Development and validation of postoperative circulating tumor DNA combined with clinicopathological risk factors for recurrence prediction in patients with stage I-III colorectal cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) detection following curative-intent surgery could directly reflect the presence of minimal residual disease, the ultimate cause of clinical recurrence. However, ctDNA is not postoperatively detected in ≥ 50% of patients with stage I-III colorectal cancer (CRC) who ultimately recur. Herein we sought to improve recurrence risk prediction by combining ctDNA with clinicopathological risk factors in stage I-III CRC. METHODS: Two independent cohorts, both consisting of early-stage CRC patients who underwent curative surgery, were included: (i) the discovery cohort (N = 124) with tumor tissues and postoperative plasmas for ctDNA determination; and (ii) the external validation cohort (N = 125) with available ctDNA results. In the discovery cohort, somatic variations in tumor tissues and plasmas were determined via a 733-gene and 127-gene next-generation sequencing panel, respectively. RESULTS: In the discovery cohort, 17 of 108 (15.7%) patients had detectable ctDNA. ctDNA-positive patients had a significantly high recurrence rate (76.5% vs. 16.5%, P < 0.001) and short recurrence-free survival (RFS; P < 0.001) versus ctDNA-negative patients. In addition to ctDNA status, the univariate Cox model identified pathologic stage, lymphovascular invasion, nerve invasion, and preoperative carcinoembryonic antigen level associated with RFS. We combined the ctDNA and clinicopathological risk factors (CTCP) to construct a model for recurrence prediction. A significantly higher recurrence rate (64.7% vs. 8.1%, P < 0.001) and worse RFS (P < 0.001) were seen in the high-risk patients classified by the CTCP model versus those in the low-risk patients. Receiver operating characteristic analysis demonstrated that the CTCP model outperformed ctDNA alone at recurrence prediction, which increased the sensitivity of 2 year RFS from 49.6% by ctDNA alone to 87.5%. Harrell's concordance index, calibration curve, and decision curve analysis also suggested that the CTCP model had good discrimination, consistency, and clinical utility. These results were reproduced in the validation cohort. CONCLUSION: Combining postoperative ctDNA and clinical risk may better predict recurrence than ctDNA alone for developing a personalized postoperative management strategy for CRC.

Correlation between preoperative peripheral blood NLR, PLR, LMR and prognosis of patients with head and neck squamous cell carcinoma.

BACKGROUND: Markers that can be used to evaluate the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) remain undefined. OBJECTIVE: This study aimed to investigate the prognostic impact of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in patients with HNSCC who underwent surgery-based treatment for the first time. METHODS: This retrospective study included patients HNSCC who underwent surgery-based treatment at our institution between January 2018 and December 2020. Specificity and sensitivity were analyzed using receiver operating characteristic (ROC) curves and the critical value was determined. Patients were divided into low and high groups according to NLR, PLR, and LMR the critical value. Log-rank and Cox proportional hazards models were used to evaluate the associations between preoperative NLR, PLR, LMR, and overall survival (OS). RESULTS: A total of 304 patients with HNSCC were included, of whom 190 (62.5%) and 114 (37.5%), 203 (66.8%) and 101 (33.2%), 98 (32.2%), and 206 (67.8%) cases were classified as low NLR and high NLR groups, low PLR and high PLR groups, and low LMR and high LMR groups, respectively. Univariate analysis showed that white blood cell count (WBC), neutrophil count (NEU), platelet count (PLT), NLR, pathologic N stage (pN stage), TNM stage and postoperative complications were significantly associated with OS (p < 0.05). Multivariate analysis showed that NEU, NLR, TNM stage and postoperative complications were independent negative prognostic factors for HNSCC (p < 0.05). CONCLUSION: Preoperative NLR is an independent negative prognostic factor for HNSCC. Patients with an increased NLR may have a poor OS.

Perineal defect reconstruction after surgery for advanced or locally recurrent rectal cancer involving organ resection: Multiple flaps combined with lining repair.

AIM: The aim of this study was to investigate the efficacy of multiple perineal perforator flaps in repairing deep perineal defects after pelvic exenteration for locally advanced or recurrent rectal cancer. METHOD: We investigated the outcomes of eight patients whose repairs involved a novel method of using an internal pudendal artery perforator (IPAP) flap combined with an inferior gluteal artery perforator (IGAP) flap. RESULTS: There were four male and four female patients with a mean age of 56 years (36-72 years). Bilateral IPAP flaps combined with bilateral IGAP flaps were used in five patients, unilateral IPAP flaps combined with bilateral IGAP flaps were used in two patients and bilateral IPAP flaps were used in one patient. There were no functional limitations in daily activities during the 6-month follow-up period. CONCLUSION: Our study showed that using multiple perineal perforator flaps combined with lining repair is feasible for repairing deep perineal defects in patients who have undergone rectal cancer surgery that includes pelvic exenteration.

MiR-338-3p inhibits cell migration and invasion in human hypopharyngeal cancer via downregulation of ADAM17.

Studies have confirmed that microRNAs play important roles in the development and progression of cancer. Therefore, to identify the differentially expressed microRNAs between the cancer and the normal tissues, microRNAs will provide new clues for exploring the molecular mechanisms of cancer development and potential targeted therapies. In the present study, we found that miR-338-3p was downregulated in hypopharyngeal carcinoma and inversely correlated with the pathological grade. When the miR-338-3p was further downregulated, the migration and invasion ability of the FaDu hypopharyngeal carcinoma cells were enhanced, and these functions were inhibited when the miR-338-3p was upregulated. In addition, we demonstrated that ADAM17 was a target of miR-338-3p, and that ADAM17 directly activated the wnt/ß-catenin signaling pathway and promoted the expression of its target gene MMP2, Nanog and SOX2, which affected the growth, migration and invasion of hypopharyngeal carcinoma cells. In conclusion, our results demonstrate for the first time that miR-338-3p targets ADAM17 and blocks the development of hypopharyngeal carcinoma involving the wnt/ß-catenin signaling pathway, which may be a new target for clinical intervention in human cancer.

Survival analysis of distant metastasis of laryngeal carcinoma: analysis based on SEER database.

BACKGROUND: The purpose of this study was to investigate the prognostic factors and the value of surgical treatment of patients with newly diagnosed laryngeal cancer with distant metastasis (DM). METHODS: The Surveillance, Epidemiology and End Result database (SEER) was used to analyze 446 patients with laryngeal cancer with DM at the time of initial diagnosis from 2010 to 2014.The survival prognosis of patients with DM was performed by using Kaplan-Meier and log-rank test. The prognostic factors and the effect of surgery were analyzed using the Cox regression analysis and R-language data package. RESULTS: The incidence of DM was 3.21% (446/13865). Lung was the most common distant metastatic site of laryngeal cancer (62.6%), and brain metastases had the worst prognosis in patients at 2 months. T stage and brain metastasis were independent risk factors affecting the survival (P < 0.05). The hazard ratio (HR) of DM in T4 stage was nearly twice than that in T1 stage. Surgical treatment of primary and metastatic tumors can cause better survival for patients. Patients who didn't underwent primary tumor surgery were approximately twice as likely to die from cancer as those who did. The nomogram model was constructed to visually present the 1-, 2- and 3-year survival rates of patients. CONCLUSIONS: T stage, brain metastasis and surgical treatment are prognostic factors of patients with M1 stage laryngeal cancer. Surgical treatment of primary tumors and metastases can lead to better survival for patients. TRIAL REGISTRATION: Not applicable.

Reconstruction of laryngeal function by thyroid cartilage fenestration and draw-out resection followed by internal fixation with titanium microplates for early glottic carcinoma: a novel and efficient surgical approach.

OBJECTIVE: To explore the clinical effectiveness of reconstructing laryngeal function using thyroid cartilage fenestration and "draw-out" resection, supplemented by internal fixation with titanium microplates in early glottic carcinoma. METHODS: Data from 99 patients with glottic carcinoma treated in the Second Affiliated Hospital of Fujian Medical University between January 2014 and September 2021 were retrospectively analyzed. Forty-eight patients who underwent thyroid cartilage fenestration and resection followed by internal fixation with titanium microplates for laryngeal function reconstruction were assigned to the thyroid cartilage fenestration group (TCF group), while the other 51 patients who underwent sternohyoid muscle and fascia repair for laryngeal function reconstruction were assigned to the sternohyoid muscle repair group (SMR group). Patients were followed up for 1-8 years. Data on postoperative phonatory function, respiratory function, swallowing function, and survival status were collected. RESULTS: Compared to the SMR group, patients in the TCF group showed better postoperative recovery in phonatory function and verbal communication (all P<0.05). In the TCF group, patients demonstrated stable respiration and the extubation rate was 100.00%, which was significantly higher than 82.35% in the SMR group (P<0.05). Patients in both groups showed good postoperative recovery of swallowing function (P>0.05). CONCLUSION: One-stage reconstruction of laryngeal function by thyroid cartilage fenestration and "draw-out" resection with adjuvant internal titanium microplate fixation in early glottic carcinoma demonstrates good postoperative recovery and good preservation of the laryngeal function.

A recurrence-predictive model based on eight genes and tumor mutational burden/microsatellite instability status in Stage II/III colorectal cancer.

BACKGROUND: Although adjuvant chemotherapy (ACT) is widely used to treat patients with Stage II/III colorectal cancer (CRC), administering ACT to specific patients remains a challenge. The decision to ACT requires an accurate assessment of recurrence risk and absolute treatment benefit. However, the traditional TNM staging system does not accurately assess a patient's individual risk of recurrence. METHODS: To identify recurrence risk-related genetic factors for Stage II/III CRC patients after radical surgery, we conducted an analysis of whole-exome sequencing of 47 patients with Stage II/III CRC who underwent radical surgery at five institutions. Patients were grouped into non-recurrence group (NR, n = 24, recurrence-free survival [RFS] > 5 years) and recurrence group (R, n = 23, RFS <2 years). The TCGA-COAD/READ cohort was employed as the validation dataset. RESULTS: A recurrence-predictive model (G8plus score) based on eight gene (CUL9, PCDHA12, HECTD3, DCX, SMARCA2, FAM193A, AATK, and SORCS2) mutations and tumor mutation burden/microsatellite instability (TMB/MSI) status was constructed, with 97.87% accuracy in our data and 100% negative predictive value in the TCGA-COAD/READ cohort. For the TCGA-COAD/READ cohort, the G8plus-high group had better RFS (HR = 0.22, p = 0.024); the G8plus-high tumors had significantly more infiltrated immune cell types, higher tertiary lymphoid structure signature scores, and higher immunological signature scores. The G8plus score was also a predict biomarker for immunotherapeutic in advanced CRC in the PUCH cohort. CONCLUSIONS: In conclusion, the G8plus score is a powerful biomarker for predicting the risk of recurrence in patients with stage II/III CRC. It can be used to stratify patients who benefit from ACT and immunotherapy.

Sandwich-type electrochemical immunosensing of hypopharyngeal carcinoma biomarker carcinoembryonic antigen based on N-doped hollow mesoporous nanocarbon spheres/gold hybrids as sensing platform and gold/ferrocene as signal amplifier.

In the present work, a highly sensitive sandwich-type electrochemical immunosensor of carcinoembryonic antigen (CEA) was developed by preparing N-doped hollow mesoporous nanocarbon spheres/gold hybrids (NHMN/Au) hybridsas sensing platformand Au/ferrocene (Au/Fc) as signal amplifiers. The large surface area and high conductivity as well as good biocompatibility of NHMN/Au can increase the loading of primary antibody (Ab1) and accelerate the electron transport rate of the electrode surface, while Au can carry immobilized secondary antibodies (Ab2) and Fc derivative (Fc-SH).By using Fc-SH as response probe, the experiments show that the peak current of probe could increase after occurring the specific recognition of Ab1-CEA-Ab2, thus a novel sandwich-type immunosensor of CEA was developed. Finally, the proposed method for CEA detection was applied in human serum and the obtained results are satisfactory, indicating the developed method has important clinical applications for CEA determination.

Particle Counting Methods Based on Microfluidic Devices.

Particle counting serves as a pivotal constituent in diverse analytical domains, encompassing a broad spectrum of entities, ranging from blood cells and bacteria to viruses, droplets, bubbles, wear debris, and magnetic beads. Recent epochs have witnessed remarkable progressions in microfluidic chip technology, culminating in the proliferation and maturation of microfluidic chip-based particle counting methodologies. This paper undertakes a taxonomical elucidation of microfluidic chip-based particle counters based on the physical parameters they detect. These particle counters are classified into three categories: optical-based counters, electrical-based particle counters, and other counters. Within each category, subcategories are established to consider structural differences. Each type of counter is described not only in terms of its working principle but also the methods employed to enhance sensitivity and throughput. Additionally, an analysis of future trends related to each counter type is provided.

Surgical treatment of massive stoma site tumors after a curative operation for rectal cancer.

OBJECTIVE: This study aimed to evaluate the clinical and oncological outcomes of selected rectal cancer patients with massive stoma site tumors who underwent radical resection and reconstruction. METHODS: We reviewed 8 cases of massive stoma site tumors in patients who had permanent gastrointestinal stoma in the abdominal wall following radical resection of rectal cancer between March 2013 and May 2018 at the Peking University Cancer Hospital and Peking University Shougang Hospital. RESULTS: There were seven males and one female patient, with a median age of 50.6 years. The average time between the initial surgery and the development of a malignant tumor at the stoma site was 5 years (range, 0.5-14 years). The average diameter of the stoma site tumors was 8.1 cm, and the diameter of the largest tumor was 12 cm. After tumor resection, the area of the largest abdominal wall defect was about 15 × 14 cm2. Abdominal wall repair included the use of a tensor fasciae latae muscle flap, local fasciocutaneous rotational flap, and pedicled anterolateral thigh flap. No patient died in the 30 days following surgery. The longest follow-up period was 81 months, and 5 patients died. CONCLUSIONS: Multidisciplinary clinical management fosters positive outcomes in treating massive stoma site tumors. Local R0 resection and abdominal wall reconstruction are safe and feasible, and function to removes local disease, allowing patients to live a higher quality of life.

A deep learning algorithm for detection of oral cavity squamous cell carcinoma from photographic images: A retrospective study.

BACKGROUND: The overall prognosis of oral cancer remains poor because over half of patients are diagnosed at advanced-stages. Previously reported screening and earlier detection methods for oral cancer still largely rely on health workers' clinical experience and as yet there is no established method. We aimed to develop a rapid, non-invasive, cost-effective, and easy-to-use deep learning approach for identifying oral cavity squamous cell carcinoma (OCSCC) patients using photographic images. METHODS: We developed an automated deep learning algorithm using cascaded convolutional neural networks to detect OCSCC from photographic images. We included all biopsy-proven OCSCC photographs and normal controls of 44,409 clinical images collected from 11 hospitals around China between April 12, 2006, and Nov 25, 2019. We trained the algorithm on a randomly selected part of this dataset (development dataset) and used the rest for testing (internal validation dataset). Additionally, we curated an external validation dataset comprising clinical photographs from six representative journals in the field of dentistry and oral surgery. We also compared the performance of the algorithm with that of seven oral cancer specialists on a clinical validation dataset. We used the pathological reports as gold standard for OCSCC identification. We evaluated the algorithm performance on the internal, external, and clinical validation datasets by calculating the area under the receiver operating characteristic curves (AUCs), accuracy, sensitivity, and specificity with two-sided 95% CIs. FINDINGS: 1469 intraoral photographic images were used to validate our approach. The deep learning algorithm achieved an AUC of 0·983 (95% CI 0·973-0·991), sensitivity of 94·9% (0·915-0·978), and specificity of 88·7% (0·845-0·926) on the internal validation dataset (n = 401), and an AUC of 0·935 (0·910-0·957), sensitivity of 89·6% (0·847-0·942) and specificity of 80·6% (0·757-0·853) on the external validation dataset (n = 402). For a secondary analysis on the internal validation dataset, the algorithm presented an AUC of 0·995 (0·988-0·999), sensitivity of 97·4% (0·932-1·000) and specificity of 93·5% (0·882-0·979) in detecting early-stage OCSCC. On the clinical validation dataset (n = 666), our algorithm achieved comparable performance to that of the average oral cancer expert in terms of accuracy (92·3% [0·902-0·943] vs 92.4% [0·912-0·936]), sensitivity (91·0% [0·879-0·941] vs 91·7% [0·898-0·934]), and specificity (93·5% [0·909-0·960] vs 93·1% [0·914-0·948]). The algorithm also achieved significantly better performance than that of the average medical student (accuracy of 87·0% [0·855-0·885], sensitivity of 83·1% [0·807-0·854], and specificity of 90·7% [0·889-0·924]) and the average non-medical student (accuracy of 77·2% [0·757-0·787], sensitivity of 76·6% [0·743-0·788], and specificity of 77·9% [0·759-0·797]). INTERPRETATION: Automated detection of OCSCC by deep-learning-powered algorithm is a rapid, non-invasive, low-cost, and convenient method, which yielded comparable performance to that of human specialists and has the potential to be used as a clinical tool for fast screening, earlier detection, and therapeutic efficacy assessment of the cancer.

Complete mitochondrial genome sequence and mutations of the laryngeal cancer model inbred nude rat strain.

In the present work, we undertook the complete mitochondrial genome sequencing of an important laryngeal cancer model inbred rat strain for the first time. The total length of the mitogenome was 16,308 bp. It harbored 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and one non-coding control region (D-loop region). The mutation events were also reported.

[Analysis of clinical diagnosis and treatment of 112 cases of parapharyngeal space tumors].

OBJECTIVE: To explore the diagnosis, treatment and surgical approaches of parapharyngeal space tumors. METHOD: This retrospective study consisted of 112 patients with parapharyngeal space tumors underwent surgeries. The data included clinical symptoms and signs, pathological types, imaging examinations, surgical approaches and postoperative complications. RESULT: Computerized tomography (CT), magnetic resonance imaging (MRD and digital subtraction angiography (DSA) made clear the tumor size, localization and its relation to adjacent structures. The postoperative histopathology varied and showed benign in 98 cases consisting of salivary gland tumors (52 cases), neurogenic tumors(33 cases) and other types (13 cases). During the 3 years follow-up period, local recurrence appeared in 3 patients with salivary pleomorphic adenoma and 1 patient with neurofibromatosis. These recurrent tumor cases were cured with second surgery. In 14 patients with malignant tumors reported, 8 cases survived for 5 years, 2 cases (1 adenoid cystic carcinoma and 1 carcinoma in pleornorphic adenoma) recurred in the two and a half years cured with second surgery affiliated radiation therapy through 3 years follow-up time and the rest were followed up 1 to 3 years without recurrence. Peripheral facial paralysis was observed in 25 patients, and 3 patients experienced hypoglossal nerve palsy. Only 1 patient encountered vagus nerve injury, and 2 patients appeared Horner's syndrome, and 4 patients endured Frey syndrome. Gills leakage was discovered in 3 cases and cavity infection was noted in 1 patient. CONCLUSION: CT, MRI and DSA were important in the diagnosis and differential diagnosis of parapharyngeal space tumors. The key to successful treatment is knowing the anatomy of the parapharyngeal space, preoperative assessment and appropriate surgical approach.

[The application of decompression in the treatment of gnathous cystic lesions].

OBJECTIVE: To explore the application of decompression in the treatment of ganthous cystic lesions. METHOD: Decompression surgery were performed on 32 patients with gnathous cystic lesions, the cavities of cysts were open and the cysts pressure was relieved. The cavities of cysts were flushed after the operation and the prognosis were assessed in the regular follow-up. RESULT: All cysts cavities were shrinks afer decompression operation. Through the X-line and/or CT scans, we could observe that the new bones formed around cysts cavities, tilt shift teeth were gradually corrected and the permanent tooth germs of pediatric patients almost returned to the right places and erupted; There were the only remaining small bone indentations in the 18 cases, which do not need the Phase II surgery. Eight cases of cysts cavities shrinks more than 50%, which needed cystectomy. Six cases of cysts cavities shrinks less than 50%, which were still in the follow-up treatment. CONCLUSION: The decompression surgery is a simple, economical and effective method for the treatment of gnathous cystic lesions.

[Isolated sphenoid sinus disease presented the primary symptom as headache or ocular disturbance].

OBJECTIVE: To improve the understanding of the symptoms and signs of isolated sphenoid sinus disease and decrease the occurrence of misdiagnoses. METHOD: The clinical manifestation and the advantage of endoscopic sinus surgery were analyzed in 22 cases of isolated sphenoid sinus disease. RESULT: Twelve cases had endoscopic sphenoidotomy, 7 cases had external ethmoidal sphenoidotomy, 3 cases had antibiotic, steroid and neurotrophic therapy. All of the patients were free of headache,improvement in vision and ocular motility after treatment. After 3 to 6 months' follow up, 1 case recurred and symptom relieved after endoscopic sinus surgery. 1 case adenoid cystoid carcinoma underwent post operative radiotherapy without recurrence after 3 years follow up. CONCLUSION: Isolated sphenoid sinus disease presented the primary symptom as headache and/or ocular disturbance is prone to be misdiagnosed, application of CT, MRI and endoscopy improve its diagnosis and treatment standard. Endoscopic sinus surgery is the primary therapy for isolated sphenoid sinus disease.

[The arteria reconstruction of the carotid artery involved with advanced head and neck cancer].

OBJECTIVE: To investigate the application of arteria reconstruction in the therapy of the carotid artery involved with advanced head and neck cancer. METHOD: The artificial blood vessel made of polytetrafluoroethylene (PTFE) was used in two patients with supraglottic carcinoma to reconstruct the carotid artery. In the two cases, their common carotid artery and internal carotid artery involved with metastatic lymph nodes, were resected before reconstruction. RESULT: The wound of two cases had grade I healing, no serious cranium-cerebrum complication occurred. The patency of the artificial blood vessel was observed by ultrasonography. The vessels were at good condition. Two patients died two and three years later. CONCLUSION: The artificial blood vessel reconstruction for vascular damaged by head and neck cancer is safe and convenient in clinical practice. At the same time, it is an alternative method to solve the deficiency of auto vessels in the body.

[The clinical observation of nasal packing with rhino rapid nasal dressing with gel knit].

OBJECTIVE: To explore the value of using Rapid Nasal Dressing with Gel Knit in the patients with the postoperative nasal cavity and sinuses or severe epistaxis. METHOD: A comparative study was carried out for the clinical effects of traditional Vaseline gauze with that of Rhino Rapid Nasal Dressing with Gel Knit as nasal packing materials, through a valuation on the patient discomfort with headache and control of postoperative bleeding and ease of removal. RESULT: There was a significant difference in headache during the period of packing and removal between two groups (P < 0.01, P < 0.05). There was no significant difference in the volume of bleeding during the 24 hours packing (P > 0.05), but there was one time during removal (P < 0.01), and it was also more ease of removal than that of the group with Vaseline gauze (P < 0.01 ). CONCLUSION: Rhino Rapid Nasal Dressing with Gel Knit is a kind of ideal material for nasal packing, because of its effect of drug hemostasis and compressive hemostasis.

[Clinical analysis of 38 patients with cephalic and cervical adenoid cystic carcinoma].

OBJECTIVE: To assess the clinical features and the treatment result of cephalic and cervical adenoid cystic carcinoma (ACC). METHOD: A retrospective analysis was performed on 38 patients with cephalic and cervical ACC by their clinical manifestation, the therapy and follow-up results. RESULT: We had 38 patients of operation. All patients followed up from 3 years to 13 years. The overall 3-year survival rate of patients was 71.1%, the overall 5-year survival rate of patients was 63.2%. CONCLUSION: Cephalic and cervical ACC is not easy to exact diagnosis in early stage. It progresses slowly. It also has the tendency of recurrence and cancerous metastasis. Thus it, is necessary to do both thorough surgery.