Efficacy, toxicities, and prognostic factors of stereotactic body radiotherapy for unresectable liver metastases.

INTRODUCTION: This study aims to determine the outcomes of stereotactic body radiotherapy (SBRT) for liver metastases in patients not eligible for surgery. METHODS: This study included 31 consecutive patients with unresectable liver metastases who received SBRT between January 2012 and December 2017; 22 patients had primary colorectal cancer and nine patients had primary non-colorectal cancer. Treatments ranged from 24 Gy to 48 Gy in 3 to 6 fractions over 1 to 2 weeks. Survival, response rates, toxicities, clinical characteristics, and dosimetric parameters were evaluated. Multivariate analysis was performed to identify significant prognostic factors for survival. RESULTS: Among these 31 patients, 65% had received at least one prior regimen of systemic therapy for metastatic disease, whereas 29% had received chemotherapy for disease progression or immediately after SBRT. The median follow-up interval was 18.9 months; actuarial in-field local control rates at 1, 2, and 3 years after SBRT were 94%, 55%, and 42%, respectively. The median survival duration was 32.9 months; 1-year, 2-year, and 3-year actuarial survival rates were 89.6%, 57.1%, and 46.2%, respectively. The median time to progression was 10.9 months. Stereotactic body radiotherapy was well-tolerated, with grade 1 toxicities of fatigue (19%) and nausea (10%). Patients who received post-SBRT chemotherapy had significant longer overall survival (P=0.039 for all patients and P=0.001 for patients with primary colorectal cancer). CONCLUSION: Stereotactic body radiotherapy can be safely administered to patients with unresectable liver metastases, and it may delay the need for chemotherapy. This treatment should be considered for selected patients with unresectable liver metastases.

Effects of generalization descriptions on risk perception.

The study addresses the effects of generalization descriptions on risk perceptions. In a 1-factorial online experiment, 629 participants were randomly allocated to one of three groups. Group G1 received an excerpt of an original press release from the International Agency for Research on Cancer (IARC) regarding mobile phones and cancer, classifying RF EMF as possibly carcinogenic to humans. Group G2 received an additional explanatory text module, and Group G3 received a rewritten text, with both G2 and G3 highlighting that the possible cancer risk only refers to mobile phones. Risk perceptions regarding cell phones and related personal devices, base stations, and high voltage power lines were used as dependent variables measured before and after text reading. Further, the degree to which participants generalized from cell phone-related to other RF EMF exposures was assessed to determine whether this was predictive of their post-text risk perceptions. Regarding risk perceptions, no differences between the three groups were observed after reading the presented texts. Instead, all three experimental groups indicated increased risk perceptions for all electromagnetic field sources. However, we found significant differences according to the prevailing risk generalization belief. Respondents expressing a strong risk generalization belief showed significantly higher risk perceptions for all tested EMF sources (except mobile phones) than subjects with a weak risk generalization belief.

Multi-center planning study of radiosurgery for intracranial metastases through Automation (MC-PRIMA) by crowdsourcing prior web-based plan challenge study.

BACKGROUND: Planning radiosurgery to multiple intracranial metastases is complex and shows large variability in dosimetric quality among planners and treatment planning systems (TPS). This project aimed to determine whether autoplanning using the Muliple Brain Mets (AutoMBM) software can improve plan quality and reduce inter-planner variability by crowdsourcing results from prior international planning study. METHODS: Twenty-four institutions autoplanned with AutoMBM on a five metastases case from a prior international planning competition from which population statistics (means and variances) of 23 dosimetric metrics and resulting composite plan score (maximum score = 150) of other TPS (Eclipse, Monaco, RayStation, iPlan, GammaPlan, MultiPlan) were crowdsourced. Plan results of AutoMBM and each of the other TPS were compared using two sample t-tests for means and Levene's tests for variances. Plan quality of AutoMBM was correlated with the planner' experience and compared between academic and non-academic centers. RESULTS: AutoMBM produced plans with comparable composite plan score to GammaPlan, MultiPlan, Eclipse and iPlan (127.6 vs. 131.7 vs. 127.3 vs. 127.3 and 126.7; all p > 0.05) and superior to Monaco and RayStation (118.3 and 108.6; both p < 0.05). Inter-planner variability of overall plan quality was lowest for AutoMBM among all TPS (all p < 0.05). AutoMBM's plan quality did not differ between academic and non-academic centers and uncorrelated with planning experience (all p > 0.05). CONCLUSIONS: By plan crowdsourcing prior international plan challenge, AutoMBM produces high and consistent plan quality independent of the planning experience and the institution that is crucial to addressing the technical bottleneck of SRS to intracranial metastases.

Current management of pregnancy-associated breast cancer.

Pregnancy-associated breast cancer is the most common malignancy during pregnancy with an expected rise in incidence. The belief in the need for termination of pregnancy and that chemotherapy is contra-indicated during pregnancy is challenged by recent evidence. Patients can consider breast-conserving surgery and sentinel lymph node biopsy with acceptably low fetal risk from radiation exposure. A range of chemotherapeutics is possible in the second trimester in terms of drug class and frequency. Hormonal therapy and monoclonal antibody therapy are contra-indicated during pregnancy and lactation. Fetal outcome after in-utero exposure to chemotherapy appears similar to that in a non-pregnant population. Future pregnancy, in most situations, does not appear to be contra-indicated but a multidisciplinary and patient-centred approach is recommended. Fertility preservation techniques are also being developed with reported success and consequent pregnancies.

Remission With Donor Lymphocyte Infusion in a Child With Marrow Relapse After Haploidentical Stem Cell Transplantation for Relapsed Stage 4 Neuroblastoma.

A 7-year-old male with Stage 4 neuroblastoma was treated with chemotherapy and autologous hematopoietic stem cell transplantation (HSCT), resulting in partial response with residual bone and marrow disease. He proceeded to haploidentical-HSCT with his mother as donor and achieved remission. The patient developed marrow relapse 2 years after haploidentical-HSCT with cytopenia and dropping donor chimerism. Donor lymphocyte infusion (DLI) using mother's whole blood was given resulting in clearance of marrow disease, resolution of cytopenia, and full donor chimerism. This is the first report of successful treatment for neuroblastoma relapse after haploidentical-HSCT using DLI alone, supporting the role of adoptive cell therapy post-HSCT in neuroblastoma.

Economic evaluation of a computed tomography directed referral strategy for chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is a prevalent chronic inflammatory disease. The basis of a clinical diagnosis of CRS for primary care physicians (PCPs) is based upon the recognition of a symptom constellation that manifests with the disease. However, because the symptomatology of CRS may overlap with other diagnoses, the referral of patient to the most appropriate specialist may not always occur, leading to further delays in evaluation and treatment. METHODS: Given the emphasis on improving the value of health care in Canada, a decision tree model was designed to evaluate whether an upfront computed tomography (CT) scan of the paranasal sinuses ordered by the PCP for a suspected case of CRS would be more cost-effective when compared to symptom-based specialist referral practice. RESULTS: The CT-based strategy resulted in the patient arriving at the most appropriate specialist 95% (±5%) of the time while the symptom-based referral strategy resulted in the patient arriving at the correct specialist 77% (±18%) of the time. The incremental cost effectiveness ratio (ICER) for the CT-based strategy was $1522 per patient arriving at the correct specialist. CONCLUSION: These results suggest that PCPs can improve the effectiveness of their referrals for CRS by utilising an upfront CT referral strategy. However, it would create an additional cost of approximately $1500 per patient referred. Given these findings, the potential clinical benefits of using an upfront CT scan in the Canadian primary care setting should be further studied to determine the value of the additional money spent to improve the effectiveness of CRS referral.

Male breast cancer: a population-based comparison with female breast cancer in Hong Kong, Southern China: 1997-2006.

BACKGROUND: Male breast cancer (MBC) is uncommon. As a result, there is limited availability of studies and reviews and even fewer reports from Asia. This is the largest population-based study to compare Chinese MBC patients with female patients during a 10-year period in Hong Kong, Southern China. METHODS: A retrospective review of medical records of 132 male and 8,118 female breast cancer patients between year 1997 and 2006 in Hong Kong was performed. Each MBC patient was matched with three female breast cancer patients for further analysis. Different characteristics, overall, breast-cancer specific, and disease-free survivals (DFS) were compared. RESULTS: Mean age at diagnosis of male and female patients was 64.5 and 52.7 years respectively. Male patients showed lower histological grade, overall stage, smaller tumor size, and more positive sensitivity in hormone receptors. They were more likely to die of causes other than breast cancer. Matched analysis found that the 5-year overall survival (OS), breast-cancer-specific mortality, and DFS for male and female patients were 78.7, 90.5, 90.5, and 77.9, 86.4, and 81.4 % respectively. Male patients had poorer OS at early overall stage but better breast-cancer-specific mortality rates at any age (p < 0.01). Male patients had a significant risk of dying due to any cause in the presence of distant relapse and had less risk of dying when tumor was ER-positive and HER2-positive. CONCLUSIONS: Chinese male breast cancer patients tend to have poorer OS but better breast-cancer-specific survival compared with their female counterparts.

Aeroacoustics of T-junction merging flow.

This paper reports a numerical study of the aeroacoustics of merging flow at T-junction. The primary focus is to elucidate the acoustic generation by the flow unsteadiness. The study is conducted by performing direct aeroacoustic simulation approach, which solves the unsteady compressible Navier-Stokes equations and the perfect gas equation of state simultaneously using the conservation element and solution element method. For practical flows, the Reynolds number based on duct width is usually quite high (>10(5)). In order to properly account for the effects of flow turbulence, a large eddy simulation methodology together with a wall modeling derived from the classical logarithm wall law is adopted. The numerical simulations are performed in two dimensions and the acoustic generation physics at different ratios of side-branch to main duct flow velocities VR (=0.5,0.67,1.0,2.0) are studied. Both the levels of unsteady interactions of merging flow structures and the efficiency of acoustic generation are observed to increase with VR. Based on Curle's analogy, the major acoustic source is found to be the fluctuating wall pressure induced by the flow unsteadiness occurred in the downstream branch. A scaling between the wall fluctuating force and the efficiency of the acoustic generation is also derived.

Coexisting ductal carcinoma in situ independently predicts lower tumor aggressiveness in node-positive luminal breast cancer.

Primary breast invasive ductal carcinoma coexisting with ductal carcinoma in situ (IDC-DCIS) is characterized by lower proliferation rate and metastatic propensity than size-matched pure IDC. IDC-DCIS is also more often ER-positive, PR-positive and/or HER2-positive. This analysis aims to clarify whether the presence of coexisting DCIS in IDC affects tumor aggressiveness in various biological subtypes of breast cancer, respectively. Tumor data obtained from 1,355 consecutive female patients undergoing upfront surgery for primary breast cancer were analyzed retrospectively; 196 patients with pure DCIS were excluded. Based on evidence that immunohistochemistry (IHC) provides a reasonable approximation of molecular phenotypes, the tumor samples were divided into 4 groups: (1) luminal A (ER and/or PR-positive, HER2-negative, Ki67 ≤ 12), (2) luminal B (ER and/or PR-positive, HER2-negative, Ki67 > 12), (3) HER2 (HER2-positive) and (4) basal-like (triple-negative) disease. Ki67 expression and nodal involvement of IDC with or without DCIS in these groups were compared. The number of patients with luminal A, luminal B, HER2 and basal-like breast cancer were 396, 265, 258 and 117, respectively. Ki-67 was lower in IDC-DCIS than in size-adjusted pure IDC of both luminal A and luminal B subtypes (P = 0.15 and <0.005, respectively). In HER2 or basal-like tumors, there were no significant difference between pure IDC and IDC-DCIS. The presence of coexisting DCIS in IDC predicts lower biological aggressiveness in luminal cancers but not in the conventionally more aggressive HER2-positive and triple-negative subtypes.

Technique of traction-free nerve-sparing robotic prostatectomy: delicate tissue handling by real-time penile oxygen monitoring.

It is postulated that intraoperative injury to the cavernosal nerves results in hemodynamic and histologic changes within the penis, which manifest clinically as ED. We hypothesize that non-neuronal cause, such as vascular insults due to intraoperative tissue handling, may also have a minor but definite role in penile ischemia and consequent postoperative sexual dysfunction. Between May 2008 and July 2008, 64 patients were enrolled in the study (group 1). Following sterilization, the Odissey Tissue Oximeter probe was placed on the shaft of the penis, 2 cm from its base. The patient underwent continuous penile tissue saturation monitoring. Surgical dissection was altered whenever the oxygen saturation alarm went off until it was restored to 85%. In addition, 192 patients, matched for age, preoperative prostate-specific antigen, clinical stage, baseline sexual function, Charlson comorbidity index and nerve-sparing status operated between October 2007 and July 2008, formed the control group (group 2). These patients did not have any intraoperative tissue oxygenation monitoring. Opening of the endopelvic fascia and steps of nerve sparing were associated with significant drops in oxygen levels, especially if done using torque. Drop in oxygen levels were also noted whenever excessive traction was applied on the Foley catheter, seminal vesicles or prostate during apical dissection. We deliberately modified our surgical steps to make surgery more traction free. A significantly higher percentage of group 1 patients with bilateral nerve sparing had no ED compared with group 2 patients at 6 weeks (24.5% vs 10.4%; P=0.014) and 52 weeks (83.7% vs 68%; P=0.029). Overall, 93.9% of patients in study group had Sexual Health Inventory for Men (SHIM) score of 17 (mild to no ED) at 1 year compared with 78.4% of patients in the control group. We demonstrated that avoidance of ischemic stress, aided by intraoperative penile oxygenation monitoring, may help surgeons improve their technique and thus functional outcomes in patients.

Indolent T-cell large granular lymphocyte leukaemia after haematopoietic SCT: a clinicopathologic and molecular analysis.

Four women and three men after allogeneic (n=4) and autologous (n=3) haematopoietic SCT (HSCT) were observed to have an increase in T-cell large granular lymphocytes (T-LGLs) of CD3+CD8+ phenotype for a median of 41 (15-118) months. Clonal rearrangement of the T-cell receptor gene was verified by two PCR techniques and direct DNA sequencing, confirming that the cases were neoplastic and therefore classifiable as T-LGL leukaemia. In the allogeneic HSCT cases, T-LGL leukaemia was derived from donor T cells in three patients, as shown by DNA chimerism analysis, and recipient T cells in one patient who had graft failure previously. None of the patients showed cytopenia, autoimmune phenomenon or organ infiltration, which were features typical of de novo T-LGL leukaemia. Six patients had remained asymptomatic with stable large granular lymphocyte counts. One patient died from cerebral relapse of the original lymphoma. T-LGL leukaemias occurring post-HSCT are distinct from de novo T-LGL leukaemia and may have a different pathogenesis and clinical course. Patients did not require specific treatment, and the disease remained stable for long periods.

Flexor pollicis longus tendon ruptures after palmar plate fixation of fractures of the distal radius.

Palmar plate fixation of distal radial fractures is becoming a standard treatment for this common injury. Ruptures of the extensor pollicis longus tendon have been reported in 8.6% of cases after this procedure. Although palmar plate fixation has also been associated with flexor pollicis longus (FPL) tendon problems, the majority of reported cases pre-date the use of newer anatomically precontoured locking plates. In this paper seven cases of FPL rupture are presented. This complication does not appear to be unique to one type of implant. The possible aetiologies for FPL ruptures are discussed and ways to reduce the incidence of this complication are suggested.

Imaging of the petrous apex: a pictorial review.

A wide variety of pathologies arise from the petrous apex. Such lesions may present with symptoms caused by mass effect or cranial nerve palsies, or may be detected during an investigation for an unrelated disease. CT and MRI are complementary in providing an appropriate differential diagnosis and in aiding surgical planning. This pictorial review appraises the anatomy and contents of the petrous apex. Benign (e.g. cholesterol granuloma, cholesteatoma), inflammatory (e.g.apical petrositis) and dysplastic (e.g. Pagets disease) lesions of the petrous apex are discussed and illustrated. Whilst it is more frequent for neoplastic lesions to extend from adjacent structures, we demonstrate a variety of aggressive tumours and tumour-like conditions (e.g. metastasis, rhabdomyosarcoma, Langerhan's cell histiocytosis, endolymphatic sac tumour) that directly involve the petrous apex. A range of normal radiological appearances are seen, some of which may be mistaken for significant pathology (e.g. asymmetric marrow space development, simple effusions, cephaloceles). An imaging algorithm to aid the formulation of a differential diagnosis is also presented.

Plasma levels of fibrinogen and C-reactive protein are related to interleukin-6 gene -572C>G polymorphism in subjects with and without hypertension.

Hypertension is an important risk factor for cardiovascular diseases. There is increasing evidence suggesting that inflammation is involved in the development of hypertension. Interleukin-6 (IL-6) is an important mediator of inflammatory response and the major regulator of hepatic production of acute phase proteins, such as fibrinogen and C-reactive protein (CRP), which have been associated with hypertension and cardiovascular diseases. Therefore, we studied the association of single nucleotide polymorphism (SNP) in the IL-6 gene (IL6) promoter with plasma levels of fibrinogen, CRP and hypertension. Five hundred and two Hong Kong Chinese subjects (282 normotensives and 220 hypertensives) were recruited. IL-6 gene promoter was examined for polymorphism and the study subjects were genotyped for any SNP identified. The IL6 -572C>G polymorphism (rs1800796) was found with a frequency of 0.23 for the minor G allele. Subjects with the -572G allele had significantly higher plasma fibrinogen (3.06+/-0.57 vs 2.83+/-0.60, P=0.002) and CRP (interquartile range 0.33-1.56 vs 0.12-0.93, P=0.003) levels than those without. The -572C>G polymorphism was found to be an independent predictor of fibrinogen and CRP levels after adjusting for confounding factors. Plasma concentrations of fibrinogen and CRP correlated with systolic blood pressure. However, the -572C/G genotype frequencies did not differ between hypertensive and normotensive subjects, and there was no association between -572C>G polymorphism and blood pressure. Our results provide evidence that there is a clear genetic influence of IL6 -572C>G polymorphism on plasma levels of fibrinogen and CRP, but this polymorphism does not lead to elevated blood pressure.

Severity of juvenile onset recurrent respiratory papillomatosis is not associated with socioeconomic status in a setting of universal health care.

BACKGROUND: Juvenile onset recurrent respiratory papillomatosis (JORRP) results from HPV transmission. Cervical cancer, also transmitted via HPV, is known to be correlated with socioeconomic status (SES). This study aims to determine if an association exists between SES and severity of JORRP. METHODS: Cross-sectional study of all active JORRP patients at the Hospital for Sick Children in Toronto in 2005. SES information from Hollingshead surveys, Postal walk Census data, and Low Income Cutoff Data were compared with Derkay-Wiatrak disease severity scores, peak annual surgical frequency, and age of diagnosis. Statistical analysis was performed using Spearman, Mann-Whitney, and linear regression analyses. RESULTS: Twenty-one patients were surveyed. Hollingshead results were as follows: two patients (10%) were class I (major business and professional); 11 patients (52%) were class II (medium business, minor professional, technical); 4 patients (19%) were class III (skilled craftsmen, clerical, sales workers); 4 patients (19%) were class IV (machine operators, semiskilled workers); 0% were from class V (unskilled laborers, menial service workers). Interestingly, based on postal code data nine patients (45%) were below the low income cutoff as compared to the Toronto (metropolitan) and Ontario (provincial) rates of low income (17% and 14%, respectively). There was significant correlation between each of the SES measures and between disease severity measures. However, analysis of the SES measures versus disease severity measures did not demonstrate any significant relationship. CONCLUSIONS: Though almost half the patients lived below the low income cutoff, this study did not demonstrate a significant correlation between socioeconomic status and severity of disease in JORRP. One possible explanation is that universal access to the Canadian health care system is able to provide support despite a large proportion of patients being socioeconomically vulnerable. A national level study is underway to further detect any relationship between SES and JORRP severity in the general population.

Efficacy of multidisciplinary approach in treatment of constipation: a pilot study.

OBJECTIVE: To evaluate a multidisciplinary Hong Kong treatment programme for patients with constipation. DESIGN: Pilot study. SETTING: A joint collaboration among the departments of surgery, physiotherapy, and dietetics in a regional hospital in Hong Kong. PATIENTS: Thirty-one constipated patients with normal colonic transit and pelvic floor dyssynergia. INTERVENTION: Multidisciplinary treatment including dietary modification, bowel habit adjustment, and physiotherapy. MAIN OUTCOME MEASURES: Anorectal manometry, fibre intake, subjective improvement, bowel frequency, Bristol score, and straining time and effort. RESULTS: Significant improvement was found in mean fibre intake, straining time and effort, but not in anal manometric results. A total of 78% of patients demonstrated more than 50% improvement in subjective symptoms, whereas 70% of the patients enjoyed objective improvement in pelvic floor dyssynergia documented by electromyography and anal pressure during a push effort. CONCLUSION: The multidisciplinary rehabilitative programme for constipated patients significantly improved symptoms. Electromyography and anal pressure during a push effort are useful tools for objective assessment of the treatment effect.

Adrenomedullin--a potential disease activity marker and suppressor of nephritis activity in systemic lupus erythematosus.

OBJECTIVES: To investigate whether plasma adrenomedullin (AM) level is elevated in lupus nephritis and to examine if plasma AM level is correlated with systemic lupus erythematosus (SLE) disease activity and severity of lupus nephritis after multivariate adjustment. METHODS: Consecutive SLE patients and healthy volunteers of age >/=16 were recruited from the rheumatology clinics of two hospitals in Hong Kong. SLE patients with nephritis fulfilled the American College of Rheumatology criteria for renal involvement and had percutaneous renal biopsy performed. Subjects were divided into three groups: (i) SLE patients with nephritis, (ii) SLE patients without nephritis and (iii) normal controls. The demographic and clinical variables were compared between these groups of patients and plasma AM level was determined by radioimmunoassay. Factors associated with plasma AM level were explored by regression analysis with adjustment of confounding factors. RESULTS: Sixty SLE patients (39 with nephritis and 21 without) and 23 normal subjects were studied. The plasma AM level of SLE patients was significantly higher than that of normal controls. SLE patients with nephritis had significantly higher plasma AM level than those without nephritis and normal controls (P<0.001). In regression analysis, proteinuria was negatively associated with plasma AM level (P=0.006) whereas SLE disease activity index was positively associated with plasma AM level after multivariate adjustment (P=0.002). CONCLUSIONS: Plasma AM is elevated in lupus nephritis, which correlates with lupus disease activity. It is negatively associated with urine protein excretion although it is unrelated to the type of renal pathology per se. Plasma AM may play a role to suppress the activity of lupus nephritis.

Gallbladder cancer presenting with acute cholecystitis: a population-based study.

BACKGROUND: The role of laparoscopic cholecystectomy (LC) in acute cholecystitis remains controversial. The aim of the present study was to determine the incidence, clinicopathological characteristics, and outcome of patients with gallbladder cancer presenting with acute cholecystitis. METHODS: We performed a retrospective analysis of patients with gallbladder cancer who presented with acute cholecystitis and were treated at the public hospitals in Hong Kong between 1998 and 2002. RESULTS: Among 2,700 patients with acute cholecystitis managed with cholecystectomy (1,347 open and 1,353 LC), 63 patients (2.3%) were found to have gallbladder cancer. There were 44 women and 19 men with a mean age of 74.7 (+/-12.8) years. Adenocarcinoma (90.5%) was the most common cancer. The overall median survival was 5 months (95% CI = 2.6-7.4). The 5-year survival rate was 20.8%. Laparoscopic cholecystectomy was attempted in 11 patients and was completed successfully in six of them. There was no difference between the LC and open groups in the complication rate, hospital mortality rate, or survival rate. CONCLUSIONS: In the ethnic Chinese population of Hong Kong, the incidence of gallbladder cancer presenting with acute cholecystitis is higher than the same finding in patients undergoing elective cholecystectomy for cholelithiasis. Long-term survival is possible because such patients may be diagnosed at an early stage of the disease.