Cognitive decline in thrombotic thrombocytopenic purpura survivors: The role of white matter health as assessed by MRI.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare condition caused by severe ADAMTS13 deficiency, leading to platelet aggregation and thrombosis. Despite treatment, patients are prone to cognitive impairment and depression. We investigated brain changes in iTTP patients during remission using advanced magnetic resonance imaging (MRI) techniques, correlating these changes with mood and neurocognitive tests. Twenty iTTP patients in remission (30 days post-haematological remission) were compared with six healthy controls. MRI scans, including standard and specialized sequences, were conducted to assess white matter health. Increased T1 relaxation times were found in the cingulate cortex (p < 0.05), and elevated T2 relaxation times were observed in the cingulate cortex, frontal, parietal and temporal lobes (p < 0.05). Pathological changes in these areas are correlated with impaired cognitive and depressive scores in concentration, short-term memory and verbal memory. This study highlights persistent white matter damage in iTTP patients, potentially contributing to depression and cognitive impairment. Key regions affected include the frontal lobe and cingulate cortex. These findings have significant implications for the acute and long-term management of iTTP, suggesting a need for re-evaluation of treatment approaches during both active phases and remission. Further research is warranted to enhance our understanding of these complexities.

2 years is a reasonable age cut-off level for prognostic assessment of children with hepatoblastoma.

OBJECTIVE: We aimed to elucidate the prognostic significance of age in hepatoblastoma patients. PATIENTS AND METHODS: Data from 783 patients with hepatoblastoma were obtained from the Surveillance, Epidemiology and End Results database (2000-2018). The best age cut-off level was determined by X-tile, and the Kaplan-Meier method was used to estimate overall survival (OS) and cancer-specific survival (CSS). The results of the X-tile were verified by selecting the appropriate cut-off value to maximize the difference in survival outcomes at intervals of 1 year. The Cox regression model was used to determine the prognostic impact of risk factors and age. RESULTS: X-tile analysis determined that 2 years was the best cut-off age for OS and CSS. The overall prognosis in the ≥ 2 years group was worse than that in the < 2 years group (OS: p = 0.00017; CSS: p < 0.0001). In Cox univariate analysis, when 2 years was used as the standard group, the numbers of patients in the two groups were similar, with high hazard ratio (HR) value and narrow 95% confidence interval (CI) (OS: HR, 1.834; 95% CI, 1.329 - 2.532; p < 0.001; CSS: HR, 1.988; 95% CI, 1.410 - 2.801; p < 0.001), which was consistent with the age cut-off point determined by X-tile. Cox multivariate analysis showed that age ≥ 2 years, black ethnicity, no surgery, no chemotherapy, distant metastasis, and tumor size ≥ 5 cm were independent predictors of poor OS and CSS. On subgroup analysis, patients aged ≥ 2 years had worse survival if they were Caucasian, had elevated alpha-fetoprotein, tumor size ≥ 5 cm, or distant metastasis. CONCLUSIONS: Age is an important prognostic factor for hepatoblastoma. Age ≥ 2 years at diagnosis may predict poor prognosis and more active treatment measures can be implemented.

Spin independence of the strongly enhanced effective mass in ultra-clean SiGe/Si/SiGe two-dimensional electron system.

The effective mass at the Fermi level is measured in the strongly interacting two-dimensional (2D) electron system in ultra-clean SiGe/Si/SiGe quantum wells in the low-temperature limit in tilted magnetic fields. At low electron densities, the effective mass is found to be strongly enhanced and independent of the degree of spin polarization, which indicates that the mass enhancement is not related to the electrons' spins. The observed effect turns out to be universal for silicon-based 2D electron systems, regardless of random potential, and cannot be explained by existing theories.

[Anatomical and histological investigation of the area anterior to the anorectum passing through the levator hiatus].

Objective: To document the anatomical structure of the area anterior to the anorectum passing through the levator hiatus between the levator ani slings bilaterally. Methods: Three male hemipelvises were examined at the Laboratory of Clinical Applied Anatomy, Fujian Medical University. (1) The anatomical assessment was performed in three ways; namely, by abdominal followed by perineal dissection, by examining serial cross-sections, and by examining median sagittal sections. (2) The series was stained with hematoxylin and eosin to enable identification of nerves, vessels, and smooth and striated muscles. Results: (1) It was found that the rectourethralis muscle is closest to the deep transverse perineal muscle where the longitudinal muscle of the rectum extends into the posteroinferior area of the membranous urethra. The communicating branches of the neurovascular bundle (NVB) were identified at the posterior edge of the rectourethralis muscle on both sides. The rectum was found to be fixed to the membranous urethra through the rectourethral muscle, contributing to the anorectal angle of the anterior rectal wall. (2) Serial cross-sections from the anal to the oral side were examined. At the level of the external anal sphincter, the longitudinal muscle of the rectum was found to extend caudally and divide into two muscle bundles on the oral side of the external anal sphincter. One of these muscle bundles angled dorsally and caudally, forming the conjoined longitudinal muscle, which was found to insert into the intersphincteric space (between the internal and external anal sphincters). The other muscle bundle angled ventrally and caudally, filling the gap between the external anal sphincter and the bulbocavernosus muscle, forming the perineal body. At the level of the superficial transverse perineal muscle, this small muscle bundle headed laterally and intertwined with the longitudinal muscle in the region of the perineal body. At the level of the rectourethralis and deep transverse perineal muscle, the external urethral sphincter was found to occupy an almost completely circular space along the membranous part of the urethra. The dorsal part of the external urethral sphincter was found to be thin at the point of attachment of the rectourethralis muscle, the ventral part of the longitudinal muscle of the rectum. We identified a venous plexus from the NVB located close to the oral and ventral side of the deep transverse perineal muscle. Many vascular branches from the NVB were found to be penetrating the longitudinal muscle and the ventral part of rectourethralis muscle at the level of the apex of the prostate. The rectourethral muscle was wrapped ventrally around the membranous urethra and apex of the prostate. The boundary between the longitudinal muscle and prostate gradually became more distinct, being located at the anterior end of the transabdominal dissection plane. (3) Histological examination showed that the dorsal part of the external urethral sphincter (striated muscle) is thin adjacent to the striated muscle fibers from the deep transverse perineal muscle and the NVB dorsally and close by. The rectourethral muscle was found to fill the space created by the internal anal sphincter, deep transverse perineal muscle, and both levator ani muscles. Many tortuous vessels and tiny nerve fibers from the NVB were identified penetrating the muscle fibers of the deep transverse perineal and rectourethral muscles. The structure of the superficial transverse perineal muscle was typical of striated muscle. These findings were reconstructed three-dimensionally. Conclusions: In intersphincteric resection or abdominoperineal resection for very low rectal cancer, the anterior dissection plane behind Denonvilliers' fascia disappears at the level of the apex of the prostate. The prostate and both NVBs should be used as landmarks during transanal dissection of the non-surgical plane. The rectourethralis muscle should be divided near the rectum side unless tumor involvement is suspected. The superficial and deep transverse perineal muscles, as well as their supplied vessels and nerve fibers from the NVB. In addition, the cutting direction should be adjusted according to the anorectal angle to minimize urethral injury.

[Anatomical classification of and laparoscopic surgery for left-sided colorectal cancer with persistent descending mesocolon].

Objective: To investigate anatomical morphology and classification of persistent descending mesocolon (PDM) in patients with left-sided colorectal cancer, as well as the safety of laparoscopic radical surgery for these patients. Methods: This is a descriptive study of case series. Relevant clinical data of 995 patients with left colon and rectal cancer who had undergone radical surgery in Fujian Medical University Union Hospital from July 2021 to September 2022 were extracted from the colorectal surgery database of our institution and retrospectively analyzed. Twenty-four (2.4%) were identified as PDM and their imaging data and intra-operative videos were reviewed. We determined the distribution and morphology of the descending colon and mesocolon, and evaluated the feasibility and complications of laparoscopic surgery. We classified PDM according to its anatomical characteristics as follows: Type 0: PDM combined with malrotation of the midgut or persistent ascending mesocolon; Type 1: unfixed mesocolon at the junction between transverse and descending colon; Type 2: PDM with descending colon shifted medially (Type 2A) or to the right side (Type 2B) of the abdominal aorta at the level of the origin of the inferior mesentery artery (IMA); and Type 3: the mesocolon of the descending-sigmoid junction unfixed and the descending colon shifted medially and caudally to the origin of IMA. Results: The diagnosis of PDM was determined based on preoperative imaging findings in 9 of the 24 patients (37.5%) with left-sided colorectal cancer, while the remaining diagnoses were made during intraoperative assessment. Among 24 patients, 22 were male and 2 were female. The mean age was (63±9) years. We classified PDM as follows: Type 0 accounted for 4.2% (1/24); Type 1 for 8.3% (2/24); Types 2A and 2B for 37.5% (9/24) and 25.0% (6/24), respectively; and Type 3 accounted for 25.0% (6/24). All patients with PDM had adhesions of the mesocolon that required adhesiolysis. Additionally, 20 (83.3%) of them had adhesions between the mesentery of the ileum and colon. Twelve patients (50.0%) required mobilization of the splenic flexure. The inferior mesenteric artery branches had a common trunk in 14 patients (58.3%). Twenty-four patients underwent D3 surgery without conversion to laparotomy; the origin of the IMA being preserved in 22 (91.7%) of them. Proximal colon ischemia occurred intraoperatively in two patients (8.3%) who had undergone high ligation at the origin of the IMA. One of these patients had a juxta-anal low rectal cancer and underwent intersphincteric abdominoperineal resection because of poor preoperative anal function. Laparoscopic subtotal colectomy was considered necessary for the other patient. The duration of surgery was (260±100) minutes and the median estimated blood loss was 50 (20-200) mL. The median number of No. 253 lymph nodes harvested was 3 (0-20), and one patient (4.2%) had No.253 nodal metastases. The median postoperative hospital stay was 8 (4-23) days, and the incidence of complications 16.7% (4/24). There were no instances of postoperative colon ischemia or necrosis observed. One patient (4.2%) with stage IIA rectal cancer developed Grade B (Clavien-Dindo III) anastomotic leak and underwent elective ileostomy. The other complications were Grade I-II. Conclusions: PDM is frequently associated with mesenteric adhesions. Our proposed classification can assist surgeons in identifying the descending colon and mesocolon during adhesion lysis in laparoscopic surgery. It is crucial to protect the colorectal blood supply at the resection margin to minimize the need for unplanned extended colectomy, the Hartmann procedure, or permanent stomas.

[The value of MR diffusion tensor imaging in assessing white matter changes in short-term methamphetamine withdrawal].

Objective: To explore the value of MRI diffusion tensor imaging (DTI) in the white matter changes of short-term methamphetamine (MA) abstinence. Methods: The data of DTI, demographics features, general information of addiction and impulsivity scale eleven (BIS-11) of 55 short-term MA addicts who were from Changsha, Zhuzhou and Yueyang compulsory detoxification centers in Hunan province, including 40 males and 15 females, aged 14-45 (37.24±7.31) years old, and 52 healthy controls, including 40 males and 12 females aged 18-59 (40.3±9.1) years were collected prospectively from August 2017 to December 2018. The differences of DTI indicators between the two groups were compared by tract-based spatial statistics (TBSS), and then the correlation between the different indicators and the age of first MA use, time of MA use, daily dose used, BIS-11 score were performed. Results: There were significant differences in BIS total score(P<0.001), BIS motivational impulsivity(P<0.001) and BIS attentional impulsivity(P=0.003) between MA group and healthy control group in short-term withdrawal. And compared with the healthy control group, the fractional anisotropy (FA) (0.58±0.02 vs 0.56±0.02,0.77±0.02 vs 0.75±0.04,0.79±0.04 vs 0.76±0.06; all P<0.05), axial diffusivity (AD) (0.57±0.01 vs 0.56±0.02,P=0.001) and mean diffusivity (MD) (0.66±0.02 vs 0.65±0.02,0.52±0.07 vs 0.51±0.06; both P<0.05)values in the MA group were all increased (P<0.05), but there was no significant difference in the radial diffusivity (RD) value (P>0.05). The white matter areas with increased FA value were located in the knee and body of corpus callosum, bilateral anterior corona radiata and left superior corona radiata; the areas with increased AD value were located in the knee, body and pressure of corpus callosum, bilateral anterior limb of internal capsule, posterior limb of internal capsule, anterior, superior and posterior corona radiata, external capsule and superior longitudinal fasciculus; and the areas with increased MD value were mainly located in the right superior longitudinal fasciculus, anterior and posterior limb of internal capsule. The corpus callosum, where there was a difference in FA between the two groups, was positively correlated with the daily dose of MA (r=0.301, P=0.026). Conclusion: MA addicted individuals with short-term withdrawal have white matter edema and damage, and the degree of corpus callosum damage is positively correlated with the daily dose of MA,which is helpful to understand the pathophysiological process of white matter damage in the nervous system and the potential mechanism of neuropsychiatric symptoms in short-term withdrawal MA addicted individuals.

[Delayed gastric emptying after surgery for transverse colon cancer: diagnosis, management and prevention].

Delayed gastric emptying is a syndrome of gastric motility disorder with slow gastric emptying as the main sign, provided that mechanical factors such as intestinal obstruction and anastomotic stricture are excluded. The incidence of delayed gastric emptying after colon cancer surgery is 1.4%, mainly after transverse colon cancer surgery. Most of the studies on delayed gastric emptying are case reports, lacking systematic studies. The diagnoses and treatments can be draw on the experience of delayed gastric emptying after pancreatic surgery. Our retrospective study indicated that the incidence of delayed gastric emptying after surgery for transverse colon cancer was 4.0%, higher than that for other colon cancer. Patients who underwent gastrocolic ligament lymph node dissection were at higher risk than those who did not (3.6% vs. 0.8%). Gastrocolic ligament lymph node dissection and stress are causative factors for delayed gastric emptying after surgery for transverse colon cancer. We add the gastrografin test upon the diagnostic criteria of the International Study Group for Pancreatic Surgery, which is simple and practical. Nasogastric tube decompression, enteral nutrition combined with parenteral nutrition, glucocorticoids, and prokinetic agents can cure most patients with postoperative delayed gastric emptying. All the patients with postoperative delayed gastric emptying were cured in our studies. Strict indications for gastrocolic ligament lymph node dissection (patients with cT3-4 and cN+) may decrease the occurrence of delayed gastric emptying after surgery for transverse colon cancer.

Spin effect on the low-temperature resistivity maximum in a strongly interacting 2D electron system.

The increase in the resistivity with decreasing temperature followed by a drop by more than one order of magnitude is observed on the metallic side near the zero-magnetic-field metal-insulator transition in a strongly interacting two-dimensional electron system in ultra-clean SiGe/Si/SiGe quantum wells. We find that the temperature [Formula: see text], at which the resistivity exhibits a maximum, is close to the renormalized Fermi temperature. However, rather than increasing along with the Fermi temperature, the value [Formula: see text] decreases appreciably for spinless electrons in spin-polarizing (parallel) magnetic fields. The observed behaviour of [Formula: see text] cannot be described by existing theories. The results indicate the spin-related origin of the effect.

[Prevalence and influencing factors of Enterobius vermicularis infections among children in Fanxian County of Henan Province in 2019].

OBJECTIVE: To investigate the prevalence and influencing factors of Enterobius vermicularis infections among children in Fanxian County, Henan Province in 2019, so as to provide insights into the management of enterobiasis. METHODS: Five kindergartens were selected in urban and rural areas of Fanxian County, Henan Province using the stratified sampling method in 2019, and a census of E. vermicularis infections was performed among all children in the kindergartens. E. vermicularis eggs were detected using adhesive and scotch cellophane-tape anal swab methods, and the basic characteristics of children and their families, health habits and the kindergartens' information were investigated with questionnaires. Logistic regression analysis was used to investigate the risk factors and protective factors of pinworm infection in children. RESULTS: A total of 671 children were tested, and the mean prevalence of E. vermicularis infections was 15.50% (104/671). The prevalence of E. vermicularis infections was higher among children in rural kindergartens (28.13%, 72/256) than in urban kindergartens (7.71%, 32/415) (χ2 = 50.380, P < 0.01), and greater in private kindergartens (32.26%, 60/186) than in public kindergartens (9.07%, 44/485) (χ2 = 55.183, P < 0.01). There was no gender-specific prevalence of E. vermicularis infections among children (χ2 = 1.442, P > 0.05), and the prevalence of E. vermicularis infections presented a tendency towards a rise with age (χ2trend = 8.373, P < 0.05) and school grade (χ2trend = 30.274, P < 0.05). Logistic regression analysis identified rural kindergartens and high grades as risk factors, and separate washing of children's and adults' cloths, frequent bathing and frequent dinnerware disinfection in kindergartens as protective factors for E. vermicularis infections among children. In addition, there was no significant difference in the detection of E. vermicularis infections among children by using adhesive (73.08%, 76/104) and scotch cellophane-tape anal swab methods (56.73%, 59/104) (χ2 = 3.959, P > 0.05). CONCLUSIONS: The prevalence of E. vermicularis infection is high among children in Fanxian Country, Henan Province. Health education and surveillance of enterobiasis are required to be intensified among children in rural kindergartens and senior grades and their parents and teachers.

The Potential Impact and Usability of the Eighth Edition TNM Staging Classification in Oral Cavity Cancer.

AIMS: In the current eighth edition head and neck TNM staging, extranodal extension (ENE) is an adverse feature in oral cavity squamous cell cancer (OSCC). The previous seventh edition N1 with ENE is now staged as N2a. Seventh edition N2+ with ENE is staged as N3b in the eighth edition. We evaluated its potential impact on patients treated with surgery and postoperative intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: OSCC patients treated with primary surgery and adjuvant (chemo)radiotherapy between January 2005 and December 2014 were reviewed. Cohorts with pathological node-negative (pN-), pathological node-positive without ENE (pN+_pENE-) and pathological node-positive with ENE (pN+_pENE+) diseases were compared for local control, regional control, distant control and overall survival. The pN+ cohorts were further stratified into seventh edition N-staging subgroups for outcomes comparison. RESULTS: In total, 478 patients were evaluated: 173 pN-; 159 pN+_pENE-; 146 pN+_pENE+. Outcomes at 5 years were: local control was identical (78%) in all cohorts (P = 0.892), whereas regional control was 91%, 80% and 68%, respectively (P < 0.001). Distant control was 97%, 87%, 68% (P < 0.001) and overall survival was 75%, 53% and 39% (P < 0.001), respectively. Overall survival for N1 and N2a subgroups was not significantly different. In the seventh edition N2b subgroup of pENE- (n = 79) and pENE+ (n = 79) cohorts, overall survival was 67% and 37%, respectively. In the seventh edition N2c subgroups, overall survival for pENE- (n = 17) and pENE+ (n = 38) cohorts was 65% and 35% (P = 0.08), respectively. Overall, an additional 128 patients (42% pN+) were upstaged as N3b. CONCLUSIONS: When eighth edition staging was applied, stage migration across the N2-3 categories resulted in expected larger separations of overall survival by stage. Patients treated with primary radiation without surgical staging should have outcomes carefully monitored. Strategies to predict ENE preoperatively and trials to improve the outcomes of pENE+ patients should be explored.

Copper Centers in the Cryo-EM Structure of Particulate Methane Monooxygenase Reveal the Catalytic Machinery of Methane Oxidation.

The particulate methane monooxygenase (pMMO) is the first enzyme in the C1 metabolic pathway in methanotrophic bacteria. As this enzyme converts methane into methanol efficiently near room temperature, it has become the paradigm for developing an understanding of this difficult C1 chemistry. pMMO is a membrane-bound protein with three subunits (PmoB, PmoA, and PmoC) and 12-14 coppers distributed among different sites. X-ray crystal structures that have revealed only three mononuclear coppers at three sites have neither disclosed the location of the active site nor the catalytic mechanism of the enzyme. Here we report a cyro-EM structure of holo-pMMO from Methylococcus capsulatus (Bath) at 2.5 Å, and develop quantitative electrostatic-potential profiling to scrutinize the nonprotein densities for signatures of the copper cofactors. Our results confirm a mononuclear CuI at the A site, resolve two CuIs at the B site, and uncover additional CuI clusters at the PmoA/PmoC interface within the membrane (D site) and in the water-exposed C-terminal subdomain of the PmoB (E clusters). These findings complete the minimal set of copper factors required for catalytic turnover of pMMO, offering a glimpse of the catalytic machinery for methane oxidation according to the chemical principles underlying the mechanism proposed earlier.

[Construction of artificial neural network model for predicting the efficacy of first-line FOLFOX chemotherapy for metastatic colorectal cancer].

Objective: To explore and establish an artificial neural network (ANN) model for predicting the efficacy of first-line FOLFOX chemotherapy for metastatic colorectal cancer. Methods: A set of FOLFOX chemotherapy data from a group of patients with metastatic colorectal cancer (mCRC) (GSE104645) was downloaded from the GEO database as a training set. According to the FOLFOX protocol, the efficacy was divided into two groups: the chemo-sensitive group (including complete response and partial response) and the chemo-resistant group (including stable disease and progressive disease), including 31 cases in the sensitive group and 23 in the resistant group. Then, chip data (accessible number: GSE69657) from Fujian Medical University Union Hospital were chosen as a test set. A total of 30 patients were enrolled in the study, including 13 in the sensitive group and 17 in the resistant group. The batch effect correction was performed on the expression values of the two sets of matrices using the R 3.5.1 software Combat package. The gene expression difference of sensitive and resistant group in GSE104645 was analyzed by the GEO2R platform. P<0.05 and the absolute value of log(2)FC>0.33 (FC abbreviation of fold change) were used as the threshold value to screen the drug resistance and sensitive genes of the FOLFOX regimen. An ANN was constructed using the multi-layer perceptron (MLP) to perform the FOLFOX regimen on the GSE104645 dataset. The GSE69657 expression matrix and clinical efficacy parameters were then used for retrospective verification. Receiver operating characteristic(ROC) curves were used to evaluate the test results and predictive power. Results: A total of 2, 076 differentially expressed genes in GSE104645 were selected, of which 822 genes were up-regulated and 1, 254 genes were down-regulated in the chemo-resistance group. The down-regulated genes were sensitive genes. GO analysis of the biological processes in which the differentially expressed genes were involved, revealed that they were mainly involved in the regulation of substance metabolism. A total of 39 genes were included in the final model construction. This was a neural network model with two hidden layers. The accuracy of predicting training samples and test samples was 75.7% and 76.5%, respectively, and the area under the ROC curve was 0.875. The chip data set of our department (GSE69657) was set as the test set, and the area under the ROC curve was 0.778. Conclusions: In this study, an artificial neural network model is successfully constructed to predict the efficacy of first-line FOLFOX regimen for metastatic colorectal cancer based on the microarray, and an independent external verification is also conducted. The model has good stability and well prediction efficiency. Besides, the results of this study suggest that the gene functions related to oxaliplatin resistance are mainly enriched in the regulation process of substance metabolism.

Analytical Solutions Based on Fourier Cosine Series for the Free Vibrations of Functionally Graded Material Rectangular Mindlin Plates.

This study aimed to develop series analytical solutions based on the Mindlin plate theory for the free vibrations of functionally graded material (FGM) rectangular plates. The material properties of FGM rectangular plates are assumed to vary along their thickness, and the volume fractions of the plate constituents are defined by a simple power-law function. The series solutions consist of the Fourier cosine series and auxiliary functions of polynomials. The series solutions were established by satisfying governing equations and boundary conditions in the expanded space of the Fourier cosine series. The proposed solutions were validated through comprehensive convergence studies on the first six vibration frequencies of square plates under four combinations of boundary conditions and through comparison of the obtained convergent results with those in the literature. The convergence studies indicated that the solutions obtained for different modes could converge from the upper or lower bounds to the exact values or in an oscillatory manner. The present solutions were further employed to determine the first six vibration frequencies of FGM rectangular plates with various aspect ratios, thickness-to-width ratios, distributions of material properties and combinations of boundary conditions.

Parametric Acoustic Array and Its Application in Underwater Acoustic Engineering.

As a sound transmitting device based on the nonlinear acoustic theory, parametric acoustic array (PAA) is able to generate high directivity and low frequency broadband signals with a small aperture transducer. Due to its predominant technical advantages, PAA has been widely used in a variety of application scenarios of underwater acoustic engineering, such as sub-bottom profile measurement, underwater acoustic communication, and detection of buried targets. In this review paper, we examine some of the important advances in the PAA since it was first proposed by Westervelt in 1963. These advances include theoretical modelling for the PAA, signal processing methods, design considerations and implementation issues, and applications of the PAA in underwater acoustic engineering. Moreover, we highlight some technical challenges which impede further development of the PAA, and correspondingly give a glimpse on its possible extension in the future. This article provides a comprehensive overview of some important works of the PAA and serves as a quick tutorial reference to readers who are interested to further explore and extend this technology, and bring this technology to other application areas.

[Rectum-preserving surgery after consolidation neoadjuvant therapy or totally neoadjuvant therapy for low rectal cancer: a preliminary report].

Objective: To investigate the feasibility and safety of sphincter-preserving surgery after neoadjuvant chemoradiotherapy (nCRT) with consolidation chemotherapy in the interval period or total neoadjuvant therapy (TNT) for low rectal cancer. Methods: A descriptive case series study was carried out. Clinical data of patients with locally advanced low rectal cancer (LALRC) who achieved complete clinical response (cCR) or nearly cCR (near-cCR) after nCRT at the Department of Colorectal Surgery of Fujian Medical University Union Hospital from May 2015 to February 2019 were retrospectively analyzed. Case inclusion criteria: (1) Low rectal adenocarcinoma within 6 cm from the anal verge. (2) After nCRT, tumor presented markedly regression as mucosal nodule or abnormalities, superficial ulcer, scar or a mucosal erythema (< 2 cm); no regional lymph node metastasis or distant metastasis was found in rectal ultrasonography, pelvic MRI and PET-CT; MRI showed obvious fibrosis in the original tumor site; and post-treatment CEA was normal. (3) The patient and the family members adhered to receive the transanal full-thickness local excision with informed consent. (4) When the residual lesions were difficult to detect after nCRT, patients received the watch and wait (W&W) strategy. Exclusion criteria: (1) Before nCRT, pathological results showed poorly differentiated or signet-ring cell carcinoma; lateral lymph node metastasis was suspected. (2) When the residual lesion size was more than 3 cm after nCRT, it was difficult to perform local excision. The consolidation nCRT group received 3-4 cycles of CAPOX regimen (oxaliplatin and capecitabine) or six cycles of mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluorouracil) combined with the long-course radiotherapy (intensity-modulated radiation therapy with a total dose of 50.4Gy). Patients with concurrent chemotherapy more than or equal to five cycles of CAPOX or eight cycles of mFOLFOX6 were defined as total neoadjuvant therapy (TNT) group. Local resection was recommended for patients who were near-cCR according to modified MSKCC criteria 8-33 weeks after the end of radiotherapy. Patients with a near-cCR, who were judged as ycN0 according to PET-CT and MRI and were ypT0 after local excision, could enter the W&W strategy. Patients with pathologic stage more advanced than ypT1, and those with positive resection margin, or lymphovascular invasion were recommended for salvage radical surgery after local excision. The ypT1 patients with a negative resection margin and without lymphovascular invasion might receive the W&W management carefully if they refused radicalsurgery to sacrifice the sphincter for low rectal cancer. Results: Of 32 patients, 14 were males and 18 were females with the average age of 59 years old. Twenty-three patients underwent consolidation nCRT, and 9 received TNT. The first evaluation after treatments showed 19 cases with cCR and 13 with near-cCR. Twenty-nine patients received local excision while 3 patients with undetectable lesions received W&W policy. Four cases (12.5%) underwent salvage radical surgery with abdominoperineal resection. After local excision, 3 cases underwent salvage radical surgery immediately, and the final pathologic result was ypT3N0, ypT2N0, and ypT2N0 respectively, of whom 2 cases were in the group of consolidation CRT and 1 was in the TNT group. Of these 3 cases, 1 case with an initial cT3 stage showed a pathologic stage of ypT1 and a negative circumferential resection margin after consolidation nCRT and local excision, however, the final pathologic stage was ypT3 with fragmented tumor deposits in the mesorectum after the salvage radical surgery. Meanwhile 1 patient in the TNT group receiving W&W suffered from intraluminal regrowth after 7.4 months follow-up and underwent salvage abdominoperineal resection. One patient in the consolidation nCRT group died of stroke 42.5 months after local resection. Another patient in the TNT group had cerebral metastasis 10 months after the W&W policy, but no local recurrence was found in the pelvic cavity, then received resection of the metastatic tumors. The average follow-up for all the patients was 23 (5-51) months. The cumulative local regrowth rate was 5.0%. The overall survival rate was 85.7%, and the sphincter-preservation rate was increased from 25.0% (28/32) in the original plan to 87.5% (28/32) actually. The 3-year disease-free survival rate was 89.7%. The 3-year organ-preserving survival rate was 85.7%, and the 3-year stoma-free survival rate was 82.5%. At present, 31 patients still survived. Conclusions: After nCRT with consolidation chemotherapy or TNT for low rectal cancer, patients with cCR, ycN0 according to PET-CT and MRI, and ypT0 after local excision, can consider the W&W strategy. Strict patient selection with a near-cCR for local resection and sphincter-preserving strategy can reduce the local regrowth of cancer, and the short-term outcomes are satisfactory.

Development and validation of a clinical prediction-score model for distant metastases in major salivary gland carcinoma.

BACKGROUND: The most common pattern of failure in major salivary gland carcinoma (SGC) is development of distant metastases (DMs). The objective of this study was to develop and validate a prediction score for DM in SGC. PATIENTS AND METHODS: Patients with SGC treated curatively at four tertiary cancer centers were divided into discovery (n = 619) and validation cohorts (n = 416). Multivariable analysis using competing risk regression was used to identify predictors of DM in the discovery cohort and create a prediction score of DM; the optimal score cut-off was determined using a minimal P value approach. The prediction score was subsequently evaluated in the validation cohort. The cumulative incidence and Kaplan-Meier methods were used to analyze DM and overall survival (OS), respectively. RESULTS: In the discovery cohort, DM predictors (risk coefficient) were: positive margin (0.6), pT3-4 (0.7), pN+ (0.7), lymphovascular invasion (0.8), and high-risk histology (1.2). High DM-risk SGC was defined by sum of coefficients greater than two. In the discovery cohort, the 5-year incidence of DM for high- versus low-risk SGC was 50% versus 8% (P < 0.01); this was similar in the validation cohort (44% versus 4%; P < 0.01). In the pooled cohorts, this model performed similarly in predicting distant-only failure (40% versus 6%, P < 0.01) and late (>2 years post surgery) DM (22% versus 4%; P < 0.01). Patients with high-risk SGC had an increased incidence of DM in the subgroup receiving postoperative radiation therapy (46% versus 8%; P < 0.01). The 5-year OS for high- versus low-risk SGC was 48% versus 92% (P < 0.01). CONCLUSION: This validated prediction-score model may be used to identify SGC patients at increased risk for DM and select those who may benefit from prospective evaluation of treatment intensification and/or surveillance strategies.

[Identification of gene biomarkers to predict responses to neoadjuvant chemoradiotherapy in patients with rectal cancer and pathways enrichment analysis].

Objective: To screen out the potential gene biomarkers to predict responses to neoadjuvant chemoradiotherapy (CRT) in patients with rectal cancer and to explore the main downstream pathways of resistance. Methods: The gene expression profiles (GSE35452) of locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy from 46 specimens (24 responders, TRG 0/1, and 22 non-responders, TRG 2/3) were downloaded from the GEO database. The differentially expressed genes were identified to screen out the potential biomarkers by use of the GCBI platform. GO and KEGG pathways enrichment analysis were performed to integrate enrichment results of differentially expressed genes. Signal-signal interaction network was constructed and analyzed to screen out potential main downstream pathways. Results: A total of 1079 differentially expressed genes were screened, including 657 up-regulated and 422 down-regulated ones. Among these genes, REG4 had the maximum fold change value of -6.029 491. In GO term, these differentially expressed genes were mainly enriched in molecule metabolic process, cell cycle, DNA-dependent transcription, signal transduction and apoptotic process. The KEGG pathways enrichment analysis showed that the differentially expressed genes were enriched in 65 KEGG pathways, including metabolic pathways, cell cycle and metabolism pathways. Signal-signal interaction network analysis showed that MAPK signaling pathway and cell cycle pathway might play a determinant role in the development of neoadjuvant chemoradiotherapy resistance. Further analysis showed that CDKN1B, CDKN2A, RBL1, TFDP1, CCND2, CCNE2, CDC6 and CDK6 in cell cycle might induce chemoradiotherapy resistance by blocking G1/S phase cell cycle arrest, decreasing the apoptosis of tumor cells and increasing S phase ratio of chemoradiotherapy resistance. Conclusion: G1/S phase cell cycle arrest blocking plays an important role in the development of chemoradiotherapy resistance in patients with rectal cancer. Moreover, the key genes, such as REG4, may be useful in predicting responses to neoadjuvant chemoradiotherapy.

HPV Status Improves Classification of Head and Neck Gray Zone Cancers.

In epidemiologic studies, patients with head and neck squamous cell carcinoma (HNSCC) are classified mainly by the International Classification of Diseases (ICD) codes. However, some patients are of an unclear subsite, the "gray zone" cases, which could reflect ICD coding error, absence of primary subsite, or extensive primary tumors that cross over multiple subsites of the oral cavity and oropharynx. Patients with gray zone squamous cell carcinomas were compared with patients with oral cavity squamous cell carcinoma (OSCC) or oropharyngeal squamous cell carcinoma (OPSCC) and stratified by human papillomavirus (HPV) status that was determined by p16 immunostaining or HPV serology. Comparisons consisted of clinicodemographic features and prognostic outcomes presented by Kaplan-Meier curves and Cox proportional hazards regression models, reported as hazard ratios. There were 158 consecutive patients with gray zone HNSCC diagnosed at the Princess Margaret Cancer Center between 2006 and 2017: 66 had subsite coding discrepancies against the clinician's documentation ("discrepant" cases; e.g., the diagnosis by the clinician was OSCC, while the classification by ICD coding was OPSCC), while 92 were squamous cell carcinoma of unknown primary of the head and neck (SCCUPHN) after complete diagnostic workup. Comparators included 721 consecutive OSCC and 938 OPSCC adult cases. All HPV-positive cohorts (OPSCC, discrepant, and SCCUPHN) had similar clinicodemographic characteristics and better 3- and 5-y overall survival and disease-free survival than their HPV-negative counterparts. In contrast, HPV-negative discrepant cases had prognostic outcomes most similar to HPV-negative OPSCC cases, while HPV-negative SCCUPHN had survival outcomes most similar to those of patients with OSCC in this study. HPV-positive status can improve the classification of patients with unclear or discrepant oral/oropharyngeal subsite, an improvement over classification systems that are solely clinician defined or conducted through ICD coding. However, due to clinical practice, we could not make definitive reclassification for patients with HPV-negative gray zone HNSCC.