Lymph node retrieval rates in melanoma: a quality assessment parameter.

INTRODUCTION: Regional lymph node dissection (rlnd) for melanoma with nodal metastasis is a specialized procedure that is associated with improved disease-specific survival in selected patients. Furthermore, there is evidence that a higher lymph node retrieval rate (lnrr) is associated with improved local control. Currently, no consensus has been reached on the definition of an adequate lnrr. A minimum lnrr has been proposed as a quality assessment parameter that has to be validated. METHODS: We conducted a retrospective cohort analysis at the Princess Margaret Cancer Centre (University Health Network, Toronto, ON). The lnrrs for all patients who underwent rlnd for malignant cutaneous melanoma during 2000-2010 were recorded. Indications for rlnd were a positive sentinel lymph node biopsy or clinical lymphadenopathy (palpable or radiologically detected). RESULTS: Of the 207 identified rlnds, 146 (70.5%) were subsequent to a positive sentinel lymph node biopsy, and 61 (29.5%) were performed for clinical lymphadenopathy. The median lnrr was 24 nodes (range: 9-47 nodes; 10th percentile: 14 nodes) for axillary rlnd, 12 nodes (range: 5-30 nodes; 10th percentile: 8 nodes) for inguinal rlnd, and 16 nodes (range: 10-21 nodes; 10th percentile: 11 nodes) for ilioinguinal rlnd. The results were similar when comparing patients with positive sentinel lymph nodes and those with clinical lymphadenopathy, and the same surgical techniques were used in both groups. CONCLUSIONS: The lnrrs at our institution are similar to rates reported at other tertiary-care melanoma centres. A minimum acceptable lnrr can be considered a quality assessment parameter in the surgical management of melanoma with nodal metastasis.

An Ontario Health (Cancer Care Ontario) Clinical Practice Guideline: Surveillance Strategies in Patients with Stage I, II, III or Resectable IV Melanoma Who Were Treated with Curative Intent.

AIMS: To make recommendations on managing the surveillance of patients with stage I, II, III or resectable IV melanoma who are clinically free of disease following treatment with curative intent. MATERIALS AND METHODS: This guideline was developed by Ontario Health's (Cancer Care Ontario's) Program in Evidence-Based Care and the Melanoma Disease Site Group (including seven medical oncologists, four surgical oncologists, three dermatologists, one radiation oncologist and one patient representative). The MEDLINE, EMBASE, Cochrane Library, PROSPERO databases and the main relevant guideline websites were searched. Internal and external reviews were conducted, with final approval by the Program in Evidence-Based Care and the Melanoma Disease Site Group. The Grading of Recommendations, Assessment, Development and Evaluation approach was followed, and the Modified Delphi method was used. RESULTS: Based on the current evidence (eight eligible original study papers and four relevant guidelines) and the clinical opinions of the authors of this guideline, the initial recommendations were made. To reach 75% agreement for each recommendation, the Melanoma Disease Site Group (16 members) voted twice and one recommendation was voted on three times. After a comprehensive internal and external review process (including national and international reviewers), 12 recommendations, three weak recommendations and six qualified statements were ultimately made. CONCLUSIONS: After a systematic review, a comprehensive internal and external review process and a consensus process, the current guideline has been created. The guideline authors believe that this guideline will help clinicians, patients and policymakers make well-informed healthcare decisions that will guide them in clinical melanoma surveillance and ultimately assist in improving patient outcomes.

Primary excision margins, sentinel lymph node biopsy, and completion lymph node dissection in cutaneous melanoma: a clinical practice guideline.

Background: For patients who are diagnosed with early-stage cutaneous melanoma, the principal therapy is wide surgical excision of the primary tumour and assessment of lymph nodes. The purpose of the present guideline was to update the 2010 Cancer Care Ontario guideline on wide local excision margins and sentinel lymph node biopsy (slnb), including treatment of the positive sentinel node, for melanomas of the trunk, extremities, and head and neck. Methods: Using Ovid, the medline and embase electronic databases were systematically searched for systematic reviews and primary literature evaluating narrow compared with wide excision margins and the use of slnb for melanoma of the truck and extremities and of the head and neck. Search timelines ran from 2010 through week 25 of 2017. Results: Four systematic reviews were chosen for inclusion in the evidence base. Where systematic reviews were available, the search of the primary literature was conducted starting from the end date of the search in the reviews. Where systematic reviews were absent, the search for primary literature ran from 2010 forward. Of 1213 primary studies identified, 8 met the inclusion criteria. Two randomized controlled trials were used to inform the recommendation on completion lymph node dissection.Key updated recommendations include:■ Wide local excision margins should be 2 cm for melanomas of the trunk, extremities, and head and neck that exceed 2 mm in depth.■ slnb should be offered to patients with melanomas of the trunk, extremities, and head and neck that exceed 0.8 mm in depth.■ Patients with sentinel node metastasis should be considered for nodal observation with ultrasonography rather than for completion lymph node dissection. Conclusions: Recommendations for primary excision margins, sentinel lymph node biopsy, and completion lymph node dissection in patients with cutaneous melanoma have been updated based on the current literature.

Discussion of death and dying in surgical textbooks.

BACKGROUND: Quality end-of-life care is an increasing concern for the public and the medical profession. Surgical textbooks could serve as an important educational and reference resource to improve this care. METHODS: Four general surgical textbooks were scored for helpful information on death and dying for eight surgical diseases. For each disease, nine content domains related to care of the dying patient were evaluated. Three texts included a chapter on cancer that was evaluated separately. RESULTS: Disease epidemiology, prognosis/prevention, progression, and medical interventions were generally well discussed in all textbooks. However, little helpful information was provided with regards to breaking bad news/advanced care planning, mode of death, treatment decision-making, effect on family/surgeon, and symptom management. Cancer chapters also addressed only a few of these concerns. CONCLUSION: Death and the dying patient are sufficiently frequent in surgical practice that it would be appropriate to increase the amount of information provided.

Palliative general surgical procedures.

Two types of procedure may be indicated in incurable patients. The first is palliative, in which the goal of intervention is relief of symptoms. The second type is supportive, where the procedure is a technical intervention done as part of a multidisciplinary treatment plan. The most minimally invasive but effective procedure is chosen. Procedures are categorized by the type of symptom the procedure is intended to relieve. This article emphasizes the principles involved in patient selection and outcome assessment in order to identify areas where more research is needed.

Primary excision margins and sentinel lymph node biopsy in clinically node-negative melanoma of the trunk or extremities.

AIMS: For patients with early-stage melanoma, uncertainty exists regarding optimal surgical excision margins of the primary tumour and surgical management of the clinically node-negative lymph node basin. We describe the process of creating a provincial guideline for the treatment of node-negative melanoma of the trunk and extremities. The following research questions were addressed: What are the optimal excision margins for clinically node-negative cutaneous melanoma and should these patients undergo sentinel lymph node biopsy? MATERIALS AND METHODS: Outcomes were local and regional recurrence, overall and disease-free survival, and morbidity. The MEDLINE and EMBASE databases, National Guideline Clearinghouse, CMA Infobase and websites of guideline development organisations were systematically searched. Using the AGREE instrument, relevant guidelines were assessed and an updated literature search completed. A systematic review and practice guideline was written, reviewed and approved by the Melanoma Site Group and the Program in Evidence-based Care Report Approval Panel. External review by three melanoma experts was completed, as was an online consultation with healthcare professionals who were intended users of the guideline. RESULTS: One guideline was selected for adoption: the Australian Cancer Network National Health and Medical Research Council and the New Zealand Guidelines group 2008 melanoma guideline. An updated literature search was undertaken to include relevant studies published since the adopted guideline was completed. CONCLUSIONS: Excision margins range from 5mm to 2cm depending on the melanoma depth. Patients with a melanoma greater than 1.0mm in thickness should be given the opportunity to discuss sentinel lymph node biopsy to provide staging and prognostic information.

Calcification in colorectal hepatic metastases correlates with longer survival.

BACKGROUND: Calcification occurs in 12-27% of hepatic colorectal metastases, but its clinical significance and its influence on prognosis are unknown. METHODS: All patients diagnosed with colorectal liver metastases at the Ottawa Regional Cancer Center in 1991 (n = 97), as well as those enrolled in chemotherapy trials in 1990-1992 (n = 51), were entered into a retrospective cohort study. Thirty-six patients were excluded due to inadequate follow-up. In the remaining 112, abdominal CT scans and/or ultrasound examinations were used to determine the presence of calcification. Charts were reviewed for variables, including primary tumour pathology, amount of liver involvement by tumour (< 25%, 25-50%, > 50%), and the chemotherapeutic agents received, and were subjected to multivariate and regression analysis. End point was survival in months or to December 1993 (median follow up 24 months). RESULTS: Patients with calcification (n = 31) (28%) were compared to those who did not have calcifications (n = 81). The groups were comparable with respect to sex, age, time to calcification, time to metastases, and treatment type. Calcification occurred independent of the degree of tumour differentiation, the presence of mucinous adenocarcinoma, or the hepatic tumour burden. Nine patients with calcified metastases (30%) had calcification at presentation. Biopsies showed calcification next to viable tumour cells with an absence of an inflammatory reaction. Survival was improved with better primary tumour differentiation and less tumour burden. The presence of calcification had a statistically highly significant improvement in survival (P < 10(-6), relative risk = .19) independent of other variables. CONCLUSIONS: The presence of calcification within a colorectal liver metastasis appears to imply a significantly better prognosis.

Effects of endotoxin challenge on hepatic amino acid transport during cancer.

BACKGROUND: The hepatic uptake of amino acids is increased in both sepsis and cancer, and this response appears to be both global and essential in the catabolic host. Because immunocompromised cancer patients are susceptible to episodes of gram-negative sepsis, we examined the capacity of hepatocytes from normal and tumor-influenced livers to respond to the additional challenge of endotoxemia via increases in the Na+-dependent uptake of glutamine and zwitterionic amino acids by System N and System A, respectively. MATERIALS AND METHODS: Fischer 344 rats were implanted with methylcholanthrene-induced fibrosarcomas. Control rats were sham-operated and pair-fed. Animal pairs (tumor burden = 8-32% carcass weight) were injected intraperitoneally with either Escherichia coli endotoxin (10 mg/kg) or PBS, and after 4 h, hepatocytes were isolated from the livers of the animals via collagenase perfusion and placed in primary culture. Three hours later, amino acid transport rates were measured using radiolabeled glutamine for System N and alpha-methylaminoisobutyric acid (MeAIB), a nonmetabolizable substrate specific for System A. RESULTS: Cancer-independent of tumor size-and endotoxin each elicited similar 1.5- to 2-fold inductions of System N activity. When combined, their effects were additive rather than synergistic. In contrast, endotoxin induced an insignificant increase in System A activity, whereas cancer stimulated this carrier 2-fold in either the absence or the presence of endotoxin. CONCLUSIONS: The primary glutamine and alanine carriers in hepatocytes are differentially influenced during catabolic states, and the tumor-influenced liver is competent to further increase glutamine uptake in response to additional catabolic insults.

Ontario familial colon cancer registry: methods and first-year response rates.

The Ontario Familial Colon Cancer Registry (OFCCR) is a novel registry that collects family history information, epidemiologic data, blood samples and tumour specimens from a population-based sample of colorectal cancer patients and their families. Families are classified as either high familial risk, intermediate familial/other risk or low (sporadic) risk for colorectal cancer. Obtaining high response rates in genetic family studies is especially challenging because of both the time commitment required and issues of confidentiality. The first-year response rate was 61%, resulting in 1,395 participating probands. In an attempt to assess potential response bias, we compared participants with non-participants. The age and sex of participants did not differ from non-participating probands; however, cases in rural areas were somewhat more likely to participate. To date, 57% of 1,587 relatives participated; females were more likely to participate, and relatives of low familial risk were least likely to participate. The OFCCR is an excellent resource that will facilitate the study of genetic and environmental factors associated with colorectal cancer.

Tumor-influenced amino acid transport activities in zonal-enriched hepatocyte populations.

Cancer influences hepatic amino acid metabolism in the host. To further investigate this relationship, the effects of an implanted fibrosarcoma on specific amino acid transport activities were measured in periportal (PP)- and perivenous (PV)-enriched rat hepatocyte populations. Na(+)-dependent glutamate transport rates were eightfold higher in PV than in PP preparations but were relatively unaffected during tumor growth. System N-mediated glutamine uptake was 75% higher in PV than in PP preparations and was stimulated up to twofold in both regions by tumor burdens of 9 +/- 4% of carcass weight compared with hepatocytes from pair-fed control animals. Excessive tumor burdens (26 +/- 7%) resulted in hypophagia, loss of PV-enriched system N activities, and reduced transporter stimulation. Conversely, saturable arginine uptake was enhanced fourfold in PP preparations and was induced twofold only after excessive tumor burden. These data suggest that hepatic amino acid transporters are differentially influenced by cancer in a spatial and temporal manner, and they represent the first report of reciprocal zonal enrichment of system N and saturable arginine uptake in the mammalian liver.