Preoperative systemic inflammation response index: Clinicopathologic predictor of pathological complete response in HER2-positive breast cancer patients receiving neoadjuvant systemic therapy.

BACKGROUND: Multiple pretreatment systemic inflammatory markers (SIMs) have been reported as predictors of pathological complete response (pCR) after neoadjuvant systemic therapy (NST) in patients with breast cancer (BC). However, the most significant SIM remains to be conclusively identified, and variations among different molecular subtypes remain unknown. The objective of the study was to identify the most significant SIM in patients with human epidermal growth factor receptor 2 (HER2) positive BC, to construct a pCR-predictive nomogram combining it with other clinicopathologic factors, and to evaluate its prognostic value on survival. METHODS: We retrospectively reviewed the findings for 240 patients with stage I-III HER2-positive BC who underwent NST and subsequent surgery at Kaohsiung and Taichung Veterans General Hospital from 2011 to 2021. Clinicopathologic factors were analyzed by stepwise logistic regression with backward selection. The data were used to construct a nomogram plot for determining the pCR probability. Kaplan-Meier curves and log-rank test were used to evaluate disease-free survival (DFS) and overall survival (OS). RESULTS: Among the pretreatment SIMs, only the systemic inflammation response index (SIRI) was significantly related to pCR, with an optimal cutoff value of 1.27 × 10 9 /L. Stepwise logistic analyses indicated that clinical N stage, HER2 immunohistochemistry score, hormone receptor status, targeted therapy regimen, and SIRI were independent predictors of pCR, with an area under the curve of 0.722. The Hosmer-Lemeshow test and calibration curve revealed that the predictive ability was a good fit to actual observations. A nomogram was constructed based on the logistic model. The external validation of the model also revealed satisfactory discrimination and calibration. Kaplan-Meier analysis showed that patients with SIRI <1.27 had longer DFS and OS. CONCLUSION: Pretreatment SIRI <1.27 is predictive of pCR, DFS, and OS in HER2-positive BC. Our nomogram could efficiently predict pCR and facilitate clinical decision-making before neoadjuvant treatment.

How Soda Ingestion Facilitates the Distinction between a Killian-Jamieson Diverticulum and a Malignant Thyroid Nodule.

A 66-year-old woman presented with an incidental left thyroid nodule during a health examination. She had no voice change, shortness of breath, cough, or dysphagia. Repeated sonography showed a dynamic change of the lesion, which was more evident following soda consumption. A subsequent esophagography confirmed the diagnosis of a Killian-Jamieson diverticulum. This rare left-sided pharyngoesophageal diverticulum is often asymptomatic. On a sonography, air bubbles in the esophageal lumen can cause a ring-down artifact that mimics microcalcifications, which are characteristic of thyroid malignancy, and misdiagnosis may lead to unnecessary interventions, including fine-needle aspiration or thyroidectomy. A dynamic ultrasound, specifically done during soda consumption, offered a simple diagnostic distinction. No surgical intervention was pursued; the patient was monitored in the clinic.

Neck Reoperation for Recurrent or Persistent Renal Hyperparathyroidism.

BACKGROUND: Patients with renal hyperparathyroidism undergoing parathyroidectomy may experience relapse. Reoperation for persistent or recurrent disease, particularly in the neck region, is challenging and has a high complication rate because of difficult exploration. We aimed to evaluate the effectiveness of neck reoperation in renal hyperparathyroidism. METHODS: Patients with recurrent or persistent renal hyperparathyroidism who underwent neck reoperation between January 2015 and August 2022 were investigated, focusing on operative findings, perioperative biochemical changes, and significance of intraoperative parathyroid hormone (PTH) measurements. RESULTS: During reoperation, 35 parathyroid glands were identified and removed from the 26 enrolled patients, with one, two, and three glands retrieved from 19 (73.2%), five (19.2%), and two (7.6%) patients, respectively. Most removed glands (68.6%) were located in the lower neck, followed by the mediastinum, carotid sheath, and upper neck. Successful resection, defined as a postoperative PTH level of <300 pg/mL, was achieved in 21 patients (80.8%). The remaining four (15.4%) and one (3.9%) patients were classified as having persistent and recurrent disease, respectively. The extent of PTH reduction was correlated with specimen weight, specimen volume, and preoperative alkaline phosphatase (ALP) level. The mean intraoperative PTH ratio (10 min after excision/pre-excision) was 0.23, and all patients with persistent or recurrent disease had a PTH ratio >0.3. Severe hypocalcemia (<7.5 mg/dL) occurred in 19 (73.0%) patients after reoperation. CONCLUSIONS: Neck reoperation is an effective therapeutic option in patients with recurrent or persistent renal hyperparathyroidism. A decrease in PTH level by >70% during reoperation (PTH ratio <0.3) predicts successful resection.

Pre-incisional, trans-isthmic injection of indocyanine green for lymph node mapping during the transoral endoscopic thyroidectomy vestibular approach.

Indocyanine green (ICG) is a useful tracer for lymph node mapping and retrieval. However, during endoscopic surgery, it is challenging to administer ICG into the thyroid without spillage. We developed a simple technique of delivering ICG, thereby preventing leakage. Patients who underwent the transoral endoscopic thyroidectomy were retrospectively reviewed. In 20 patients, who constituted the ICG group, 0.1 mL ICG was injected into the peri-tumoral space under ultrasound guidance, soon after the patients received general anesthesia. Patients with papillary thyroid carcinoma who did not receive the ICG injection comprised the control group (n = 43). The location, size, and number of harvested lymph nodes were recorded in conjunction with parathyroid-related parameters. No ICG spillage occurred in the ICG group, and 76 ICG-stained lymph nodes were detected in the pretracheal (57.9%), paratracheal (25.0%), and prelaryngeal regions (17.1%). The ICG group demonstrated a significantly higher number of total (5.3 vs 2.1) and metastatic (1.5 vs 0.6) lymph nodes, a larger metastatic deposit in the positive node (3.5 mm vs 1.6 mm), and a higher rate of pathologically node-positive disease (70.0% vs 27.9%) than did the control group. The postoperative calcium level (7.8 mg/dL vs 7.2 mg/dL) was also higher in the ICG group. Pre-incisional, trans-isthmic injection of ICG under ultrasound guidance is a simple technique to prevent the leakage of ICG. Under fluorescence imaging, an adequate number of lymph nodes can be harvested for examination, which may assist in intraoperative decision-making.

Comparison of intraoperative neural monitoring between endoscopic transoral and bilateral axillo-breast approach thyroidectomy.

BACKGROUND: The use of intraoperative neuromonitoring (IONM) during endoscopic thyroidectomy has not been fully explored, with limited studies focusing solely on the recurrent laryngeal nerve (RLN) and neglecting the external branch of the superior laryngeal nerve (EBSLN). This study aimed to compare the effectiveness of IONM in two endoscopic thyroidectomy techniques, namely the transoral and bilateral axillo-breast approach (BABA). METHODS: We retrospectively reviewed patients who underwent endoscopic thyroidectomy with IONM and compared the outcomes between those who underwent different surgical techniques (transoral or BABA). We recorded the detection method and identification rate of the EBSLN and RLN, along with the amplitude and latency of the evoked potential. RESULTS: We monitored 98 nerves at risk (NAR) from 74 patients (60 and 38 in the transoral and BABA groups, respectively). Almost all EBSLNs were identified using electromyography (EMG) signals and/or cricothyroid muscle twitches, except for one patient in the transoral group who developed EBSLN palsy. Patients in the transoral group were more likely to have the sternothyroid muscle divided (75.0% vs. 15.8%, p < 0.001) and had a lower rate of visual recognition of the EBSLN fibers (10.0% vs. 31.6%, p = 0.007) than did those in the BABA group. All RLNs were identified in both groups; however, patients in the BABA group had a relatively higher rate of post-dissection amplitude reduction > 50% (15.8% vs. 5.0%, p = 0.072), and one patient had transient RLN palsy. CONCLUSIONS: Both the EBSLN and RLN could be adequately identified and monitored during endoscopic transoral and BABA thyroidectomies using IONM.

Cannula Fracture during Transoral Endoscopic Thyroidectomy Vestibular Approach: Causes and Prevention.

In the transoral endoscopic thyroidectomy vestibular approach (TOETVA), three oral vestibular incisions are used to access the thyroid. This approach leaves no scar on the body surface; however, unexpected complications may occur. Three patients (two women, one man) underwent TOETVA using the standard three-port technique. Broken cannulas of the 12 mm central port were noted in all cases. All cannulas broke on the ventral side of the distal shaft. The fracture lines were 3-4 cm in length, with some fragments scattered throughout the operative field and oral cavity. The fractures were caused by compression against the mandible while tilting the cannula during surgical manipulation. Male sex, short stature, and protruding chin may be risk factors for cannula fracture in TOETVA. Measures should be taken to prevent this complication, particularly in high-risk patients.

Working Space Creation in Transoral Thyroidectomy: Pearls and Pitfalls.

Transoral thyroidectomy is a novel technique that uses three small incisions hidden in the oral vestibule to remove the thyroid gland. It provides excellent cosmetic results and outcomes comparable to the open approach. One of the main obstacles for this technique is the creation of a working space from the lip and chin to the neck. The anatomy of the perioral region and the top-down surgical view are both unfamiliar to general surgeons. As a result, inadequate manipulation might easily occur and would lead to several unconventional complications, such as mental nerve injury, carbon dioxide embolism, and skin perforation, which are rarely observed in open surgery. Herein, we summarize the basic concepts, techniques, and rationales behind working space creation in transoral thyroidectomy to assist surgeons in obtaining an adequate surgical field while eliminating preventable complications.

The Efficacy of Thrombin-Gelatin Matrix in Hemostasis for Large Breast Tumor after Vacuum-Assisted Breast Biopsy.

BACKGROUND: Vacuum-assisted breast biopsy (VABB) for benign breast tumor excision is a developing trend in breast surgery. The most common complication of VABB is hematoma. We assessed the efficiency of the thrombin-gelatin matrix (TGM) for hemostasis after VABB. METHODS: From December 2013 to June 2017, 147 patients with breast tumors > 2 cm in size were treated with a 7-gauge ultrasound-guided EnCor EnSpire® breast biopsy system. After VABB, the TGM was applied using an iron-tube device. After injection, brief external compression for 15 min and postoperative bandage compression for approximately 12 h were applied. The medical records were reviewed and analyzed for hematoma and acute bleeding at 1 and 3 months after VABB. RESULTS: A total of 72 patients received hemostasis via TGM, and 75 patients received hemostasis by compression. The rates of postoperative acute bleeding in the TGM group were significantly lower than those in the non-TGM group (5.5% vs. 22.7%, p = 0.003). Among patients with hematoma, there was no statistically significant difference between the two groups (25% vs. 26.7%, p = 0.85). CONCLUSIONS: This is the first cohort study to apply the TGM hemostatic matrix for post-VABB hemostasis. The TGM hemostatic matrix could be an option for patients with large breast tumors.

Multimodal Assessments of Altered Sensation after Transoral Endoscopic Thyroidectomy.

BACKGROUND: Transoral endoscopic thyroidectomy, a novel technique, uses oral vestibule as the entry point and leaves no scar on the body surface. However, because the incisions are close to the mental nerve, nerve damage and the associated sensory impairment are concerning. Herein, we evaluated sensory alteration after transoral endoscopic thyroidectomy and determined factors associated with the prolonged sensory alteration. METHODS: Patients who underwent transoral endoscopic thyroidectomy were enrolled. Sensation over the lower lip, chin, and neck was evaluated before and after the surgery. A self-assessment questionnaire, Semmes-Weinstein monofilament test, and two-point discrimination test were used to subjectively and objectively evaluate sensory changes. RESULTS: Fifty-one patients were enrolled; most of them reported altered sensation, with chin (72.5%) being the most common site, followed by lower lip (52.9%), upper neck (33.3%), and lower neck (5.9%) on postoperative day 2. The sensory disturbance resolved within 3 months. Factors associated with prolonged sensory alteration are male sex and old age. Fourteen patients (27.5%) experienced mild drooling from the mouth, which was usually self-limiting in 1 month. Sensory impairments in light touch pressure threshold and two-point discrimination were significant in the chin and neck on postoperative day 2 and at 1 week. The ability to discern two-point was also compromised in the lower lip on postoperative day 2. All these significant changes normalized to preoperative baseline at 1 month. CONCLUSIONS: There was an altered sensation after transoral endoscopic thyroidectomy with the most common and disturbed in the chin. Sensory impairment was usually transient and recovered in 3 months.

Indocyanine Green Angiography for Parathyroid Gland Evaluation during Transoral Endoscopic Thyroidectomy.

Indocyanine green (ICG) angiography, a real-time intraoperative imaging technique, is associated with better parathyroid identification and functional evaluation during open thyroidectomy. However, the benefits of ICG fluorescence imaging application in transoral endoscopic thyroidectomy are not well-documented. Consecutive patients who underwent transoral endoscopic thyroidectomy were retrospectively reviewed. Parathyroid glands were assessed with visual inspection followed by ICG angiography. The fluorescence intensity of all parathyroid glands was recorded. In total, 158 parathyroid glands from 60 patients (41 underwent lobectomy and 19 underwent total thyroidectomy) were eligible for evaluation. A total of 135 parathyroid glands (85.4%) were identified, including nine glands (5.7%) that were solely localized because of ICG angiography. Incidental parathyroidectomy occurred in 12 patients with predominant inferior gland (83.3%) and associated with central neck dissection (66.7%). Among patients receiving total thyroidectomy, patients who retained at least one well-perfused parathyroid gland had higher parathyroid hormone (PTH) level and were less likely to develop hypoparathyroidism on postoperative day one than those without any well-perfused ICG-enhanced parathyroid gland (p = 0.038). In addition, the duration of calcium supplementation to maintain normocalcemia was also shorter. ICG angiography is a feasible adjunct procedure for parathyroid identification and postoperative functional prediction in transoral endoscopic thyroidectomy.

Vocal cord granuloma after transoral thyroidectomy using oral endotracheal intubation: two case reports.

BACKGROUND: Transoral thyroidectomy can be performed using nasal or oral intubation. Recently, we encountered two cases of vocal cord granuloma that were suspected to result from intraoperative compression by the oral endotracheal tube. CASES PRESENTATION: Two women underwent transoral endoscopic thyroidectomy with oral endotracheal tubes fixed at the mouth angle. Their initial postoperative recovery was uneventful, but they developed hoarseness 2 months after the surgery. Subsequent strobolaryngoscopy revealed vocal cord granulomas at the side of contact of the endotracheal tube. One patient received medication and voice therapy, and her granuloma shrank significantly one month later. The other patient underwent granuloma resection. Thereafter, the symptoms improved in both the patients. CONCLUSIONS: Oral intubation with tube placement at the mouth angle might result in the formation of vocal cord granulomas. Therefore, we suggest positioning the tube at the midline to avoid excessive irritation on one side of the vocal cord.

Outcome Comparison between Endoscopic Transoral and Bilateral Axillo-Breast Approach Thyroidectomy Performed by a Single Surgeon.

BACKGROUND: The transoral approach and the bilateral axillo-breast approach (BABA) are remote access approaches for endoscopic thyroidectomy. Both follow a symmetric design and use CO2 insufflation to maintain the working space. The outcome differences between the techniques are rarely compared in the literature. METHODS: All patients who underwent endoscopic transoral (n = 72) and BABA (n = 63) thyroidectomy between October 2018 and August 2020 by a single surgeon were retrospectively reviewed. The following peri-operative data were collected and compared: operative time, blood loss, postoperative drainage amount, hospital stay, pain score, number of retrieved lymph nodes, and complications. RESULTS: Patients in the transoral group were younger (44.7 vs. 49.3 years, p = 0.022) and had smaller tumors (2.4 vs. 2.8 cm, p = 0.020) than those in the BABA group. The operative times were significantly longer in the transoral group than in the BABA group (lobectomy, 194.1 vs. 177.0 min, p = 0.026; total thyroidectomy, 246.0 vs. 214.3 min, p = 0.042). Nevertheless, the time difference became insignificant after completing the initial 20 cases of transoral thyroidectomy. The drainage fluid collected after the surgery was serosanguinous, and a lower drainage volume was observed in the transoral group than that in the BABA group (64.9 vs. 78.5 ml, p = 0.017). However, there was no significant difference regarding the blood loss, hospital stay, postoperative pain score, and lymph nodes retrieved. The rate of postoperative complications, such as hypoparathyroidism and vocal cord palsy was comparable between the two groups. CONCLUSIONS: Transoral approach and BABA are comparable with regard to surgical outcomes. Selected patients may choose either technique based on their preferences.

Multidimensional Analyses of the Learning Curve of Endoscopic Thyroidectomy.

BACKGROUND: Endoscopic thyroidectomy has comparable surgical outcomes and superior cosmetic satisfaction to open thyroidectomy. However, steep learning curve is a concern. This study evaluated the learning curve of endoscopic thyroidectomy using various parameters and statistical methods. METHODS: A total of 90 consecutive patients who underwent endoscopic thyroidectomy using bilateral axillo-breast approach (BABA) between March 2016 and April 2020 were enrolled. Operative time, postoperative drainage amount, and blood loss were assessed by cumulative sum (CUSUM) analysis and moving average to evaluate the learning curve. RESULTS: Using the CUSUM analysis, the peak point of both operative time and drainage amount occurred at the 30th case. No clear single peak was identified in the CUSUM plot for blood loss. The moving average also showed significant reduction in operative time and drainage amount after, approximately, the first 30 cases. The blood loss decreased after the 25th case. We therefore divided the patients into 2 phases: phase 1 (1-30 cases) and phase 2 (31-90 cases). The operative time, drainage amount, and blood loss decreased significantly in the phase 2 compared with phase 1. Lower pain score in first postoperative day and shorter hospital stay were also observed in the phase 2. Although the reduction in transient hypoparathyroidism did not reach statistical significance, no permanent hypoparathyroidism was noted in the phase 2. CONCLUSIONS: The learning curve for endoscopic thyroidectomy is approximately 30 cases. Aside from the operative time, drainage amount may also serve as a surrogate for the learning curve evaluation.

Correlation of 18F-FDG uptake and thyroid cancer stem cells.

BACKGROUND: 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (18F-FDG PET) has the potential to detect various types of cancers, including thyroid cancer (TC), at a potentially curable stage. Increased uptake of 18F-FDG was observed in anaplastic and poorly differentiated thyroid cancer cells, and PET-positive tumors are more likely to be resistant to 131I treatment. As cancer stem cells (CSCs) possess a dedifferentiated phenotype and are resistant to many anticancer therapies, we hypothesized that the expression of CSC-related markers is correlated with the ability of tumor cells in TC to uptake FDG. METHODS: The present study cohort included 12 patients with TC, who underwent 18F-FDG PET/CT imaging before surgery. Quantitative polymerase chain reaction (QPCR) and immunohistochemical (IHC) staining were performed to analyze the expression patterns of gene markers related to embryonic stem (ES) cells and CSCs in TC. RESULTS: The mRNA expression levels of CSC- (CD133 and CD44) and ES-related genes (Oct4 and Nanog) were higher in TC tissue than in normal thyroid tissue, whereas the mRNA expression levels of thyroid-specific genes (Tg, TSHR, and TTF1) were higher in normal thyroid tissue than in TC tissue. There was a positive and statistically significant correlation between FDG uptake (SUVmax) of tumor and relative mRNA levels of CD133, CD44, Oct4, and Nanog. The IHC results demonstrated that CD133 and Nanog were expressed in TC tissue but not in normal thyroid tissue, however, CD44 expression was observed in both TC and normal thyroid tissue. Comparisons of the clinicopathological parameters between TC tissues with low and high SUVmax demonstrated significant differences in protein level of CD133 but not in that of Nanog. CONCLUSIONS: The pre-therapeutic tumor SUVmax obtained from 18F-FDG PET/CT may be a potential predictor for evaluating the proportion of CSC population in individual patients with TC.

X-shaped Breast Lift to Improve Surgical Ergonomics in Bilateral Axillo-Breast Approach Thyroidectomy.

BACKGROUND: Endoscopic thyroidectomy through the bilateral axillo-breast approach (BABA) is a good option for patients who have been advised thyroid resection but are concerned about the cosmetic results. This technique uses the breast tissue as a pivot to facilitate maneuvering of the surgical instruments. However, it is difficult to use this technique in patients with small breasts or having a flat chest. MATERIALS AND METHODS: The authors developed an "X-shaped breast lift" method using fabric adhesive tape, to push up and augment the breast tissue to facilitate the thyroid dissection procedure. Changes before and after the breast lift were quantified by measuring the angle of breast tilt and the distance between relevant anatomic landmarks. RESULTS: Fifteen consecutive patients underwent this procedure before undergoing BABA thyroidectomy. The mean breast tilt angle increased from 3.2 to 9.8 degrees, which is a >3-fold increase (+6.6 degree, 206%). The mean distance between the cricoid cartilage and nipple was reduced by 1.9 cm (-8%), and the mean distance between the axillary incision and nipple increased by 1.1 cm (9%). No skin trauma or ulceration was observed. CONCLUSIONS: X-shaped breast lift is easy to perform, and it significantly improves the thyroid dissection process with no significant adverse effects. It can be used for all cases of BABA thyroidectomy.

Single Biaxillary Tunneling for Working Space Creation in Bilateral Axillo-Breast Approach (BABA) Thyroidectomy.

BACKGROUND: Endoscopic thyroidectomy using the bilateral axillo-breast approach (BABA) achieves excellent cosmetic results. However, concerns have been raised about the extensive dissection and violation of the breast during working space preparation. MATERIALS AND METHODS: We developed a "single biaxillary tunneling" technique for working space creation in BABA thyroidectomy; this technique was applied in 30 cases. RESULTS: Skin bruise was hardly visible, and only minor and small bruises were observed. The whole process of working space creation typically finished within 20 to 30 minutes. CONCLUSIONS: Limited blunt dissection by a single stroke of biaxillary tunneling is a simple method, which significantly reduces ecchymosis formation and is time-efficient. This method can be used in routine practice and is feasible for beginner surgeons.

Ten-eleven translocation 1 dysfunction reduces 5-hydroxymethylcytosine expression levels in gastric cancer cells.

A sixth base, 5-hydroxymethylcytosine (5hmC), is formed by the oxidation of 5-methylcytosine (5mC) via the catalysis of the ten-eleven translocation (TET) protein family in cells. Expression levels of 5hmC are frequently depleted during carcinogenesis. However, the detailed mechanisms underlying the depletion of 5hmC expression in gastric cancer cells remains unclear, and further research is required. The present study examined the expression levels of 5mC and 5hmC and the expression levels of TET1 and TET2 in gastric cancer tissues using immunohistochemistry. The results revealed that 5hmC expression levels were markedly lower in gastric cancer tissues compared with corresponding adjacent normal tissues. Furthermore, a decrease in 5hmC expression levels was associated with a decrease in TET1 protein expression levels in gastric cancer tissues. The ectopic expression level of TET1 may increase the 5hmC expression level in gastric cancer cells. In addition, the results revealed that TET1 protein expression was markedly different in regards to subcellular localization, and mislocalization was significantly associated with the depletion of 5hmC expression levels in gastric cancer. Together, the results of the present study indicated that TET1 dysfunction reduces 5hmC expression levels, and this phenomenon may serve a crucial role in gastric cancer progression.

Analysis of gallstone disease after gastric cancer surgery.

BACKGROUND: The incidence rate of newly developed gallstone disease after gastrectomy for gastric cancer is thought to be higher than that in the general population. However, the presentation and management of these gallstones remain under debate, and the role of prophylactic cholecystectomy remains questionable. METHODS: Data on adult patients who were diagnosed with gastric cancer and received gastrectomy between 2000 and 2011 were extracted from the Taiwan National Health Insurance Research Database. A patient was excluded if he or she had gallstone disease or received cholecystectomy before the index date. The incidence of newly developed gallstone disease and its subsequent management were recorded. Data were analyzed to evaluate the factors associated with gallstone development and treatment options. RESULTS: A total of 17,325 gastric cancer patients who underwent gastrectomy were eligible for analysis. During the follow-up period (mean 4.1 years; median, 2.9 years), 1280 (7.4%) patients developed gallstone disease and 560 (3.2%) patients subsequently underwent cholecystectomy. The in-hospital mortality for cholecystectomy was 1.8% (10/560). Development of gallstone disease was associated with older age, total gastrectomy, duodenal exclusion, diabetes, cirrhosis, and more comorbidities. Factors associated with the use of cholecystectomy to treat gallstone disease included younger age, fewer comorbidities, medical center admission, and presentation as cholecystitis. CONCLUSIONS: Although few patients required further gallbladder removal after gastrectomy for gastric malignancy, the increased mortality rate for subsequent cholecystectomy was worth noting. The decision to undergo prophylactic cholecystectomy might be individualized based upon patient characteristics and the surgeon's discretion.

Isocitrate Dehydrogenase 2 Dysfunction Contributes to 5-hydroxymethylcytosine Depletion in Gastric Cancer Cells.

The isocitrate dehydrogenase (IDH) family of enzymes comprises of the key functional metabolic enzymes in the Krebs cycle that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG). α-KG acts as a cofactor in the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). However, the relationship between 5hmC and IDH in gastric cancer remains unclear. Our study revealed that the 5hmC level was substantially lower and 5mC level was slightly higher in gastric cancer tissues; however, 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) levels did not change significantly in these tissues. We further examined the expression levels of IDH1 and IDH2 in gastric cancer tissues and observed that IDH2 levels were significantly lower in gastric cancer tissues than in the adjacent normal tissues. The ectopic expression of IDH2 can increase 5hmC levels in gastric cancer cells. In conclusion, our results suggested that IDH2 dysfunction is involved in 5hmC depletion during gastric cancer progression.