Effect of enterostomy on analgesic pattern in patients with advanced digestive tract cancer / 中华胃肠外科杂志

Objective@#To explore the effect of enterostomy on analgesic pattern in advanced digestive tract cancer.@*Methods@#A retrospective cohort study was carried out, which was approved by the Ethics Committee of the Sixth Affiliated Hospital of Sun Yat-sen University (E2018026). Inclusion criteria were as follows: (1)age and gender were not limited; (2) all the gastrointestinal malignancies were confirmed histologically, and local recurrence or metastasis were confirmed by CT or MR; (3) numerical rating scale (NRS) ≥4 points, opioid analgesic drugs were required; (4) informed consents were signed by patients of their own. Exclusion criteria were as follows: (1) malignancies of early stage; (2) suspicious adverse mental states which might lead to poor administration compliance; (3) hypersensitivity or allergic reactions to opioids. Clinical data of patients with advanced gastrointestinal cancer receiving comprehensive treatment at the Medical Oncology Department of the Sixth Affiliated Hospital of Sun Yat-sen University from September 2016 to April 2017 were retrospectively collected. The patients were divided into the stoma group and the non-stoma group. The clinical findings of two groups were analyzed, including age, sex, ostomy status, pain location, presence or absence of intestinal obstruction, pain characteristics, selection of opioid analgesic agents, treatment of side effects of analgesics. Pain was assessed using brief pain inventory(BPI) table and NRS score. Strong opioids were prescribed for patients of NRS ≥4. Patients who were intolerant to opioids required opioid titration. The titration drugs included oral or IV morphine and oxycodone. After achievement of adequate pain control, long-acting opioids were administered, which included sustained-release morphine tablets, controlled release oxycodone and transdermal fentanyl. Criteria for pain relief included NRS≤3, breakthrough pain <3 times/day and duration of adequate pain control >3 days. The χ2 test and the Wilcoxon signed rank sum test (nonparametric test) were used to analyze the clinical features of patients in the stoma and non-stomach groups. In order to find the factors associated with maintenance therapy and the use of laxatives, the variables were compared as well as in multivariate analysis with multiple regression models. For all the statistical tests, a value of P<0.05 in a two-tailed test was established as the alpha significance level.@*Result@#A total of 123 patients were enrolled in this study, including 79 males (64.2%) and 44 females (35.8%) with a median age of 51 years. Fifty-two patients were in stoma group, including 30 (24.4%) of ileostomy and 22 (17.9%) of colostomy, and 71 patients were in non-stoma group. Pain of 40 (76.9%) patients in stoma group located in abdomenopelvic site while the pain of 44 (62.0%) patients in non-stoma group located in other sites. Compared with non-stoma group, cases in stoma group complained more abdominopelvic pain (73% vs. 62.0%, P<0.001).The median NRS pain score before treatment in the stoma group and the non-stoma group was 5.7 and 5.6, respectively, without statistically significant difference (P=0.741). After analgesic management, the above scores reduced to 2.1 and 2.3, respectively, without statistically significant difference as well (P=0.092). Analgesic treatment was effective in 111 cases (90.2%), including 49 cases (94.2%) in the stoma group, and 62 cases (87.3%) in the non-stoma group, and there was no statistically significant difference between the two groups (P=0.202). There was more application of fentanyl transdermal patch [34.6%(18/52) vs. 9.8%(7/71)] in the stoma group, while more application of lactulose laxative [78.9%(56/71) vs. 61.5%(32/52)](χ2=10.023, P=0.002) in the non-stoma group. Multivariate analysis revealed that ostomy (OR=0.290, 95%CI: 0.102-0.824, P=0.009) and pain site (OR=5.691, 95%CI:1.709-18.948, P=0.005) were independent factors affecting the choice of the first line opioid sustained release agent. Of the 123 patients with maintaining analgesia, 98 had available data of laxative use, of whom 46 used laxatives to prevent or treat constipation, and the proportion of laxatives in stoma group (21.2%, 11/52) was significantly lower than that in non-stoma group (49.3%, 35/71) (χ2=6.957, P=0.008). Multivariate analysis of the application of laxative use showed that age (OR=0.281, 95% CI: 0.123-0.684, P=0.010) and ostomy (OR=2.621, 95% CI: 1.033-6.687, P=0.045) were independent factors affecting the use of lactulose laxatives.@*Conclusions@#Enterostomy may affect the analgesic pattern in advanced digestive tract cancer. Patients with stoma are more likely to use fentanyl transdermal patches and younger patients with stoma do not need prophylactic use of laxatives.

Analysis on safety and preliminary efficacy of dose-modified regimen of 5-fluorouracil plus oxaliplatin and irinotecan (FOLFOXIRI) in advanced colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the safety and preliminary efficacy of dose-modified regimen of 5-fluorouracil plus oxaliplatin and irinotecan (mFOLFOXIRI) for patients with advanced colorectal cancer (CRC).</p><p><b>METHODS</b>Data of 312 CRC patients confirmed by pathology receiving triplet drug alone or combined with target therapy between October 2012 and December 2016 at the Sixth Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. CRC patients who had previously completed adjuvant therapy (or neoadjuvant therapy) within 6 months or palliative chemotherapy were excluded, meanwhile those with poor general condition (ECOG score > 2) or grade 2 neuropathy and allergy to oxaliplatin were excluded as well. Regimen of mFOLFOXIRI: oxaliplatin 85 mg/m² dissolved in 5% glucose solution 500 ml by intravenous infusion for 2 h; irinotecan 150 to 165 mg/m² dissolved in 0.9% sodium chloride 250 ml by intravenous infusion for 90 min; following intravenous infusion of leucovorin 400 mg/m² for 2 h, day 1; 5-FU 2800 mg/m², 48-h continuous intravenous infusion; once every 2 weeks. Therapy could be combined with a targeted drug, bevacizumab 5 mg/kg every two weeks; cetuximab 500 mg/m² every two weeks. Side effect was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE 4.0.3). The objective response rate was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) after administering at least four cycles of chemotherapy.</p><p><b>RESULTS</b>The median age was 52 years (range 16-73) in the whole group; 113 patients (36.2%) had locally advanced CRC, and 199 (63.8%) had metastatic CRC. Most patients (274/312, 87.8%) did not receive any treatment earlier. There were a total of 1651 chemotherapy cycles in the whole group, with a median of 6(1-19) cycles. Of these 1651 cycles, 124 cycles of chemotherapy(7.5%) were dose-adjusted; 176 cycles of chemotherapy(10.7%) were delayed for median 5(3-13) days; 124 cycles(7.5%) required dose decrease. The overall relative dose intensity was >90%; the specific drug dose intensity was 93.6%(2620 mg×m⁻²×d⁻¹) for fluorouracil, 97.8%(83 mg×m⁻²×d⁻¹) for oxaliplatin, and 94.2%(155 mg×m⁻²×d⁻¹) for irinotecan. Twenty-three patients (7 of intestinal perforation, 7 of intestinal obstruction, 1 of grade 4 hematologic toxicity, and 8 of grade 3 fatigue) refused subsequent chemotherapy due to intolerable toxicity. Main grade 3 or 4 adverse events in patients were neutropenia in 69 cases (22.1%), fatigue in 35 cases (11.2%), and anemia in 28 cases (8.9%). Twenty serious adverse events (6.4%) occurred, including 13 patients of febrile neutropenia (4.2%), 7 patients of intestinal perforation (2.2%, 4 patients in upper rectum, 2 in sigmoid colon, and 1 in transverse colon cancer), and 9 of them had subsequent sepsis (2.9%). All the patients with intestinal perforation underwent emergency operation. No treatment-related deaths occurred. In 199 patients with metastatic CRC, because 22 patients did not receive image evaluation, the preliminary efficacy of 177 patients was actually evaluated. A total of 113 objective response events were observed. The overall response rate was 63.8%(113/177), partial response rate was 61.6%(109/177), clinically complete response rate was 2.3%(4/177), stable disease was 29.9% (53/177), progressive disease was 6.2%(11/177), and the disease control rate was 93.8%(166/177). In 127 patients receiving triplet drug, objective response rate was 40.9% for those with less than four cycles and 81.1% for those with more than four cycles (P<0.001).</p><p><b>CONCLUSION</b>The mFOLFOXIRI regimen with reduced dose can be safely used in advanced CRC and has achieved promising results in terms of short-term efficacy.</p>

Safety and efficacy analysis on modified FOLFOXIRI as first-line treatment for advanced colorectal cancer in China-single center experience / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the safety and preliminary efficacy of modified FOLFOXIRI (combination of reducing dosage irinotecan, oxaliplatin and fluorouracil) in first-line treatment for patients with metastatic colorectal cancer.</p><p><b>METHOD</b>A total of 53 patients with advanced colorectal cancer receiving modified FOLFOXIRI regimen were recruited continuously from January 2010 to January 2014. Safety profile was recorded based on NCI Common Terminology Criteria for Adverse Events version 3.0 (NCI-CTCAE v3.0). Objective response was evaluated by Response Evaluation Criteria in Solid Tumors version1.1 (RECIST 1.1) after administration of at least 4 cycles chemotherapy. Kras and Braf gene sequencing was tested by dideoxy chain-termination method. Relation between efficacy and two genes was examined.</p><p><b>RESULTS</b>Among 53 patients, no treatment-related mortality was presented. The rate of grade 3 to 4 adverse event was 32.1% (17/53), including neutropenia 13.2%(7/53), anemia 11.3% (6/53) and fatigue 9.4% (5/53). Overall response rate (ORR) and disease control rate (DCR) were respectively 65.9% (29/44) and 90.0% (40/44). Radical resection rate (R0) was 29.5% (13/44). Efficacy of mFOLFOXIRI regimen plus targeting therapy was assessed in 44 patients. mFOLFOXIRI regimen plus targeting therapy achieved an ORR of 72.7% (8/11), which was higher than the ORR 65.9% (21/33) of triplet regimen alone, but the difference was not statistically significant (P=0.198). Paraffin specimens of 48 colorectal cancer cases were tested. Twenty-one cases were Kras mutant (43.75%), 3 cases were Braf mutant (6.25%). There were no significant differences between two groups (P>0.05).</p><p><b>CONCLUSION</b>Reducing dosage mFOLFOXIRI can be safely used in advanced colorectal cancer and can achieve promising results in terms of short term efficacy.</p>

Effect of TUBB3, TS and ERCC1 mRNA expression on chemoresponse and clinical outcome of advanced gastric cancer by multiplex branched-DNA liquid chip technology / 中南大学学报(医学版)

OBJECTIVE@#To analyze the impact of β-tubulin-III (TUBB3), thymidylate synthase (TS) and excision repair cross complementation group 1 (ERCC1) mRNA expression on chemoresponse and clinical outcome of patients with advanced gastric cancer treated with TXT/CDDP/FU (DCF) regimen chemotherapy.@*METHODS@#The study population consisted of 48 patients with advanced gastric cancer. All patients were treated with DCF regimen palliative chemotherapy. The mRNA expressions of TUBB3, TS and ERCC1 of primary tumors were examined by multiplex branched-DNA liquid chip technology.@*RESULTS@#The patients with low TUBB3 mRNA expression had higher response rate to chemotherapy than patients with high TUBB3 expression (P=0.011). There were no significant differences between response rate and TS or ERCC1 expression pattern. Median overall survival (OS) and median time to progression (TTP) were significantly longer in patients with low TUBB3 mRNA expression (P=0.002, P<0.001). TS or ERCC1 expression was not correlated with TTP and OS. In the combined analysis including TUBB3, TS and ERCC1, the patients with 0 or 1 high expression gene had better response rate, TTP and OS than the remaining patients (all P<0.001). Multivariate analysis revealed that ECOG (Eastern Cooperative Oncology Group)≥2 (HR=2.42, P=0.009) and TUBB3 (HR=2.34, P=0.036) mRNA expression significantly impacted on OS.@*CONCLUSION@#High TUBB3 mRNA expression is correlated with resistance to DCF regimen chemotherapy. TUBB3 might be a predictive and prognostic factor in patients with advanced gastric cancer treated with TXT-based chemotherapy. The combined evaluation of TUBB3, TS and ERCC1 expression can promote the individual treatment in advanced gastric cancer.

Study of regimen based on L-asparaginase for 36 cases with nasal type extranodal NK/T cell lymphoma / 白血病·淋巴瘤

Object To evaluate the efficacy and toxicity of L-asparaginase based regimen for extranodal nasal type NK/T cell lymphoma (ENKTL).Methods 36 patients were treated with L-asparaginase based regimen from February 2008 to November 2011. 20 stage Ⅰ /Ⅱ patients were administered with VLD regimen based chemo-radiotherapy. 4 of 16 stage Ⅲ/Ⅳ patients received modified SMILE regimen chemotherapy, followed by involved field radiation therapy (IFRT), while others received modified SMILE regimen chemotherapy alone.Results Among 36 patients,35 were eligible for treatment response evaluation.The overall response rate (RR) was 68.6％ (24/35) with complete response (CR) rate of 54.3％ (19/35).After the median follow-up of 13.5 (range 3-31) months,for all patients,the 1-year overall survival (OS) rate was 82 ％,and the rate of progression-free survival (PFS) at 1 year was 65 ％.The patients who attained response with treatment showed better 1-year OS (93 ％) and PFS (80 ％) as compared with patients without response (35 ％; 33 ％),and the differences were statistically significant (x2=13.909,P =0.000; x2=8.216,P =0.004).The major adverse event was myelosuppression. No chemotherapy-related mortality occurred. Conclusion L-asparaginase based regimen is obviously effective and well tolerant for ENKTL. The large prospective clinical trials of L-asparaginase based regimen in the first-line treatment for ENKTL are worth for further investigation.