[Long-term outcome of patients with rectal cancer who achieve complete or near complete clinical responses after neoadjuvant therapy: a multicenter registry study of data from the Chinese Watch and Wait Database].

Objective: To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT). Methods: This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups. Results: Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion: Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

Removal of intraglandular calculi in Wharton's duct: clinical outcome and treatment algorithm.

The aim of this study was to propose a treatment strategy for intraglandular submandibular calculi based on calculus site. Seventy-three consecutive patients with impalpable intraglandular submandibular calculi were enrolled retrospectively. The calculi were classified as either post-hilar type, central type, or superficial type. Treatment approaches included transoral duct slitting (TDS), interventional basket retrieval (IBR), intraductal laser lithotripsy (ILL), and transcervical lithotomy (TCL). Complete calculus removal with gland preservation was achieved in 64 patients (87.7%). The success rate for post-hilar, central, and superficial calculi was 86.4% (51/59), 90.9% (10/11), and 100% (3/3), respectively. The treatment approach applied in patients with treatment success was TDS in 32 cases, IBR in 20, ILL in nine, and TCL in three. During follow-up (median 17.3 months), one patient experienced gland atrophy and three had ductal stenosis; the remaining 60 patients (93.8%, 60/64) had good clinical outcomes. In the eight failure cases operated by TDS, the deeply situated calculi could not be detached despite the parenchymal incision in five cases, while the procedure was ceased due to the patient's inability to cooperate in the other three cases. In the remaining failure case, the submandibular gland was sacrificed after calculus extraction via TCL. Application of the proposed treatment algorithm might help preserve gland function in patients with intraglandular submandibular calculi.

Claudin-10 Decrease in the Submandibular Gland Contributes to Xerostomia.

Tight junction proteins play a crucial role in paracellular transport in salivary gland epithelia. It is clear that severe xerostomia in patients with HELIX syndrome is caused by mutations in the claudin-10 gene. However, little is known about the expression pattern and role of claudin-10 in saliva secretion in physical and disease conditions. In the present study, we found that only claudin-10b transcript was expressed in human and mouse submandibular gland (SMG) tissues, and claudin-10 protein was dominantly distributed at the apicolateral membranes of acini in human, rat, and mouse SMGs. Overexpression of claudin-10 significantly reduced transepithelial electrical resistance and increased paracellular transport of dextran and Na+ in SMG-C6 cells. In C57BL/6 mice, pilocarpine stimulation promoted secretion and cation concentration in saliva in a dose-dependent increase. Assembly of claudin-10 to the most apicolateral portions in acini of SMGs was observed in the lower pilocarpine (1 mg/kg)-treated group, and this phenomenon was much obvious in the higher pilocarpine (10 mg/kg)-treated group. Furthermore, 7-, 14-, and 21-wk-old nonobese diabetic (NOD) and BALB/c mice were used to mimic the progression of hyposalivation in Sjögren syndrome. Intensity of claudin-10 protein was obviously lower in SMGs of 14- and 21-wk-old NOD mice compared with that of age-matched BALB/c mice. In the cultured mouse SMG tissues, interferon-γ (IFN-γ) downregulated claudin-10 expression. In claudin-10-overexpressed SMG-C6 cells, paracellular permeability was decreased. Furthermore, IFN-γ stimulation increased p-STAT1 level, whereas pretreatment with JAK/STAT1 antagonist significantly alleviated the IFN-γ-induced claudin-10 downregulation. These results indicate that claudin-10 functions as a pore-forming component in acinar epithelia of SMGs, assembly of claudin-10 is required for saliva secretion, and downregulation of claudin-10 induces hyposecretion. These findings may provide new clues to novel therapeutic targets on hyposalivation.

Ru-Based Organometallic Agents Bearing Phenyl Hydroxide: Synthesis and Antibacterial Mechanism Study against Staphylococcus aureus.

The development of antimicrobial agents with novel model of actions is a promising strategy to combat multiple resistant bacteria. Here, three ruthenium-based complexes, which acted as potential antimicrobial agents, were synthesized and characterized. Importantly, three complexes all showed strong bactericidal potency against Staphylococcus aureus. In particular, the most active one has a MIC of 6.25 µg/mL. Mechanistic studies indicated that ruthenium complex killed S. aureus by releasing ROS and damaging the integrity of bacterial cell membrane. In addition, the most active complex not only could inhibit the biofilm formation and hemolytic toxin secretion of S. aureus, but also serve as a potential antimicrobial adjuvant as well, which showed synergistic effects with eight traditional antibiotics. Finally, both G. mellonella larva infection model and mouse skin infection model all demonstrated that ruthenium complex also showed significant efficacy against S. aureus in vivo. In summary, our study suggested that ruthenium-based complexes bearing a phenyl hydroxide are promising antimicrobial agents for combating S. aureus.

[The impact of extended waiting time on tumor regression after neoadjuvant chemoradiotherapy for locally advanced rectal cancer].

Objective: To investigate the influence of extending the waiting time on tumor regression after neoadjuvant chemoradiology (nCRT) in patients with locally advanced rectal cancer (LARC). Methods: Clinicopathological data from 728 LARC patients who completed nCRT treatment at the First Affiliated Hospital, Naval Medical University from January 2012 to December 2021 were collected for retrospective analysis. The primary research endpoint was the sustained complete response (SCR). There were 498 males and 230 females, with an age (M(IQR)) of 58 (15) years (range: 22 to 89 years). Logistic regression models were used to explore whether waiting time was an independent factor affecting SCR. Curve fitting was used to represent the relationship between the cumulative occurrence rate of SCR and the waiting time. The patients were divided into a conventional waiting time group (4 to <12 weeks, n=581) and an extended waiting time group (12 to<20 weeks, n=147). Comparisons regarding tumor regression, organ preservation, and surgical conditions between the two groups were made using the t test, Wilcoxon rank sum test, or χ2 test as appropriate. The Log-rank test was used to elucidate the survival discrepancies between the two groups. Results: The SCR rate of all patients was 21.6% (157/728). The waiting time was an independent influencing factor for SCR, with each additional day corresponding to an OR value of 1.010 (95%CI: 1.001 to 1.020, P=0.031). The cumulative rate of SCR occurrence gradually increased with the extension of waiting time, with the fastest increase between the 10th week. The SCR rate in the extended waiting time group was higher (27.9%(41/147) vs. 20.0%(116/581), χ2=3.901, P=0.048), and the organ preservation rate during the follow-up period was higher (21.1%(31/147) vs. 10.7%(62/581), χ2=10.510, P=0.001). The 3-year local recurrence/regrowth-free survival rates were 94.0% and 91.1%, the 3-year disease-free survival rates were 76.6% and 75.4%, and the 3-year overall survival rates were 95.6% and 92.2% for the conventional and extended waiting time groups, respectively, with no statistical differences in local recurrence/regrowth-free survival, disease-free survival and overall survival between the two groups (χ2=1.878, P=0.171; χ2=0.078, P=0.780; χ2=1.265, P=0.261). Conclusions: An extended waiting time is conducive to tumor regression, and extending the waiting time to 12 to <20 weeks after nCRT can improve the SCR rate and organ preservation rate, without increasing the difficulty of surgery or altering the oncological outcomes of patients.

[The role of the national oral health program in the development of oral health service and related thinkings].

Conception of public health was firstly put forward by American professor Winslow. Ensuring and promoting the health of general population is the key connotation for the definition of public health. Oral disease has become a public health problem. Caries which preventable and curable is the most common oral disease and the etiology is also clear. Oral health comprehensive intervention program for children in central and western regions was set up in 2008 by Chinese government. The program included sealing on the first permanent molar and oral health education towards primary school children covering mid-west area. This was the first oral health program invested by government and managed by Chinese Stomatological Association. Six years later, the program was popularized to the whole nation, and renamed as national oral health comprehensive intervention program for children in China. The program had made deep impact on development of oral health service in China. The study tries to analyze the challenges of oral health service through reviewing the background, content, organization and effectiveness of the program, aiming to provide suggestions on policy, financing, system, ability and technology for the future development.

Utility of navigation system-guided submandibular gland core needle biopsy in the diagnosis of immunoglobulin G4-related sialadenitis.

Pathological diagnosis is important for the definite diagnosis of immunoglobulin G4-related sialadenitis (IgG4-RS). Core needle biopsy (CNB) is a scarless technique; however the pathological heterogeneity of IgG4-RS (a particular feature of this disease) could be the potential cause of the inferior diagnostic capability of submandibular gland CNB (SMG-CNB) for IgG4-RS. The aim of this study was to explore technical improvements in SMG-CNB and improve its diagnostic power in IgG4-RS diagnosis. Eighteen patients clinically suspected for IgG4-RS were enrolled and underwent both SMG-CNB and SMG surgical biopsy. A navigation system (Brainlab) was employed during SMG-CNB to obtain representative samples and avoid blood vessel injury. Histopathological and immunopathological findings for the SMG-CNB samples were in good concordance with SMG surgical biopsy. There was no statistically significant difference between SMG-CNB and SMG surgical biopsy in IgG-positive cell count (132.4 ± 59.3 vs 132.2 ± 47.5, P = 0.99), IgG4-positive cell count (102.2 ± 39.7 vs 97.2 ± 27.6, P = 0.67), or IgG4-positive/IgG-positive cell count ratio (78.6% ± 0.1% vs 75.2% ± 0.1%, P = 0.29). A moderate or strong significant correlation was found between SMG-CNB and SMG surgical biopsy for these cell counts and ratio (all P < 0.01). The diagnostic consistency of SMG-CNB and SMG surgical biopsy was 100%. The Brainlab navigation system may assist in collecting representative SMG-CNB samples from typical pathological lesions. Tissues obtained from SMG-CNB are sufficient for the pathological diagnosis of IgG4-RS. Standardized SMG-CNB is expected to replace SMG surgical biopsy for IgG4-RS diagnosis.

[Recent progress in the treatment of intractable sialolithiasis].

Sialolithiasis occurs in approximately 0.45% to 1.20% of the general population. The typical clinical symptom manifests as a painful swelling of the affected glands after a meal or upon salivary stimulation, which extremely affects the life quality of the patients. With the development of sialendoscopy and lithotripsy, most sialoliths can be successfully removed with preservation of the gland. However, sialoliths in the deep hilar-parenchymal submandibular ducts and impacted parotid stones located in the proximal ducts continue to pose great challenges. Our research center for salivary gland diseases (in Peking University School and Hospital of Stomatology) has used sialendoscopy for 17 years and treated >2 000 patients with salivary gland calculi. The success rate was approximately 92% for submandibular gland calculi and 95% for parotid calculi. A variety of minimally invasive surgical techniques have been applied and developed, which add substantial improvements in the treatment of refractory sialolithiasis. Further, the radiographic positioning criteria and treatment strategy are proposed for these intractable stones. Most of the hilar-parenchymal submandibular stones are successfully removed by a transoral approach, including transoral duct slitting and intraductal basket grasping, while a small portion of superficial stones can be removed by a mini-incision in submandibular area. Impacted stones located in the distal third of parotid gland ducts are removed via "peri-ostium incision", which is applied to avoid a cicatricial stenosis from a direct ostium incision. Impacted parotid stones located in the middle and proximal third of the Stensen's duct are removed via a direct mini-incision or a peri-auricular flap. A direct transcutaneous mini-incision is commonly performed under local anesthesia with an imperceptible scar, and is indicated for most of impacted stones located in the middle third, hilum and intraglandular ducts. By contrast, a peri-auricular flap is performed under general anesthesia with relatively larger operational injury of the gland parenchyma, and should be best reserved for deeper intraglandular stones. Laser lithotripsy has been applied in the treatment of sialolithiasis in the past decade, and holmium ∶YAG laser is reported to have the best therapeutic effects. During the past 3 years, our research group has performed laser lithotripsy for a few cases with intractable salivary stones. From our experiences, withdrawal of the endoscopic tip 0.5-1.0 cm away from the extremity of the laser fiber, consistent saline irrigation, and careful monitoring of gland swelling are of vital importance for avoidance of injuries of the ductal wall and the vulnerable endoscope lens during lithotripsy. Larger calculi require multiple treatment procedures. The risk of ductal stenosis can be alleviated by endoscopic dilation. In summary, appropriate use of various endoscopy-assisted lithotomy helps preserve the gland function in most of the patients with refractory sialolithiasis. Further studies are needed in the following aspects: Transcervical removal of intraglandular submandibular stones, intraductal laser lithotripsy of impacted parotid stones and deep submandibular stones, evaluation of long-term postoperative function of the affected gland, et al.

[Clinicopathological characteristics and prognosis of non-Hodgkin lymphoma in oral and maxillofacial regions: An analysis of 369 cases].

OBJECTIVE: To investigate the clinicopathological characteristics and factors influencing the prognosis of non-Hodgkin lymphoma (NHL) in oral and maxillofacial regions. METHODS: Clinicopathological data of 369 patients with oral and maxillofacial NHL initially diagnosed in Peking University Hospital of Stomatology from 2008 to 2020 were collected and analyzed retrospectively. RESULTS: There were 180 males and 189 females. The median age of the patients was 56 years (3 months to 92 years), and the median duration was three months. Clinically, 283 cases manifested as mass, 38 cases as ulcerative necrotizing lesions, and 48 cases as diffuse soft tissue swelling. The lesions of 90 cases located in face and neck (75 cases neck, 20.3%), 99 cases were of major salivary glands (79 cases parotid glands, 20.9%), 103 cases of oral cavity, 50 cases of maxillofacial bones, 20 cases of Waldeyer's ring, and 7 cases of infratemporal fossa. In the study, 247 of the 369 patients had cervical lymphadenopathy, only 40 cases had B symptoms, and 23 cases had the bulky disease. Of the 369 NHLs, 299 (81%) were B-cell NHL, and 70(19%) were T-cell NHL. Diffuse large B-cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, follicular lymphoma, and extranodal natural killer (NK)/T-cell lymphoma nasal type were the most common pathological subtypes. According to Ann Arbor staging, 87, 138, 106, and 38 cases were classified as staged Ⅰ, Ⅱ, Ⅲ, Ⅳ, respectively. The me-dian follow-up time was 48 months, 164 patients died during the follow-up period. The overall survival rates for one year, two years, and five years were 90.1%, 82.4%, and 59.9%, respectively, and the median survival was (86.00±7.98) months. Multivariate analysis showed that age (P < 0.001), Ann Arbor staging (P < 0.001), elevated lactate dehydrogenase (P=0.014), and pathological subtype (P=0.049) were the independent factors influencing the overall survival rate of NHL patients. CONCLUSION: Oral and maxillofacial NHL has unique clinical characteristics and distribution patterns of pathological subtypes. Fewer patients had systemic symptoms. Neck and parotid glands were the most common sites invaded by NHL. Advanced age, Ann Arbor stage Ⅲ-Ⅳ, B symptoms, and T-cell NHL may predict a poor prognosis in oral and maxillofacial NHL patients.

Comparison of two transcutaneous approaches for the removal of impacted parotid stones.

The aim of this study was to comparatively evaluate the indications and treatment outcomes of two transcutaneous approaches for the removal of impacted parotid stones. Sixty-eight consecutive patients with impacted parotid stones underwent endoscopy-assisted lithotomy via a direct mini-incision or a peri-auricular flap. Clinical safety and outcomes were evaluated. Complete stone extraction was achieved in all patients. In the mini-incision group (52 patients), the stones were in the middle third of the main duct in 31 patients, at the hilum in 16, and in the intraglandular duct in five. In the flap group (16 patients), they were in the middle third of the main duct in one patient, at the hilum in seven, and in the intraglandular duct in eight. Salivary fistula occurred in five mini-incision group patients (9.6%) and four flap group patients (25%). The clinical outcome in the mini-incision group (47 patients, median 25 months of follow-up) was good in 28 patients, fair in 13, and poor in six (12.8%). The clinical outcome in the flap group (16 patients, median 84 months of follow-up) was good in nine patients, fair in five, and poor in two (12.5%). The direct mini-incision approach was found to be safe and effective for impacted stones in the middle third, hilum, and proximal third of the main duct, while the peri-auricular approach would be best reserved for deeper intraglandular stones.

The Role of Endothelial Barrier Function in the Fibrosis of Salivary Gland.

In the salivary glands, fibrosis occurs in many pathological conditions. Endothelial tight junction (TJ)-based barrier function plays a vital role in maintaining the homeostasis of the salivary glands. However, whether endothelial barrier function is changed and involved in the pathogenesis of glandular fibrosis is unknown. Here, by using a mouse model in which the main excretory duct of the submandibular gland (SMG) was ligated to induce inflammation and fibrosis, endothelial barrier function and TJ protein expression and distribution were examined. Both 4-kDa and 70-kDa fluorescence-labeled dextrans permeated more in the 1-, 3-, and 7-d ligated SMGs. Meanwhile, the mRNA level of claudin-5 was increased with an obvious redistribution from apicolateral membranes to lateral membranes and cytoplasm in the fibrotic glands. Notably, the TJ sealer AT1001 significantly attenuated the disrupted endothelial barrier function and thereby ameliorated the glandular fibrosis. Cytokine array detection showed that monocyte chemoattractant protein-1 (MCP-1) was highly enriched in the 3-d ligated SMGs, and MCP-1 directly impaired barrier function, increased claudin-5 expression, induced the relocalization of claudin-5, and activated p-ERK1/2 in cultured human endothelial cells. Furthermore, the upregulation and disorganization of claudin-5 as well as the elevation of MCP-1 and p-ERK1/2 signaling were also confirmed in fibrotic SMGs from patients with chronic sialadenitis and immunoglobulin G4-related sialadenitis. Altogether, our findings revealed that disrupted endothelial barrier function contributed to the progression of glandular fibrosis, and targeting endothelial TJs might be a promising approach to alleviate salivary gland fibrosis-related diseases.

[Establishment and application of new techniques for submandibular gland preservation].

The saliva secreted from submandibular gland (SMG) accounts for 60%-65%. It plays an important role in maintaining the human function of swallow, digestion, testing, speech, protection of oral mucosa, and prevention from dental carries. The SMG is frequently resected during the treatment for various kinds of oral and maxillofacial diseases, resulting in xerostomia and decreased quality of life. During the past 15 years, Research Center of Salivary Gland Diseases in Peking University School and Hospital of Stomatology conducted a series of studies on new techniques for preservation of SMG and achieved remarkable results. The clinicopathologic and imaging characteristics of IgG4-related sialadenitis (IgG4-RS) were clarified based on systematic studies. The results of studies on the pathogenesis of IgG4-RS showed that unbalance of inflammatory factors mediated the abnormality of secretion of SMG. IL-4 participates in occurring and development of glandular fibrosis of SMG. Regulation of tumor necrosis factor α (TNF-α) and cleaning of senescent cells might be taken as the targets for treatment of IgG4-RS. The combination of glucocorticoid and steroid-sparing agents showed effective results for treating IgG4-RS, clinical remission was achieved in all the patients, serum IgG4 levels decreased, and salivary gland secretion significantly increased. Sialoendoscopy-assisted sialolithectomy was applied in the treatment of about 1 000 cases with submandibular hilar calculi with a success rate of more than 90%. Transfer of SMG was used for prevention from radiation-induced xerostomia in the patients with head and neck carcinoma. SMG was transferred to the submental region before radiotherapy and was kept away from the ra-diation field. The results of prospective clinical controlled study showed this technique could effectively preserve the function of SMG and prevent from xerostomia. Based on the micro-anatomical study on the blood vessels and ducts of SMG, partial sialoadenectomy was applied for treatment of benign tumors in the SMG. A clinical controlled study confirmed its safety for control of the tumors and its advantage of preservation of SMG function. The studies on the involvement of SMG in oral squamous cell carcinoma (OSCC) provided the anatomical and histopathological basis for preservation of SMG during neck dissection for early cases with OSCC. A innovated surgical modality "four preservations including SMG" was used during the neck dissection for the early cases with OSCC. A prospective randomized clinical controlled study confirmed its safety, feasibility, effectiveness for control of the carcinoma, and advantages of preservation of SMG function.

Analysis of synthetic electron cyclotron emission from the high field side of HL-2M tokamak plasmas.

A synthetic electron cyclotron emission (ECE) diagnostic is used to interpret ECE signals from preset plasma equilibrium profiles, including magnetic field, electron density, and electron temperature. According to the simulation results, the electron temperature (Te) profile covering the harmonic overlap region can be obtained by receiving ECE signals at the high field side (HFS) of the HL-2M plasma. The third harmonic ECE at the low field side (LFS) cannot pass through the second harmonic resonance layer at the HFS unless the optical thickness (τ) of the second harmonic becomes gray (τ ≤ 2). In addition, the impact of the relativistic frequency down-shift has been evaluated and corrected. The measurable range of the HFS ECE has been calculated by scanning different parameters (electron density, temperature, and magnetic field). Higher plasma parameters allow a wider radial range of electron temperature measurements. The minimum inner measurable position can reach R = 120 cm (r/a = -0.89) when the product of core temperature (Te0) and density (ne0) is greater than 35 × 1019 keV m-3, which is extended by more than 30 cm inward compared with that of the LFS measurement. The HFS ECE will greatly improve the diagnostic ability of ECE systems on the HL-2M tokamak.

[A prospective cohort study on the clinical value of pelvic peritoneal reconstruction in laparoscopic anterior resection for middle and low rectal cancer].

Objective: To investigate the safety and efficacy of pelvic peritoneal reconstruction and its effect on anal function in laparoscopy-assisted anterior resection of low and middle rectal cancer. Methods: A prospective cohort study was conducted. Consecutive patients with low and middle rectal cancer who underwent laparoscopy-assisted transabdominal anterior resection at Naval Military Medical University Changhai Hospital from February 2020 to February 2021 were enrolled. Inclusion criteria: (1) the distance from tumor to the anal verge ≤10 cm; (2) laparoscopy-assisted transabdominal anterior resection of rectal cancer; (3) complete clinical data; (4) rectal adenocarcinoma diagnosed by postoperative pathology. Exclusion criteria: (1) emergency surgery; (2) patients with a history of anal dysfunction or anal surgery; (3) preoperative diagnosis of distant (liver, lung) metastasis; (4) intestinal obstruction; (5) conversion to open surgery for various reasons. The pelvic floor was reconstructed using SXMD1B405 (Stratafix helical PGA-PCL, Ethicon). The first needle was sutured from the left anterior wall of the neorectum to the right. Insertion of the needle was continued to suture the root of the sigmoid mesentery while the Hemo-lok was used to fix the suture. The second needle was started from the beginning of the first needle, after 3-4 needles, a drainage tube was inserted through the left lower abdominal trocar to the presacral space. Then, the left peritoneal incision of the descending colon was sutured, after which Hemo-lok fixation was performed. The operative time, perioperative complications, postoperative Wexner anal function score and low anterior resection syndrome (LARS) score were compared between the study group and the control group. Three to six months after the operation, pelvic MRI was performed to observe and compare the pelvic floor anatomical structure of the two groups. Results: A total of 230 patients were enrolled, including 58 who underwent pelvic floor peritoneum reconstruction as the study group and 172 who did not undergo pelvic floor peritoneum reconstruction as the control group. There were no significant differences in general data between the two groups (all P>0.05). The operation time of the study group was longer than that of control group [(177.5±33.0) minutes vs. (148.7±45.5) minutes, P<0.001]. There was no significant difference in the incidence of perioperative complications (including anastomotic leakage, anastomotic bleeding, postoperative pneumonia, urinary tract infection, deep vein thrombosis, and intestinal obstruction) between the two groups (all P>0.05). Eight cases had anastomotic leakage, of whom 2 cases (3.4%) in the study group were discharged after conservative treatment, 5 cases (2.9%) of other 6 cases (3.5%) in the control group were discharged after the secondary surgical treatment. The Wexner score and LARS score were 3.1±2.8 and 23.0 (16.0-28.0) in the study group, which were lower than those in the control group [4.7±3.4 and 27.0 (18.0-32.0)], and the differences were statistically significant (t=-3.018, P=0.003 and Z=-2.257, P=0.024). Severe LARS was 16.5% (7/45) in study group and 35.5% (50/141) in control group, and the difference was no significant differences (Z=4.373, P=0.373). Pelvic MRI examination 3 to 6 months after surgery showed that the incidence of intestinal accumulation in the pelvic floor was 9.1% (3/33) in study group and 46.4% (64/138) in control group (χ(2)=15.537, P<0.001). Conclusion: Pelvic peritoneal reconstruction using stratafix in laparoscopic anterior resection of middle and low rectal cancer is safe and feasible, which may reduce the probability of the secondary operation in patients with anastomotic leakage and significantly improve postoperative anal function.

Hyper-IgE syndrome caused by DOCK8 mutation with a tumour-like lesion of the lip: a case report.

Autosomal recessive hyper-IgE syndrome caused by DOCK8 gene mutation is an immunodeficiency. However, the presentation of a tumour-like lesion of the lip in autosomal recessive hyper-IgE syndrome has not yet been reported. This article reports the case of a 20-year-old man with autosomal recessive hyper-IgE syndrome who presented with a tumour-like lesion of the lip, and hyperplasia and erosion of the gingiva. The clinical manifestations included coarse face and neck skin, a diffuse tumour-like lesion on the upper lip showing a reddish erosive nodular surface with yellowish-white exudation, erosive buccal mucosa, and severe periodontitis. The swollen gingival and palatal mucosa indicated nodular hyperplasia and redness with pseudomembrane. The patient had a significantly increased peripheral blood eosinophil count and serum IgE level and an abnormal T lymphocyte count. His oral lesions improved markedly after prednisolone acetate use and local symptomatic treatment for 2 years. However, the patient unfortunately died of a cerebral infection 6 months after the oral lesions had resolved. The novel features of the labial tumour-like lesion described here extend our understanding of the manifestations of autosomal recessive hyper-IgE syndrome.

[Clinicopathologic analysis of micro and mini parotid gland tumors].

OBJECTIVE: To investigate the clinicopathological characteristics of micro and mini parotid gland tumors and to provide reference for their clinical diagnosis and treatment. METHODS: Patients with parotid gland tumors treated in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from December 2012 to April 2020 were selected. Relevant clinical data of the patients with tumor diameter ≤20 mm detected by preoperative CT were collected to analyze the clinicopathological characteristics and prognosis of micro and mini parotid gland tumors. And the collected data were divided into two groups with diameter 11-20 mm and diameter ≤10 mm according to tumor diameter measured by preoperative CT. The clinicopathological differences between the two groups were statistically analyzed. RESULTS: A total of 2 067 patients with primary epithelial parotid gland tumors were collected, and 685 patients with tumor diameter ≤20 mm were examined by CT, accounting for 33.1%. The ratio of male to female patients with micro and mini parotid gland tumors was 1 ∶1.93, the average age was (45.3±13.8) years (12-83 years), and the median course of disease was 12 months (1 week to 30 years). Among them, 635 cases (92.7%) were benign tumors, 50 cases (7.3%) were malignant tumors, and the ratio of benign to malignant was 12.7 ∶1. The most common benign tumor was pleomorphic adenoma, and the most common malignant tumor was mucoepidermoid carcinoma. The micro and mini parotid gland tumors were divided into 11-20 mm group (n=611) and ≤10 mm group (n=74), the clinical characteristics comparison of the two groups of gender ratio, average age, course of di-sease had no statistical difference (P>0.05). In the 11-20 mm diameter group, the percentage of benign and malignant tumor was 92.8% (567/611) and 7.2% (44/611) respectively, and the ratio of benign to malignant tumors was 12.9 ∶1. In the ≤10 mm diameter group, the percentage of benign and malignant tumor was 91.9% (68/74) and 8.1% (6/74) respectively, and the ratio of benign to malignant tumors was 11.3 ∶1. There was no significant difference between the two groups (P>0.05). Fifty patients with malignant tumor were followed up for the median follow-up period of 39.5 months (1-91 months). Local recurrence occurred in 2 patients with one death. The overall 2-year survival rate was 93.7% and the 5-year survival rate was 89.3%. CONCLUSION: The majority of micro and mini parotid gland tumors was benign lesion. There was a good prognosis for micro and mini parotid gland carcinoma. Early surgical treatment was recommended for micro and mini parotid gland tumors.

[Clinical analysis of selective tracheostomy necessary for patients undergoing head and neck surgery with free flap reconstruction].

OBJECTIVE: To discover the factors that may affect the use of selective tracheostomy among patients who have undergone head and neck surgeries with free flap reconstruction, so that the patients will not need tracheostomy nor receive the unnecessary treatment. METHODS: Five hundred and thirty-three patients who had undergone head and neck surgery with free flap reconstruction operated by the same team of surgery at Department of Oral and Maxillofacial Surgery at Peking University School of Stomatology from 2015 to 2016 were reviewed. Three hundred and twenty-one (60.2%) of these patients underwent selective tracheostomy. All the patients' demographic information, operation-related information, prior treatments, comorbidities and complications were recorded and analyzed. RESULTS: The patients with defects of the tongue, mouth floor, oropharynx and bilateral mandible, who underwent neck dissection and with previous radiotherapy and smoking habit were more likely to get selective tracheostomy. Usage of bulky soft tissue flap might also add to the risk of airway obstruction and the need of selective tracheostomy, while other factors were not significantly related to the risk of postoperative airway obstruction and the patients could be kept safe without selective tracheostomy. Most cases without tracheostomy were kept safe except one case, while 8.39% of the patients with tracheostomy suffered from tracheostomy related complications, mainly pneumonia and hemorrhage of the tracheostomy wound, yet none led to serious consequences or even death. CONCLUSION: Selective tracheostomy is not necessary for patients who have undergone head and neck surgeries with free flap reconstruction except that there are defects at the tongue, oropharynx and mandible. Neck dissection, bulky soft tissue flap reconstruction, previous radiotherapy and smoking habit may also add to the risk of postoperative airway obstruction, while a favorable decision would involve a combination of all the above factors to assure the safety of the postoperative airway for the patients undergone head and neck surgeries with free flap reconstruction.

[Multicenter real-world study on safety and efficacy of neoadjuvant therapy in combination with immunotherapy for colorectal cancer].

Objective: To provide reference and evidence for clinical application of neoadjuvant immunotherapy in patients with colorectal cancer through multicenter large-scale analysis based on real-world data in China. Methods: This was a retrospective multicenter case series study. From January 2017 to October 2021, data of 94 patients with colorectal cancer who received neoadjuvant immunotherapy in Peking University Cancer Hospital (55 cases), Union Hospital of Tongji Medical College of Huazhong University of Science and Technology (19 cases), Sun Yat-sen University Cancer Center (13 cases) and Changhai Hospital of Navy Medical University (7 cases) were retrospectively collected, including 48 males and 46 females. The median age was 58 years. Eighty-one cases were rectal cancer and 13 cases were colon cancer (2 cases of double primary colon cancer). Twelve cases were TNM staging II and 82 cases were stage III. Forty-six cases were well differentiated, 37 cases were moderately differentiated and 11 cases were poorly differentiated. Twenty-six patients (27.7%) with mismatch repair defects (dMMR) and microsatellite instability (MSI-H) were treated with immunotherapy alone, mainly programmed cell death protein-1 (PD-1); sixty-eight cases (72.3%) with mismatch repair proficient (pMMR) and microsatellite stability (MSS) were treated with immune combined with neoadjuvant therapy, mainly CapeOx (capecitabine+oxaliplatin) combined with PD-1 antibody plus long- or short-course radiotherapy, or PD-1 antibody combined with cytotoxic T lymphocyte associated antigen 4 (CTLA-4) antibody. Analysis and evaluation of adverse events during neoadjuvant immunotherapy were performed according to the National Cancer Institute Common Toxicity Standard version 3.0; the surgical complications were evaluated according to the Clavien-Dindo grading standard; the efficacy evaluation of neoadjuvant immunotherapy included the following indicators: major pathological remission (MPR) was defined as tumor regression induced by neoadjuvant therapy in pathology residual tumor ≤10%; pathological complete response (pCR) was defined as tumor regression induced by neoadjuvant therapy without residual tumor in pathology; the tumor response rate was disease control rate (DCR), namely the proportion of complete response (CR), partial response (PR) and stable disease (SD) in the whole group; the objective response rate (ORR) was CR+PR. Results: The median cycle of neoadjuvant immunotherapy was 4 (1-10) in whole group, and the incidence of immune-related adverse reactions was 37.2% (35/94), including 35 cases (37.2%) of skin-related adverse reactions, 21 cases (22.3%) of thyroid dysfunction and 8 cases (8.5%) of immune enteritis, of which grade III or above accounted for 1.1%. The median interval between completion of neoadjuvant therapy and surgery was 30 (21-55) days. There were 81 cases of radical resection of rectal cancer, 11 cases of radical resection of colon cancer, and 2 cases of colon cancer combined with other organ resection. The primary tumor resection of all the patients reached R0. The incidence of surgical-related complications was 22.3% (21/94), mainly anastomotic leakage (4 cases), pelvic infection (4 cases), abdominal effusion (3 cases), anastomotic stenosis (3 cases ) and abdominal and pelvic hemorrhage (2 cases). Grade I-II complications developed in 13 cases (13.8%), grade III and above complications developed in 8 cases (8.5%), no grade IV or above complications were found. During a median follow-up of 32 (1-46 ) months, DCR was 98.9% (93/94), ORR was 88.3 % (83/94), pCR was 41.5% (39/94), MPR was 60.6% (57/94). The pCR rate of 26 patients with dMMR and MSI-H undergoing simple immunotherapy was 57.7% (15/26), and MPR rate was 65.4% (17/26). The pCR rate of 68 pMMR and MSS patients undergoing combined immunotherapy was 35.3%(24/68), and MPR rate was 58.8% (40/68). Conclusions: Neoadjuvant immunotherapy has favorable tumor control rate and pathological remission rate for patients with initial resectable colorectal cancer. The incidences of perioperative adverse reactions and surgical complications are acceptable.

[Studies on newly recognized chronic sialadenitis].

Some kinds of chronic sialadenitis were recognized during the recent years. They have specific pathogenesis, clinical and histopathologic appearances, and require specific treatment. IgG4-related sialadenitis (IgG4-RS) is one of the immune-mediated diseases, characterized by tumefactive lesions. The incidence of IgG4-RS obviously increased during the past 30 years. The study on the potential relationship between occupational exposure to chemical substances and the incidence of IgG4-RS showed that subjects with occupational exposure to agents known to cause IgG4-RD had an increased risk for IgG4-RS. Surgical excision of involved SMG could not control the disease progression, which is not recommended for treatment of IgG4-RS. The combination of glucocorticoid and steroid-sparing agents is effective for treating IgG4-RS, and restores salivary gland function. Radioiodine induced sialadenitis (RAIS) is one of the common complications of postoperative adjuvant treatment of differentiated thyroid cancer by 131I. The incidence of the disease is related to radiation dosage. Clinically, the patients suffered from swelling and tenderness in the buccal or submandibular regions, especially during the mealtime. Imaging appearances are similar to those of chronic obstructive sialadenitis. Conservative managements, such as gland massage, sialagogues, are the mainstream methods in the treatment of RAIS. Sialendoscopy is feasible for RAIS, but not as effective as conventional obstructive sialadenitis (COS). Therefore the prevention of RAIS is crucial. Eosinophilic sialodochitis (ES) is a new type of chronic inflammatory disease of the salivary gland related to allergy. It has characteristics of swelling of multiple major salivary glands, strip-like gelatinous plugs discharged from the duct orifice of the gland, elevated level of serum IgE and eosinophils in peripheral blood, infiltration of eosinophils and IgE positive plasma cells in the tissues, allergic history, increased expression of allergy-related cytokines, such as IL-4, IL-5, IL-13, and eotaxin, which suggest allergic reactions as a potential pathogenesis of the disease. The clinical, laboratory, histological, and immunohistochemical characteristics of ES are significantly different from conventional obstructive sialadenitis (COS). Therefore, it is suitable to separate ES from COS. Conservative managements, such as self-maintenance therapy and anti- allergic modality are the choices of treatment for ES. Based on the results of our comprehensive studies a new classification of chronic sialadenitis is suggested.

[Effects of acid stimulation on saliva flow rate and compositions of human parotid and submandibular glands].

OBJECTIVE: To investigate the effect of acid stimulation on salivary flow rate and compositions of human parotid and submandibular glands, so as to provide basis for comprehensive evaluation of salivary gland function in both health and disease status. METHODS: In the study, 210 healthy participants' whole saliva samples were collected under passive drooling, and their parotid gland and submandibular gland secretions were collected by negative pressure suction. 2% citric acid was dropped on the tip of tongue every 1 min for acid stimulation for a total of 5 times to collect stimulated whole saliva, parotid and submandibular gland saliva. The collected saliva was weighed and saliva flow rate was calculated. The K+, Na+, Cl-, Ca2+, total protein, total phosphorus and α-amylase in saliva samples were detected by biochemical analyzer, and the changing features of flow rate and compositions of different kinds of saliva were compared and analyzed. RESULTS: After acid stimulation, saliva flow rate significantly increased. The increase proportion of parotid gland saliva (10.7 folds) was much higher than that of submandibular gland saliva (2.9 folds). The concentrations of Na+, Cl-, Ca2+, total protein and α-amylase in parotid gland saliva increased significantly (P < 0.05), but there was no significant difference in total phosphorus and K+ (P=0.89, P=0.34). The concentration of Na+ and Ca2+ in saliva of submandibular gland increased significantly(P < 0.05), the concentration of total phosphorus decreased significantly(P < 0.05), and the concentration of Cl- increased, but the difference was not significant(P=0.068). There was no significant difference in total protein, K+ and α-amylase (P=0.85, P=0.07, P=0.95). The compound secretion rate of total phosphorus in saliva of submandibular gland remained unchanged(P=0.066), while the secretion rate of K+, Na+, Cl-, Ca2+, total protein and α-amylase significantly increased(P < 0.01). The compound secretion rate of K+, Na+, Cl-, Ca2+, total protein and total phosphorus and α-amylase in parotid gland saliva increased(P < 0.01). The concentrations of Na+, Cl-, K+, total phosphorus, total protein and α-amylase in parotid were higher than those in submandibular gland (P < 0.01), and the concentration of Ca2+ in submandibular gland saliva was significantly higher than that in parotid (P < 0.001). CONCLUSION: The response of parotid to acid stimulation is stronger, and the secretion of submandibular gland is more stable. Acid stimulation significantly influences the concentrations of electrolytes in saliva, and the composited secretion rate is an evaluation index to reflect both flow rate and composition concentration of saliva. The parotid gland plays an important role in the secretion of total protein, total phosphorus and α-amylase in saliva, and the submandibular gland is the main source of Ca2+ in saliva.