The long-term efficacy of imatinib with hepatic resection or other local treatment for gastrointestinal stromal tumours liver metastases: a retrospective cohort study.

BACKGROUND: The liver is the most common site of metastasis from gastrointestinal stromal tumors (GISTs). The authors aimed to evaluate imatinib (IM) combined with hepatic resection (HR) or other local treatments such as radiofrequency ablation (RFA) and transarterial chemoembolization (TACE), compared to IM monotherapy in long-term survival benefits in patients suffering from GIST liver metastases. METHODS: Our research encompassed 238 patients diagnosed with liver metastases of GISTs from January 2002 to April 2022 at the First Affiliated Hospital of Sun Yat-Sen University. The oncological outcomes of concern included overall survival (OS), progression-free survival (PFS), and liver-specific PFS. RESULTS: Of all 238 patients, 126 were treated with IM alone (IM group), 81 with IM combined with HR (IM+HR group), and 31 with IM combined with RFA/TACE (IM+RFA/TACE group). The median follow-up time was 44.83 months. The median OS in the IM group was 132.60 months and was not reached in either the IM+HR group or the IM+RFA/TACE group. The 10-year OS rate in the IM+HR group was significantly superior to the IM group and the IM+RFA/TACE group (91.9% vs. 61.1% vs. 55.2%, respectively, P =0.015), and the liver-specific PFS ( P =0.642) and PFS ( P =0.369) in the three groups showed a beneficial trend in the combined treatment group. Multivariate analyses showed that age less than or equal to 60 years (HR 0.280, P< 0.001) and IM+HR (HR 0.361, P =0.047) were independently associated with better OS. Achieving no evidence of disease through surgical intervention was independently correlated with enhanced OS (HR 0.099, P =0.034), liver-specific PFS (HR 0.388, P =0.014), and PFS (HR 0.402, P =0.004). CONCLUSIONS: In patients with GIST liver metastases, IM combined with HR might improve OS in selected patients compared with IM alone and IM combined with RFA/TACE. Achieving no evidence of disease status with surgical treatment of patients results in significant prolonging of OS, liver-specific PFS, and PFS.

CT features combined with RECIST 1.1 criteria improve progression assessments of sunitinib-treated gastrointestinal stromal tumors.

OBJECTIVES: To explore the auxiliary value of combining CT features with existing response evaluation criteria in the prediction of progressive disease (PD) in gastrointestinal stromal tumors (GIST) patients treated with sunitinib. MATERIAL AND METHODS: Eighty-one patients with GISTs who received sunitinib were included in this retrospective multicenter study and divided into training and external validation cohorts. Progression at six months was determined as a reference standard. The predictive performance of the RECIST 1.1 and Choi criteria was compared. CT features at baseline and the first follow-up were analyzed. Logistic regression analyses were used to determine the most significant predictors and develop modified criteria. RESULTS: A total of 216 lesions showed a good response and 107 showed a poor response in 81 patients. The RECIST 1.1 criteria performed better than the Choi criteria in predicting progression (AUC, 0.75 vs. 0.69, p = 0.04). The expanded/intensified high-enhancement area, blurred tumor-tissue interface, and progressive enlarged vessels feeding or draining the mass (EVFDM) differed significantly between lesions with good and poor responses in the training cohort (p = 0.001, 0.003, and 0.000, respectively). Multivariate analysis revealed that the expanded/intensified high-enhancement area (p = 0.001), progressive EVFDM (p = 0.000), and RECIST PD (p = 0.000) were independent predictive factors. Modified RECIST (mRECIST) criteria were developed and showed significantly higher AUCs in the training and external validation cohorts than the RECIST 1.1 criteria (training: 0.81 vs. 0.73, p = 0.002; validation: 0.82 vs. 0.77, p = 0.04). CONCLUSION: The mRECIST criteria, combining CT features with the RECIST 1.1 criteria, demonstrated superior performance in the prediction of early progression in GIST patients receiving sunitinib. CLINICAL RELEVANCE STATEMENT: The mRECIST criteria, which combine CT features with the RECIST 1.1 criteria, may facilitate the early detection of progressive disease in GIST patients treated with sunitinib, thereby potentially guiding the timely switch to late-line medications or combination with surgical excision. KEY POINTS: • The RECIST 1.1 criteria outperformed the Choi criteria in identifying progression of GISTs in patients treated with sunitinib. • GISTs displayed different morphologic features on CT depending on how they responded to sunitinib. • Combining CT morphologic features with the RECIST 1.1 criteria allowed for the prompt and accurate identification of progressing GIST lesions.

Sunitinib versus imatinib dose escalation after failure of imatinib standard dose in patients with advanced Gastrointestinal stromal tumors - a real-world multi-center study.

BACKGROUND: Whether to escalate imatinib dosage or directly switch to sunitinib in gastrointestinal stromal tumors (GISTs) failing on standard dose 400 mg/d of imatinib is still controversial. METHODS: We evaluated progression-free survival (PFS), overall survival (OS), and time to sunitinib failure (TTSF) of patients selecting imatinib dose escalation or directly switching to sunitinib after the failure of imatinib 400 mg/d therapy from 3 tertery referring centers between January 2008 to December 2016. RESULTS: A total of 240 patients receiving sunitinib (37.5 mg continuous daily dose or 50 mg 4 weeks on with 2 weeks off) for at least 8 weeks were examined. After failure on imatinib 400 mg/d, 100 (49.3%) patients had dose escalation to 600 mg or 800 mg per day (IM group, imatinib group), and 103 (50.7%) directly switched to sunitinib (SU group, sunitinib group). The PFS in the SU and IM groups was 12 months and 5.0 months (P < 0.001), respectively. TTSF or OS in both groups was not statistically significantly different. CONCLUSIONS: After the progression of imatinib standard-dose treatment in recurrent/metastatic GISTs, the PFS of patients directly switching to sunitinib was significantly longer compared with the PFS of patients with imatinib dose escalation. However, when the patients continued with sunitinib therapy after the failure of IM dose escalation, TTSF and OS in the IM group were similar to those in the SU group. Further exploration of the characteristics of the population benefiting from imatinib dose escalation are warranted.

Risk stratification for 1- to 2-cm gastric gastrointestinal stromal tumors: visual assessment of CT and EUS high-risk features versus CT radiomics analysis.

OBJECTIVES: To investigate the ability of CT and endoscopic sonography (EUS) in predicting the malignant risk of 1-2-cm gastric gastrointestinal stromal tumors (gGISTs) and to clarify whether radiomics could be applied for risk stratification. METHODS: A total of 151 pathologically confirmed 1-2-cm gGISTs from seven institutions were identified by contrast-enhanced CT scans between January 2010 and March 2021. A detailed description of EUS morphological features was available for 73 gGISTs. The association between EUS or CT high-risk features and pathological malignant potential was evaluated. gGISTs were randomly divided into three groups to build the radiomics model, including 74 in the training cohort, 37 in validation cohort, and 40 in testing cohort. The ROIs covering the whole tumor volume were delineated on the CT images of the portal venous phase. The Pearson test and least absolute shrinkage and selection operator (LASSO) algorithm were used for feature selection, and the ROC curves were used to evaluate the model performance. RESULTS: The presence of EUS- and CT-based morphological high-risk features, including calcification, necrosis, intratumoral heterogeneity, irregular border, or surface ulceration, did not differ between very-low and intermediate risk 1-2-cm gGISTs (p > 0.05). The radiomics model consisting of five radiomics features showed favorable performance in discrimination of malignant 1-2-cm gGISTs, with the AUC of the training, validation, and testing cohort as 0.866, 0.812, and 0.766, respectively. CONCLUSIONS: Instead of CT- and EUS-based morphological high-risk features, the CT radiomics model could potentially be applied for preoperative risk stratification of 1-2-cm gGISTs. KEY POINTS: • The presence of EUS- and CT-based morphological high-risk factors, including calcification, necrosis, intratumoral heterogeneity, irregular border, or surface ulceration, did not correlate with the pathological malignant potential of 1-2-cm gGISTs. • The CT radiomics model could potentially be applied for preoperative risk stratification of 1-2-cm gGISTs.

Bladder paraganglioma, gastrointestinal stromal tumor, and SDHB germline mutation in a patient with Carney-Stratakis syndrome: A case report and literature review.

Background: Carney-Stratakis syndrome (CSS) is a rare dyad of paraganglioma (PGL)/pheochromocytoma (PHEO) and gastrointestinal stromal tumor (GIST). PGLs are neuroendocrine tumors of neural crest origin which are mostly found in the head, neck, and retroperitoneal space. GISTs are the most common mesenchymal tumors of the digestive tract, usually caused by KIT/PDGFRA mutations. Here, we reported a case of CSS with unusual bladder PGL and succinate dehydrogenase (SDH) deficient GIST due to a germline mutation in SDH-subunit B (SDHB) gene. Case presentation: A 39-year-old female patient initially diagnosed with gastric GIST and isolated pelvic metastasis was eventually found to be CSS with bladder PGL and SDH-deficient GIST after surgery. This patient underwent resection of gastric and bladder tumors, and postoperative pathology confirmed the diagnosis of CSS. According to the next-generation sequencing (NGS), the patient carried a germline mutation in the SDHB gene, which was the cause of the disorder. The patient had no tumor recurrence with regular follow-up in 10 months. Conclusions: CSS is an autosomal genetic disorder with no gender difference in incidence, and PGLs are more frequent than GISTs. SDH germline mutation is the molecular biological mechanism of CSS while the most common type is SDHB mutation. The unique mechanism of tumorigenesis including hypoxia and hypermethylation caused by SDH deficiency renders target therapy with tyrosine kinase inhibitors ineffective, therefore complete surgical resection is the optimal treatment in the absence of tumor metastases.

Combination of Type I and II tyrosine kinase inhibitors-avapritinib and sunitinib-in refractory gastrointestinal stromal tumor after failure to multi-line therapy: a case report.

Background: Tyrosine kinase inhibitors (TKIs) are currently the main treatment choice for gastrointestinal stromal tumors (GISTs). However, the long-term use of TKIs can lead to drug resistance. There is no study or clinical report of combination therapies of TKIs that have been approved for marketing. Combination pharmacotherapy is a new approach for patients who do not respond to monotherapy. This case provides a reference value for selective combination of TKIs in treating advanced GIST. Case Description: In this article, we report the case of a 55-year-old female who was diagnosed with duodenal GIST in April 2018 and underwent R0 resection. KIT exon 9 mutation was detected. The patient had disease recurrence with multiple abdominal metastases during imatinib adjuvant therapy after 27 months, and failure to 2nd-line sunitinib treatment after 6 months. She underwent a cytoreductive surgery (R1), and the postoperative mutation analysis suggested KIT exon 9 mutation, with newly found secondary KIT_exon16_p. L783V mutation and other mutations on TP53, POT1, and SETD2, etc. The patient experienced short-term tumor control of standard 3rd-line therapy of regorafenib and the rapid progression of the 4th-line of ripretinib afterwards. Different TKI combination therapies (i.e., ripretinib plus sunitinib, ripretinib plus avapritinib and avapritinib plus sunitinib) were administered to the patient sequentially. Ripretinib plus sunitinib led to stable disease but was discontinued due to intolerable adverse effects. Finally, the patient received a combination regimen of avapritinib plus sunitinib. The patient's tumor showed continuous shrinking in 2 consecutive computed tomography scan evaluations within 4 months with acceptable side effects. Conclusions: Combined type I and type II TKIs of avapritinib combined with sunitinib therapy achieved tumor regression for a heavily multi-line treated patient. Our case provides a reference for a savage treatment choice in refractory GISTs after failure to all standard treatment.

The convoluted process of diagnosing pulmonary mycosis caused by Exophiala dermatitidis: a case report.

BACKGROUND: Etiological diagnosis is a key step in the treatment of patients with rare pulmonary mycosis, and the lack of understanding of this disease and lack of specific markers for the detection of rare species, such as Exophiala dermatitidis, add to the difficulty in diagnosing the condition. Therefore, improving the diagnostic strategies for this disease is very important. CASE PRESENTATION: A 52-year-old man presented with cough, sputum production and hemoptysis; chest computed tomography (CT) revealed multiple bilateral lesions. The pathogen was unable to be identified after three biopsies. Subsequently, we performed combined tissue metagenomic next-generation sequencing (mNGS). The results of mNGS and a good therapeutic response helped to identify the causative pathogen as Exophiala dermatitidis. Finally, the patient was diagnosed with Exophiala dermatitidis pneumonia. CONCLUSIONS: Combining molecular techniques, such as mNGS, with clinical microbiological tests will improve the rate of positivity in the diagnosis of rare fungal infections, and the importance of follow-up should be emphasized.

hsa_circ_0072309 Expression Profiling in Non-small-Cell Lung Carcinoma and Its Implications for Diagnosis and Prognosis.

Circular RNAs (circRNAs), which fall into the category of endogenous ncRNAs, are linked to disease progression of neoplastic diseases. Whereas, it remains uncharacterized regarding hsa_circ_0072309's function and implications in lung carcinoma (LC). Gene Expression Omnibus (GEO) database was utilized for identifying circRNAs with aberrantly expression in LC. qRT-PCR was responsible for determining hsa_circ_0072309 levels in lung adenocarcinoma (LAC). Also, its involvement in LC cell progression was investigated. Experimentally, hsa_circ_0072309 was identified as one of the most aberrantly down-regulated circRNAs in the GEO database (GSE101684 and GSE112214). qRT-PCR revealed notably down-regulated hsa_circ_0072309 in LAC tissue, which had a close association with adverse 3-year survival, as well as LNM and advanced TNM stage. Based on ROC, the AUC of hsa_circ_0072309 was determined to be 0.887, and its specificity and susceptibility can be improved by combined detection of either CYFRA21-1 or CEA. In a word, hsa_circ_0072309 is lowly expressed in lung cancer patients and the survival rate of lowly expressed patients is significantly lower, a candidate marker with prognostic utility for the disease.

Genotyping guided ripretinib directly after the progression of first-line imatinib therapy in advanced gastrointestinal stromal tumor: a case report.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Surgery and tyrosine kinase inhibitor (TKI) therapy are the main choices of treatment. However, the long-term use of TKIs is prone to drug resistance. Herein, we report the case of a 47-year-old female with primary gastric GIST with liver metastases since June 2015. The patient achieved disease control under imatinib therapy and underwent primary lesion resection. She took postoperative imatinib maintenance therapy, but discontinued imatinib for 10 months about 2 years after surgery. The patient suffered from disease progression in May 2019, with recurrence of liver metastases and new abdominal metastases. From then on, imatinib was resumed and partial response (PR) persisted for another 2 years. The patient subsequently experienced tumor progression due to secondary KIT exon 17 mutation confirmed by tissue biopsy and circulating tumor DNA (ctDNA) detection. After multidisciplinary team discussion, the patient received ripretinib as a second-line therapy, and ctDNA monitoring demonstrated that the KIT mutations turned negative. After disease control from ripretinib for 2+ months, she underwent cytoreductive surgery (R0/1) and received ripretinib maintenance treatment postoperatively. We believe that this case provides a reference value for individualized ripretinib precise therapy according to mutational analysis after the progression of first-line GIST treatment, and ctDNA can predict effectiveness to guide treatment.

Effects of continuing nursing care under cognitive behavioral intervention on psychological state and living quality in patients with double J catheter after ureterolithiasis surgery.

OBJECTIVE: The effects of continuing nursing care under cognitive behavioral intervention on the psychological state and living quality of patients with double J catheter after ureterolithiasis surgery were analyzed in this research. METHODS: The research subjects in this study were 142 patients who were discharged from our hospital with a double J tube after ureterolithiasis surgeries from June 2019 to June 2020. According to the patient care plan, the subjects were divided into the control group (n=71) and the observation group (n=71) and respectively treated with routine basic nursing measures and continuing nursing care under cognitive-behavior intervention. Subsequently, the psychological state, living quality and the complications that occurred were compared between the two groups. RESULTS: The depression and anxiety scores of the two groups after 4 weeks of intervention, comparing to thoes before intervention, were seen with remarkably decreased significance (P<0.05). The scores of living quality and self-care quality of patients in the observation group were obviously higher than those in the control group (P<0.05). In addition, the incidence of complications in the observation group was critically lower than that in control group (P<0.05). CONCLUSION: Continuous nursing care under cognitive behavioral intervention can substantially improve the psychological state, living quality and self-care ability of patients with double J tube after ureterolithiasis surgery, and reduce the incidence of complications, which is worthy of clinic promotion.

[The clinical efficacy of hemoperfusion in treatment of drug poisoning].

OBJECTIVE: To investigate the ability of hemoperfusion to remove some drugs or toxin from the body and its clinical efficacy. METHODS: Sixty-nine cases of poisoning due to tetramine or other drugs poisoning in our hospital between July 1990 and December 2003 were studied. Thirty-four patients among them received conventional treatment (including early gastric lavage, hepatoprotection, diuresis or respiratory support), and the remaining were given conventional treatment and hemoperfusion. Toxin concentration changes in blood before and after hemoperfusion, survival rate, time from come onset to regaining consciousness and convulsion termination and duration of clinical course were compared. RESULTS: In the hemoperfusion group, three patients died, the survival rate was 91.4%, whereas in the non-hemoperfusion group, the survival rate was 85.3% (P > 0.05). Meanwhile the clinical course was markedly shortened in the hemoperfusion group (P < 0.05). The time from coma onset to regaining consciousness and convulsion termination in the hemoperfusion group was significantly shorter than that in the non-hemoperfusion group. The clearance rate was different for different poisons, among them the benzodiazepines had an excellent clearance. CONCLUSIONS: Hemoperfusion could adsorb from blood a different amount of poisons. There is obvious efficacy in shortening clinical course and reducing complications. It could possibly raise survival rate in serious poisoning.

[Experimental treatment of respiratory failure caused by omethoate poisoning in rats].

OBJECTIVE: To examine the therapeutic effect of combined use of pralidoxime-Cl and atropine with artificial ventilation on respiratory muscle paralysis caused by omethoate poisoning in rats. METHODS: Rats were administered with same doses of 2LD(50) omethoate and then treated with atropine (10 mg/kg) to resist effectively chlolinergic symptoms. When the rats had slow respiratory frequency and breathed with difficulty, the trachea was intubated and artificial ventilation was carried out (except for group A). The rats in group B were continuously treated with atropine. The doses of pralidoxime-Cl for group C, D and E were 15 mg/kg, 20 mg/kg and 40 mg/kg respectively, given at the same time as artificial ventilation and 1, 2 and 3 hours later. The dose of atropine was reduced to 1/3 to 2/3 of the first dose so as to maintain the rats atropinized. If the rat survived beyond 60 minutes after withdrawal of artificial ventilation, the combined treatment was considered successful. The function of isolated phrenic diaphragm of the rats was observed with MS-302 analyses instrument physiologically and pharmacologically. RESULTS: None of the rats in group B successfully withdraw from artificial ventilation. The rats in group C all successfully withdraw from artificial ventilation in 3 hours and the function of the isolated phrenic muscle remained good. The survival rats in group D and E were very low after withdrawal, even though the function of isolated phrenic muscle was good. CONCLUSIONS: The therapeutic effect of the combined use of suitable dose of pralidoxime-Cl and atropine with artificial ventilation on respiratory muscle paralysis caused by omethoate poisoning in rats was significant. This measure can facilitate reversal of the function of poisoned diaphragm and reduced the death rate in poisoned rats.

[Antidotal effects of vitamin B(6) and sodium dimercaptopropane sulfonate on acute poisoning with tetramethylene disulphotetramine in animals].

OBJECTIVE: The study was designed to examine the antidotal effects of vitamin B(6) (Vit B(6)) with sodium dimercaptopropane sulfonate (Na-DMPS) on acute poisoning with tetramethylene disulphotetramine (TETS) in animals. METHODS: Through the acute toxicity experiments, the antidotal effects of Vit B(6) with Na-DMPS on mice immediately and 10 minutes after poisoning were observed. RESULTS: Used of Vit B(6) with Na-DMPS in early stage showed excellent inhibition of tetanic convulsion in acute poisoning with TETS in mice and can reduce very significantly the death rate (P < 0.001). Vit B(6) with Na-DMPS used 10 minutes after poisoning also significantly elongate the death time (68.8 +/- 15.2) and reduce significantly the death rate (60%) then control group's death time (31.6 +/- 7.8) and the death rate (100%) on acute poisoning in mice (P < 0.01). CONCLUSION: Antidotal effects of Vit B(6) with Na-DMPS were significant on acute TETS poisoning in animals. Vit B(6) with Na-DMPS is an excellent antidote for acute TETS poisoning. It is suggested that Vit B(6) with Na-DMPS may be clinically used to rescue patients poisoned by TETS.

[Study on the therapeutic effect of combined use of obidoxime and atropine with respiratory machine on respiratory muscle paralysis caused by omethoate poisoning of rats].

OBJECTIVE: To examine the therapeutic effect of combined use of obidoxime and atropine with artificial ventilation on respiratory muscle paralysis caused by omethoate poisoning in rats. METHODS: Rats were exposed to 2 times the dose of LD50 omethoate and treated with atropine (10 mg/kg) to counteract cholinergic symptoms. When the rats' respiratory frequency became slower and breathed with difficulty, the trachea intubation and artificial ventilation was carried out. The rats in group A were continuously treated with atropine. The dose of obidoxime for Group B, C and D were 8, 15, 20 mg/kg respectively, given at the same time as artificial ventilation and 1, 2, 3 hours later. The doses of atropine was reduced to 1/3 - 2/3 of the first dose so as to maintain the rats atropinized. If the rat survival was beyond 60 minutes after withdrawal of artificial ventilation, the combined treatment was considered successful. The function of isolated phrenic diaphragm of the rats was observed with MS-302 physiological and pharmacological analysis instrument. RESULTS: None of the rats in Group A was successful after withdrawal from artificial ventilation and the function of phrenic diaphragm appeared poor; whereas > 80% of the rats in B, C, D Group were successful after withdrawal from artificial ventilation in 3 h and the function of phrenic diaphragm remained well. The survival rate in B, C and D groups were higher after withdrawal from artificial ventilation than that in Group A(P < 0.01). The function of phrenic diaphragm in Group B, C and D were gradually decreased after ACh was added into the container. CONCLUSIONS: Combined use of suitable dose of obidoxime and atropine with artificial ventilation for respiratory muscle paralysis caused by omethoate poisoning could promote the recovery of diaphragm function and reduce the death rate in poisoned rats.