[A multicenter study on childhood Hodgkin lymphoma treated with HL-2013 regimen in China].

Objective: To evaluate the efficacy of the Hodgkin lymphoma (HL)-2013 regimen in the treatment of children with HL, and to investigate the prognostic factors of childhood HL. Methods: Clinical data of 145 children (aged ≤18 years) with newly diagnosed HL, treated with HL-2013 regimen in 8 tertiary referral centers for childhood cancer from August 2011 to April 2021 were analyzed retrospectively. All the diagnosis were confirmed by histopathological morphology and immunohistochemical examination. The clinical characteristics and treatment outcomes were summarized, and the patients were divided into different groups according to clinical characteristics. Kaplan-Meier method was used for survival analysis, and the comparison of survival rates between groups was performed with Log-rank test. Results: Of the 145 cases, there were 115 males and 30 females, the age at diagnosis was 7.9 (5.8, 10.6) years. Cervical lymph node enlargement (114 cases, 78.6%) was the common symptom of the disease, and 57 patients (39.3%) were accompanied by large masses. The most common pathological classification was mixed cell type (93 cases, 64.1%). According to the Ann Arbor staging system, there were 9 cases of stage Ⅰ, 62 cases of stage Ⅱ, 45 cases of stage Ⅲ, 29 cases of stage Ⅳ. According to the risk stratification: there were 14 cases of low-risk group, 76 cases of medium-risk group and 55 cases of high-risk group. Of all patients, 68 cases (46.9%) achieved an early complete remission (CR) after 2 courses of chemotherapy, and the CR rate was 93.8% (136/145) after first-line treatment. Disease recurrence or progression occurred in 22 cases (15.2%). Of all patients, 125 cases survived, 6 cases died and 14 cases were lost to follow-up. Among the survived cases, 123 cases were continuously at CR state,and the follow-up time was 55 (40, 76) months. The 5-year overall survival (OS) and event free survival (EFS) rates were (95.3±1.9)% and (84.2±3.0)% for the entire group, respectively. 5-year OS and EFS rates for patients with stage Ⅲ-Ⅳ were both lower than those for patients with stage Ⅰ-Ⅱ (χ2=6.28 and 7.58, both P<0.05), the 5-year OS and EFS rates for patients in high-risk group were both lower than those for patients in low-risk and medium-risk group (χ2=10.93, 7.79, both P<0.05). The 5-year OS rates for the patient with early CR and without early CR were 100.0% and (90.9±3.6)% (χ2=5.77, P=0.016). EFS rates for the patient with early CR (68 cases) and without early CR (77 cases) were (93.8±3.0)% and (75.8±5.0)% (χ2=8.78, P=0.003). Conclusions: HL-2013 regimen is significantly effective in the treatment of pediatric HL. However, the patients in high-risk group and those without early CR are prone to disease recurrence or progression. Stage Ⅲ-Ⅳ and without early CR were associated with worse prognosis.

Effect analysis of sacral canal therapy combined with Fufang Wulingzhi Tangjiang in the treatment of residual root pain after lumbar surgery.

OBJECTIVE: To observe the clinical effect of a combination of traditional Chinese and western medicine (sacral canal therapy combined with compound Fufang Wulingzhi Tangjiang) in the treatment of residual root pain after lumbar surgery. PATIENTS AND METHODS: From January 2019 to December 2020, 538 patients with residual root pain due to lumbar degenerative diseases were treated in our hospital [open decompression discectomy (ODD), Percutaneous Endoscopic Lumbar Discectomy (PELD) or Transforminal Lumbar Interbody Fusion (TLIF)]. They were randomly divided into control group (basic treatment + celecoxib), observation group 1 (basic treatment + compound Fufang Wulingzhi Tangjiang), observation group 2 (basic treatment + sacral canal therapy) and observation group 3 (basic treatment + sacral canal therapy + Fufang Wulingzhi Tangjiang). Follow-up 3-12 months. The therapeutic effect, VAS score, JOA score, treatment cost, complications, serum interleukin-6 (IL-6), interleukin-1 (IL-1) and tumor necrosis factor-a (TNF-α) were recorded and compared before treatment, 1 week after treatment, 2 weeks after treatment, 1 month after treatment, and the last follow-up. RESULTS: The treatment effect, VAS score, JOA, and treatment cost in the observation group were better than those in the control group (p < 0.05). There were significant differences in the above-mentioned indexes between the observation group 3 and the control group, observation group 1, and observation group 2 (p < 0 01). Inflammatory factors (IL-6, IL1, TNF-α) in the observation group were lower than those in the control group (p < 0 05). Inflammatory factors in observation group 3 were significantly lower than those in the control group, observation group 1, and observation group 2 (p < 0 01). CONCLUSIONS: Sacral canal injection combined with Fufang Wulingzhi Tangjiang can be effective in the treatment of postoperative root pain of lumbar degenerative diseases, which can reduce inflammatory factors such as IL-6, IL-1ß and TNF-α. It has the advantages of quick effect, short treatment time, low cost, high safety, in line with the concept of ERAS, easily accepted by patients and their families, and worthy of further popularizing and applying in clinic.

Identification of circulating biomarkers for differentiating patients with papillary thyroid cancers from benign thyroid tumors.

BACKGROUND: This study aimed to identify the potential circulating biomarkers of protein, mRNAs, and long non-coding RNAs (lncRNAs) to differentiate the papillary thyroid cancers from benign thyroid tumors. METHODS: The study population of 100 patients was classified into identification (10 patients with papillary thyroid cancers and 10 patients with benign thyroid tumors) and validation groups (45 patients with papillary thyroid cancers and 35 patients with benign thyroid tumors). The Sengenics Immunome Protein Array-combined data mining approach using the Open Targets Platform was used to identify the putative protein biomarkers, and their expression validated using the enzyme-linked immunosorbent assay. Next-generation sequencing by Illumina HiSeq was used for the detection of dysregulated mRNAs and lncRNAs. The website Timer v2.0 helped identify the putative mRNA biomarkers, which were significantly over-expressed in papillary thyroid cancers than in adjacent normal thyroid tissue. The mRNA and lncRNA biomarker expression was validated by a real-time polymerase chain reaction. RESULTS: Although putative protein and mRNA biomarkers have been identified, their serum expression could not be confirmed in the validation cohorts. In addition, seven lncRNAs (TCONS_00516490, TCONS_00336559, TCONS_00311568, TCONS_00321917, TCONS_00336522, TCONS_00282483, and TCONS_00494326) were identified and validated as significantly downregulated in patients with papillary thyroid cancers compared to those with benign thyroid tumors. These seven lncRNAs showed moderate accuracy based on the area under the curve (AUC = 0.736) of receiver operating characteristic in predicting the occurrence of papillary thyroid cancers. CONCLUSIONS: We identified seven downregulated circulating lncRNAs with the potential for predicting the occurrence of papillary thyroid cancers.

Distinct prognostic roles of HSPB1 expression in non-small cell lung cancer.

Lung cancer is the leading cause of cancer morbidity and mortality around world. Heat shock protein beta-1 (HSPB1) expression is aberrantly increased in non-small cell lung cancer (NSCLC) patients. However, the roles of HSPB1 expression in the prognosis of NSCLC are still elusive. In this study, we investigated the prognostic roles of HSPB1 in NSCLC by using "The Kaplan-Meier plotter" (KM plotter) database. Our data indicated that HSPB1 mRNA low expression was correlated to better overall survival (OS) for all NSCLC patients, hazard ratio (HR) 1.41 (1.24-1.61), p=1.1e-7, and better OS in lung adenocarcinoma (LUAD) patients, HR 1.81 (1.42-2.32), p=1.5e-06, but not in lung squamous cell carcinoma (LUSC) patients, HR 1.21 (0.94-1.55), p=0.14. In addition, mRNA low expression of HSPB1 is also significantly associated with better OS of NSCLC patients in different smoking status, in different chemotherapy status, in clinical stage I et II, as well as patients with successful surgery treatment. Our results indicated that HSPB1 expression may have distinct prognostic values in NSCLC patients, and may provide an effective clinical strategy to accurately predict the prognosis of NSCLC patients.

[Clinical significance of combined detection of urine NTX and serum ICTP for breast cancer patients with bone metastases].

OBJECTIVE: To study the clinical significance and prognostic value of combined detection of urinary N-terminal telopeptide of type Ⅰ collagen (NTx) and serum C-terminal telopeptide of type Ⅰ collagen (ICTP) in breast cancer patients with bone metastases. METHODS: Serum and urine samples from 68 women with advanced breast cancer who received the treatment in Jilin Cancer Hospital between October 2012 and October 2008 were collected before and 2 months after treatment. Among them, 35 patients had bone metastases (group A), including 12 cases with single bone metastasis and 23 cases with multiple bone metastases. 33 out of the 68 patients had other organ metastases (group B). 30 healthy females were included as the control group (group C). The levels of urine NTX and serum ICTP were measured by ELISA. RESULTS: The levels of NTx and ICTP of group A were significantly higher than those of groups B and C [NTx: (7.17±1.11) nmol/L vs. (2.08±0.22) nmol/L and (2.09±0.24) nmol/L, respectively, (P<0.05); ICTP: (7.75±1.14) ng/ml vs. (2.15±0.34) ng/ml and (2.22±0.31) ng/ml, respectively, (P<0.05)], while no significant difference was found between the groups B and C. Compared with the patients with single bone metastasis, the patients with ≥2 bone metastases had significantly higher NTx and ICTP levels [NTx: (7.69±0.93) nmol/L vs. (6.16±0.62) nmol/L, P<0.05; ICTP: (8.21±1.00) ng/ml) vs. (6.88±0.81) ng/ml (P<0.05)]. At two months after treatment, 40.0%(14/35) of patients with bone metastasis had partial remission (PR), 42.9%(15/35) of patients had stable disease (SD), and 6 patients with progressive disease (PD). Both urinary NTx and serum ICTP of the patients with PR and SD were significantly decreased compared with those before treatment (P<0.05). 10 cases of patients (28.6%) with bone metastases had skeletal-related events (SREs) during the treatment, including one PR patient (1/14, 7.1%), 5 SD patients (5/15, 33.3%) and 4 PD patients (4/6, 66.7%). CONCLUSION: The combined detection of urinary NTx and serum ICTP is of important significance for early diagnosis and efficacy evaluation and to control skeletal-related adverse events in breast cancer patients with bone metastases.

[Comparison of clinical outcomes of patients with non-small cell lung cancer harboring different types of epidermal growth factor receptor sensitive mutations after first-line EGFR-TKI treatment].

OBJECTIVE: To analyze whether there are differences in the efficacy and clinical outcomes to first-line tyrosine kinase inhibitors (TKI) therapy in Chinese patients with metastatic non-small-cell lung cancer (NSCLC) harboring different subtypes of epidermal growth factor receptor (EGFR) mutations. METHODS: A retrospective analysis was made on the clinical data of stage ⅢB or Ⅳ NSCLC patients who were diagnosed by histology and received EGFR mutation test, in order to confirm if there is any difference between the therapeutic effects of TKIs as first-line therapy and the prognosis. RESULTS: A total of 165 patients harboring EGFR exon 19 deletion (19del, n=71), exon 21 L858R mutation (L858R, n=80) or uncommon sensitive mutation (n=14) were treated with EGFR-TKIs for first-line treatment. The comparison among different groups of common types of sensitive mutations revealed that the objective response rate (ORR) of group 19del and group L858R were 57.8% and 45.0%, respectively (P=0.113). The disease control rate (DCR) was 93.0% and 93.8%, respectively (P=0.158). However, the ORR and DCR of uncommon sensitive mutation were 35.7% and 78.6%, which were significantly lower than that of the group 19del (P=0.035) and group L858R (P=0.020). The median progression-free survival (PFS) of group 19del, group L858R and uncommon sensitive mutation were 14.0 months, 7.8 months and 5.1 months, respectively (P=0.001). The median PFS of the group 19del was significantly longer than that of the group L858R (P=0.009). The median overall survival (OS) of these three groups had significant difference (22.8, 15.2 and 10.0 months) (P=0.048). But those of group 19del and group L858R were similar (P=0.152). The multivariate analysis indicated that ECOG-PS (P=0.030), cigarette smoking (P=0.013) and EGFR mutation types (P=0.034) are independent prognostic factors of OS. CONCLUSIONS: For Chinese NSCLC patients with different types of sensitive mutation, there are differences between their efficacy and prognosis of EGFR-TKIs as first-line treatment. The PFS of group 19del is obviously longer than that of other types of sensitive mutations, but have no significant differences in OS. The PFS and OS of patients with common types of sensitive mutation are better than those with uncommon sensitive mutation.

Clonal evolution in hematological malignancies and therapeutic implications.

The ability of cancer to evolve and adapt is a principal challenge to therapy in general and to the paradigm of targeted therapy in particular. This ability is fueled by the co-existence of multiple, genetically heterogeneous subpopulations within the cancer cell population. Increasing evidence has supported the idea that these subpopulations are selected in a Darwinian fashion, by which the genetic landscape of the tumor is continuously reshaped. Massively parallel sequencing has enabled a recent surge in our ability to study this process, adding to previous efforts using cytogenetic methods and targeted sequencing. Altogether, these studies reveal the complex evolutionary trajectories occurring across individual hematological malignancies. They also suggest that while clonal evolution may contribute to resistance to therapy, treatment may also hasten the evolutionary process. New insights into this process challenge us to understand the impact of treatment on clonal evolution and inspire the development of novel prognostic and therapeutic strategies.

Pneumonia caused by Aeromonas species in Taiwan, 2004-2011.

We investigated the clinical characteristics of patients with pneumonia caused by Aeromonas species. Patients with pneumonia caused by Aeromonas species during the period 2004 to 2011 were identified from a computerized database of a regional hospital in southern Taiwan. The medical records of these patients were retrospectively reviewed. Of the 84 patients with pneumonia due to Aeromonas species, possible Aeromonas pneumonia was diagnosed in 58 patients, probable Aeromonas pneumonia was diagnosed in 18 patients, and pneumonia due to Aeromonas was conclusively diagnosed in 8 patients. Most of the cases of Aeromonas pneumonia developed in men and in patients of advanced age. A. hydrophila (n = 50, 59.5 %) was the most common pathogen, followed by A. caviae (n = 24, 28.6 %), A. veronii biovar sobria (n = 7, 8.3 %), and A. veronii biovar veronii (n = 3, 3.6 %). Cancer (n = 37, 44.0 %) was the most common underlying disease, followed by diabetes mellitus (n = 27, 32.1 %). Drowning-associated pneumonia developed in 6 (7.1 %) patients. Of 47 patients who were admitted to the intensive care ward, 42 patients developed acute respiratory failure and 24 of those patients died. The overall in-hospital mortality rate was significantly associated with liver cirrhosis, cancer, initial presentation of shock, and usage of mechanical ventilation. In conclusion, Aeromonas species should be considered as one of the causative pathogens of severe pneumonia, especially in immunocompromised patients, and should be recognized as a cause of drowning-associated pneumonia. Cirrhosis, cancer, and shock as the initial presenting symptom are associated with poor outcome.

Melatonin suppresses apoptosis and stimulates progesterone production by bovine granulosa cells via its receptors (MT1 and MT2).

Melatonin and its receptors have been detected in the ovary of many species, and mediate ovarian functions. The present study was designed to investigate the expression and subcellar location of melatonin receptors in bovine granulosa cells (GCs), using reverse transcription (RT) polymerase chain reaction, Western blot, and immunofluorescence analyses. Furthermore, expression level of melatonin receptors mRNA (real-time polymerase chain reaction) after treatment with various concentrations of melatonin, as well as its effects on cell apoptosis, proliferation, and steroidogenesis (by flow cytometry and RIA), were determined. In bovine GCs, melatonin receptors MT1 and MT2 were differentially located at the cell membrane, the cytoplasm, and nuclear membranes. The expression of MT1 and MT2 mRNA was regulated differently by melatonin in time- and dose-dependent manners. Exogenous melatonin suppressed cell apoptosis (P < 0.05) but not proliferation (P > 0.05). After 72 h, the apoptotic rate was significantly inhibited in all treatment groups. Meanwhile, melatonin supplementation stimulated progesterone production, but inhibited estradiol biosynthesis, in a time-dependent manner. Progesterone production was highest (P < 0.05) at 72 h. Estradiol concentrations were almost unaffected (P > 0.05) at 24 h, but were decreased (P < 0.05) at 48 h. In conclusion, exogenous melatonin acts via receptors and has important roles in regulation of development and function of bovine GCs.

Negative argininosuccinate synthetase expression in melanoma tumours may predict clinical benefit from arginine-depleting therapy with pegylated arginine deiminase.

BACKGROUND: Arginine-depleting therapy with pegylated arginine deiminase (ADI-PEG20) was reported to have activity in advanced melanoma in early phase I-II trial, and clinical trials are currently underway in other cancers. However, the optimal patient population who benefit from this treatment is unknown. METHODS: Advanced melanoma patients with accessible tumours had biopsy performed before the start of treatment with ADI-PEG20 and at the time of progression or relapse when amenable to determine whether argininosuccinate synthetase (ASS) expression in tumour was predictive of response to ADI-PEG20. RESULTS: Twenty-seven of thirty-eight patients treated had melanoma tumours assessable for ASS staining before treatment. Clinical benefit rate (CBR) and longer time to progression were associated with negative expression of tumour ASS. Only 1 of 10 patients with ASS-positive tumours (ASS+) had stable disease, whereas 4 of 17 (24%) had partial response and 5 had stable disease, when ASS expression was negative (ASS-), giving CBR rates of 52.9 vs 10%, P=0.041. Two responding patients with negative ASS expression before therapy had rebiopsy after tumour progression and the ASS expression became positive. The survival of ASS- patients receiving at least four doses at 320 IU m(-2) was significantly better than the ASS+ group at 26.5 vs 8.5 months, P=0.024. CONCLUSION: ADI-PEG20 is safe and the drug is only efficacious in melanoma patients whose tumour has negative ASS expression. Argininosuccinate synthetase tumour positivity is associated with drug resistance and tumour progression.

Non-typhoidal Salmonella bacteraemia in elderly patients: an increased risk for endovascular infections, osteomyelitis and mortality.

Non-typhoidal Salmonella (NTS) is a common pathogen causing foodborne infections, bacteraemia, and extra-intestinal focal infections (EFIs) in humans. The study compares the clinical characteristics of elderly patients with NTS bacteraemia with those of young adults. Of 272 adults with NTS bacteraemia identified in this study, 162 (59·6%) were aged ⩾55 years. EFIs were observed in 36% of the 162 patients. The most common EFIs in the elderly patients (⩾55 years) was mycotic aneurysm, followed by pulmonary infections and bone/joint infections. Elderly patients more often had chronic heart, lung, renal and malignant diseases, had more EFIs, and a higher 30-day mortality rate. Independent factors of 30-day mortality in elderly patients were solid-organ tumour [adjusted odds ratio (aOR) 4·4, P=0·003], mycotic aneurysm (aOR 3·7, P=0·023) and shock (aOR 12·1, P<0·0001). HIV infection, autoimmune diseases, and receipt of immunosuppressive therapy were more often observed in young patients.

Phase-specific cone beam computed tomography reduces reconstructed volume loss of moving phantom.

PURPOSE: The accurate volumetric calculation of moving targets/organs is required to use cone-beam computed tomography (CBCT) for replanning purposes. This study was aimed to correct the reconstructed volume losses of moving phantoms by phase-specific CBCT. MATERIALS AND METHODS: Planning fan-beam CT (FBCT) of five hepatobiliary/gastrointestinal/pancreatic cancer patients were acquired under active breathing control and compared with free-breathing CBCT for kidney volumes. Three different-sized ball phantoms were scanned by FBCT and CBCT. Images were imported to a planning system to compare the reconstructed volumes. The phantoms were moved longitudinally on an oscillator with different amplitudes/frequencies. The phase-specific projections of CBCT for moving phantoms were selected for volume reconstruction. RESULTS: The differences in reconstructed volumes of static small, medium, large phantoms between FBCT and CBCT were - 6.7%, - 2.3%, and - 2.0%, respectively. With amplitudes of 7.5-20 mm and frequencies of 8-16 oscillations/min, volume losses on CBCT were comparable with FBCT in large moving phantoms (range 9.1-27.2%). Amplitudes were more subject to volume losses than frequencies. On phase-specific CBCT, volume losses were reduced to 2.3-6.5% by reconstruction using 2-3 projections at end/midoscillation phase. CONCLUSION: Amplitude had more impact than frequency on volume losses of moving phantoms on CBCT. Phase-specific CBCT reduced volume losses.

Extratesticular epidermoid cyst mimicking enlarged testis.

Epidermoid cysts are benign simple epithelial tumors usually appearing as hypoechoic lesions with scattered echogenic reflectors on sonography. Herein, we present a 53-year-old man with an extratesticular epidermoid cyst in the right scrotum which shows confusing sonographic findings, normal-appearing echogenicity of the lesion and atrophied testis, which lead to a diagnostic dilemma. With a variety of sonographic presentations in extratesticular epidermoid cysts, magnetic resonance (MR) imaging could play a complementary role in difficult cases.

Community-acquired Klebsiella pneumoniae complicated skin and soft-tissue infections of extremities: emphasis on cirrhotic patients and gas formation.

BACKGROUND: Klebsiella pneumoniae was rarely reported to cause complicated skin and soft tissue infections (cSSTIs). Our study was to delineate clinical characteristics and outcome of cSSTIs involving extremities caused by K. pneumoniae. PATIENTS AND METHODS: Adult patients aged 16 years or more with community-acquired cSSTIs, which involved the extremities and were caused by four common aerobic pathogens at a medical center in southern Taiwan during a 54-month period, were reviewed. RESULTS: Of 76 cases enrolled, Staphylococcus aureus was the most common pathogen (52 cases, 68%), followed by K. pneumoniae (16, 21%), beta-hemolytic streptococci (5, 7%), and Escherichia coli (3, 4%). Forty-six (61%) had underlying conditions, and diabetes mellitus was most common among K. pneumoniae and non-K. pneumoniae groups (63% and 45%, respectively). Compared to patients with cSSTIs caused by other bacteria, those with K. pneumoniae cSSTIs were predominantly male, more often had liver cirrhosis, malignant neoplasm and alcoholism. In addition, they were more likely to have fever, shock, bacteremia, gas formation, pyomyositis, metastatic infections, as well as longer durations of hospitalization. Using multivariate analysis, liver cirrhosis (adjusted odds ratio [aOR] 12.5, 95% confidence interval [CI] 2.0-79.1, p = 0.007) and male gender (aOR 11.5, 95% CI 1.1-116.8, p = 0.039) were significantly associated with K. pneumoniae cSSTIs. CONCLUSIONS: We highlight the role of K. pneumoniae in Taiwanese patients with cSSTIs involving extremities, and its potential for gas and pus formation, and metastatic infections. Empiric antimicrobial coverage of K. pneumoniae and close monitoring of metastatic infections are mandatory for patients with risk factors.

Arginine deprivation as a targeted therapy for cancer.

Certain cancers may be auxotrophic for a particular amino acid, and amino acid deprivation is one method to treat these tumors. Arginine deprivation is a novel approach to target tumors which lack argininosuccinate synthetase (ASS) expression. ASS is a key enzyme which converts citrulline to arginine. Tumors which usually do not express ASS include melanoma, hepatocellular carcinoma, some mesotheliomas and some renal cell cancers. Arginine can be degraded by several enzymes including arginine deiminase (ADI). Although ADI is a microbial enzyme from mycoplasma, it has high affinity to arginine and catalyzes arginine to citrulline and ammonia. Citrulline can be recycled back to arginine in normal cells which express ASS, whereas ASS(-) tumor cells cannot. A pegylated form of ADI (ADI-PEG20) has been formulated and has shown in vitro and in vivo activity against melanoma and hepatocellular carcinoma. ADI-PEG20 induces apoptosis in melanoma cell lines. However, arginine deprivation can also induce ASS expression in certain melanoma cell lines which can lead to in vitro drug resistance. Phase I and II clinical trials with ADI-PEG20 have been conducted in patients with melanoma and hepatocellular carcinoma, and antitumor activity has been demonstrated in both cancers. This article reviews our laboratory and clinical experience as well as that from others with ADI-PEG20 as an antineoplastic agent. Future direction in utilizing this agent is also discussed.