. The histology was consistent with RCC recurrence in all cases. All of the patients were followed with computed tomography at regular intervals. At a median follow-up of 1.0 (1.65, 0.25-6.5) years, five patients remain disease-free, four have local and distant relapse, and five developed distant metastasis only. The presence of tumour at the resection margin was a significant factor in predicting local and distant disease-free survival (P < 0.05). CONCLUSIONS: En bloc excision of isolated locally recurrent RCC is possible, and complete surgical extirpation can lead to prolonged disease-free survival.