A propensity score matching analysis of gasless endoscopic transaxillary thyroidectomy with five-settlement technique versus conventional open thyroidectomy in patients with papillary thyroid microcarcinoma.

BACKGROUND: In a previous study, we proposed a novel anatomy-based five-settlement method for transaxillary endoscopic thyroidectomy (fs-TAT) for patients with papillary thyroid carcinoma. The safety of this new method has been reported in a retrospective study of a single cohort. The safety and short-term oncological outcome of this method was confirmed by comparing it with conventional open surgery (COT) in patients with papillary thyroid microcarcinoma. METHODS: The medical records of patients who underwent fs-TAT or COT by a single surgeon from February 2019 to December 2021 were reviewed retrospectively. All patients were diagnosed with papillary thyroid microcarcinoma and underwent lobectomy and ipsilateral central compartment neck dissection. Propensity score matching was used to compare the technical safety and short-term oncologic outcomes of fs-TAT and COT for the purpose of reducing potential selection bias. Reporting was consistent with the STROCSS 2021 guidelines. RESULT: After propensity score matching, 460 (fs-TAT: 230; COT: 230) patients remained in the study population. There were no significant differences in sex, age, tumor size, Hashimoto's thyroiditis, or tumor multifocality between the groups. The operative time was longer [104.5 (90.3, 120.0) vs. 62.0 (52.0, 76.0), P < 0.001] and the total postoperative drainage volume [135(90, 210) vs. 75 (55, 115), P < 0.001] was greater in the fs-TAT group than in the COT group. However, intraoperative bleeding [3.0 (2.0, 5.0) vs. 5.0 (5.0, 7.5), P < 0.001] was greater, and the median number of lymph nodes yielded [5.0 (2.3, 8.0) vs. 7.0 (5.0, 11.0), P < 0.001] was greater in the COT group than in the fs-TAT group. The groups exhibited no significant difference in the rate of complications (fs-TAT: 2.2% vs. COT: 2.6%, P = 0.856), rate of positive lymph nodes (fs-TAT: 32.2% vs. COT: 36.5%, P = 0.377), length of postoperative hospital stay (3 days vs. 3 days, P = 0.305) or total medical costs (26,936 vs. 26,549, P = 0.144). CONCLUSION: Compared to conventional open surgery, fs-TAT offered excellent safety and acceptable short-term oncological outcomes in a selected cohort of patients with papillary thyroid microcarcinoma.

The effect of preservation of the supraclavicular nerve on sensation recovery in endoscopic thyroidectomy via a gasless anterior chest approach: A prospective study.

BACKGROUND: Factors to sensory change on the neck and chest after endoscopic thyroidectomy were not well studied. The aim of this study was to assess whether preservation of the supraclavicular nerve (SCN) could make a difference. METHODS: 33 cases with the SCN preserved (Group A) and 32 cases with the SCN damaged (Group B) were recruited. Evaluation of tactile sensitivity and pain sensitivity as well as a questionnaire concerning subjective symptoms and quality of life was also administered preoperatively and postoperatively. RESULTS: Sensation in the anterior chest of Group A had milder loss and reached preoperative level within the 1-year follow-up while that of Group B still showed deficit beneath the clavicle. Group A also had smaller proportion of numbness, symptomatic extension, psychological impact in early postoperative time. CONCLUSION: Protection of the SCN can improve sensation recovery in the anterior chest and enhance the quality of life after surgery.

Characteristics of the parathyroid gland in endoscopic thyroidectomy with the application of an image enhancement system.

BACKGROUND: To assist surgeons in identifying and preserving the parathyroid gland (PTG) in endoscopic thyroidectomy (ET), we have summarized the characteristics of the PTG and the surrounding tissues in ET by applying the Storz Professional Image Enhancement System (SPIES). METHODS: From November 2014 to May 2016, 182 patients with 613 suspected PTGs were included in our study. The shape, color, area, and density of surface blood vessels (SBVs); whether they were encapsulated with adipose tissue; and whether congestion was present during the operation were summarized. The κ coefficient of interobserver agreement in assessing the area and the density of SBVs of suspected PTGs with and without Spectra A (SA) and Spectra B (SB) modalities were calculated. Multiple binary logistic regression analyses were performed to determine the predictive value of different characteristics for detecting the PTG in ET with the application of SPIES. RESULTS: With visual identification and histopathological results as reference standards, 291 targeted tissues were identified as PTGs, 256 as adipose tissue, 43 as lymph nodes, and 23 as thyroid tissue. The κ coefficients of interobserver agreement in assessing SBV density with or without the SA and SB modalities were 0.944 ± 0.013 and 0.859 ± 0.021, respectively, and those in assessing SBV area were 0.937 ± 0.014 and 0.841 ± 0.022, respectively. In the comparison between PTGs and other tissues, multiple binary logistic regression analysis revealed that shape, color, SBV density, congestion, and whether tissue was encapsulated with adipose tissue were independent predictive factors of PTGs. CONCLUSION: With the application of SPIES, the shape, color, density of SBVs, adipose tissue encapsulation, and congestion were independent factors that predicted PTGs in ET. The SA and SB modalities of SPIES could improve the reliability of SBV density and area classifications in targeted tissues.

Three-dimensional versus two-dimensional endoscopic-assisted thyroidectomy via the anterior chest approach: a preliminary report.

OBJECTIVE: The objective of the study was to evaluate the safety and effectiveness of three-dimensional (3D) endoscopy for thyroidectomy and compare it to two-dimensional (2D) endoscopy. The major limitations of conventional endoscopy include its lack of depth perception and tactile feedback. The 3D endoscopy technique, which involves 3D imaging, is widely used. However, few reports have described the use of 3D endoscopic systems in thyroid surgery. METHOD: In this single-institutional study, 103 consecutive patients who underwent endoscopic thyroidectomy between July 2013 and April 2014 were enrolled. Of these, 32 patients chose 3D endoscopy, and 71 patients chose 2D endoscopy and were used as a control group. All patients were stratified by type of operation. RESULT: All 103 patients underwent a successful endoscopic-assisted thyroidectomy with no conversion to open surgery. There were no differences in operation time, intraoperative bleeding, postoperative drainage, the number of lymph nodes (LNs) dissected, major complications, and hospital stays. During a median follow-up of 28.0 months, no patients experienced a recurrence of thyroid cancer. CONCLUSION: Our preliminary report demonstrates that 3D endoscopy achieved the same level of safety and effectiveness as 2D endoscopy in endoscopic-assisted thyroidectomies. Additionally, 3D endoscopy provided good depth perception and allowed the surgeon to easily recognize critical anatomical landmarks. Further large-scale studies, preferably prospective randomized control trials, are required to confirm this finding.

Endoscopic-assisted selective neck dissection via small lateral neck incision for early-stage (T1-2N0M0) head and neck squamous cell carcinoma: 3-year follow-up results.

BACKGROUND: Primary tumors of early-stage (T1-2N0M0) head and neck squamous cell carcinoma (HNSCC) can be treated by transoral minimally invasive surgery, but the cervical lymph node lacks corresponding minimally invasive treatment. Therefore, our study was to evaluate the safety and effectiveness of endoscopic-assisted selective neck dissection (EASND) via small lateral neck incision in treatment of early-stage HNSCC. METHODS: From May 2008 to April 2012, 29 patients with early-stage HNSCC were enrolled in this retrospective study. EASND via small lateral neck incision was followed by primary tumors treated by transoral endoscopy or CO2 laser microsurgery in all patients. The clinical data and follow-up results were analyzed retrospectively. RESULTS: Twenty-nine patients (male 22, female 7) were successfully treated by EASND and no case conversed to open surgery. EASND included eight cases of level I-III and 21 cases of level II-IV. The operative time was 68.4 ± 10.3 min, and the operative bleeding was 40.8 ± 12.4 ml. The number of lymph nodes was 19.1 ± 4.1. There were 19 cases of T1, 10 cases of T2, 22 cases of N0, 7 cases of N1, no cases with positive margin or extracapsular spread in lymph node. Temporary sensory changes in the postauricular area occurred in two cases, both recovered within 3 months after the surgery, postoperative seromas occurred in one case. No patient showed postoperative bleeding, chylous fistula, incision infection, facial nerve injury, and accessory nerve injury. All patients were satisfied with the postoperative cosmetic results. The 3-year OS was 96.5 %, while DFS, LRFS, and DMFS were 100 %. CONCLUSION: EASND via small lateral neck incision is a feasible and safe technique with achieved short-term oncologic outcomes in early-stage (T1-2N0M0) HNSCC patients. But the long-term results of EASND on oncologic safety and functional outcomes are required to confirm by larger, randomised studies.

Endoscope-Assisted Resection of Elongated Styloid Process Through a Retroauricular Incision: A Novel Surgical Approach to Eagle Syndrome.

PURPOSE: Conventional resection of the elongated styloid process is associated with large-scale tissue dissection and poor surgical exposure. The purpose of this study was to show the feasibility, efficacy, and safety of a novel surgical approach using an endoscopic technique to treat Eagle syndrome. MATERIALS AND METHODS: The authors implemented a retrospective cohort study composed of 133 patients undergoing endoscope-assisted styloidectomy (EAS) from June 2010 to August 2015 at a university teaching hospital. Outcome measurements included the length of the styloid process, blood loss, and duration of surgery. The simple verbal response scale for symptom relief, cosmetic appearance of the incision, and postoperative incision pain was used for the assessment of patients' subjective satisfaction. RESULTS: All patients underwent EAS without conversion to conventional surgery. One hundred seven patients (80.5%) achieved complete relief of symptoms, with 20 (15%) achieving partial relief. The residual length of the styloid process was 10.1 ± 4.4 mm. One hundred seventy-two incision sides (75.8%) had no pain during the postoperative evaluation. One side (0.4%) showed slight transient facial paresis and 4 sides (1.8%) presented transient ear numbness. The vast majority of patients (122 of 133; 91.7%) considered the cosmetic appearance of the incision to be excellent. CONCLUSIONS: The results of this study suggest that EAS provides a viable surgical approach for Eagle syndrome in efficacy and safety.

The experience of gasless endoscopic-assisted thyroidectomy via the anterior chest approach for Graves' disease.

The aim of this study was to evaluate the safety, feasibility, effectiveness, and cosmesis of a gasless endoscopic-assisted thyroidectomy via the anterior chest in patients with Graves' disease. We retrospectively reviewed 38 patients with Graves' disease treated with thyroidectomy from November 2007 to June 2015. We analyzed clinical characteristics of patients, type of operation, operative indications, operative duration, length of postoperative hospital stay, and postoperative complications. The thyroidectomies were classified as total thyroidectomy (n = 12) or near-total thyroidectomy with a remnant of <1 g (n = 26). Surgical indications were recurrence after antithyroid drugs (ATDs) and unwillingness to undergo radioiodine therapy (n = 27), local compressive symptoms (n = 2), adverse drug reactions to ATDs (n = 5), and patient's preference (n = 4). Mean resection weight was 71.7 ± 16.2 g (range 44-109 g), mean operative duration 87.7 ± 17.3 min (range 66-136 min), intraoperative blood loss 70.6 ± 11.3 mL (range 43-92 mL), and drainage was 42.0 ± 8.5 mL (range 20-62 mL). Temporary postoperative recurrent laryngeal nerve palsy and temporary hypoparathyroidism occurred in 3 cases (7.89 %) each. Mean hospital stay was 2.5 ± 0.3 days (range 2-4 days). There was no recurrence of hyperthyroidism over the follow-up period of for 68.1 ± 5.6 months (range 6-89 months). All patients were satisfied with their cosmetic results. Gasless endoscopic-assisted thyroidectomy via the anterior chest approach for Graves' disease is a safe, feasible, and effective and provides an excellent cosmetic outcome procedure. It is a valid option in appropriately selected patients.

A modified, single-incision, gasless, endoscopic thyroidectomy and bilateral central neck dissection via axillary approach technique for bilateral papillary thyroid microcarcinoma: A preliminary report.

Background: Our objective was to assess the viability and oncological security of a gasless, transaxillary single-incision endoscopic procedure for performing total thyroidectomy and bilateral central neck dissection (TT + BCND). This study focused on patients diagnosed with bilateral papillary thyroid microcarcinoma (PTMC). Method: Between April 2020 and November 2021, 22 patients with bilateral PTMC underwent single-incision, gasless, transaxillary endoscopic TT + BCND. The patients' clinicopathologic characteristics, surgical completeness and complications were analyzed. Result: Single-incision, gasless, transaxillary endoscopic TT + BCND was successful performed in all patients. The median (IQR) total surgical time was 143 (85-160) min. Only two patients experienced transient unilateral RLN palsy or transient hypocalcemia. All these complications resolved within 1 month after surgery. The median duration of hospital stay after surgery was 4 (3-4.5) days. The median hospitalization expense for these patients was 3848 (3781-4145) USD. The median number of lymph node yielded was 10.5 (8-15). The cosmetic outcomes were well-received by all individuals. Conclusion: In certain cases, gasless, transaxillary endoscopic TT + BCND procedure performed through a single incision proved to be a secure alternative for managing bilateral PTMC.

Analysis of scene-guided camera assistance in transaxillary gasless endoscopic thyroidectomy: a minor improvement in operative technique.

Background: Transaxillary gasless endoscopic thyroidectomy (TGET) is a widely performed operation, but its side view angle and instrument interference have caused concerns for most surgical groups. The aim of this study was to introduce scene-guided camera assistance (SGA) and analyze its role in facilitating TGET. Methods: We put forward key points for camera holders, including one pivot, two positions, and three planes, and separated TGET operations into five parts. We also established the view angle for each part of the operation for the camera holder to follow. Then, we reviewed 416 patients who underwent TGET with or without SGA and analyzed their demographic characteristics, operative outcomes, pathologic outcomes, and early complications. Results: The TGET and TGET-SGA groups were similar in terms of age, sex ratio, height, weight, tumor size, Hashimoto's thyroiditis ratio, and cN1 ratio. The operation time and postoperative hospital stay were significantly longer in the TGET group than in the TGET-SGA group (114.43 ± 17.20 minutes vs. 101.82 ± 19.39 minutes and 3.16 ± 0.77 days vs. 2.16 ± 0.55 days, respectively, P < 0.001). The account of retrieved lymph nodes was less in the TGET group than in the TGET-SGA group (5.61 ± 4.27 vs. 6.57 ± 4.96, P = 0.038). Conclusion: SGA provided guidance for camera holders, and the data showed that it was an improvement for TGET operations.

The learning curve for gasless transaxillary posterior endoscopic thyroidectomy for thyroid cancer: a cumulative sum analysis.

Gasless transaxillary posterior endoscopic thyroidectomy (GTPET) is a new approach for thyroid cancer. It allows en bloc resection of the thyroid and central lymph nodes. Few studies have reported on the learning curve for GTPET.We examined the learning curve of GTPET for thyroid cancer by cumulative sum (CUSUM) analysis by retrospectively analyzing patients who underwent hemithyroidectomy with ipsilateral central neck dissection between December 2020 and September 2021 at a tertiary medical center, including the first patient. Moving average analysis and sequential time-block analysis were used for validation. Data on the clinical factors between the two periods were compared. In the overall cohort, the average time for GTPET for thyroid cancer was 113.25 min to harvest an average of 6.4 central lymph nodes. The CUSUM curve of the operative time indicated an inflection point after 38 patients. Moving average analysis and sequential time-block analysis validated the number of procedures needed for GTPET proficiency. (124.05 min vs. 107.63 min for the unproficient period vs. proficient period, respectively; P < 0.001) The number of retrieved lymph nodes was not associated with a certain level of proficiency per the learning curve. The main complication during the surgeon's unproficient period was transient hoarseness (3/38), which was similar to that in their proficient period (2/73, p = 0.336). Proficiency in GTPET is associated with performing more than 38 procedures. Standard course training and instruction on careful management are required prior to introducing the procedure.

A novel anatomy-based five-settlement method for endoscopic thyroid lobectomy and ipsilateral central compartment neck dissection via gasless unilateral axillary approach: a preliminary report.

Background: Endoscopic thyroidectomy (ET) via gasless unilateral axillary (GUA) approach has been widely implemented worldwide. Based on our concept of mesothyroid excision in open surgery, we proposed a novel anatomy-based five-settlement method in ET via the GUA approach. This preliminary report aimed to explore the efficacy and safety of this method in patients with papillary thyroid carcinoma (PTC). Methods: PTC patients who underwent endoscopic ET and unilateral central compartment neck dissection (CCND) via GUA approach with the five-settlement method at the Department of General Surgery, Nanfang Hospital, Southern Medical University from March 2020 to December 2021 were retrospectively collected. The data included general clinicopathological characteristics, surgical information (including duration, complication, and clinicopathological features), and hospital stay information, and other medical records were documented. Results: In total, 521 patients underwent lobectomy and CCND under the GUA approach with the five-settlement method. The mean number of lymph nodes yielded (LNY) and positive lymph nodes (PLN) was 5.7 ± 4.3 (range, 1-30) and 1.0 ± 1.8 (range, 0-12), respectively. The incidence of transient recurrent laryngeal nerve injury was 1.1%. Chyle leakage and Horner's syndrome respectively occurred in one patient (0.2%). Five (0.9%) patients developed a hematoma. No severe complications or conversion to open surgery have occurred. Conclusion: The five-settlement method could be implemented safely and efficiently in ET+CCND via the GUA approach in selected PTC patients.

Right gasless transaxillary endoscopic total thyroidectomy (RGTETT) with video: our experience with the posterior approach: Lei's seven-sinking method.

Our video demonstrates a modified gasless transaxillary endoscopic thyroid surgery with the posterior approach for bilateral low-risk thyroid cancer. In this paper, we provided a detailed introduction to the right gasless transaxillary endoscopic total thyroidectomy surgical procedure for bilateral low-risk thyroid cancer, and briefly summarized the Lei's seven-sinking method: sinking the clavicular head of the sternocleidomastoid muscle (CHSCM); sinking the cervical vascular sheath; sinking the right wall of the esophagus; sinking the right recurrent laryngeal nerve (RLN); sinking the trachea; sinking the left RLN and sinking the thyroid. A 5-cm incision was made starting from the anterior axillary line along the natural fold at the axilla. A trocar was placed in the axillary incision approximately 3-5 cm away from the side of the breast and slightly below the anterior axillary line. Using blunt dissection and electrocautery, a working space was created by elevating a subcutaneous flap above the pectoralis major muscle. The thyroid bed was accessed through the two heads of the SCM, and then the thyroid was separated from the strap muscles. Thyroidectomy and central lymph node dissection were fully endoscopically performed with the posterior approach using conventional endoscopic instruments. Through the posterior approach and the operation steps of the seven-sinking method, total thyroidectomy and bilateral central lymph node dissection can be achieved relatively easily.

The lymph node yield in the initial lateral neck dissection predicts recurrence in the lateral neck of papillary thyroid carcinoma: a revision surgery cohort study.

BACKGROUND: This study aimed to evaluate the relationship between lateral lymph node yield (LLNY) and the ratio of lateral positive lymph nodes to lymph node yield (LPLR) from initial lateral neck dissection (LND) in patients with papillary thyroid carcinoma (PTC), as well as the risk of recurrence in patients undergoing LND reoperations. METHODS: This retrospective cohort study enrolled patients with PTC who underwent revision LND between 1 January 2012, and 31 December 2021. The initial and revised clinical data were retrieved. Patient demographics, clinicopathological features, clinical records, and follow-up information were also reviewed. LLNY and LPLR were determined during the initial LND. RESULTS: In total, 156 patients with PTC were included in this study, with a median follow-up of 36.5 months; 107 had recurrent lateral neck disease. The optimal LLNY and LPLR cutoff values for recurrent/persistent disease were 24.5 and 32.74%, respectively. The high-risk group (LLNY<25) had the lowest recurrence-free survival rate compared with to moderate-risk group (LLNY≥25, LPLR≥32.74%) and low-risk group (LLNY≥25, LPLR<32.74%) ( P <0.001). The moderate-risk group had lower recurrence-free survival than the low-risk group. Multivariate analysis revealed that an LLNY less than 25 in the initial LND was an independent risk factor for recurrence/persistence of lateral neck ( P <0.001). CONCLUSIONS: This study identified that LLNY and LPLR were associated with recurrence/persistence in PTC patients at the time of revision surgery was performed.

Comparison of quality of life and cosmetic result between open and transaxillary endoscopic thyroid lobectomy for papillary thyroid microcarcinoma survivors: A single-center prospective cohort study.

BACKGROUND: Transaxillary endoscopic thyroidectomy has been introduced to achieve better cosmetic outcomes. However, the benefits of this technology on the patients' health-related quality of life (HRQoL) remain unclear. We aimed to investigate whether transaxillary endoscopic lobectomy is comparable to conventional open lobectomy in terms of QOL and cosmetic results in order to provide more evidence for establishing appropriate clinical decisions. METHODS: Between August 2019 and May 2020, transaxillary endoscopic lobectomy and conventional open lobectomy were performed in 73 and 99 patients with papillary thyroid microcarcinoma, respectively. HRQoL was assessed at 1, 3, 6, and 12 months after surgery using the Thyroid Cancer-Specific Quality of Life Questionnaire. The cosmetic outcomes were assessed 12 months after surgery using the Patient and Observer Scar Assessment Scale (POSAS). RESULTS: No significant difference was observed in the surgical results between the two groups. However, the data showed that the average operative time and postoperative hospital stay of the transaxillary group were longer than those of the open group (p < 0.001). Both groups showed similar changes in the QOL scores over time. However, the transaxillary group had fewer complaints of the throat or oral problems at 1 month postoperatively than the open group (p < 0.001). During the follow-up, the cosmetic results of scars in the transaxillary group were significantly better than those in the open group (p < 0.05). Patients who underwent transaxillary endoscopic lobectomy had higher overall satisfaction with their scar appearance, determined using POSAS, at 12 months postoperatively. CONCLUSIONS: The current findings suggest that transaxillary endoscopic lobectomy may offer better cosmetic and HRQoL outcomes.

Primary Vitreoretinal Lymphoma: A Retrospective Study of 20 Eyes.

Purpose: This study aimed to describe and analyze the clinical features of 20 eyes of 15 primary vitreoretinal lymphoma (PVRL) patients. Methods: This was a retrospective case series and a review of the literature. Fifteen PVRL patients (20 affected eyes) referred between February 2011 and December 2019 were recruited, and their medical records were retrospectively reviewed. Results: Among these 15 PVRL patients, seven were men (46.67%), and five had bilateral PVRL (33.33%). The median onset age was 66 ± 9.26 years and six (40%) patients had central nervous system (CNS) involvement, and two of them died of CNS-related complications. The ocular symptoms varied from decreased vision to binocular diplopia. The ocular manifestations were diverse and involved both the anterior and posterior segments, including the vitreous cells, subretinal white-yellow lesions, cotton-wool spots, and ophthalmoplegia. The rate of misdiagnosis and failure to diagnose was 100%, and 30% of them were misdiagnosed as uveitis. We found five cases revealing rare characteristics of this malignancy. Among them, there were two cases with mild hypertensive retinopathy exhibiting cotton-wool spots, one case mimicking age-related macular degeneration (AMD), one case with systemic lupus erythematosus (SLE), and one patient had extraocular muscle involvement. To the best of our knowledge, we reported PVRL exhibiting cotton-wool spots as the main manifestation and coexisting with extraocular myopathy for the first time. Conclusions: PVRL is a rare intraocular malignancy that commonly masquerades as uveitis. As the clinical signs and symptoms are atypical, ophthalmologists must carefully examine patients to avoid misdiagnosis or a failure to diagnose. Cotton-wool spots and extraocular myopathy might be the dominant initial symptoms in PVRL patients, and AMD should be considered a differential diagnosis of PVRL. SLE patients under immunosuppressive treatment could have spontaneous PVRL.

SYTL5 Promotes Papillary Thyroid Carcinoma Progression by Enhancing Activation of the NF-κB Signaling Pathway.

The function and mechanism of SYTL5 in papillary thyroid carcinoma (PTC) are still unclear. In this research, we found that SYTL5 was significantly overexpressed in PTC tissues compared with normal thyroid tissues. SYTL5 downregulation significantly weakened the proliferative, migratory, and invasive abilities of PTC cells. In addition, upregulated SYTL5 could promote cancer progression by activating the NF-κB signaling pathway. RAC1b expression is positively associated with SYTL5, and overexpressed RAC1b abrogated the antitumor effect after SYTL5 inhibition. In conclusion, our findings identify the oncogenic role of SYTL5 in PTC by activation of the NF-κB signaling pathway, thus facilitating PTC development and progression.

Kang-Ai Injection Inhibits Gastric Cancer Cells Proliferation through IL-6/STAT3 Pathway.

OBJECTIVE: To explore the mechanisms underlying the proliferative inhibition of Chinese herbal medicine Kang-Ai injection (KAI) in gastric cancer cells. METHODS: Gastric cancer cell lines MGC803 and BGC823 were treated by 0, 0.3%, 1%, 3% and 10% KAI for 24, 48 and 72 h, respectively. The cell proliferation was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The apoptosis and cell cycle were evaluated by flow cytometry. Interleukin (IL)-6 mRNA and protein expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immune sorbent assay (ELISA), respectively. The protein expression levels of cyclin A, cyclin E, cyclin B1, cyclin D1, p21, retinoblastoma (RB), protein kinase B (AKT), extracellular regulated protein kinases (ERK), signal transducer and activator of transcription (STAT) 1 and STAT3 were detected by Western blot. RESULTS: KAI inhibited the proliferation of MGC803 and BGC823 gastric cancer cells in dose- and time-dependent manner. After treated with KAI for 48 h, the proportion of G1 phase was increased, expression level of cyclin D1 and phosphorylation-RB were down-regulated, whereas the expression of p21 was up-regulated (all P<0.01). Furthermore, 48-h treatment with KAI decreased the phosphorylation level of STAT3, inhibited the mRNA and protein expressions of IL-6 (all P<0.01). IL-6 at dose of 10 ng/mL significantly attenuated the proliferative effect of both 3% and 10% KAI, and recovered KAI-inhibited STAT3 phosphorylation and cyclin D1 expression level (all P<0.01). CONCLUSION: KAI exerted an anti-proliferative function by inhibiting IL-6/STAT3 signaling pathway followed by the induction of G1 phase arrest in gastric cancer cells.

PAK6 promotes homologous-recombination to enhance chemoresistance to oxaliplatin through ATR/CHK1 signaling in gastric cancer.

Chemoresistance remains the primary challenge of clinical treatment of gastric cancer (GC), making the biomarkers of chemoresistance crucial for treatment decision. Our previous study has reported that p21-actived kinase 6 (PAK6) is a prognostic factor for selecting which patients with GC are resistant to 5-fluorouracil/oxaliplatin chemotherapy. However, the mechanistic role of PAK6 in chemosensitivity remains unknown. The present study identified PAK6 as an important modulator of the DNA damage response (DDR) and chemosensitivity in GC. Analysis of specimens from patients revealed significant associations between the expression of PAK6 and poorer stages, deeper invasion, more lymph node metastases, higher recurrence rates, and resistance to oxaliplatin. Cells exhibited chemosensitivity to oxaliplatin after knockdown of PAK6, but showed more resistant to oxaliplatin when overexpressing PAK6. Functionally, PAK6 mediates cancer chemoresistance by enhancing homologous recombination (HR) to facilitate the DNA double-strand break repair. Mechanistically, PAK6 moves into nucleus to promote the activation of ATR, thereby further activating downstream repair protein CHK1 and recruiting RAD51 from cytoplasm to the DNA damaged site to repair the broken DNA in GC. Activation of ATR is the necessary step for PAK6 mediated HR repair to protect GC cells from oxaliplatin-induced apoptosis, and ATR inhibitor (AZD6738) could block the PAK6-mediated HR repair, thereby reversing the resistance to oxaliplatin and even promoting the sensitivity to oxaliplatin regardless of high expression of PAK6. In conclusion, these findings indicate a novel regulatory mechanism of PAK6 in modulating the DDR and chemoresistance in GC and provide a reversal suggestion in clinical decision.

Noninvasive imaging of the tumor immune microenvironment correlates with response to immunotherapy in gastric cancer.

The tumor immune microenvironment (TIME) is associated with tumor prognosis and immunotherapy response. Here we develop and validate a CT-based radiomics score (RS) using 2272 gastric cancer (GC) patients to investigate the relationship between the radiomics imaging biomarker and the neutrophil-to-lymphocyte ratio (NLR) in the TIME, including its correlation with prognosis and immunotherapy response in advanced GC. The RS achieves an AUC of 0.795-0.861 in predicting the NLR in the TIME. Notably, the radiomics imaging biomarker is indistinguishable from the IHC-derived NLR status in predicting DFS and OS in each cohort (HR range: 1.694-3.394, P < 0.001). We find the objective responses of a cohort of anti-PD-1 immunotherapy patients is significantly higher in the low-RS group (60.9% and 42.9%) than in the high-RS group (8.1% and 14.3%). The radiomics imaging biomarker is a noninvasive method to evaluate TIME, and may correlate with prognosis and anti PD-1 immunotherapy response in GC patients.