Report from the 17th Annual Western Canadian Gastrointestinal Cancer Consensus Conference; Edmonton, Alberta; 11-12 September 2015.

The 17th annual Western Canadian Gastrointestinal Cancer Consensus Conference (wcgccc) was held in Edmonton, Alberta, 11-12 September 2015. The wcgccc is an interactive multidisciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management of gastric cancer.

Consensus statement: the 16th Annual Western Canadian Gastrointestinal Cancer Consensus Conference; Saskatoon, Saskatchewan; September 5-6, 2014.

The 16th annual Western Canadian Gastrointestinal Cancer Consensus Conference was held in Saskatoon, Saskatchewan, September 4-5, 2014. The Consensus Conference is an interactive, multidisciplinary event attended by health care professionals from across western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) involved in the care of gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancer.

Hepatic arterial infusion pump chemotherapy in the management of colorectal liver metastases: expert consensus statement.

Despite significant improvements in systemic therapy for patients with colorectal liver metastases (crlms), response rates in the first-line setting are not optimal, and response rates in the second-line setting remain disappointing. Hepatic arterial infusion pump (haip) chemotherapy has been extensively studied in patients with crlms, but it remains infrequently used. We convened an expert panel to discuss the role of haip in the contemporary management of patients with crlm. Using a consensus process, we developed these statements: haip chemotherapy should be given in combination with systemic chemotherapy.haip chemotherapy should be offered in the context of a multidisciplinary program that includes expertise in hepatobiliary surgery, medical oncology, interventional radiology, nursing, and nuclear medicine.haip chemotherapy in combination with systemic therapy should be considered in patients with unresectable crlms who have progressed on first-line systemic treatment. In addition, haip chemotherapy is acceptable as first-line treatment in patients with unresectable colorectal liver metastases.haip chemotherapy is not recommended in the setting of extrahepatic disease outside the context of a clinical trial.haip chemotherapy in combination with systemic therapy is an option for select patients with resected colorectal liver metastases. These consensus statements provide a framework that clinicians who treat patients with crlm can use when considering treatment with haip.

Prevention and management of chemotherapy-induced diarrhea in patients with colorectal cancer: a consensus statement by the Canadian Working Group on Chemotherapy-Induced Diarrhea.

Chemotherapy-induced diarrhea (cid) is a common side effect of cancer treatment and can cause significant morbidity and mortality. Diarrhea is frequently severe enough to require a dose reduction of, a delay in, or a discontinuation of chemotherapy. Diarrhea-associated mortality has been reported to be as high as 3.5% in clinical trials of irinotecan and bolus 5-fluorouracil in colorectal cancer. The frequency of cid and its impact on patient management are frequently under-recognized in clinical practice.A Canadian working group, consisting of medical oncologists and an oncology pharmacist, was formed in 2001 to review the optimal approach to managing cid and to identify and implement new areas of research. The recommendations that follow are the result of the group's work.Acute medical management of cid includes loperamide or diphenoxylate as first-line agents. Subcutaneous octreotide is recommended for intractable grade 2 diarrhea and may be considered for grade 1 cid that does not resolve with high-dose loperamide. Hospitalization is recommended for patients with grades 3 and 4 cid; in-hospital care includes rehydration, antibiotic therapy, and octreotide.A chemotherapy dose reduction is generally advised for patients who have experienced grade 3 or 4 diarrhea in a previous chemotherapy cycle. If a dose reduction is not desired, prophylaxis with intramuscular long-acting release octreotide may be considered.The foregoing recommendations are based on expert opinion and require validation in prospective clinical trials.

Single-agent monoclonal antibody efficacy in bulky non-Hodgkin's lymphoma: results of a phase II trial of rituximab.

PURPOSE: A phase II trial was performed to evaluate the safety and efficacy of rituximab, a chimeric anti-CD20 monoclonal antibody, in patients with bulky (> 10-cm lesion) relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Thirty-one patients received intravenous infusions of rituximab 375 mg/m(2) weekly for four doses. All patients had at least one prior therapy (median, three; range, one to 13) and had progressive disease at study entry. Patients were a median of 4 years from diagnosis. RESULTS: No patient had treatment discontinued because of an adverse event. No patient developed human antichimeric antibody. The overall response rate in 28 assessable patients was 43% with a median time to progression of 8.1 months (range, 4.5 to 18.6+ months) and median duration of response of 5.9 months (range, 2.8 to 12.1+ months). The average decrease in lesion size in patients who achieved a partial response was 76%, and patients with stable disease had a decrease in average lesion size of 26%. Median serum antibody concentration was higher in responders compared with nonresponders, and a negative correlation was shown between antibody concentration and tumor bulk at baseline. CONCLUSION: Rituximab single-agent outpatient therapy is safe and shows significant clinical activity in patients with bulky relapsed or refractory low-grade or follicular B-cell NHL.

Combination immunotherapy of relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma with rituximab and interferon-alpha-2a.

Rituximab and IFN have each demonstrated single-agent activity in patients with low-grade non-Hodgkin's lymphoma (NHL). A single-arm, multicenter, Phase II trial was conducted to assess the safety and efficacy of combination therapy with rituximab and IFN-alpha-2a in 38 patients with relapsed or refractory, low-grade or follicular, B-cell NHL. IFN-alpha-2a [2.5 or 5 million units (MIU)] was administered s.c., three times weekly for 12 weeks. Starting on the fifth week of treatment, rituximab was administered by i.v. infusion (375 mg/m2) weekly for 4 doses. All 38 patients received four complete infusions of rituximab and were evaluable for efficacy, although 11 patients (29%) did not-receive all 36 injections of IFN. The mean number of IFN-alpha-2a injections was 31 doses; the mean total units received were 141 MIU (maximum, 180 MIU). The study treatment was reasonably well tolerated with no unexpected toxicities stemming from the combination therapy. No grade 4 events were reported. Frequent adverse events during the treatment period included asthenia (35 of 38 patients), chills (31 of 38), fever (30 of 38), headache (28 of 38), nausea (23 of 38), and myalgia (22 of 38). The overall response rate was 45% (17 of 38 patients); 11% had a complete response, and 34% had a partial response. The Kaplan-Meier estimates for the median response duration and the median time to progression in responders are 22.3 and 25.2 months, respectively. Further follow-up is needed to determine whether this treatment combination leads to a significantly longer time to progression than single-agent treatment with rituximab.

Relationships between anxiety sensitivity, hyperventilation, and emotional reactivity to displays of facial emotions.

Undergraduate women who scored in the top (n = 24) and bottom 15% (n = 24) on the Anxiety Sensitivity Index viewed randomly counterbalanced sets of three neutral and three dysphoric faces after having either hyperventilated or relaxed. Participants rated the amount of change they experienced in Happiness, Sadness, Fear, Anger, Surprise, Disgust, and Contempt after viewing each face. High Anxiety Sensitive (AS) women reported significantly greater changes on six of the seven emotions, even though pretreatment differences in somatically experienced anxiety were covaried out. Significant three-way interactions were found for participants self-rated changes in Fear and Surprise, with tendencies toward significance (p < .10) also emerging for Anger and Disgust. The pattern of interactions was identical for all four variables. Low AS women manifested greater reductions in these four emotions when viewing neutral as opposed to dysphoric faces, regardless of whether they hyperventilated or relaxed. High AS women who relaxed manifested similar discriminative abilities. High AS women who hyperventilated, however, reported no relative changes in emotional arousal to both dysphoric and neutral faces. The blunted discrimination shown by high AS women who hyperventilated suggests that, when these individuals are in a physiologically challenged state, they may be less responsive to "early warning" indicators of social distress displayed by others which may, in turn, cause them to experience subsequent interpersonal difficulties.

Consensus recommendations for the use of anti-egfr therapies in metastatic colorectal cancer.

In January 2010, a panel of Canadian oncologists with particular expertise in colorectal cancer (crc) gathered to develop a consensus guideline on the use of therapies against the epidermal growth factor receptor (egfr) in the management of metastatic crc (mcrc). This paper uses a case-based approach to summarize the consensus recommendations developed during that meeting.These are the consensus recommendations:Testing for the KRAS status of the tumour should be performed as soon as an egfr inhibitor is being considered as an option for treatment.Anti-egfr therapies are not recommended for the treatment of patients with tumours showing mutated KRAS status.For a patient with wild-type KRAS and an Eastern Cooperative Oncology Group status of 0-2, whose mcrc has previously been treated with a fluoropyrimidine, irinotecan, and oxaliplatin, switching to an egfr inhibitor is a recommended strategy.Cetuximab, cetuximab plus irinotecan, and panitumumab are all options for third-line therapy in patients with wild-type KRAS, provided that tolerability is acceptable.

Comparison of the microhemagglutination assay for antibodies to Treponema pallidum and the automated fluorescent treponemal antibody-absorption test.

The qualitative microhemagglutination assay for detection of antibodies to Treponema pallidum and the automated fluorescent treponemal antibody-absorption tests were directly compared as confirmatory tests for syphilis. They were compared on 2,790 specimens from patients of New York City Social Hygiene Clinics. Overall agreement between the two assay methods was 89.6%. Only 1.5% of the total specimens tested were reactive by the automated fluorescent treponemal antibody-absorption test, and nonreactive by the microhemagglutination assay. The majority of specimens which disagreed were reactive only by the microhemagglutination assay. These comprised 8.9% of the total specimens tested. When such specimens were further tested by the manual fluorescent treponemal antibody-absorption test, 63% were also reactive in that test, and 16.7% gave borderline reactions. Fifty-four per cent of those reactive specimens were from patients suspected of being in a latent stage of syphilis, 10% from patients suspected of being in other stages, and 36% from patients not suspected of having syphilis. Because of the increased sensitivity of the microhemagglutination assay, its use is recommended instead of the automated fluorescent test. However, the manual fluorescent test should be performed when the result of the microhemagglutination assay is completely inconsistent with the clinician's impression.

R46-derived recombinant plasmids affecting DNA repair and mutation in E. coli.

Recombinant plasmids which render their host less mutable and more sensitive to some DNA-damaging agents have been isolated from the N-group plasmid R46. These plasmids have been physically mapped and found to originate from the region of R46 that has been deleted in pKM101. This deleted region is well removed from the muc region of R46 and pKM101 which is responsible for the mutator effects of these plasmids. The effect of these anti-mutagenic plasmids on the ability of pKM101 to complement umuC mutations has been examined, and they have been found to inhibit the complementation of such strains. We propose that these plasmids may code for a negative control function acting on the muc gene.

UV inducible UV protection and mutation functions on the I group plasmid TP110.

The UV protection and mutation properties of the I group plasmid TP110 have been investigated. It is demonstrated that the genes responsible for these effects are able to complement the deficiency in umuC36 mutants of E. coli, as are the similar genes carried by the B group plasmid R16. Mu-lac inserts into TP110 have been isolated which abolish the UV protection and mutation functions. Restriction mapping of these inserts locates them within a single region of the genome. A comparison of the restriction sites of this region with the muc region of pKM101 reveals very little similarity. Expression of beta-galactosidase in those Mu-lac inserts in which the lacZ gene is fused to the promoter for the protection and mutation functions is inducible by DNA damaging agents, and induction in mutant strains suggests that these genes are under the direct control of the lexA repressor.

Cloning and expression in Escherichia coli of a Streptomyces coelicolor A3(2) argCJB gene cluster.

From a partial Sau3AI library of Streptomyces coelicolor A3(2) DNA in pIJ916, two hybrid plasmids pGX1 and pGX2 were isolated that complemented S. coelicolor A3(2) or S. lividans arginine auxotrophs. Subcloning DNA from pGX1 in the Escherichia coli expression vector pRK9 containing the Serratia marcescens trp promoter gave rise to one plasmid, pZC2, that complemented E. coli argB, C, E and H auxotrophs, and another, pZC1, that complemented only the first three. The plasmids were markedly unstable in the various complemented hosts, to varying extents; pZC1 was characterized further as providing the stablest host/plasmid combinations. In vitro deletion of part of the vector's trp promoter did not affect complementation of the argB and C auxotrophs, implying that the S. coelicolor A3(2) arg genes may be expressed from their own promoter. The trp promoter-less plasmids included isolates, such as pZC177, that had suffered extensive further deletion without loss of complementing ability. Extracts of an E. coli argE auxotroph carrying pZC177 showed ornithine acetyltransferase activity, indicating that the complementing gene is of the argJ type. The complementation properties of in vitro deletion derivatives of pZC177 indicated the gene order argC-J-B. Part of argC and the upstream region were sequenced; an ORF was identified whose predicted product showed appreciable homology with the E. coli and Bacillus subtilis ArgC polypeptide. Upstream of this ORF a consensus-type promoter and ribosome binding site could be discerned; overlapping its promoter was a sequence with homology to arginine operators in these two other organisms.(ABSTRACT TRUNCATED AT 250 WORDS)