Rare case of mantle cell lymphoma of the lacrimal sac

ABSTRACT Mantle cell lymphoma of the ocular and periorbital regions is extremely rare but should be considered in the differential diagnosis of lesions affecting the periorbital tissues. In this study, we present a rare case of mantle cell lymphoma of the lacrimal sac in a 65-year-old male presenting with a mass in the lacrimal sac region and epiphora. After clinical examinations and imaging studies, the mucocele was misdiagnosed. Considering the unexpected findings during external dacryocystorhinostomy, a frozen biopsy was performed, which confirmed the diagnosis of lymphoma.

Standardized intrapulmonary lymph node dissection in lung cancer specimens: A national Colombian analysis.

Objective: In patients with non-small cell lung cancer, lymph node assessment is essential for appropriate staging. The intrapulmonary lymph nodes (IPLNs) should be considered when assigning the N stage but are infrequently evaluated in Colombian centers, resulting in understaging that may hinder optimal treatment. Methods: We conducted a prospective study of IPLN dissection in patients with clinical stage I or II non-small cell lung cancer who underwent surgical resection at 9 institutions in Colombia between 2021 and 2023. IPLN dissection was performed by trained surgeons who collected lymph nodes from fresh specimens after resection and before formalin fixation. Results: One hundred patients were eligible for the analysis. Their mean age was 67 ± 10.9 years, and 76% were women. Most (74%) had adenocarcinoma, 20% had neuroendocrine tumors, and 6% had squamous cell carcinoma. Successful sampling and histopathologic analysis of at least one IPLN station was obtained in 85% of patients, 9% had upstaging due to positive N2 lymph nodes, and 5% had upstaging due to positive N1 lymph nodes. Among the patients with pN0 or pN1 disease, 3.2% (3 out of 91) were upstaged exclusively due to positive IPLNs. Conclusions: Fresh-specimen dissection to collect IPLNs is appropriate and feasible to achieve more accurate pathological staging in Colombian lung cancer patients. In clinical N0 patients, IPLN dissection maximizes selection for adjuvant therapy.

Enlarged perivascular space burden predicts declines in cognitive and functional performance.

INTRODUCTION: We evaluated the relationship between baseline enlarged perivascular space (ePVS) burden and later cognitive decline. METHODS: 83 community-dwelling, older adults (aged 56-86) completed three annual cognitive assessments that included the Clinical Dementia Rating (CDR®) Dementia Staging Instrument Sum of Boxes (CDR-SB) and composite measures of executive function and episodic memory. An MRI scan at baseline was used to count ePVS in the basal ganglia and centrum semiovale. Mixed effects models were run with ePVS as the predictor variable and cognitive measures as the dependent variable. Covariates included age, sex, education, cerebral small vessel disease (cSVD) risk factors, and cSVD neuroimaging biomarkers. RESULTS: At baseline, high basal ganglia ePVS counts were associated with lower executive function scores and episodic memory scores. Moreover, baseline basal ganglia ePVS predicted worse longitudinal CDR-SB scores over the study period. DISCUSSION: Basal ganglia ePVS burden is a promising biomarker for cSVD-related cognitive and functional decline.

Oncological long-term outcomes of laparoscopic versus open gastrectomy for cT3-4 gastric cancer at surgical staging: a propensity-score matched cohort study.

BACKGROUND: The oncological efficacy of laparoscopic surgery for advanced gastric cancer (AGC) has been evaluated by several randomized trials. However, the inclusion of earlier-stage disease was a limitation in previous studies. METHODS: Patients with cT3-4 gastric cancer, determined by surgical staging to minimize migration of earlier stages, treated at a tertiary cancer center from 2009 to 2018 were included. Based on the surgical approach, the patients were divided into two groups: the laparoscopic gastrectomy (LG) and the open gastrectomy (OG) and matched for age, sex, macroscopic appearance (type 4 or non-type 4), body mass index, estimated tumor size, clinical stage T3'T4, clinical N stage, pathologic T stage (T3 or T4), and type of surgery (total or distal gastrectomy). RESULTS: 588 patients (221 LG, 367 OG) were included in the analysis. After 1:1 propensity-score matching, 386 patients (193 LG, 193 OG) were assigned for analysis. In the LG group, operation time was longer with lower blood loss. The incidence of postoperative complications (≥ grade III) did not differ significantly between the groups (OG: 8.3%, vs. LG: 9.3%). Overall survival (OS) was longer in the LG group (5-year OS: 79.3 vs. 73% HR 0.66, 95% CI 0.44-0.99, P = 0.0497). Relapse-free survival (RFS) did not show a statistical difference (5-year RFS: 69.5 vs. 68.7 HR 0.88, 95% CI 0.62-1.26, P = 0.487). Subgroup analysis for OS also demonstrated equivalent outcomes. CONCLUSION: LG demonstrates comparable safety and efficacy to OG for advanced gastric cancer at surgical staging, with similar rates of severe complications and long-term oncological outcomes. Further research is needed to validate these findings, particularly for total gastrectomy and for patients from Western populations.

Incidence and Pitfalls of Adipose Tissue Encountered in Urinary Bladder Biopsy/Transurethral Resection Specimens.

Despite the College of American Pathologists' recommendation against diagnosing "fat invasion" in urinary bladder biopsies and transurethral resection of bladder tumor specimens (TURBT), some pathologists still consider this scenario as pathologic stage T3. However, a formal evaluation of fat in biopsies/TURBT has not been performed. Material obtained from TURBT is considered as clinical staging (cT) and that obtained from cystectomy is true pathologic staging (pT). Herein, we analyze adipose tissue incidence/distribution, cancer involving fat, staging ramifications, and clinical outcomes in a large series of biopsies/TURBT. Among 366 biopsies/TURBT specimens, data on adipose tissue presence, location, and quantity were analyzed. An initial analysis of 200 consecutive biopsies/TURBT specimens (including benign/cancer), adipose tissue was identified in 37% of 200 specimens (22% biopsies, 78% TURBT), primarily in the lamina propria (57%) or both lamina propria/muscularis propria (32%). A subsequent analysis of 183 invasive cancer (cT1/cT2) biopsies/TURBT revealed adipose tissue in 40% of specimens, predominantly within both the lamina propria and muscularis propria. Among all cT1/cT2 specimens, 26% (23/88) had cancer involving fat. Clinical follow-up on these putative "cT3" specimens revealed 10 patients who underwent radical cystectomy of which only 1 of 10 remained pT3/pT4 (although 8 patients had neoadjuvant chemotherapy). Adipose tissue is commonly found in biopsies/TURBT, predominantly localized in the lamina propria and sometimes extending into the muscularis propria. Importantly, the presence of tumor "invading" fat on biopsies/TURBT does not necessarily indicate pT3 disease. This underscores the need for standardized reporting practices, emphasizing the importance of reserving pathologic staging for cystectomy specimens.

New staging criteria predicting m-tor inhibitors treatment effect of renal angiomyolipoma in tuberous sclerosis complex patients.

BACKGROUND: We aimed to launched new staging criteria to predict mTOR inhibitors treatment effect of renal angiomyolipomas (r-AMLs) in TSC patients. METHODS: 40 TSC patients with 69 r-AMLs were divided into two groups based on the efficacy of 6-month mTOR inhibitor treatment. Epidemiological data, therapeutic response, and predictive factors of enrolled patients were collected and analyzed. Age, sex, maximum diameter, maximum cross-sectional area (CSAmax), unenhanced mean CT value, enhanced mean CT value, and added value of enhanced CT of largest r-AML at baseline were assessed as potential influencing factors. Receiver operating characteristic (ROC) curve analysis and the area under the ROC curve (AUC) was used to estimate prediction power. RESULTS: After 6 months of mTOR inhibitor treatment, the tumor reduction rates in the two groups were 55.87% and 16.44% (P < 0.001). At the start of treatment, the maximum diameters, CSAmax, added value of enhanced CT of the target lesion in two groups were 7.70 ± 0.73 cm vs. 13.18 ± 1.23 cm(P = 0.028), 57.40 ± 10.76cm2 vs. 167.29 ± 33.09cm2 (P = 0.015), and 62.32 ± 5.03HU vs. 33.06 ± 3.13HU (P = 0.009), respectively. AUCs of CSAmax, added value of enhanced CT, and combination of both were 0.8024, 0.7672, and 0.8116, respectively (P < 0.001). Cut-off values of CSAmax combined with the added value of enhanced CT were 40cm2 and 46HU. AUCs of maximum diameters, combination of maximum diameters and added value of enhanced CT were 0.7600 and 0.8100, respectively (P < 0.001), with cut-off values of 6.6 cm and 46 HU. CONCLUSION: New staging criteria, based on CSAmax and added value of enhanced CT, can predict the treatment efficiency of m-TOR inhibitors for r-AMLs in TSC patients. A simplified version based on maximum diameter and added value of enhanced CT of lesion has also been proposed.

Understanding the Social Risk Factors That Avert Equitable Lung Cancer Care.

BACKGROUND: Lung cancer remains the leading cause of cancer death in the United States. There is an association between certain social determinants of health (SDOH) and adverse cancer outcomes. These include Black race and low-income, which are associated with poorer adherence to lung cancer screening and presentation at a later stage of disease. METHODS: We conducted a retrospective review of all patients with a diagnosis of lung cancer at a single urban, academic center from 2015 to 2021. Demographic data including race and clinical data including time taken to progress through various checkpoints (ie, concerning CT scan to diagnosis, diagnosis to treatment) were collected. Income data was approximated based on population medians at patient's home address zip code. RESULTS: A total of 550 patients were included in the final analysis. The study population was 57.4% Black and 61.2% of patients presenting with a household income of $40,000 US Dollars or lower based on approximated median household income. The time from CT scan to first treatment for the entire cohort was 121.3 days with no statistically significant variance by race. However, among patients presenting at stage IV, 72.7% were black and 76.0% resided in a zip code with a median income < $40,000. CONCLUSIONS: This study demonstrated no significant delays in progressing through checkpoints of lung cancer diagnosis and treatment on the basis of race or income approximation. Black patients and patients in low-income households were diagnosed with lung cancer at a more advanced stage. Efforts to close the gap in lung cancer disparities should be focused on targeting screening and early identification toward social groups that may be at highest risk of late presentation. Institutional focus on patient navigation through these stages should be paramount. TWEETABLE ABSTRACT: There were no delays in progression to lung cancer diagnostic and therapeutic milestones based on race or income approximation. Black race and residing in a low-income area are predictors for presenting at stage IV.

The prognostic impact of tumor deposits in colorectal cancer: More than just N1c.

BACKGROUND: The identification of tumor deposits (TD) currently plays a limited role in staging for colorectal cancer (CRC) aside from N1c lymph node designation. The objective of this study was to determine the prognostic impact, beyond American Joint Committee on Cancer N1c designation, of TDs among patients with primary CRC. METHODS: Patients who had resected stage I-III primary CRC diagnosed between 2010 and 2019 were identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Cancer-specific survival (CSS) stratified by TD status and lymph node (N) status was calculated using the Kaplan-Meier method and multivariable Cox proportional hazards regression analyses. RESULTS: In total, 147,783 patients with primary CRC were identified. TDs were present in 15,444 patients (10.5%). The presence of TDs was significantly associated with adverse tumor characteristics, including advanced pathologic stage, nodal status, and metastasis status. The presence of TDs was associated with worse CSS (hazard ratio [HR], 3.12; 95% confidence interval [CI], 3.02-3.22), as it was for each given N category (e.g., N2a and TD-negative [HR, 2.50; 95% CI, 2.37-2.64] vs. N2a and TD-positive [HR, 3.75; 95% CI, 3.49-4.03]). The presence of multiple TDs was also associated with decreased CSS for each given N category compared with a single TD (e.g. N2a with one TD [HR, 3.09; 95% CI, 2.65-3.61] vs. N2a with two or more TDs [HR, 4.32; 95% CI, 3.87-4.82]). CONCLUSIONS: TDs were identified as an independent predictor of a worse outcome in patients with CRC. The presence of TDs confers distinctly different CSS and provides important prognostic information among patients with CRC and warrants further investigation as a unique variable in future iterations of CRC staging.

Stage-by-stage exploration of normal embryonic development in the Arabian killifish, Aphanius dispar.

BACKGROUND: Arabian killifish, Aphanius dispar, lives in marine coastal areas of the Middle East, as well as in streams that experience a wide range of salinities and temperatures. It has been used as a mosquito control agent and for studying the toxicities of environmental pollutants. A. dispar's eggshell (chorion) and embryos are highly transparent and are suitable for high resolution microscopic observations, offering excellent visibility of live tissues. RESULTS: In this study, the staging of normal embryonic development of A. dispar was described and investigated at different temperatures. Embryonic development was then examined under different thermal environments from 26 to 34°C. Our data suggest that temperature has a significant effect on embryonic development, with accelerated development at higher temperatures. CONCLUSION: A. dispar exhibits broad thermal tolerance and extended independent feeding capabilities, making it a promising model organism for toxicology and pathogenesis studies conducted over an extended period of time (12 days post-fertilization).

A retrospective study describing the acetabular consequences of Legg- Calve-Perthes disease.

PURPOSE: Legg Calve Perthes disease (LCPD) is a paediatric hip disorder caused by ischemia of the femoral epiphysis, causing femoral head deformity when untreated. This study aims to determine if previously validated pelvic obliquity radiographic parameters, used for assessing acetabular retroversion in developmental dysplasia of the hip, are applicable to patients with LCPD and its prognostic value. METHOD: A retrospective study of patients with Legg Calve Perthes disease was carried out, analysing 4 pelvic parameters: Ilioischial Angle, Obturator Index, Sharp's Angle and Acetabular Depth-Width Ratio (ADR). The differences between healthy and affected hips were studied, and subsequently, it was assessed whether these parameters have prognostic value in the disease outcome. RESULTS: Statistically significant differences have been obtained in the ilioischial angle, obturator index and ADR, between the affected and healthy hip. However, only the Acetabular Depth-Width Ratio showed predictive value for the disease outcome. CONCLUSION: Although this study revealed differences in pelvic parameters between healthy and diseased hips, with only the ADR showing statistical significance in the disease's evolution and prognosis, further studies with larger sample sizes are necessary.

Image directed redesign of bladder cancer treatment pathways: the BladderPath RCT.

Background: Transurethral resection of bladder tumour has been the mainstay of bladder cancer staging for > 60 years. Staging inaccuracies are commonplace, leading to delayed treatment of muscle-invasive bladder cancer. Multiparametric magnetic resonance imaging offers rapid, accurate and non-invasive staging of muscle-invasive bladder cancer, potentially reducing delays to radical treatment. Objectives: To assess the feasibility and efficacy of the introducing multiparametric magnetic resonance imaging ahead of transurethral resection of bladder tumour in the staging of suspected muscle-invasive bladder cancer. Design: Open-label, multistage randomised controlled study in three parts: feasibility, intermediate and final clinical stages. The COVID pandemic prevented completion of the final stage. Setting: Fifteen UK hospitals. Participants: Newly diagnosed bladder cancer patients of age ≥ 18 years. Interventions: Participants were randomised to Pathway 1 or 2 following visual assessment of the suspicion of non-muscle-invasive bladder cancer or muscle-invasive bladder cancer at the time of outpatient cystoscopy, based upon a 5-point Likert scale: Likert 1-2 tumours considered probable non-muscle-invasive bladder cancer; Likert 3-5 possible muscle-invasive bladder cancer. In Pathway 1, all participants underwent transurethral resection of bladder tumour. In Pathway 2, probable non-muscle-invasive bladder cancer participants underwent transurethral resection of bladder tumour, and possible muscle-invasive bladder cancer participants underwent initial multiparametric magnetic resonance imaging. Subsequent therapy was determined by the treating team and could include transurethral resection of bladder tumour. Main outcome measures: Feasibility stage: proportion with possible muscle-invasive bladder cancer randomised to Pathway 2 which correctly followed the protocol. Intermediate stage: time to correct treatment for muscle-invasive bladder cancer. Results: Between 31 May 2018 and 31 December 2021, of 638 patients approached, 143 participants were randomised; 52.1% were deemed as possible muscle-invasive bladder cancer and 47.9% probable non-muscle-invasive bladder cancer. Feasibility stage: 36/39 [92% (95% confidence interval 79 to 98%)] muscle-invasive bladder cancer participants followed the correct treatment by pathway. Intermediate stage: median time to correct treatment was 98 (95% confidence interval 72 to 125) days for Pathway 1 versus 53 (95% confidence interval 20 to 89) days for Pathway 2 [hazard ratio 2.9 (95% confidence interval 1.0 to 8.1)], p = 0.040. Median time to correct treatment for all participants was 37 days for Pathway 1 and 25 days for Pathway 2 [hazard ratio 1.4 (95% confidence interval 0.9 to 2.0)]. Limitations: For participants who underwent chemotherapy, radiotherapy or palliation for multiparametric magnetic resonance imaging-diagnosed stage T2 or higher disease, it was impossible to conclusively know whether these were correct treatments due to the absence of histopathologically confirmed muscle invasion, this being confirmed radiologically in these cases. All patients had histological confirmation of their cancers. Due to the COVID-19 pandemic, we were unable to realise the final stage. Conclusion: The multiparametric magnetic resonance imaging-directed pathway led to a substantial 45-day reduction in time to correct treatment for muscle-invasive bladder cancer, without detriment to non-muscle-invasive bladder cancer participants. Consideration should be given to the incorporation of multiparametric magnetic resonance imaging ahead of transurethral resection of bladder tumour into the standard pathway for all patients with suspected muscle-invasive bladder cancer. The improved decision-making accelerated time to treatment, even though many patients subsequently needed transurethral resection of bladder tumour. A proportion of patients can avoid transurethral resection of bladder tumour completely, reducing costs and morbidity, given the much lower cost of magnetic resonance imaging and biopsy compared to transurethral resection of bladder tumour. Future work: Further work to cross-correlate with the recently developed Vesical Imaging-Reporting and Data System will improve accuracy and aid dissemination. Longer follow-up to examine the effect of the pathway on outcomes is also required. Incorporation of liquid deoxyribonucleic acid-based biomarkers may further improve the quality of decision-making and should also be investigated further. Study registration: This study is registered as ISRCTN 35296862. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR135775) and is published in full in Health Technology Assessment; Vol. 28, No. 42. See the NIHR Funding and Awards website for further award information.

The BladderPath trial explored how to accelerate diagnosis and avoid unnecessary surgery for patients with bladder cancer which had grown into the muscle wall of the bladder, referred to as muscle-invasive bladder cancer. Following initial outpatient diagnosis, bladder cancer patients currently undergo inpatient or day-case surgical tumour removal using a telescope (transurethral resection of bladder tumour). This surgery is fundamental to the treatment of early bladder cancer (non-muscle-invasive). However, for muscle-invasive disease, the main role of transurethral resection of bladder tumour is to confirm that the tumour has grown into the bladder muscle, and this is often inaccurate; the actual correct treatment for muscle-invasive bladder cancer patients should include chemotherapy, radiotherapy and/or bladder removal. For these patients, having transurethral resection of bladder tumour may delay this correct treatment and impact survival. Additionally, for patients determined to need palliative care due to advanced disease, the transurethral resection of bladder tumour may represent over-treatment. A magnetic resonance imaging scan with contrast agent (called multiparametric magnetic resonance imaging) gives a clearer picture of the bladder than normal scans, allowing distinction between invasive and non-invasive tumours. The BladderPath trial investigated adding multiparametric magnetic resonance imaging for patients with suspected muscle-invasive bladder cancer and the effect on treatment times. Subsequent therapy could include transurethral resection of bladder tumour if clinically determined as necessary by the treating team. Trial participants were randomly allocated either to the standard pathway (Pathway 1: all underwent transurethral resection of bladder tumour) or to a new pathway (Pathway 2). In Pathway 2, urologists conducting the initial outpatient diagnostic bladder inspections used a scale to assess whether tumours appeared to be either probably non-muscle-invasive or possibly muscle-invasive. Participants whose tumours appeared possibly muscle-invasive had initial multiparametric magnetic resonance imaging as their next investigation instead of transurethral resection of bladder tumour. We then compared the duration of time from initial diagnosis to receiving the correct treatment for participants in each pathway. Of the 143 participants, 75 (52.1%) were diagnosed as possibly muscle invasive. In Pathway 1, the duration for half of the participants in the group to have received their correct treatment for muscle-invasive bladder cancer was 98 days, which reduced to 53 days in Pathway 2. Furthermore, the duration for half of all the participants in the two groups to have received their correct treatment was 37 days for Pathway 1 and 31 days for Pathway 2. In summary, use of initial multiparametric magnetic resonance imaging in suspected muscle-invasive bladder cancer participants substantially reduced the time to correct treatment (surgery, radiotherapy, chemotherapy or instigation of palliative care) and avoided unnecessary surgery. There was no negative impact on participants with non-invasive disease. Adopting multiparametric magnetic resonance imaging into the pathway ahead of transurethral resection of bladder tumour for patients with suspected muscle-invasive bladder cancer is recommended.

Prognostic performance of Hong Kong Liver Cancer with Barcelona Clinic Liver Cancer staging systems in hepatocellular carcinoma.

BACKGROUND: Accurate staging is necessary for predicting hepatocellular carcinoma (HCC) prognosis and guiding patient management. The Barcelona Clinic Liver Cancer (BCLC) staging system has limitations due to heterogeneity observed among patients in BCLC stages B and C. In contrast, the Hong Kong Liver Cancer (HKLC) staging system offers more aggressive treatment strategies. AIM: To compare the prognostic performance of HKLC and BCLC staging systems in Egyptian patients with HCC. METHODS: We conducted a retrospective study at the National Liver Institute, Menoufia University, Egypt, on 1015 HCC patients. Data was collected from patients' medical records over 10 years (from 2008 to 2018). The BCLC and HKLC stages were identified, and Kaplan-Meier survival analysis was used to compare patients' overall survival rates within each staging system. Additionally, we evaluated the comparative prognostic performance of the two staging systems. RESULTS: Hepatitis C was identified as the underlying etiology in 799 patients (78.7%), hepatitis B in 12 patients (1.2%), and non-viral causes in 204 patients (20.1%). The survival analysis demonstrated significant differences across the various stages within both the BCLC and HKLC systems. The receiver operating characteristic (ROC) curves indicated a marginally superior performance of the HKLC system in predicting survival at 1, 2, and 3 years compared to the BCLC system. Furthermore, the HKLC staging provided a slightly enhanced prognostic capability, particularly for patients classified under BCLC stages B and C, suggesting a potential survival benefit. CONCLUSION: HKLC classification had a slightly better prognostic performance than BCLC staging system and may offer a survival advantage for certain patients with HCC in BCLC stage B and C HCC cases.

Whole-body MRI for staging prostate cancer: a narrative review.

OBJECTIVE: To present a narrative review regarding the diagnostic accuracy of whole-body magnetic resonance imaging (WBMRI) in staging patients with high-risk prostate cancer (HRPCa) and compare it to established imaging modalities. METHODS: A narrative review was carried out using PubMed using the following keywords: 'whole body', 'magnetic resonance imaging', 'MRI', 'prostate cancer', 'risk stratification', and 'staging'. Articles that evaluated WBMRI as the imaging modality to stage patients with HRPCa were included, while studies that solely assessed for biochemical recurrence or metastatic disease progression were excluded. RESULTS: In the evaluation of lymphatic metastases, WBMRI has demonstrated a comparable, if not improved, sensitivity and specificity compared to conventional imaging of computed tomography (CT). Furthermore, WBMRI demonstrates improved sensitivity and specificity in detecting bone metastases compared to bone scintigraphy (BS). However, with advent of prostate-specific membrane antigen (PSMA) radioligands for positron emission tomography (PET), the diagnostic performance of WBMRI to detect metastatic disease appears inferior. CONCLUSIONS: The diagnostic capabilities of WBMRI exceed that of conventional imaging of CT and BS in detecting metastatic disease in patients with HRPCa. However, WBMRI does not perform as well as PSMA PET/CT. Further study on cost comparisons between WBMRI and PSMA PET/CT are needed, as well as evaluations of combined PSMA PET/MRI are needed.

Comparison of Prognostic Performance of 8th and 7th Edition of AJCC Staging System for Patients With Gallbladder Cancer Undergoing Curative Intent Surgery.

BACKGROUND: We compared the predictive performance of the 7th and 8th editions of the AJCC staging systems in stratifying disease-related survival outcomes in patients with GBC undergoing curative intent surgery. METHODS: Patients that underwent curative intent surgery for GBC at our institution (2014 and 2021) were included in the study. Various clinico-pathological data were extracted to perform Kaplan-Meier survival analysis. RESULTS: A total of 240 patients were included in the study. Both, TNM-7, and TNM-8 staging systems can stratify patients into stages with statistically significant differences in disease-free and overall survival. Survival rates drop with stage progression. Using TNM-8, 8/240 (3.33%) patients were upstaged from Stage IIIB (TNM-7) to IVB (TNM-8) and 12/240 (5%) were down-staged from Stage IVB(TNM-7) to IIIB(TNM-8). Survival curves of the re-classified patients matched those of the corresponding TNM-8 stage. Additionally, there was statistically significant difference in their survival (p < 0.001) compared to their corresponding TNM-7 stage. There was no statistically significant difference in survival rates between stages IIA, IIB (TNM-8), and stage II (TNM-7). However, stage IIA had a slightly better survival than stage IIB. CONCLUSION: Though both TNM-7 and TNM-8 are useful for stratifying patients with GBC, TNM-8 has a better prognostic performance than TNM-7.

New findings on the orientation of the mouse anterior-posterior (A-P) axis before and during the initiation of gastrulation using a more refined embryo staging.

A clinically significant event of early mammalian embryogenesis is the generation and early development of the anterior-posterior (A-P) axis, the imaginary line along which the structures from head to tail will form. This axis not only appears before gastrulation but is also oriented in a specific way in relation to the long and short diameters of the bilaterally symmetric epiblast. In mice, the most widely used mammalian in vivo model of early embryogenesis, the A-P axis is normally aligned with the long epiblast diameter by the early streak (ES) stage, a time during early gastrulation around embryonic day 6.5 (E6.5). Incorrect orientation of the A-P axis by the ES stage, that is, being aligned with the short epiblast diameter, leads to failure in completing gastrulation and results in embryo death soon after. Knowing the orientation of this axis from when it forms before gastrulation (around E5.5) until just before the ES stage is crucial for: (a) understanding the ill-defined factors involved in its formation and early development since they must be spatially related to it, and (b) providing explanations for the underlying mechanism when it is incorrectly orientated. However, the orientation of the A-P axis in pre-ES embryos of the E5.5-E6.5 period remains unclear. Specifically, although it is thought that this axis initially aligns with the short epiblast diameter and subsequently changes its orientation to become aligned with the long diameter by an unidentified pre-gastrulation stage before the ES stage, this proposition remains unresolved. This is largely due to the lack of clearly defined morphological criteria for staging certain periods of pre-ES mouse embryos (especially when the A-P axis initiates and when gastrulation begins prior to the ES stage), which are a prerequisite for identifying A-P axis orientation at specific pre-ES stages. Furthermore, although the orientation of an extraembryonic trophoblast asymmetry, specifically the tilt of the ectoplacental cone (EPC), coincides with that of the A-P axis by the ES stage, it is unknown whether such an association also exists at pre-gastrulation stages during A-P axis formation. Knowing this would exclude or implicate this trophoblast asymmetry as an upstream factor in orientating the A-P axis when it forms. To address these issues, we established a more refined embryo staging for the E5.5-E6.5 period using a novel combination of live morphological criteria and used it to examine the orientation of the A-P axis and that of the EPC tilt at specific stages. First, contrary to current thinking, we show that when the A-P axis first appears at our newly described anterior visceral endoderm-1 (AVE-1) and AVE-2 stages, it aligns with the long epiblast diameter in all embryos. This orientation is maintained in most embryos at all subsequent pre-gastrulation stages, specifically at our AVE-3 and pre-streak stages (the remaining embryos of these stages had this axis aligned with the short epiblast diameter). Second, we identified for the first time the pre-ES stage when gastrulation initiates, which we named the nascent streak (NS) stage, and further subdivided it into NS-1 and NS-2. At variance with current belief, we provide evidence that the earliest stage just before the ES stage when all embryos align their A-P axis with the long epiblast diameter is not a pre-gastrulation stage, but the NS-2 stage (at NS-1, most but not all embryos had this A-P axis orientation). Third, we implicate the EPC tilt as a possible extraembryonic factor in promoting correct A-P axis orientation, as this tilt exists before the AVE-1 stage and its orientation coincided with that of the A-P axis in all embryos at AVE-1, AVE-2 and ES stages and almost all embryos at AVE-3, pre-streak and NS stages. Overall, our work: (a) identified the previously unresolved orientation of the mouse A-P axis within the epiblast before the ES stage during the E5.5-E6.5 period; (b) provides an alternative explanation for when this axis is incorrectly oriented by the ES stage, namely, its defective alignment with the short epiblast diameter by this stage could be due to its failure to align with the long epiblast diameter from the time of its formation; and (c) implicates the pre-existing orientation of the EPC tilt as a possible factor in orientating the newly formed A-P axis.

Overnight Sleep Staging Using Chest-Worn Accelerometry.

Overnight sleep staging is an important part of the diagnosis of various sleep disorders. Polysomnography is the gold standard for sleep staging, but less-obtrusive sensing modalities are of emerging interest. Here, we developed and validated an algorithm to perform "proxy" sleep staging using cardiac and respiratory signals derived from a chest-worn accelerometer. We collected data in two sleep centers, using a chest-worn accelerometer in combination with full PSG. A total of 323 participants were analyzed, aged 13-83 years, with BMI 18-47 kg/m2. We derived cardiac and respiratory features from the accelerometer and then applied a previously developed method for automatic cardio-respiratory sleep staging. We compared the estimated sleep stages against those derived from PSG and determined performance. Epoch-by-epoch agreement with four-class scoring (Wake, REM, N1+N2, N3) reached a Cohen's kappa coefficient of agreement of 0.68 and an accuracy of 80.8%. For Wake vs. Sleep classification, an accuracy of 93.3% was obtained, with a sensitivity of 78.7% and a specificity of 96.6%. We showed that cardiorespiratory signals obtained from a chest-worn accelerometer can be used to estimate sleep stages among a population that is diverse in age, BMI, and prevalence of sleep disorders. This opens up the path towards various clinical applications in sleep medicine.

Mucosal Melanoma: Review from a Pathologist Point of View.

Mucosal melanomas are rare malignant tumors arising from the epithelia lining the inner mucosal surfaces of the body. Unlike cutaneous melanoma, we have a limited understanding of mucosal melanomas is currently limited. Mucosal melanomas are characterized by genetic alterations quite distinct from cutaneous melanomas; however, their causative and promoting factors are unknown. These melanomas are characteristically diagnosed at a later stage due to their occult locations, leading to a worse prognosis. Dedicated staging systems for mucosal melanomas exist only for sinonasal and conjunctival melanomas. Therefore, risk stratification of patients with mucosal melanomas, particularly those arising from the anogenital area, is challenging. Recent studies have shown that minor modifications of the AJCC 8th Edition cutaneous melanoma staging system can group patients fairly robustly; however, the proposed T-categorization systems have yet to be validated in larger cohorts. We summarize the demographic, clinical, histopathologic, and molecular features of common subtypes of mucosal melanomas and highlight the outstanding needs in this field.