Genetic characteristics of a patient with multiple primary cancers: A case report.

BACKGROUND: Two or multiple primary malignant neoplasms (MPMNs) rarely occur in the same patient. It has been reported that MPMNs are easily misdiagnosed as the recurrence or metastasis of malignancies in clinical practice, affecting the choice of treatment for the patients, thereby resulting in the delay of optimal diagnosis. Next generation sequencing (NGS) can be used to distinguish between multiple primary lung cancers and intrapulmonary metastasis, and may distinguish the origin of tumours in different sites of the body. CASE SUMMARY: We report the case of 66-year-old woman who suffered from different malignant neoplasms in the rectum and esophageal and gastrointestinal tract. The first neoplasm rectal adenocarcinoma was diagnosed and removed in 2016. The second and third lesions were diagnosed with esophageal squamous-cell carcinoma (ESCC) and gastrointestinal stromal tumour (GIST), respectively, in 2019. Next-generation whole exome sequencing was performed on the tissue specimens of rectal carcinoma, esophageal cancer, GIST, and white blood cells to investigate the relationship between malignancies at different timeframe and determine whether the ESCC and GIST evolved from the rectal adenocarcinoma. Mutations including v-Ki-ras2-Kirsten rat sarcoma viral oncogene homolog, adenomatosis polyposis coli, and mothers against decapentaplegic homolog 4 were detected in rectal adenocarcinoma sample, mast/stem cell growth factor receptor was detected in GIST tissue, and lysine methyltransferase 2D was detected in ESCC specimen. Overall, ESCC and GIST were not genetically evolved from rectal adenocarcinoma, and this patient did not have a trunk driven clone. CONCLUSION: NGS is an effective tool to study clonal evolution of tumours and distinguish between MPMNs and intrapulmonary metastasis.

Effects of melatonin to arecoline-induced reactive oxygen species production and DNA damage in oral squamous cell carcinoma.

BACKGROUND/PURPOSE: Arecoline, the major alkaloid of areca nut, is known to induce reactive oxygen species (ROS) and DNA damage during oral cancer progression. This study aim to evaluate whether melatonin, an antioxidant, supported or repressed the arecoline-induced carcinogenesis phenotypes in oral squamous cell carcinoma (OSCC). METHODS: The cytotoxicity of arecoline or melatonin treatment alone and their co-treatment in the OSCC cell line OEC-M1 were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cell cycle, cell death, and total ROS production were analyzed using flow cytometer. The protein expression was determined using western blot analysis. The genotoxicity and mutation rate were determined using micronucleus assay and hypoxanthine phosphoribosyl transferase (HPRT) forward mutation assay, respectively, in CHO-K1 cells. The ataxia telangiectasia mutated (ATM) promoter activity and DNA repair ability were determined through reporter assay. RESULTS: The result showed that both the arecoline and melatonin induced ROS production and antioxidant enzymes expression. Melatonin treatment enhanced arecoline-induced ROS production, cytotoxicity, G2/M phase arrest, and cell apoptosis in OSCC cells. On the other hand, melatonin treatment activated DNA repair activity to reverse arecoline-induced DNA damage and mutation. CONCLUSION: These results indicated that melatonin is a potential chemopreventive agent for betel quid chewers to prevent OSCC initiation and progression.

[Time-dependent heart rate variability in the head-up tilt test in children with postural orthostatic tachycardia syndrome].

OBJECTIVE: To study the time-dependent heart rate (HR) variability in the head-up tilt test (HUTT) in children with postural orthostatic tachycardia syndrome (POTS) and to explore the HR diagnostic criteria for POTS in children. METHODS: A retrospective analysis was performed on the clinical data of 105 children diagnosed with POTS with HR≥120 beats per minute (bpm) within the first 10 minutes of HUTT between January 2007 and December 2014. Their HR variability within the first 10 minutes of HUTT was analyzed. RESULTS: The HR of children with POTS increased gradually from the supine position to a 60° head-up tilt position, and the increase in HR was 24±12 bpm at the beginning of HUTT, 30±14 bpm at 3 minutes of HUTT, 32±13 bpm at 5 minutes of HUTT, and 38±12 bpm at 10 minutes of HUTT. The average maximal HR increase within the first 10 minutes of HUTT was 43±10 bpm. CONCLUSIONS: In children with POTS, the HR variability gradually increases with time, and therefore, it is suggested that HR increase ≥40 bpm is more suitable for diagnosis of POTS in children.

[Evaluation of psychological fear in children undergoing head-up tilt test].

OBJECTIVE: To investigate the effects of different tilt angles of head-up tilt test (HUTT) and different responses to HUTT on the psychological fear in children undergoing the test. METHODS: HUTT was performed on children with unexplained syncope or pre-syncope (107 cases: 52 males and 55 females), aged 5.5-17.8 years (mean 12.0±2.8 years). All subjects were randomly assigned to undergo HUTT at an angle of 60°, 70° or 80°; the negative cases underwent sublingual nitroglycerin-provocation HUTT at the same tilt angle. The Wong-Baker Faces Pain Rating Scale was used for self-assessment of psychological fear in subjects during HUTT at the end point of the test. RESULTS: The positive rate, hemodynamic changes and distribution of response types showed no significant differences between children at tilt angles of 60°, 70° and 80° (P>0.05). The greater the tilt angle, the higher the degree of psychological fear in children undergoing the test, but there were no significant differences between them (P>0.05). The degree of psychological fear in children who showed a positive response to HUTT (n=76) was significantly higher than that in children who showed a negative response (n=31) (P<0.01). CONCLUSIONS: HUTT can cause psychological fear in children undergoing the test, and the degree of psychological fear increases in children tested at tilt angles from 60° to 80°, but the differences have no statistical significance. A positive response to HUTT can significantly increase the psychological fear in children.

[Clinical significance of changes in T wave and ST segment amplitudes on electrocardiogram from supine to standing position among children with unexplained chest tightness or pain in resting stage].

OBJECTIVE: To investigate the clinical significance of changes in T wave and ST segment amplitudes on electrocardiogram (ECG) from supine to standing position in children with unexplained chest tightness or pain in resting stage. METHODS: A total of 122 6-14-year-old children with a chief complaint of unexplained chest tightness or pain (resting stage) underwent head-up tilt test (HUTT). According to HUTT results, these children were divided into HUTT-positive (n=61) and HUTT-negative groups (n=61). They underwent 12-lead ECG in the supine and standing positions, and heart rate and T wave and ST segment amplitudes in II, III, aVF and V5 leads were measured. RESULTS: In the HUTT-negative group, heart rates were significantly higher in the standing position than in the supine position (P<0.05), T wave amplitudes in II, III, aVF, and V5 leads were significantly lower in the standing position than in the supine position (P<0.05), and ST segment amplitudes in II, aVF and V5 leads were significantly higher in the standing position than in the supine position (P<0.05). In the HUTT-positive group, heart rates were significantly higher in the standing position than in the supine position (P<0.05), T wave amplitudes in II, III, aVF and V5 leads were significantly lower in the standing position than in the supine position (P<0.05), and ST segment amplitude in V5 lead was significantly higher in the standing position than in the supine position (P<0.05). There were no significant differences between the two groups with respect to ST segment amplitude and T wave amplitude in II, III and aVF leads of the supine or standing position (P>0.05). Compared with the HUTT-negative group, the HUTT-positive group had significantly greater T wave amplitude differences in II, III, aVF and V5 leads, and heart rate difference from supine to standing position (P<0.05). CONCLUSIONS: Among the children with unexplained chest tightness or pain in resting stage, T wave amplitude differences in II, III, aVF and V5 leads and heart rate difference from supine to standing position are greater in the HUTT-positive group than in the HUTT-negative group. This suggests that the changes in T wave amplitude on ECG from supine to standing position can indicate autonomic nervous system dysfunction.

[Investigation of 24-hour blood pressure monitoring for evaluating treatment outcome of nerve-mediated syncope in children].

OBJECTIVE: To investigate the clinical significance of 24-hour blood pressure monitoring (ABPM) for evaluating the treatment outcome of nerve-mediated syncope (NMS) in children. METHODS: Twenty-eight children with NMS confirmed by a head-up tilt table test (HUTT) (12 males and 16 females, aged 6-13 years) and with a chief complaint of unexplained syncope or pre-syncope between February 2010 and August 2012, were included in the study. These children received health education combined with therapy using oral rehydration salts solution and were then reexamined for clinical symptoms as well as HUTT and ABPM results. RESULTS: Of 28 NMS cases, 22 were vasodepressive type, 5 were mixed type, and 1 was cardioinhibitory type. The follow-up showed that 27 (96%) of all cases had improved clinical symptoms, and 18 (64%) had improved HUTT results. The ABPM follow-up revealed no significant changes in 24-hour mean systolic pressure, 24-hour mean diastolic pressure, daytime mean systolic pressure, daytime mean diastolic pressure, nighttime mean systolic pressure, nighttime mean diastolic pressure, day-night difference of systolic pressure, and day-night difference of diastolic pressure after treatment (P>0.05). The percentage of children with a dipper blood pressure pattern increased from 29% (8/28) before treatment to 50% (14/28) after treatment; the percentage of children with a non-dipper blood pressure pattern decreased from 71% (20/28) before treatment to 50% (14/28) after treatment. CONCLUSIONS: As an effective, objective and non-invasive monitoring means, ABPM is of some clinical significance for evaluating the treatment outcome of NMS in children.

[Causes of unexplained syncope in children].

OBJECTIVE: To investigate the common causes of unexplained syncope in children. METHODS: A total of 434 children with unexplained syncope who were aged from 3.0 to 17.9 years (192 males and 242 females) and who saw the doctor between January 2006 and October 2011. were examined in order to explore the detailed histories and causes of syncope and to analyze variance in causes among different ages, genders, syncope frequencies and head-up tilt test (HUTT) results. RESULTS: (1) The causes of occasional syncope included persistent standing (30%), movement (13%), change in body position(9%), sitting(7%), and playing(6%). Persistent standing was more common as a cause in females than in males (P<0.01). Micturition syncope was mainly seen in males. Sultry weather was the main cause of syncope in females. Change in body position was a more common cause in the ≥12 years group than in the <12 years group (P<0.05), while other causes showed no significant differences among different age groups. Change in body position was a more common cause of syncope in children with negative HUTT results than in those with positive HUTT results (P<0.05). (2) All causes of occasional syncope can induce repeated syncope, and most repeated syncope (56%) had the same cause. CONCLUSIONS: The common causes of unexplained syncope include persistent standing, movement and changes of body position in children. Avoiding these causes is helpful for prevention of childhood syncope.

[Diagnosis of vasovagal syncope in children with postural orthostatic tachycardia syndrome].

OBJECTIVE: To study the diagnosis of vasovagal syncope (VVS) in children with postural orthostatic tachycardia syndrome (POTS). METHODS: The clinical data of 57 children with POTS diagnosed by the head-up tilt test between January 2007 and December 2010 were studied retrospectively. Of the 57 children, there were 29 boys and 28 girls who were aged from 5 to 16 years (12.2±1.9 years). RESULTS: Twenty-four (42%) out of 57 children were diagnosed with VVS by prolonging the duration of the head-up tilt test (for the children with orthostatic tolerance): cardioinhibitory (20 cases), mixed (3 cases) and vasoinhibitory (1 case). The POTS children with VVS were older than those without (13.0±1.4 years vs 11.5±2.1 years; P<0.05). There were no significant differences in gender and clinical symptoms between the POTS children with and without VVS. CONCLUSIONS: Some children with POTS may have coexisting VVS, suggesting that it is important to avoid misdiagnosis of VVS by prolonging the duration of head-up tilt test in POTS children with orthostatic tolerance. There are no obvious differences in gender and clinical symptoms between the POTS children with and without VVS.

[Arrhythmia after a positive head-up tilt table test].

OBJECTIVE: to study the characteristics of arrhythmia after a positive head-up tilt table test (HUTT). METHODS: head-up tilt table test (BHUT) or sublingual nitroglycerin-provocation head-up tilt table test (SNHUT) were performed in 1374 patients at the Second Xiangya Hospital of Central South University from March of 2001 to August of 2009. Arrhythmias were recorded in 169 patients after a positive HUTT [57 male, age 6 - 65 years, 86 children < 18 years, mean age (23.1 ± 14.8) years]. RESULTS: arrhythmias developed in 75 patients (44.38%) post a positive BHUT and in 94 patients (55.62%) post a positive SNHUT. Major types of arrhythmias were sinus bradycardia (143/169, 84.62%), junctional escape rhythm (55/169, 32.54%) and sinus arrest (26/169, 15.38%). Sinus bradycardia was more common in adult (P < 0.01). Occurrence of junctional escape rhythm and sinus arrest was not affected by age, gender and test mode. Arrhythmia and the manifestation of syncope or pre-syncope occurred simultaneously in 77 (45.56%) patients and mainly in BHUT, while arrhythmia appeared later than the syncope manifestation in 92 (54.44%) patients and mainly in SNHUT (P < 0.05). Arrhythmia and blood pressure reduction occurred simultaneously in 84 (53.50%) cases and mainly in BHUT, while arrhythmia appeared later than reduction of blood pressure in 73 (46.50%) cases and mainly in SNHUT (P < 0.01). CONCLUSIONS: (1) the common types of arrhythmia were sinus bradycardia, junctional escape rhythm and sinus arrest after a positive HUTT. Occurrence of sinus arrest was not affected by age, gender and test mode. (2) In BHUT, arrhythmia occurred mostly simultaneously with the manifestation of syncope or pre-syncope and blood pressure reduction, while arrhythmia appeared later in SNHUT.

[Clinical analysis of vasovagal syncope in children].

OBJECTIVE: To study the changes in clinical features of vasovagal syncope (VVS) in children. METHODS: From January 2000 to September 2009, 841 children with unexplained syncope or prodromata were enrolled. They were assigned to two groups according to the period of visiting hospital: group A (from January 2000 to December 2004, n=129) and group B (from January 2005 to September 2009, n=712). They were assigned to three age groups: 4-6 years old, 7-10 years old and 11-18 years old. A head-up tilt table test (HUTT) was performed on all the subjects. RESULTS: The total positive rate of HUTT was 45.3% (381/841). Compared with that in group A, the positive rate of HUTT in group B increased significantly (47.5% vs 33.3%; P<0.05). The positive rate of HUTT in female children was significantly higher than that in male children (49.3% vs 37.9%; P<0.05). The positive rate of HUTT increased with age and it was the highest in children at age of 11-18 years (49.2%), followed by in children at age of 7-10 years (44.1%) and 4-6 years (37.1%) (P<0.05). The children at age of 7-10 years and 11-18 years from group B showed significantly higher positive rate of HUTT than those from group A (46.2% vs 27.8%; 54.0% vs 32.6%, P<0.05). Vasodepressor type was the most common response type (70.9%) shown by HUTT compared with mixed type (25.5%) and cardioinhibitory type (3.6%) (P<0.05). The proportion of children with vasodepressor response type in group B was significantly higher than that in group A (72.5% vs 58.1%; P<0.05). CONCLUSIONS: There were obvious changes in the prevalence of VVS and response types before and after five years, suggesting that the development of VVS may be attributed to many factors, such as social factors, mental factor and life style.

[Efficacy of midodrine hydrochloride in the treatment of children with vasovagal syncope].

OBJECTIVE: To explore the efficacy of midodrine hydrochloride in the treatment of vasovagal syncope (VVS) in children. METHODS: Forty-eight children with unexplained syncope and prodromata (21 males, 27 females, aged 6 -17 years, mean 11 years +/- 3 years) were randomly assigned into 3 groups. They were health education group, cresol group and midodrine hydrochloride group respectively. Cresol group was comprised of children given cresol as first-line therapy in addition to health education and midodrine hydrochloride group patients given midodrine hydrochloride on the basis of cresol group. Repeated head-up tilt testing (HUTT) and follow-ups of at least 6 months were conducted to evaluate the therapeutic efficacy, side effects of midodrine hydrochloride and hemodynamic changes in treating pediatric VVS. RESULTS: (1) The HUTT-based effective rate of 3 group was 20.0% (2/10), 60.9% (14/23) and 80.0% (12/15) respectively. It was significantly higher in cases of midodrine hydrochloride group and cresol group than that of health education group (P < 0.05). However,there was no significant difference in the HUTT-based effective rate between cresol group and midodrine hydrochloride group (P > 0.05). (2) During the follow-up period, the recurrence rate of syncope was significantly lower in midodrine hydrochloride group than in other two groups (P < 0.05). However, there was no significant difference in the recurrence rate of syncope between health education and cresol groups (P > 0.05). (3) There was no statistic difference in supine hemodynamic indices (HR, SBP, DBP) between before and after treatment in 3 groups. After midodrine therapy, the effects of midodrine upon changes in systolic and diastolic pressures and heart rate, between upright beginning and supine positions, were statistically significant (P <0.05). CONCLUSION: Health education and cresol are conventional therapies for pediatric VVS. The efficacy can be enhanced by supplementing midodrine hydrochloride. Such a regimen is effective and safe in treating pediatric VVS.