Staging and surgical approaches in gastric cancer: a clinical practice guideline.

BACKGROUND: Resection is the cornerstone of cure for gastric adenocarcinoma; however, several aspects of surgical intervention remain controversial or are suboptimally applied at a population level, including staging, extent of lymphadenectomy (lnd), minimum number of lymph nodes that have to be assessed, gross resection margins, use of minimally invasive surgery, and relationship of surgical volumes with patient outcomes and resection in stage iv gastric cancer. METHODS: Literature searches were conducted in databases including medline (up to 10 June 2016), embase (up to week 24 of 2016), the Cochrane Library and various other practice guideline sites and guideline developer Web sites. A practice guideline was developed. RESULTS: One guideline, seven systematic reviews, and forty-eight primary studies were included in the evidence base for this guidance document. Seven recommendations are presented. CONCLUSIONS: All patients should be discussed at a multidisciplinary team meeting, and computed tomography (ct) imaging of chest and abdomen should always be performed when staging patients. Diagnostic laparoscopy is useful in the determination of M1 disease not visible on ct images. A D2 lnd is preferred for curative-intent resection of gastric cancer. At least 16 lymph nodes should be assessed for adequate staging of curative-resected gastric cancer. Gastric cancer surgery should aim to achieve an R0 resection margin. In the metastatic setting, surgery should be considered only for palliation of symptoms. Patients should be referred to higher-volume centres and those that have adequate support to manage potential complications. Laparoscopic resections should be performed to the same standards as those for open resections, by surgeons who are experienced in both advanced laparoscopic surgery and gastric cancer management.

Adjuvant systemic chemotherapy for stages II and III colon cancer after complete resection: a clinical practice guideline.

BACKGROUND: Updated practice guidelines on adjuvant chemotherapy for completely resected colon cancer are lacking. In 2008, Cancer Care Ontario's Program in Evidence-Based Care developed a guideline on adjuvant therapy for stages ii and iii colon cancer. With newer regimens being assessed in this patient population and older agents being either abandoned because of non-effectiveness or replaced by agents that are more efficacious, a full update of the original guideline was undertaken. METHODS: Literature searches (January 1987 to August 2015) of medline, embase, and the Cochrane Library were conducted; in addition, abstracts from the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress were reviewed (the latter for January 2007 to August 2015). A practice guideline was drafted that was then scrutinized by internal and external reviewers whose comments were incorporated into the final guideline. RESULTS: Twenty-six unique reports of eighteen randomized controlled trials and thirteen unique reports of twelve meta-analyses or pooled analyses were included in the evidence base. The 5 recommendations developed included 3 for stage ii colon cancer and 2 for stage iii colon cancer. CONCLUSIONS: Patients with completely resected stage iii colon cancer should be offered adjuvant 5-fluorouracil (5fu)-based chemotherapy with or without oxaliplatin (based on definitive data for improvements in survival and disease-free survival). Patients with resected stage ii colon cancer without "high-risk" features should not receive adjuvant chemotherapy. For patients with "high-risk" features, 5fu-based chemotherapy with or without oxaliplatin should be offered, although no clinical trials have been conducted to conclusively demonstrate the same benefits seen in stage iii colon cancer.

Continuous versus intermittent chemotherapy strategies in metastatic colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: An important goal of intermittent strategies of delivering systemic treatment as first-line treatment of metastatic colorectal cancer (mCRC) is to maintain efficacy while improving patients' quality of life (QoL). Given the varying impact on efficacy demonstrated in individual randomized, controlled trials (RCTs), a systematic review and meta-analysis of RCTs of these intermittent strategies was carried out. DESIGN: Relevant databases were systematically searched for the period 2000-2014. RCTs that compared a continuous versus intermittent strategy of delivering systemic treatment were identified by a systematic review. Overall survival (OS) hazard ratios (HRs) were extracted from the most recently reported trial results. The results of identified trials were clinically homogeneous so the data were pooled using Review Manager software (RevMan 5.1). RESULTS: Eleven RCTs were identified (n = 4 854). For the eight (n = 4508) trials with available HRs, the treatment patients received after induction was: none (five trials, n = 3036), fluoropyrimidine (one trial, n = 620), and biologic (two trials, n = 852). There were no statistically significant survival differences observed between the continuous and intermittent chemotherapy strategies. There was no statistically significant difference observed between continuous and intermittent strategies [HR = 1.03, 95% confidence interval (CI) 0.96-1.10, P = 0.38)]. Subgroup analyses demonstrated results were generally robust across induction and maintenance regimens. One subgroup analysis of the three trials (CAIRO3, OPTIMOX2, COIN, n = 2403) with combination treatment induction and no maintenance until progression revealed a statistically, but nonclinically significant benefit for continuous treatment (HR = 1.10, 95% CI 1.00-1.20, P = 0.049). QoL life was either the same in both arms in two trials (n = 912) or improved in the intermittent strategy arm in one trial (n = 1630). CONCLUSION: Intermittent strategies of delivering systemic treatment of mCRC do not result in a clinically significant reduction in OS compared with a continuous strategy of delivery, and should be part of an informed discussion of treatment options with patients with mCRC.

Computerized prescriber order entry in the outpatient oncology setting: from evidence to meaningful use.

BACKGROUND: Chemotherapy is an effective treatment in the fight against many cancers. Medication errors in oncology can be particularly serious given the narrow therapeutic window of antineoplastic drugs and their high toxicities. Computerized prescriber order entry (cpoe) has consistently been shown to reduce medication errors and adverse drug events in various settings, but its use in the oncology setting has not been well established. To gain a better understanding of the meaningful use of cpoe systems in the outpatient chemotherapy setting, we undertook a systematic review of systemic therapy cpoe. METHODS: A province-wide expert panel consisting of clinical experts, health information professionals, and specialists in human factors design provided guidance in the development of the research questions, search terms, databases, and inclusion criteria. The systematic review was undertaken by a core team consisting of a medical oncologist, nurse, pharmacist, and methodologist. The medline, embase, cinahl, and compendex databases were searched for relevant evidence. RESULTS: The database searches resulted in 5642 hits, of which 9 met the inclusion criteria and were retained. In the oncology setting, cpoe systems generally reduce chemotherapy medication errors; however, specific types of errors increase with the use of cpoe. These systems affect practice both positively and negatively with respect to time, workload, and productivity. CONCLUSIONS: Despite the paucity of oncology-specific research, cpoe should be used in outpatient chemotherapy delivery to reduce chemotherapy-related medication errors. Adoption by clinicians will be enhanced by cpoe processes that complement current practice and workflow processes.

Strategies of sequential therapies in unresectable metastatic colorectal cancer: a meta-analysis.

BACKGROUND: Before the emergence of first-line combination chemotherapy, the standard of care for unresectable metastatic colorectal cancer (mcrc) was first-line monotherapy with modulated 5-fluorouracil. Several large phase iii randomized controlled trials, now completed, have assessed whether a planned sequential chemotherapy strategy-beginning with fluoropyrimidine monotherapy until treatment failure, followed by another regimen (either monotherapy or combination chemotherapy) until treatment failure-could result in the same survival benefit produced with an upfront combination chemotherapy strategy, but with less toxicity for patients. METHODS: The medline and embase databases, and abstracts from meetings of the American Society for Clinical Oncology and the European Society for Medical Oncology, were searched for reports comparing a sequential strategy of chemotherapy with an upfront combination chemotherapy in adult patients with mcrc. Publications that reported efficacy or toxicity data (or both) were included. RESULTS: The five eligible trials that were identified included 4532 patients. A meta-analysis of those trials demonstrates a statistically significant survival advantage for combination chemotherapy (hazard ratio: 0.92; 95% confidence interval: 0.86 to 0.99). However, the median survival advantage (3-6 weeks in most trials) is small and of questionable clinical significance. Three trials reported first-line toxicities. Upfront combination chemotherapy results in significantly more neutropenia, febrile neutropenia, thrombocytopenia, diarrhea, nausea, vomiting, and sensory neuropathy. Sequential chemotherapy results in significantly more hand-foot syndrome. CONCLUSIONS: Given the small survival advantage associated with upfront combination chemotherapy, planned sequential chemotherapy and upfront combination chemotherapy can both be considered treatment strategies. Treatment should be chosen on an individual basis considering patient and tumour characteristics, toxicity of each strategy, and patient preference.

Regional Therapies for Colorectal Liver Metastases: Systematic Review and Clinical Practice Guideline.

BACKGROUND: Resection is the foundation for cure for colorectal cancer (CRC) liver metastases; however, only 20% of patients are suitable for surgery. Those suitable would be considered for resection or local therapies before being considered for regional therapies. Noncurative treatment is usually systemic chemotherapy. For patients with liver-only or liver-predominant metastases that are unresectable, regional therapies [conventional transarterial chemoembolization (cTACE), drug-eluting bead transarterial chemoembolization (DEB-TACE), and transarterial radioembolization (TARE)] may be considered. We review the current evidence for regional therapies for CRC liver metastases. PATIENTS AND METHODS: Literature searches (January 2000 to March 2019 or January 2010 to March 2019 depending on the specific systematic review question) were conducted, including Medline, Embase, Cochrane Library, and 2018 American Society of Clinical Oncology (ASCO) abstracts. RESULTS: A total of 4100 articles were identified; 15 studies were included in the review. There were no comparative data regarding the resectable population. There was either insufficient evidence (cTACE or DEB-TACE) or evidence against (TARE) the addition of regional therapies to systemic therapy in the first line in the unresectable population. There was either no evidence (cTACE) or weak evidence (DEB-TACE or TARE) for the addition of regional therapies with or without systemic therapy in the second line or later in the unresectable population. CONCLUSION: Limited evidence supports the delivery of percutaneous regional therapies in patients with unresectable CRC liver metastases. There are strong data demonstrating positive effects of TARE within the liver, but they do not translate to a benefit in patient-important outcomes. DEB-TACE appears to offer a survival benefit in the second-line setting, although the evidence is limited by small sample size and larger trials are needed.

Nonsurgical management of advanced hepatocellular carcinoma: a clinical practice guideline.

Background: Practice guidelines based on a systematic review of the literature regarding the nonsurgical management of hepatocellular carcinoma (hcc) in North America are lacking. Resection and transplantation are the foundations for cure of hcc; however, most patients are diagnosed at an advanced stage, precluding those curative treatments. A number of local or regional therapies are used and are followed by systemic therapy for advanced or progressive disease. Other treatments are available, but their efficacy, compared with those standards, is not well known. Methods: First, systematic review questions were developed. Literature searches of the medline, embase, and Cochrane library databases (January 2000 to July 2018 or January 2005 to July 2018 depending on the question) were conducted; in addition, abstracts from the 2018 annual meeting of the American Society of Clinical Oncology were reviewed. A practice guideline was drafted that was then scrutinized by internal and external reviewers. Results: Seventy-seven studies were included in the guideline: no guidelines, two systematic reviews, and seventy-five primary studies published in full (including one pooled analysis). Five recommendations were developed. Conclusions: There is no evidence for or against the use of local or regional interventions other than transarterial chemoembolization for the treatment of intermediate- or advanced-stage hcc. Furthermore, there is no evidence to support the addition of sorafenib to any local or regional therapy. Sorafenib or lenvatinib are recommended for first-line systemic treatment of intermediate-stage hcc. Regorafenib or cabozantinib provide survival benefits when given as second-line treatment. Antiviral treatment is recommended in individuals with advanced hcc who are positive for the hepatitis B surface antigen.

Adjuvant Chemotherapy for Stage II and III Colon Cancer Following Complete Resection: A Cancer Care Ontario Systematic Review.

The objective of this systematic review was to provide current evidence regarding the use of adjuvant systemic chemotherapy for stage II and III colon cancer following curative intent surgery. MEDLINE and EMBASE databases and proceedings of American Society for Clinical Oncology and European Society of Medical Oncology/European Cancer Congress were searched through to August 2015. Systematic reviews (with or without meta-analyses) and randomised controlled trials were included. Patients with completely resected stage III colon cancer have an overall survival benefit from adjuvant chemotherapy. Combination chemotherapy (5-fluorouracil/leucovorin/oxaliplatin or capecitabine/oxaliplatin) provides a larger benefit than monotherapy but with additional toxicity. For stage II colon cancer, a clear overall survival benefit has not been shown. However, based on the subgroup analysis available, patients with high-risk stage II disease may benefit from adjuvant chemotherapy. Patients younger than 70 years of age may derive greater disease-free survival and overall survival benefit from adjuvant chemotherapy (in combination with oxaliplatin) compared with those older than 70 years. Stage II patients with microsatellite instability may have an overall survival detriment if given adjuvant chemotherapy.

Phase I study of a decision aid for patients with locally advanced non-small-cell lung cancer.

PURPOSE: Many patients with locally advanced non-small-cell lung cancer (LA-NSCLC) are eligible for combined-modality therapy (CMT; chemotherapy and radiotherapy). Although CMT offers slightly higher chances of survival than radiotherapy alone (RT), it also carries a higher probability of toxicity, raising the possibility that some patients may prefer to decline CMT. We report a pilot study of a decision aid designed for patients in this setting. PATIENTS AND METHODS: The aid included a structured description of the treatment options and trade-off exercises designed to help clarify the patient's values for the relevant outcomes by determining the patient's survival advantage threshold (SAT; the increase in survival conferred by CMT over RT that the patient deemed necessary for choosing CMT). Additional outcome measures included each patient's strength of treatment preference, decisional conflict, objective understanding of survival information, and decisional role preference. RESULTS: Twenty-seven patients met the eligibility criteria for the study. Of these, seven declined the decision aid because they had a clear treatment preference. The remaining 20 participants completed the decision aid; 18 chose CMT, and two chose RT. All 20 patients wished to participate in the decision to some extent. All patients reported that using the decision support was useful to them and recommended its use for others. No patient or physician reported that the aid interfered with the physician-patient relationship. Patients' 3-year SATs and median SATs were each strongly correlated with their strengths of treatment preference (rho = 0.83, P <.001 and rho = 0.67, P =.02, respectively). For all but one patient, either their 3-year or median survival threshold was consistent with their final treatment choice. Ten patients reported a stronger treatment preference after using the decision aid. CONCLUSION: We conclude that implementing the decision-aid for patients with LA-NSCLC is feasible, that it demonstrates convergent validity, and that it is favorably evaluated by patients and their physicians. The aid seems to help patients understand the benefits and risks of treatment and to choose the treatment that is most consistent with their values. Further evaluation of the aid is warranted.

Traumatic renal artery thrombosis.

Traumatic bilateral renal artery thrombosis is a rare injury that may be under-diagnosed. The clinical hallmarks include epigastric or flank pain and proteinuria, or hematuria following blunt trauma to the back or abdomen. Traditional practice suggests that revascularization should not be attempted more than 20 hours after injury. A patient is described in whom the retroperitoneum was explored 48 hours after injury and was found to have bilateral renal artery thrombosis. Although no repair was attempted, renal function spontaneously improved over several weeks. The clinical course of this patient suggests that revascularization should be considered even if the diagnosis is made more than 20 hours after injury.

Left ventricular dyskinesia in infarction and angina.

In 29 patients, the site and extent of coronary artery obstruction were related to the position and area of abnormally contracting segments of the left ventricle, both in patients with a history of angina without myocardial infarction (group I) and in patients with prior documented myocardial infarction (group II). The degree of coronary artery obstructive disease was estimated in the standard manner and also by a coronary artery index which considered not only the degree of obstruction but also the total length of the obstructed segment. A kinetic or dyskinetic segments were present in 22 of the 29 patients. An abnormally contracting segment was present in 12 or 18 patients without prior myocardial infarction in comparison with 10 of the 11 patients with prior infarction. Complete obstruction of a coronary vessel and resultant dyskinesia were more frequent in the right coronary artery than in either the left anterior descending or the circumflex artery. There was a significant correlation between total per cent of vessel obstruction and degree of ventricular asynergy in both groups; consideration of length of obstructed segment did not improve this correlation.

Effect of direct revascularization surgery on coronary collateral circulation in man.

In 63 consecutive patients with significant coronary artery disease (more than 75 percent stenosis), the effects of direct myocardial revascularization on coronary collateral channels were studied 6 to 29 days (mean 13.4 days) after operation. Collateral vessels were identified preoperatively and their angiographic regression or reappearance after operation was noted. In 15 patients (23 percent), there was no evidence of collateral flow before or after operation. The remaining 48 patients had 186 collateral channels preoperatively. Postoperatively, 84 (45 percent) of these collateral vessels were no longer apparent, 75 (40 percent) were unchanged and 27 (15 percent) were identical with the preoperative vessels but the pattern of blood flow was reversed. The findings suggest that in the presence of established collateral channels, direct revascularization acutely alters existing flow and pressure gradients in a complex manner. Collateral channels disappear or remain unchanged when a gradient is decreased or maintained; collateral flow is reversed when a gradient is increased. These data may permit (1) objective preoperative estimation of distal vessel runoff in vessels with collateral channels, and (2) evaluation of the completeness of revascularization in assessing long-term postoperative results.

Time course of response to pulse methylprednisolone therapy in renal transplant recipients with acute allograft rejection.

All rejection episodes that occurred from 1990 to 1995 treated by the University of Colorado renal transplant service were evaluated through a review of patient charts. Seventy-one episodes of rejection were treated initially with pulse steroids consisting of pulse methylprednisolone, 500 mg/d for 3 days, with sufficient follow-up to determine whether the patient would respond to this treatment. There was no difference between responders and nonresponders to methylprednisolone treatment with respect to serum creatinine level at time of diagnosis, age of allograft, nadir serum creatinine level, or presence of oliguria. The time course of change in serum creatinine levels (in milligrams per deciliter) in responders and nonresponders was similar until day 5, at which time significant differences could be seen (P < 0.01). In the 34 patients treated with OKT3 (muromonab-CD3), statistically significant differences between responders and nonresponders were only seen at day 14, but the small number of nonresponders (n = 4) makes this analysis inconclusive. Based on these data, it appears one cannot truly evaluate whether a patient will respond to three daily pulses of methylprednisolone until at least 3 days have passed since completion of therapy.

Nephritic urinary sediment in embolic renal infarction.

Emboli to the renal arteries occurs most often in patients with underlying cardiac disease. Hematuria is a common feature of renal infarction, but the finding of erythrocyte casts in cases of renal infarction has not been commonly reported. We report a case of renal artery embolization in a patient who had transient nephritic urine sediment, and review the significance of this finding.

Cancer patients' attitudes toward treatment options for advanced non-small cell lung cancer: implications for patient education and decision support.

The purpose of this study was to determine how people weigh both median survival time and 1-year survival probability when considering a choice between palliative Cisplatin-based chemotherapy with best supportive care (C+BSC) versus best supportive care alone (BSC) as treatment for advanced non-small cell lung cancer (NSCLC). Sixty people, previously treated for cancer, were interviewed as surrogate patients making a treatment decision. The interview included a structured description of the treatment options, and trade-off exercises used to clarify the participants' attitudes pertaining to the survival probabilities associated with each treatment.Participants' attitudes ranged from choosing the more toxic treatment if it offered no survival advantage to declining C+BSC no matter how large its advantage. Fifty-seven percent of participants would choose chemotherapy if the 1-year survival were 10% higher with C+BSC than with BSC alone. For 44 participants (76%), both their median survival and 1-year survival thresholds for accepting C+BSC were consistent, and for two (3%), neither threshold was consistent with their stated treatment preference. For the remaining 12 (21%), one threshold was discordant, but in all cases, this threshold was less relevant to his/her decision. Participants' thresholds could not be predicted reliably on the basis of patient age, sex, education, preferred role in treatment decision making, or previous treatment with chemotherapy. All but one participant recommended the interview as a decision-support strategy for actual patients. The findings suggest that patients with advanced NSCLC should be offered more than one treatment option, and that a systematic process for educating patients and for eliciting their preferences is desirable. The process described herein has potential for use in this clinical setting.

Regional myocardial blood flow in regions of prior myocardial infarction before and after revascularization.

In 30 patients who received 102 saphenous vein bypass grafts, 91 were patent. Preoperative intracoronary injection of 99mTc-labeled albumin particles suspended in contrast revealed 81 regions of perfusion deficit which subsequently received successful revascularization. With postoperative graft injection of isotope, 48 of these regions no longer showed a perfusion deficit (59%), while 33 showed no change (41%). In these 30 patients, 16 of 17 (94%) revealed perfusion defects in regions of prior transmural myocardial infarction. Conversely, only 55 of 96 regions distal to coronary artery stenosis of greater than 50% revealed perfusion defects (57%). Thus, 99mTc-labeled microsphere studies seem to be valuable in detecting regions of prior infarction. After angiographically documented revascularization, the method continued to reveal perfusion deficits in 41% of abnormal regions noted preoperatively, even though almost half of these same specific regions showed improved postoperative regional contractility after postextrasystolic potentiation.