Defining the Role of Surgery for Primary Gastrointestinal Tract Melanoma

Objective The objective of the study was to determine the outcomes for primary gastrointestinal melanomas (PGIM). Material and methods The Surveillance, Epidemiology, and End Results database (1973–2004) was queried. Results Overall, 659 cases of PGIM were identified. The annual incidence of PGIM was approximately 0.47 cases per million in 2000. Overall median survival time was 17 months. Tumors were identified in the oral–nasopharynx (32.8%), anal canal (31.4%), rectum (22.2%), esophagus (5.9%), stomach (2.7%), small bowel (2.3%), gallbladder (1.4%), and large bowel (0.9%). Univariate analysis demonstrated age, tumor location, stage, surgery, and lymph node status were significant predictors of improved survival. MST has not been reached for tumors located in the large bowel, while tumors located in the stomach demonstrated the shortest median survival (5 months). Improvement in MST was observed for those patients undergoing surgical resection. The presence of lymph node involvement conferred a poorer prognosis. Multivariate analysis of the cohort identified that location, advanced tumor stage, failure to undertake surgical resection, positive lymph node status, and age were all independent predictors of poorer outcome. Conclusion PGIM occurs most often in the oral–nasopharynx and anal canal. Surgical extirpation is the only identifiable treatment modality that significantly improves survival.     

Estrogen receptor α CA dinucleotide repeat polymorphism is associated with rate of bone loss in perimenopausal women and bone mineral density and risk of osteoporotic fractures in postmenopausal women

Summary The association between a newly identified CA repeat polymorphism of the estrogen receptor alpha gene (ESR1) with osteoporosis was investigated. Postmenopausal women with <18 CA repeats had low BMD, increased rate of bone loss and increased fracture risk. Introduction Studies have shown that intronic dinucleotide repeat polymorphisms in some genes are associated with disease risk by modulating mRNA splicing efficiency. D6S440 is a newly identified intronic CA repeat polymorphism located downstream of the 5’-splicing site of exon 5 of ESR1. Methods The associations of D6S440 with bone mineral density (BMD), rate of bone loss and fracture risk were evaluated in 452 pre-, 110 peri- and 622 postmenopausal southern Chinese women using regression models. Results Post- but not premenopausal women with less CA repeats had lower spine and hip BMD. The number of CA repeats was linearly related to hip BMD in postmenopausal women (β = 0.008; p = 0.004). Postmenopausal women with CA repeats <18 had higher risks of having osteoporosis (BMD T-score<−2.5 at the spine: OR 2.46, 95% CI 1.30–4.65; at the hip: OR 3.79(1.64–8.74)) and low trauma fractures (OR 2.31(1.29–4.14)) than those with ≥18 repeats. Perimenopausal women with <18 CA repeats had significantly greater bone loss in 18 months at the hip than those with ≥18 repeats (−1.96% vs. −1.61%, p = 0.029). Conclusions ESR1 CA repeat polymorphism is associated with BMD variation, rate of bone loss and fracture risk, and this may be a useful genetic marker for fracture risk assessment. Funding Source: This project is supported by CRCG Grant, Bone Health Fund, Matching Grant and Osteoporosis and Endocrine Research Fund of the University of Hong Kong.     

The acceptance and feasibility of breast cancer screening in the East

Breast cancer, traditionally a disease prevalent among women in the West, has become an increasing disease burden in the East. In Hong Kong, breast cancer is the number one incident cancer in women. In Asian countries, due to the lower incidence rate, population screening is still controversial. Most screening programs are not population-based, and are either self-financed privately or partially subsidized by the government. Since the first government-subsidized screening program was set up in 1991 in Hong Kong, numerous private and government health centres for women have been set up. A dedicated private Breast Care Centre was set up at the Hong Kong Sanatorium and Hospital (HKSH) in 1999. Over an 8-year period from October 1999 to September 2006, 14,596 women were screened, of whom 11,408 were asymptomatic. This study aims to produce the first report on breast screening experience in the largest cohort of asymptomatic Chinese women in the private sector. An overall malignancy detection rate of 2.3 per 1000 screens and a recall rate of 9.2% were found. Despite culture differences and differences in breast characteristics (denser and smaller breasts), breast screening is feasible and acceptable in the East.     

Endovascular Treatment of Radiation-Induced Petrous Internal Carotid Artery Aneurysm Presenting with Acute Haemorrhage. A Report of Two Cases

Summary  Haemorrhage from rupture of petrous ICA aneurysm can be life threatening and emergency treatment is required. We report 2 cases of radiation-induced petrous internal carotid artery (ICA) aneurysm presenting with acute haemorrhage (epistaxis and otorrhagia) after radiotherapy (RT) for nasopharyngeal carcinoma (NPC). Both patients had a history of RT treatment for NPC. The first patient, a 54-year-old man, presented with sudden severe epistaxis and haemorrhagic shock. The second patient, a 35-year-old man, presented with episodes of severe otorrhagia. The first patient was immediately resuscitated. Obliteration of the aneurysm was performed by endovascular occlusion of the ICA with Guglielmi detachable coils and fibered platinum coils. For the second patient, the aneurysm was treated by deploying a self-expandable stent across the aneurysm neck. In an emergency situation, ruptured petrous ICA aneurysm can be treated with endovascular occlusion of the ICA with microcoils if there is a good collateral blood flow. Alternatively, the aneurysm can be treated by deployment of a stent, which can induce stasis and eventual thrombosis of the aneurysm.     

Effect of histological damage on long-term kidney transplant outcome

BACKGROUND: Chronic renal allograft failure remains a major challenge to overcome. Factors such as donor quality, delayed graft function (DGF), acute rejection, and immunosuppression are known to affect long-term outcome, but their relationship to histological damage to graft outcome is unclear. METHODS: Protocol kidney biopsies (n=112) obtained at 3 months after transplantation yielded 102 with adequate tissue. Histology was scored by the Banff schema, and compared with implantation biopsies (n=91), repeat 12-month histology (n=39), decline in serum creatinine and serial isotopic glomerular filtration rate, onset of chronic allograft nephropathy (CAN), and actuarial graft survival censored for death with a functioning graft. RESULTS: At a median follow-up of 9.3 years, 20 patients had graft failure and 26 died with a functioning graft. Banff chronic nephropathy was present in 24% of 3-month biopsies, and was predicted by microvascular disease in the donor, cold ischemia, DGF, and acute vascular rejection (P<0.001). Acute glomerulitis at 3 months correlated with segmental glomerulosclerosis at 12 months, subsequent recurrent glomerulonephritis, and graft failure (P<0.01). Subclinical rejection at 3 months occurred in 29% of biopsies, correlated with prior acute rejection and HLA mismatch, and led to chronic histological damage by 12 months (r=0.25-0.67, P<0.05-0.001). Subclinical rejection, arteriolar hyalinosis, and tubulitis present at 3 months had resolved by 12 months. The 10-year survival rates for Banff chronic nephropathy were 90.4% for grade 0, 81.0% grade 1, and 57.9% for grades 2 or greater (P<0.01). Early tubulointerstitial damage at 3 months profoundly influenced graft survival beyond 10 years. CAN was predicted by kidney ischemia, 3-month chronic intimal vascular thickening, tubular injury, proteinuria, and late rejection. Chronic fibrointimal thickening of the small arteries and chronic interstitial fibrosis at 3 months independently predicted graft loss and decline in renal function (P<0.05-0.001). CONCLUSIONS: Early transplant damage occurs in the tubulointerstitial compartment from preexisting donor kidney injury and discrete events such as vascular rejection and DGF. Subsequent chronic damage and graft failure reflect accumulated previous injury and chronic interstitial fibrosis, vascular impairment, subclinical rejection, and injury from late rejection. CAN may be conceptualized as the sequelae of incremental and cumulative damage to the transplanted kidney. The duration of graft survival is dependent and predicted by the quality of the transplanted donor kidney combined with the intensity, frequency, and irreversibility of these damaging insults.     

Liver and lung resection for colorectal metastasis

Aim: To examine the survival benefit of liver and lung resection for colorectal metastasis and the potential prognostic factors that affect patient survival. Methods: All patients who had resection of lung or liver metastasis for colorectal metastasis in Queen Elizabeth Hospital, Hong Kong from 1995 to 2004 were retrospectively reviewed. The overall and disease‐free survival was analysed, in particularly between liver and lung metastasis. All factors that may have affected the survival were entered into Cox's proportional hazards regression model to identify significant variables associated with survival. Results: At 5 years, the overall survival of patients who had resection of lung and liver metastasis was 44% and 38%, respectively; the disease‐free survival was 26% and 24%, respectively. Overall and disease‐free survival of patients with resection of lung metastasis was comparable to those with resection of liver metastasis. The differentiations of primary tumour and time to metastasis were shown to be significant prognostic factors influencing overall survival. Those patients with systemic chemotherapy after resection of colorectal metastasis demonstrated a significantly higher probability of overall survival. Conclusion: Resection of lung and liver metastases from colorectal origin was safe and both procedures improved survival. The use of chemotherapy after resection of metastasis significantly improved the overall survival.     

Outcome assessment of bracing in adolescent idiopathic scoliosis by the use of the SRS-22 questionnaire

The SRS-22 questionnaire is specifically designed for the assessment of quality of life in spinal deformity patients. This study is the first to use it to assess the quality of life of adolescent idiopathic scoliosis patients under brace treatment and compares the results with an observational group matched by age and curve magnitude. Forty-six patients were enrolled into each group. Overall, it was found that patients under observation had a significantly better quality of life than braced patients. Specifically, the domains for function/activity and self-image were most affected. This effect was most apparent in those with a curve magnitude of under 20 degrees . The scores did not improve significantly with the duration of brace wear, suggesting little adaptation. This study has implications for treatment, and more attention will need to be given to those with mild but progressive curves to help improve patients' understanding of their treatment and hence their compliance and satisfaction.     

Laparoscopic versus open appendectomy for complicated appendicitis

BACKGROUND: Laparoscopic appendectomy has been widely practiced for uncomplicated appendicitis; various reports demonstrated its merits in assisting diagnosis, reducing postoperative pain, analgesic requirement, and incidence of wound infection. The role of laparoscopy in management of complicated appendicitis, ie, gangrenous, perforated appendicitis and appendiceal abscess, remains undefined. Currently, the choice of operative approach is mostly at the surgeons' discretion. A retrospective study was conducted in our institution to review the feasibility, safety, and efficacy of laparoscopic appendectomy for patients with complicated appendicitis. STUDY DESIGN: From January 1999 to January 2004, records of patients older than 14 years of age with diagnosis of appendicitis were retrieved from computer database for analysis. All patients underwent diagnostic laparoscopy to confirm diagnosis of complicated appendicitis, and patients subsequently underwent either laparoscopic or open appendectomies. Patients' demographics data and perioperative outcomes from the two groups were compared. RESULTS: During the study period, 1,133 patients with acute appendicitis underwent operations in our institution. Two hundred forty-four patients (21.5%) with complicated appendicitis were identified by laparoscopy, of which 175 underwent laparoscopic appendectomy (LA) and 69 had open appendectomy (OA). Both groups of patients were comparable in demographics. Mean operative time was 55 minutes for LA group and 70 minutes for the OA group (p<0.001). Mean hospital stay was 5 days and 6 days for LA and OA group respectively (p<0.001). There was one conversion patient (0.6%) in the LA group who suffered from wound infection, and there were seven (10%) wound infections in the OA group (p=0.001). There were 10 cases (5.7%) of intraabdominal collection in the LA group and 3 (4.3%) in the OA group (p=0.473). There was no mortality in the current series. CONCLUSIONS: Laparoscopic appendectomy for complicated appendicitis is feasible and safe. It is associated with a significantly shorter operative time, lower incidence of wound infection, and reduced length of hospital stay when compared with patients who had open appendectomy.     

A quantitative evaluation of sealing ability of 4 obturation techniques by using a glucose leakage test.

OBJECTIVE: The aim of this study was to evaluate the sealing ability of 4 different obturation techniques by using a glucose leakage test. STUDY DESIGN: Eighty extracted single-rooted maxillary incisors were selected for the study. The teeth were decoronated and the root canals prepared using ProFile rotary instruments to an apical dimension of size 40 (0.06 taper). The specimens were then randomly divided into 4 experimental groups (n = 15) and filled with gutta-percha and sealer by using either cold lateral compaction, warm vertical compaction, Thermafil, or the E & Q Plus system. Another 10 teeth each served as the positive and negative controls. A glucose leakage model was used for quantitative evaluation of the coronal-to-apical microleakage at 24 hours, 1, 2, 3, 5, 8, and 12 weeks. RESULTS: No significant difference in the cumulative amount of leakage was found among the 4 groups at 24 hours and 1 week (Kruskal-Wallis test, P > .05). Lateral compaction showed significantly more leakage than the other 3 techniques at longer intervals (Mann-Whitney U test, P < .008). No significant difference was found between vertical compaction, Thermafil, and E & Q Plus at all observation times. CONCLUSIONS: Warm vertical compaction, Thermafil, and the E & Q Plus system showed a better sealing result than cold lateral compaction of gutta-percha at extended observation periods. The glucose leakage method used in this study was able to provide a nondestructive, quantitative, and long-term evaluation of the sealing ability of root canal fillings.     

Peripheral administration of the melanocortin-4 receptor antagonist NBI-12i ameliorates uremia-associated cachexia in mice

We have recently shown that genetic or pharmacological blockade of the melanocortin-4 receptor (MC4-R) attenuates uremia-associated cachexia. However, the potential clinical utility of this approach has been limited by the need to deliver a peptide MC4-R antagonist into the ventricles of the brain. NBI-12i is a recently developed small molecule MC4-R antagonist, with high affinity and selectivity that penetrates the central nervous system after peripheral administration. We tested whether NBI-12i would also be effective in attenuating uremia-associated cachexia in a mouse model. Intraperitoneal administration of NBI-12i stimulated food intake and weight gain in uremic mice. Furthermore, NBI-12i-treated uremic mice gained lean body mass, fat mass, and had a lower basal metabolic rate compared to vehicle-treated and diet-supplemented uremic mice, which lost both lean body mass and fat mass and had an increase in basal metabolic rate. We found that NBI-12i normalizes the expression of uncoupling protein, which is normally upregulated in uremic mice, and we speculate that this may contribute to the drug's protective effect. These data underscore the importance of melanocortin signaling in the pathogenesis of uremia-associated cachexia and demonstrate the potential of peripheral administration of MC4-R antagonists as a novel therapeutic approach.