Adherence to adjuvant with therapy imatinib in patients with gastrointestinal stromal tumor: a national multi-center cross-sectional study / 中华胃肠外科杂志

Objective: To analyze the current adherence to imatinib in patients with gastrointestinal stromal tumors (GIST) in China and its influencing factors. Methods: A cross-sectional survey was conducted. Study period: from October 1, 2020 to November 31, 2020. Study subjects: GIST patients taking imatinib who were diagnosed and treated in public tertiary level A general hospitals or oncology hospitals; those who had not been pathologically diagnosed, those who never received imatinib, or those who had taken imatinib in the past but stopped afterwards were excluded. The Questionnaire Star online surgery platform was used to design a questionnaire about the adherence to adjuvant imatinib therapy of Chinese GIST patients. The link of questionnaire was sent through WeChat. The questionnaire contained basic information of patients, medication status and Morisky Medication Adherence Scale. Results: A total of 2162 questionnaires from 31 provinces, autonomous regions, and municipalities were collected, of which 2005 were valid questionnaires, with an effective rate of 92.7%. The survey subjects included 1104 males and 901 females, with a median age of 56 (22-91) years old. Working status: 609 cases (30.4%) in the work unit, 729 cases (36.4%) of retirement, 667 cases of flexible employment or unemployment (33.3%). Education level: 477 cases (23.8%) with bachelor degree or above, 658 cases (32.8%) of high school, 782 cases (39.0%) of elementary or junior high school, 88 cases (4.4%) without education. Marital status: 1789 cases (89.2%) were married, 179 cases (8.9%) divorced or widowed, 37 cases (1.8%) unmarried. Two hundred and ninety-four patients (14.7%) had metastasis when they were first diagnosed, including 203 liver metastases, 52 peritoneal metastases, and 39 other metastases. One thousand eight hundred and sixty-nine patients underwent surgical treatment, of whom 1642 (81.9%) achieved complete resection. The median time of taking imatinib was 25 (1-200) months. Common adverse reactions of imatinib included 1701 cases (84.8%) of periorbital edema, 1031 cases (51.4%) of leukopenia, 948 cases (47.3%) of fatigue, 781 cases (39.0%) of nausea and vomiting, 709 cases (35.4%) of rash, and 670 cases (33.4%) of lower extremity edema. The score of the Morisky Medication Adherence Scale showed that 392 cases (19.6%) had poor adherence, 1023 cases (51.0%) had moderate adherence, and 590 cases (29.4%) had good adherence. Univariate analysis showed that gender, age, work status, economic income, residence, education level, marriage, the duration of taking medication and adverse reactions were associated with adherence to adjuvant imatinib therapy (all P<0.05). Multivariate analysis showed that female (OR=1.264, P=0.009), non-retirement (OR=1.454, P=0.001), monthly income ≤4000 yuan (OR=1.280, P=0.036), township residents (OR=1.332, P=0.005), unmarried or divorced or widowed (OR=1.362, P=0.026), the duration of imatinib medication >36 months (OR=1.478, P<0.001) and adverse reactions (OR=1.719, P=0.048) were independent risk factors for poor adherence to adjuvant imatinib. Among patients undergoing complete resection, 324 (19.7%) had poor adherence, 836 (50.9%) had moderate adherence, and 482 (29.4%) had good adherence. Meanwhile, 55 patients with good adherence (11.4%) developed recurrence after surgery, 121 patients with moderate adherence (14.5%) developed recurrence, 61 patients with poor adherence (18.8%) developed recurrence, and the difference was statistically significant (P=0.017). Conclusions: The adherence to adjuvant therapy with imatinib in Chinese GIST patients is relatively poor. Females, non-retirement, monthly income ≤4000 yuan, township residents, unmarried or divorced or widowed, the duration of imatinib medication >36 months, and adverse reactions are independently associated with poor adherence of GIST patients. Those with poor adherence have a higher risk of recurrence after surgery. Positive interventions based on the above risk factors are advocated to improve the prognosis of patients with GIST.

A multi-center retrospective study of perioperative chemotherapy for gastric cancer based on real-world data / 中华胃肠外科杂志

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.

New progress in the treatment for gastrointestinal stromal tumors / 医学研究生学报

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors. Surgery remains to be the primary treatment for patients with localized GISTs, but there are still many patients suffering from tumor metastasis and recurrence after surgery. Imatinib adjuvant therapy plays an important role in the prevention and treatment of tumor metastasis and recurrence, but there are still many controversies in terms of dosage and time of administration. For initial unresectable GISTs with large volume, neoadjuvant therapy may considered to be an option. Sunitinib and regorafenib have played an important role in the second and the third line treatments. BLU-285 has brought hope to patients with mutation of PDGFRA D842. The emerging immunotherapy is still in the exploration stage of gastrointestinal stromal tumors in recent years. This article reviews the research progress of surgical treatment, neoadjuvant therapy, postoperative adjuvant therapy and other treatments for GISTs.

Necessity of No.13 lymph node dissection in advanced gastric carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the feasibility and necessity of No.13 lymph node dissection for advanced gastric carcinoma.</p><p><b>METHODS</b>Clinical data of 144 cases who were diagnosed as TNMII-III stage gastric carcinoma were collected from January 2007 to December 2009 in the Department of General Surgery at the First Affiliated Hospital of Nanchang University. Seventy-two cases who received D2 radical gastrectomy plus No.13 lymph node dissection were selected as the study group, and they were matched 1:1 to 72 cases who received D2 Radical gastrectomy (the control group) for TNMII-III stage gastric carcinoma. The differences in the intraoperative and postoperative parameters and survival time were compared, and the factors associated with No.13 lymph node metastasis were analyzed.</p><p><b>RESULTS</b>There were no significant differences between the two groups in operative time [(2.8 ± 0.4) h vs. (2.7 ± 0.4) h], blood loss [(191.9 ± 81.5) ml vs. (186.0 ± 81.7) ml], the incidence of postoperative complications (18.1% vs. 15.3%), length of hospital stay [(12.3 ± 4.2) d vs. (11.9 ± 3.2) d] and 3-year survival rate (63% vs. 57%) (all P>0.05). In the study group, there were 15 patients (20.8%) with positive No.13 lymph nodes, and the 3-year survival rate was 13%, significantly lower compared to those with negative No.13 lymph node (73%, n=57) (P<0.05). Multivariate analysis showed that N stage (P<0.01) and histological type (P<0.05) were independently associated with No.13 lymph node metastasis.</p><p><b>CONCLUSION</b>No.13 lymph node dissection for TNMII-III stage gastric cancer is feasible and necessary.</p>

Association of the jejunal mucosal structure and the tolerance of early postoperative enteral nutrition in gastric carcinoma patients at different ages / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the association of the changes of the jejunal mucosal structure and the tolerance of early postoperative enteral nutrition in gastric cancer patients at different ages.</p><p><b>METHODS</b>Thirty patients of gastric carcinoma undergone total gastrectomy were enrolled in this study, including 16 cases over 65 years old and 14 cases under 40 years old. The specimens of jejunal mucosa were taken during operation and were observed by light and electronic microscopes. The height and width of the jejunal villus and the thickness of the jejunal mucosa were measured. All the patients received enteral nutrition from the second postoperative day to discharge. The complications related to enteral nutrition, such as abdominal pain, abdominal distention, and diarrhea, were observed.</p><p><b>RESULTS</b>The height of the jejunal villus was longer in young age group than that of old age group. The width of the jejunal villus was shorter in young age group than that of old age group. The thickness of the jejunal mucosa was thinner in old age group than that of young age group. The changes of ultrastructure of the jejunal mucosal epithelial cell in old age group showed that microvilli are rare and disorder, mitochondrial cristaes were broken and dissolved. The young age group was normal in the ultrastructure. The complications related to enteral nutrition were more frequent in old age group than those in young age group, especially in abdominal distention and diarrhea (P<0.01).</p><p><b>CONCLUSION</b>The atrophy of jejunal mucosa in old age patients with gastric carcinoma lead to decrease the tolerance and increase the complications of the postoperative enteral nutrition.</p>

Clinical analysis of prognostic factors for patients with gastrointestinal stromal tumors / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the prognostic factors for patients with gastrointestinal stromal tumors (GIST).</p><p><b>METHODS</b>From 2000 to 2003, clinical data of 41 cases with GIST were reviewed retrospectively. The clinicopathologic diagnosis was determined by immunochemistry. The relationships of the prognosis with mitotic counts, tumor size and location,range of tumor resection were analyzed.</p><p><b>RESULTS</b>The patients with GIST had pathological section of high expression in CD117, CD34 and vimentin (92.7%, 82.9%, 78%, respectively). Patients with tumor location in intestine, tumor size > 5 cm,mitotic counts > 5/50HPF, incomplete resection had poorer outcome, compared with those with tumor location in stomach and colon,tumor size < or = 5 cm,mitotic counts < or = 5/50HPF and complete resection (all P< 0.05).</p><p><b>CONCLUSION</b>Complete gross resection can improve prognosis for patients with GIST. Tumors with mitotic counts > or = 5/50HPF, tumor size more than 5 cm and tumor location in intestine are poor prognostic factors.</p>