Abstract The International Agency for Research on Cancer declared that areca nut was carcinogenic to human. Areca nut is the main component of betel quid (BQ), which is commonly consumed in Asia. ...Epidemiological studies have shown that BQ chewing is a predominant risk factor for oral and pharyngeal cancers. It has been known that areca nut is genotoxic to human epithelial cells. However, the molecular and cellular mechanisms underlying areca nut-associated genotoxicity are not fully understood. Here we showed that arecoline, a major alkaloid of areca nut, might contribute to oral carcinogenesis through inhibiting p53 and DNA repair. We found, on the biological aspect, that arecoline could induce γ-H2AX phosphorylation, a sensitive DNA damage marker, in KB, HEp-2, and 293 cells, suggesting that DNA damages were elicited by arecoline. This phenomenon was supported by the observations of arecoline-induced hyperphosphorylation of ATM, Nbs1, Chk1/2, p53, and Cdc25C, as well as G2/M cell cycle arrest, indicating that a cellular DNA damage response was activated. To explore the possible mechanism accounting for arecoline-elicited DNA damages, we found that arecoline could inhibit p53 by its expression and transactivation function. As a result, the expression of p53-regulated p21WAF1 and the p53-activated DNA repair were repressed by arecoline. Finally, we showed that p53 mRNA transcripts were frequently down-regulated in BQ-associated oral cancer, suggesting that arecoline-mediated p53 inhibition might play a role in BQ-associated tumorigenesis.
High-pitched voice impairment (HPVI) is not uncommon in patients without recurrent laryngeal nerve (RLN) or external branch of superior laryngeal nerve (EBSLN) injury after thyroidectomy. This study ...evaluated the correlation between subjective and objective HPVI in patients after thyroid surgery.
This study analyzed 775 patients without preoperative subjective HPVI and underwent neuromonitored thyroidectomy with normal RLN/EBSLN function. Multi-dimensional voice program, voice range profile and Index of voice and swallowing handicap of thyroidectomy (IVST) were performed during the preoperative(I) period and the immediate(II), short-term(III) and long-term(IV) postoperative periods. The severity of objective HPVI was categorized into four groups according to the decrease in maximum frequency (Fmax): <20%, 20-40%, 40-60%, and >60%. Subjective HPVI was evaluated according to the patient's answers on the IVST.
As the severity of objective HPVI increased, patients were significantly more to receive bilateral surgery (p=0.002) and have subjective HPVI (p<0.001), and there was no correlation with IVST scores. Among 211(27.2%) patients with subjective HPVI, patients were significantly more to receive bilateral surgery (p=0.003) and central neck dissection(p<0.001). These patients had very similar trends for Fmax, pitch range, and mean fundamental frequency as patients with 20-40% Fmax decrease (p>0.05) and had higher Jitter, Shimmer, and IVST scores than patients in any of the objective HPVI groups; subjective HPVI lasted until period-IV.
The factors that affect a patient's subjective HPVI are complex, and voice stability (Jitter and Shimmer) is no less important than the Fmax level. When patients have subjective HPVI without a significant Fmax decrease after thyroid surgery, abnormal voice stability should be considered and managed. Fmax and IVST scores should be interpreted comprehensively, and surgeons and speech-language pathologists should work together to identify patients with HPVI early and arrange speech therapy for them. Regarding the process of fibrosis formation, anti-adhesive material application and postoperative intervention for HPVI require more future research.
Little is known about any consequences of swallowing tobacco‐free betel‐quid (TF‐BQ) juice/remnants following chewing and its carcinogenic impact on the upper aerodigestive tract (UADT) to ...gastrointestinal tract (GIT). We investigated the neoplastic impact of TF‐BQ on different anatomical locations along UADT and GIT, and differences according to their histological categories. We conducted a multicenter case–control study examining patients with 2,163 pathology‐proven UADT and GIT cancers, comparing them with 2,250 control subjects. Generalized additive models, piecewise regression and polytomous logistic models were applied to identify possible dose‐dependent structures and cancer risks. Contrary to nonsignificant GIT‐adenocarcinoma risk (aOR = 0.9), TF‐BQ users experienced a 1.7‐ to 16.2‐fold higher risk of UADT‐squamous cell carcinomas than nonusers, with the peak risk discovered in oral neoplasms. We separately observed a curvilinear and linear TF‐BQ dose‐risk relationship in oral/pharyngeal/esophageal and laryngeal cancers. Chewers of betel inflorescence were generally at a greater UADT cancer risk. A higher first‐piecewise increased risk of esophageal cancer was recognized among areca‐fluid swallowers than among nonswallowers (continuous aOR = 1.12 vs. 1.03). TF‐BQ use accounted for 66.1–78.7% and 17.8–33.2% of the cases of oral/pharyngeal and esophageal/laryngeal cancers, respectively. However, a reduction from heavy TF‐BQ consumption to low‐to‐moderate consumption only reduced 11.3–34.6% of etiologic fraction of oral/pharyngeal cancers. Alcohol supra‐additively modified the risk of TF‐BQ in determining the development of oral, pharyngeal and esophageal cancers. In conclusion, the interplay of TF‐BQ and alcohol/tobacco use, combined with how chewing habit is practiced, influences carcinogenic consequences on anatomically diverse sites of UADT and GIT cancers, and histologically different types.
We reported an integrated platform to explore serum protein variant pattern in cancer and its utility as a new class of biomarker panel for diagnosis. On the model study of serum amyloid A (SAA), we ...employed nanoprobe‐based affinity mass spectrometry for enrichment, identification and quantitation of SAA variants from serum of 105 gastric cancer patients in comparison with 54 gastritis patients, 54 controls, and 120 patients from other cancer. The result revealed surprisingly heterogeneous and most comprehensive SAA bar code to date, which comprises 24 SAA variants including SAA1‐ and SAA2‐encoded products, polymorphic isoforms, N‐terminal–truncated forms, and three novel SAA oxidized isotypes, in which the variant‐specific peptide sequence were also confirmed by LC‐MS/MS. A diagnostic model was developed for dimension reduction and computational classification of the 24 SAA‐variant bar code, providing good discrimination (AUC = 0.85 ± 3.2E−3) for differentiating gastric cancer group from gastritis and normal groups (sensitivity, 0.76; specificity, 0.81) and was validated with external validation cohort (sensitivity, 0.71; specificity, 0.74). Our platform not only shed light on the occurrence and modification extent of under‐represented serum protein variants in cancer, but also suggested a new concept of diagnostic platform by serum protein variant profile.
The aim of this study was to assess the risk of recurrent laryngeal nerve palsy (RLNP) after thyroidectomy with routine identification of the recurrent laryngeal nerve (RLN) during the operation.
The ...present study was confined to 521 patients, 348 total lobectomies and 178 total thyroidectomies, treated by the same surgeon. Temporary and permanent RLNP rates were analyzed for patient groups with stratification of primary operation for benign thyroid disease, thyroid cancer, Graves' disease, and reoperation. Measurement of the RLNP rate was based on the number of nerves at risk. Twenty-six RLNs in 20 thyroid cancer patients with intentional sacrifice were excluded from analysis.
Forty RLNs (40 patients) developed postoperative RLNP. Complete recovery of RLN function was documented for 35 of the 37 patients (94.6%) whose RLN integrity had been ensured intraoperatively. Recovery from temporary RLNP ranged from 3 days to 4 months (mean, 30.7 days). Overall incidence of temporary and permanent RLNP was 5.1% and 0.9%, respectively. The rates of temporary/permanent RLNP were 4.0/0.2%, 2.0/0.7%, 12.0/1.1%, and 10.8/8.1% for groups classified according to benign thyroid disease, thyroid cancer, Graves' disease, and reoperation, respectively.
Operations for thyroid cancer, Graves' disease, and recurrent goiter demonstrated significantly higher RLNP rates. Invasion of RLN was identified in 19.4% of patients with thyroid cancer. Postoperatively, the RLN recovered in most of the patients without documented nerve damage during the operation. Total lobectomy with routine RLN identification is recommended as a basic procedure in thyroid operations.
Background
The prognosis and quality of life (QOL) for those with cervical esophageal cancer is extremely poor, and chemoradiotherapy remains the mainstay treatment. During the past few years, our ...surgical teams has implemented a more aggressive and radical resection: total laryngopharyngectomy with neck dissection, total esophagectomy, and reconstruction with stomach. This study compares the results of chemoradiotherapy and that of the aforementioned surgical approach.
Methods
This is a retrospective study of 15 patients who underwent radical resection and 14 patients who received chemoradiation. Their age, sex, tumor stage and grade, pre- and posttreatment dysphagia scores, operating time, blood loss, length of intensive care and postoperative stay, days to resume oral intake, complications, Eastern Cooperative Oncology Group (ECOG) status, QOL score, and disease-specific survival were recorded and compared.
Results
There were no significant differences in age, sex, pretreatment dysphagia score, cancer stage and grade, ECOG status (posttreatment), associate diseases, preoperative QOL, or follow-up period between the two groups. However, the posttreatment dysphagia score was significantly better for the operative group (
P
< 0.001). QOL improved in both groups, and the operative group seemed better although the difference was not significant. In addition, the survival between the two groups was statistically insignificant (
P
= 0.97, log-rank test).
Conclusions
Our experience showed that radical surgery that includes total laryngopharyngectomy with neck dissection, total esophagectomy, and reconstruction with stomach for cervical esophageal cancer is beneficial to patients in terms of better eating.
DOI: 10.1002/pmic.201600356
A nanoprobe‐based affinity mass spectrometry platform to explore the under‐estimated serum protein variant patterns in cancer, and its utility as a new class of biomarker ...panel for diagnosis, is reported here. Using SAA as a model, the results not only revealed the surprisingly heterogeneous and most comprehensive SAA bar code to date, but also demonstrated its good discrimination for differentiating gastric cancer patients from gastritis and normal groups. This study suggests a new concept of diagnostic platform by protein variant profile. For more details, see the research article by Deng‐Chyang Wu et al., article number 1600356.
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