Rectal Cancer: Changing Patterns Of Referral For Radiation Therapy 1982–1997

Background : The purpose of the present study was to evaluate the changing role of radiation therapy in rectal cancer and to determine the patterns of referral of patients during a 15‐year period. Methods : From 1982 to 1997, 464 patients with carcinoma of the rectum were referred to the Department of Radiation Oncology, Royal Prince Alfred Hospital; 79% of patients had locoregional disease alone and 21% had distant metastasis. Radiation therapy consisted of irradiation (definitive or palliative) alone to the primary tumour in 9.7% of cases; preoperative radiation in 7.3% of cases; preoperative chemoradiation in 7.5% of patients; postoperative radiation in 15.3% of patients; postoperative chemoradiation in 12.3% of patients; treatment of pelvic recurrence in 23.5% of patients and treatment of metastases in 9.1% of patients. The remainder were treated elsewhere (1.9%) or not treated (13.4%). Results : There was an average annual 14% increase in referrals over the accrual period. Recurrent rectal cancer decreased from approximately 30% of referrals during 1982–91 to approximately 10% in 1995–7. The use of postoperative adjuvant radiation reached a peak of 50% in 1993. The use of preoperative radiation increased suddenly in 1994 from < 10% to a sustained rate of approximately 30% of referrals. The use of chemoradiation commenced in 1990 for postoperative adjuvant treatment and in 1994 for preoperative treatment. The median survival time from initial diagnosis was 35 months, with 2‐ and 5‐year survival rates of 62 and 28%, respectively. Survivals at 5 years for patients treated with preoperative and postoperative radiation (with or without chemotherapy) and with recurrent disease were 56, 44 and 21%, respectively. Conclusions : The present study illustrates the changing role of radiation therapy in the management of rectal cancer. The increase in referrals over the observation period was due to increased multidisciplinary input into the initial management of these patients, based on reported clinical trials. The steady increase in the use of adjuvant therapy has paralleled a decrease in referrals for treatment of recurrence and reflects current clinical results. The sequencing of adjuvant therapy is changing currently, with greater emphasis on preoperative adjuvant treatment. Currently most adjuvant therapy includes chemotherapy.     

Immobilization devices for intensity-modulated radiation therapy (IMRT).

Three-dimensional conformal radiation therapy (3DCRT) and intensity-modulated radiation therapy (IMRT) plans show radiation dose distribution that is highly conformal to the target volume. The successful clinical implementation of these radiotherapy modalities requires precise positioning of the target to avoid a geographical miss. Effective reduction in target positional inaccuracies can be achieved with the proper use of immobilization devices. This paper reviews some of the immobilization devices that have been used and/or have the potential of being used for IMRT. The immobilization devices being reviewed include stereotactic frame, Talon system, thermoplastic molds, Alpha Cradles, and Vac-Lok system. The implementation of these devices at various anatomical sites is discussed.     

Radiological and clinical outcome of selective thoracic fusion for patients with Lenke 1C and 2C adolescent idiopathic scoliosis with a minimum follow-up of 2 years

Background Context

In Lenke 1C and 2C curves, the choice between selective thoracic fusion (STF) versus non-selective thoracic fusion as the optimal surgical treatment is controversial.

Metastatic Melanoma to the Colon,Rectum, and Anus: A 50-Year Experience

Background

Melanoma metastatic to the large bowel (colon, rectum, and anus) is rarely diagnosed, with more than 95% of large bowel metastases identified post-mortem. The incidence, natural history, and survival rates of patients with large bowel melanoma metastases are poorly documented in the literature.

Objective

This study aimed to identify the incidence, clinical characteristics, and survival of patients with large bowel melanoma metastases.

Methods

A review was undertaken of all patients with melanoma treated over a 50-year period (1964–2014) at a tertiary referral center. Cases selected for study were those diagnosed with melanoma metastases in the colon, rectum, and anus. Primary colorectal and anal melanomas were excluded. Data were retrieved relating to patient demographics, clinical features, and survival.

Results

Of 38,279 patients with primary melanoma, 106 patients (0.3%, mean age 51.0 years [standard deviation 16.3], 64 males) developed large bowel metastases. The median interval between diagnosis of primary melanoma and large bowel metastasis was 62.8 months (range 1–476). The most common symptom was rectal bleeding (29.2%), and the large bowel was the sole site of metastasis in 47.2% of patients. Median survival from diagnosis of large bowel metastasis was 31.7 months (range 1–315), and overall survival at 1, 2, and 5 years was 68.1, 45.9, and 26.5%, respectively.

Conclusion

Our study provides insights into melanoma metastatic to the colon, rectum, and anus, which had an incidence of 0.3%. There are potentially long intervals between diagnosis of primary melanoma and large bowel metastasis. The most common symptom was rectal bleeding, although some patients were asymptomatic.

     

1 Versus 2-cm Excision Margins for pT2-pT4 Primary Cutaneous Melanoma (MelMarT): A Feasibility Study

Background

There is a lack of consensus regarding optimal surgical excision margins for primary cutaneous melanoma?>?1 mm in Breslow thickness (BT). A narrower surgical margin is expected to be associated with lower morbidity, improved quality of life (QoL), and reduced cost. We report the results of a pilot international study (MelMarT) comparing a 1 versus 2-cm surgical margin for patients with primary melanoma?>?1 mm in BT.

Methods

This phase III, multicentre trial [NCT02385214] administered by the Australia & New Zealand Medical Trials Group (ANZMTG 03.12) randomised patients with a primary cutaneous melanoma?>?1 mm in BT to a 1 versus 2-cm wide excision margin to be performed with sentinel lymph node biopsy. Surgical closure technique was at the discretion of the treating surgeon. Patients’ QoL was measured (FACT-M questionnaire) at baseline, 3, 6, and 12 months after randomisation.

Results

Between January 2015 and June 2016, 400 patients were randomised from 17 centres in 5 countries. A total of 377 patients were available for analysis. Primary melanomas were located on the trunk (56.9%), extremities (35.6%), and head and neck (7.4%). More patients in the 2-cm margin group required reconstruction (34.9 vs. 13.6%; p?<?0.0001). There was an increased wound necrosis rate in the 2-cm arm (0.5 vs. 3.6%; p?=?0.036). After 12 months’ follow-up, no differences were noted in QoL between groups.

Discussion

This pilot study demonstrates the feasibility of a large international RCT to provide a definitive answer to the optimal excision margin for patients with intermediate- to high-risk primary cutaneous melanoma.

     

异硫氰酸荧光素标记动态观察天花粉蛋白对黑色素瘤B16细胞的损伤

目的:应用异硫氰酸荧光素标记天花粉蛋白,在激光共聚焦显微镜下直接观察天花粉蛋白进入黑色素瘤B16细胞的动态过程并分析其对黑色瘤B16细胞的损伤作用。方法:实验于2003-08/2004-08在南通大学神经再生重点实验室完成。将常规传代培养的黑色素瘤B16细胞用胰酶消化,以5×109个/L的浓度种植于24孔培养板。将天花粉蛋白、异硫氰酸荧光素-天花粉蛋白、异硫氰酸荧光素-牛血清白蛋白分别加入培养细胞中,终浓度为50mg/L,同时加入等量生理盐水作为正常对照组,每组再分别设3,6,12h不同孵育时间组。异硫氰酸荧光素标记天花粉蛋白后,利用激光共聚焦显微镜观察异硫氰酸荧光素-天花粉蛋白进入细胞的过程及其荧光强度,CCK-8细胞毒性实验评估各组细胞存活率、并用单细胞凝胶电泳及hoechst33258染核观察天花粉蛋白对黑色素瘤B16细胞致DNA损伤作用。结果:①终浓度50mg/L的异硫氰酸荧光素-天花粉蛋白孵育3h时已经进入黑色素瘤细胞,6h时进入细胞量达到最高,12h时已轻度下降,各时间点比较差异有统计学意义(P<0.01)。异硫氰酸荧光素-天花粉蛋白组与异硫氰酸荧光素-牛血清白蛋白组荧光强度差异有显著性(P<0.01)。②终浓度50mg/L异硫氰酸荧光素-天花粉蛋白、天花粉蛋白孵育黑色素瘤细胞3,6h后利用单细胞电泳和Hoechst33258染色未观察到核形态的变化;但孵育6h后CCK-8细胞毒性实验显示活细胞数量明显下降;孵育12h后出现DNA损伤的特征性彗星尾现象,并观察到明显的核浓缩和边集现象,出现特征性凋亡小体。结论:孵育6h时天花粉蛋白进入细胞量最多,但并没有明显的细胞DNA损伤的作用,而孵育12h时产生明显的细胞毒作用和凋亡的发生。     

Genome-wide association studies in Asians confirm the involvement of ATOH7 and TGFBR3, and further identify CARD10 as a novel locus influencing optic disc area

Damage to the optic nerve (e.g. from glaucoma) has an adverse and often irreversible impact on vision. Earlier studies have suggested that the size of the optic nerve head could be governed by hereditary factors. We conducted a genome-wide association study (GWAS) on 4445 Singaporean individuals (n = 2132 of Indian and n = 2313 of Malay ancestry, respectively), with replication in Rotterdam, the Netherlands (n = 9326 individuals of Caucasian ancestry) using the most widely reported parameter for optic disc traits, the optic disc area. We identified a novel locus on chromosome 22q13.1, CARD10, which strongly associates with optic disc area in both Singaporean cohorts as well as in the Rotterdam Study (RS; rs9607469, per-allele change in optic disc area = 0.051 mm(2); P(meta) = 2.73×10(-12)) and confirmed the association between CDC7/TGFBR3 (lead single nucleotide polymorphism (SNP) rs1192415, P(meta) = 7.57×10(-17)) and ATOH7 (lead SNP rs7916697, P(meta) = 2.00 × 10(-15)) and optic disc area in Asians. This is the first Asian-based GWAS on optic disc area, identifying a novel locus for the optic disc area, but also confirming the results found in Caucasian persons suggesting that there are general genetic determinants applicable to the size of the optic disc across different ethnicities.     

Meeting regulatory requirements by the use of cell phone text message notification with autoescalation and loop closure for reporting of critical laboratory results

Critical laboratory results require timely and accurate transmission to the appropriate caregiver to provide intervention to prevent an adverse outcome. We report the use of text messages to notify critical laboratory results in a large teaching hospital to manage the documentation and audit requirements of critical result reporting by regulatory agencies. The text messaging system (critical reportable result health care messaging system [CRR-HMS]) allows a receiver to acknowledge or reject a critical result by short message service reply. Failure to obtain a confirmatory receipt within 10 minutes produces an automated escalation to an alternative physician according to a roster. The median time required for physician response decreased from 7.3 minutes to 2 minutes after implementation of the CRR-HMS. The CRR-HMS is a clinically useful tool to rapidly communicate critical results to targeted physicians to facilitate rapid and timely intervention. This feature seems to be an important laboratory process mediator, and recent Joint Commission reviews have placed this as a requirement.