Efficacy of Magnifying Endoscopy with Narrow-Band Imaging in the Diagnosis of Early Gastric Cancer and Gastric Intraepithelial Neoplasia.

Early diagnosis of gastric cancer can improve the prognosis of patients, especially for those with early gastric cancer (EGC), but only 15% of patients, or less, are diagnosed with EGC and precancerous lesions. Magnifying endoscopy with narrow-band imaging (ME-NBI) can improve diagnostic accuracy. We assess the efficacy of ME-NBI in diagnosing ECG and precancerous lesions, especially some characteristics under NBI+ME. This was a retrospective analysis of 131 patients with EGC or gastric intraepithelial neoplasia (IN) who had undergone endoscopic submucosal dissection and were pathologically diagnosed with EGC or IN according to 2019 WHO criteria for gastrointestinal tract tumors. We studied the characteristics of lesions under ME-NBI ,compared the diagnostic efficacy of ME-NBI and white light endoscopy (WLI) plus biopsy, and investigated the effect of Helicobacter pylori infection on microvascular and microsurface pattern. The diagnostic accuracy of ME-NBI for EGC, high-grade IN (HGIN), and low-grade IN (LGIN) was 76.06%, 77.96%, and 77.06%, respectively. The accuracy of WLI plus biopsy in diagnosing the above lesions was 69.7%, 57.5%, and 60.53%, respectively. The rate of gyrus-like tubular pattern was highest in LGIN (60.46%), whereas the highest rate of papillary pattern was 57.14% in HGIN and villous tubular pattern was 52% in EGC. Demarcation lines have better sensitivity for differentiating EGC from IN (92.06%). The ME-NBI has higher diagnostic accuracy for EGC than WLI plus biopsy. Demarcation lines and villous and papillary-like microsurface patterns are more specific as EGC and HGIN characteristics. The cerebral gyrus-like microsurface pattern is more specific for LGIN.

Power-law growth models explain incidences and sizes of pancreatic cancer precursor lesions and confirm spatial genomic findings.

Pancreatic ductal adenocarcinoma is a rare but lethal cancer. Recent evidence suggests that pancreatic intraepithelial neoplasia (PanIN), a microscopic precursor lesion that gives rise to pancreatic cancer, is larger and more prevalent than previously believed. Better understanding of the growth-law dynamics of PanINs may improve our ability to understand how a miniscule fraction makes the transition to invasive cancer. Here, using three-dimensional tissue mapping, we analyzed >1000 PanINs and found that lesion size is distributed according to a power law. Our data suggest that in bulk, PanIN size can be predicted by general growth behavior without consideration for the heterogeneity of the pancreatic microenvironment or an individual's age, history, or lifestyle. Our models suggest that intraductal spread and fusing of lesions drive our observed size distribution. This analysis lays the groundwork for future mathematical modeling efforts integrating PanIN incidence, morphology, and molecular features to understand tumorigenesis and demonstrates the utility of combining experimental measurement with dynamic modeling in understanding tumorigenesis.

The genomic trajectory of ovarian high-grade serous carcinoma can be observed in STIC lesions.

Ovarian high-grade serous carcinoma (HGSC) originates in the fallopian tube, with secretory cells carrying a TP53 mutation, known as p53 signatures, identified as potential precursors. p53 signatures evolve into serous tubal intraepithelial carcinoma (STIC) lesions, which in turn progress into invasive HGSC, which readily spreads to the ovary and disseminates around the peritoneal cavity. We recently investigated the genomic landscape of early- and late-stage HGSC and found higher ploidy in late-stage (median 3.1) than early-stage (median 2.0) samples. Here, to explore whether the high ploidy and possible whole-genome duplication (WGD) observed in late-stage disease were determined early in the evolution of HGSC, we analysed archival formalin-fixed paraffin-embedded (FFPE) samples from five HGSC patients. p53 signatures and STIC lesions were laser-capture microdissected and sequenced using shallow whole-genome sequencing (sWGS), while invasive ovarian/fallopian tube and metastatic carcinoma samples underwent macrodissection and were profiled using both sWGS and targeted next-generation sequencing. Results showed highly similar patterns of global copy number change between STIC lesions and invasive carcinoma samples within each patient. Ploidy changes were evident in STIC lesions, but not p53 signatures, and there was a strong correlation between ploidy in STIC lesions and invasive ovarian/fallopian tube and metastatic samples in each patient. The reconstruction of sample phylogeny for each patient from relative copy number indicated that high ploidy, when present, occurred early in the evolution of HGSC, which was further validated by copy number signatures in ovarian and metastatic tumours. These findings suggest that aberrant ploidy, suggestive of WGD, arises early in HGSC and is detected in STIC lesions, implying that the trajectory of HGSC may be determined at the earliest stages of tumour development. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Evaluation of the extended Japan NBI expert team classification of subtype 2B in laterally spreading colorectal tumors based on blue laser imaging.

OBJECTIVES: The Japan NBI Expert Team (JNET) classification has good diagnostic potential for colorectal diseases. We aimed to explore the diagnostic value of the JNET classification type 2B (JNET2B) criteria for colorectal laterally spreading tumors (LSTs) based on magnifying endoscopy with blue laser imaging (ME-BLI) examination. METHODS: Between January 2017 and June 2023, 218 patients who were diagnosed as having JNET2B-type LSTs using ME-BLI were included retrospectively. Endoscopic images were reinterpreted to categorize the LSTs as JNET2B-low (n = 178) and JNET2B-high (n = 53) LSTs. The JNET2B-low and JNET2B-high LSTs were compared based on their histopathological and morphological classifications. RESULTS: Among the 178 JNET2B-low LSTs, 86 (48.3%) were histopathologically classified as low-grade intraepithelial neoplasia, 54 (30.3%) as high-grade intraepithelial neoplasia (HGIN), 37 (20.8%) as intramucosal carcinoma (IMC), and one (0.6%) as superficial invasive submucosal carcinoma (SMC1). Among the 53 JNET2B-high LSTs, five (9.4%) were classified as HGIN, 28 (52.9%) as IMC, 15 (28.3%) as SMC1, and 5 (9.4%) as deep invasive submucosal carcinoma. There were significant differences in this histopathological classification between the two groups (P < 0.001). However, there was no significant difference between JNET2B-low and JNET2B-high LSTs based on their morphological classification (granular vs nongranular) or size (<20 mm vs ≥20 mm). Besides, the κ value for JNET2B subtyping was 0.698 (95% confidence interval 0.592-0.804) between the two endoscopists who reassessed the endoscopic images. CONCLUSION: The JNET2B subtyping of LSTs has a diagnostic potential in the preoperative setting, and may be valuable for treatment decision-making.

A new, simplified endoscopic scoring system for predicting clinical outcome in gastric low-grade intraepithelial neoplasia: the "e-cout system".

BACKGROUND AND OBJECTIVES: The clinical outcomes of gastric low-grade intraepithelial neoplasia (LGIN) exhibit significant diversity, and the current reliance on endoscopic biopsy for diagnosis poses limitations in devising appropriate treatment strategies for this disease. This study aims to establish a prognostic prediction scoring system (e-Cout system) for gastric LGIN, offering a theoretical foundation for solving this clinical challenge. METHODS: Retrospectively selecting 1013 cases meeting the inclusion and exclusion criteria from over 300,000 cases of upper gastrointestinal endoscopy performed at the Digestive Endoscopy Center of our hospital between 2000 and 2022, the cohort included 484 cases as development cohort and 529 cases for validation. Employing relevant statistical analysis, we used development cohort data to establish the e-Cout system for gastric LGIN, and further used validation cohort data to for internal validation. RESULTS: In the developmental stage, based on accordant regression coefficients, we assigned point values to six risk factors for poor prognosis: 4 points for microvessel (MV) distortion, 3 points for MV thickening, 2 points for ulcer, and 1 point each for lesion size > 2cm, disease duration > 1 year, and hyperemia and redness on the lesion surface. Patients were then categorized into four risk levels: low risk (0-1 point), medium risk (2-3), high risk (4-6), and very high risk (≥7). During the validation stage, significant differences in the three different outcomes of gastric LGIN were observed across all risk levels. The probability of reversal and progression showed a significant decrease and increase, respectively, with escalating of risk levels, and these differences were statistically significant (P< 0.001). CONCLUSIONS: The proposed e-Cout system holds promise in aiding clinicians to predict the probability and risk levels of different clinical outcomes in patients with gastric LGIN. This system is expected to provide an improved foundation and guidance for the selection of clinical strategies for this disease.

Risks and benefits of sentinel lymph node evaluation in the management of endometrial intraepithelial neoplasia.

INTRODUCTION: Endometroid intraepithelial neoplasia (EIN) is a premalignant lesion to endometrial cancer. Increasing number of gynecologic oncologists are performing sentinel lymph node (SLN) evaluation during hysterectomy for EIN to ensure complete staging if there is cancer on the final specimen. However, there are no clear guidelines and the benefits and risks to performing SLN evaluation for EIN patients are unclear. AREAS COVERED: This narrative review examines the advantages and disadvantages of SLN evaluation for EIN patients and provides an algorithm to assist clinicians in selectively applying the procedure for maximal patient benefit. Relevant articles up to March 2024 were obtained from a PubMed search on SLN use with endometrial pathology. EXPERT OPINION: Sentinel lymph node evaluation for patients with EIN is safe, feasible, and particularly important for the approximately 10% of patients with high-risk endometrial carcinoma on final pathology. However, as most diagnosed carcinomas are low-risk, SLN evaluation would have limited oncologic benefit. While SLN assessment may overtreat most patients with EIN, a significant minority of patients will be improperly staged. We propose an algorithm highlighting the importance of maximal preoperative endometrial sampling and stratifying patients via risk factors to selectively identify those who would benefit most from SLN evaluation.

Endometroid intraepithelial neoplasia (EIN) is a premalignant lesion to endometrial cancer, the most common gynecologic cancer in the United States. The definitive treatment for EIN is hysterectomy. An increasing number of gynecologic oncologists are performing sentinel lymph node (SLN) assessment during surgery for EIN since 30­40% of patients with EIN will have underlying carcinoma. For those patients, lymph node evaluation is important for cancer staging, especially if high-risk or advanced stage disease is found on the pathologic specimen. The SLN procedure cannot be performed post-hysterectomy, so an improperly staged patient may require a second operation for lymphadenectomy; this has a greater chance of morbidity compared to an SLN biopsy. However, an SLN evaluation still confers perioperative risk and comes at an additional monetary cost, especially when most patients diagnosed with endometrial cancer after EIN will ultimately have low-risk, stage IA disease. We propose an algorithm for clinicians to help determine which patients with EIN would best benefit from the SLN procedure; this includes maximizing preoperative endometrial sampling and considering selective criterion with risk factors for concurrent endometrial carcinoma including age, endometrial thickness, obesity, and molecular classification.

Pancreatic juice cytology for diagnosing invasive pancreatic carcinoma/high-grade pancreatic intraepithelial neoplasia without visible tumors on endoscopic ultrasound.

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) with a diameter ≤10 mm and high-grade pancreatic intraepithelial neoplasia (HG-PanIN) require pre-operative diagnosis. Most cases present only indirect imaging findings without visible tumors on endoscopic ultrasound (EUS). Therefore, EUS-guided fine-needle aspiration/biopsy is not applicable. An alternative diagnostic method is pancreatic juice cytology (PJC) via endoscopic naso-pancreatic drainage (ENPD-PJC), which is not the standard practice. This study aimed to investigate ENPD-PJC for diagnosing suspected PDAC/HG-PanIN cases without visible tumors on EUS. METHODS: Data of patients with suspected PDAC/HG-PanIN without visible tumors who underwent PJC were retrospectively evaluated. One PJC sample was collected during endoscopic retrograde pancreatography (ERP-PJC), and 12 samples were collected during ENPD-PJC, 3-hourly for cytological analysis. ERP-PJC, ERP/ENPD-PJC, and ENPD-PJC positivity indicated cytologically positive samples. Patients with positive/negative PJC with follow-up for <4-years were excluded as undiagnosed cases. A non-malignant diagnosis was based on histopathological absence/stable imaging findings for ≥4-years. The primary endpoint was to demonstrate that ERP/ENPD-PJC has a higher diagnostic ability than ERP-PJC. RESULTS: Twenty-two patients with histopathologically diagnosed PDAC/HG-PanIN and 31 with a non-malignant diagnosis were enrolled. ERP-PJC, ERP/ENPD-PJC, and ENPD-PJC showed sensitivities of 36.4 %, 86.4 %, and 77.3 %, specificities of 93.5 %, 87.1 %, and 93.5 %, and accuracies of 69.8 %, 86.7 %, and 86.7 %, respectively. ERP/ENPD-PJC and ENPD-PJC demonstrated superior sensitivity and accuracy compared to ERP-PJC. A greater occurrence of positive outcomes markedly distinguished true positives from false positives. CONCLUSIONS: ERP/ENPD-PJC and ENPD-PJC had higher diagnostic accuracies for PDAC/HG-PanIN without visible tumors on EUS. ENPD-PJC is recommended for the diagnosis of these lesions.

Utilization and Surgical Outcomes of Sentinel Lymph Node Biopsy for Endometrial Intraepithelial Neoplasia.

OBJECTIVE: To describe the rate and surgical outcomes of sentinel lymph node (SLN) biopsy in patients with endometrial intraepithelial neoplasia (EIN). METHODS: We conducted a cohort study that used the prospective American College of Surgeons National Surgical Quality Improvement Program database. Women with EIN on postoperative pathology who underwent minimally invasive hysterectomy from 2012 to 2020 were included. The cohort was dichotomized based on the performance of SLN biopsy. Patients' characteristics, perioperative morbidity, and mortality were compared between patients who underwent SLN biopsy and those who did not. Postoperative complications were defined using the Clavien-Dindo classification system. RESULTS: Overall, 4,447 patients were included; of those, 586 (13.2%) underwent SLN biopsy. The proportion of SLN biopsy has increased steadily from 0.6% in 2012 to 26.1% in 2020 ( P <.001), with a rate of 16% increase per year. In a multivariable regression that included age, body mass index (BMI), and year of surgery, a more recent year of surgery was independently associated with an increased adjusted odds ratio of undergoing SLN biopsy (1.51, 95% CI, 1.43-1.59). The mean total operative time was longer in the SLN biopsy group (139.50±50.34 minutes vs 131.64±55.95 minutes, P =.001). The rate of any complication was 5.9% compared with 6.7%, the rate of major complications was 2.3% compared with 2.4%, and the rate of minor complications was 4.1% compared with 4.9% for no SLN biopsy and SLN biopsy, respectively. In a single complications analysis, the rate of venous thromboembolism was higher in the SLN biopsy group (four [0.7%] vs four [0.1%], P =.013). In a multivariable regression analysis adjusted for age, BMI, American Society of Anesthesiologists classification, uterus weight, and preoperative hematocrit, the performance of SLN biopsy was not associated with any complications, major complications, or minor complications. CONCLUSION: The performance of SLN biopsy in EIN is increasing. Sentinel lymph node biopsy for EIN is associated with an increased risk of venous thromboembolism and a negligible increased surgical time.

[Primary mucinous gland lesions of fallopian tube: a clinicopathological analysis of fourteen cases].

Objective: To investigate the clinical and pathological characteristics of primary mucinous gland lesions of the fallopian tubes. Methods: The clinical data, pathomorphological characteristics and immunophenotype of 14 cases of primary mucinous gland lesions of the fallopian tube diagnosed at Obstetrics and Gynecology Hospital of Fudan University from 2015 to 2023 were analyzed retrospectively. In addition, a comprehensive review of relevant literature was conducted. Results: The age of 14 patients ranged from 53 to 83 years, with an average of 65 years. Among them, 13 cases exhibited unilateral involvement while one case showed bilateral presentation. Nine cases were mucinous metaplasia of the fallopian tube, four cases were invasive mucinous adenocarcinoma and one case was mucinous carcinoma in situ. Morphologically, mucinous metaplasia of the fallopian tube was focal, with or without inflammation. The cells of mucinous adenocarcinoma or mucinous carcinoma in situ exhibited characteristics indicative of gastrointestinal differentiation. Immunohistochemical analysis revealed diffuse positive expression of CK7, and negative expression of SATB2. CDX2 demonstrated positive staining in two cases. One case exhibited diffuse and strongly positive mutant expression of p53, whereas the remaining cases displayed wild-type expression. MUC6 showed diffuse or focally positive staining in mucinous gland lesions characterized by gastric differentiation. Some cases of mucinous adenocarcinoma of fallopian tube were subject to AB-PAS staining, resulting in red to purple cytoplasmic staining. Conclusions: Primary mucinous lesions of the fallopian tube are exceedingly uncommon. All cases of mucinous adenocarcinoma of fallopian tubes in this study exhibit the morphology and immunohistochemical characteristics of gastrointestinal differentiation. Mucinous metaplasia of the fallopian tube is a benign lesion of incidental finding, which is closely related to inflammation or gastric differentiation. Mucinous lesions of cervix, ovary and digestive tract are excluded in all patients, confirming the independent existence of mucinous lesions within fallopian tubes.

Residual biliary intraepithelial neoplasia without malignant transformation at resection margin for perihilar cholangiocarcinoma does not require expanded resection: a dual center retrospective study.

BACKGROUND: Additional resection for invasive cancer at perihilar cholangiocarcinoma (pCCA) resection margins has become a consensus. However, controversy still exists regarding whether additional resection is necessary for residual biliary intraepithelial neoplasia (BilIN). METHOD: Consecutive patients with pCCA from two hospitals were enrolled. The incidence and pattern of resection margin BilIN were summarized. Prognosis between patients with negative margins (R0) and BilIN margins were analyzed. Cox regression with a forest plot was used to identify independent risk factors associated with overall survival (OS) and recurrence-free survival (RFS). Subgroup analysis was performed based on BilIN features and tumor characteristics. RESULTS: 306 pCCA patients receiving curative resection were included. 255 had R0 margins and 51 had BilIN margins. There was no significant difference in OS (P = 0.264) or RFS (P = 0.149) between the two group. Specifically, 19 patients with BilIN at distal bile ducts and 32 at proximal bile ducts. 42 patients showed low-grade BilIN, and 9 showed high-grade. Further analysis revealed no significant difference in long-term survival between different locations (P = 0.354), or between different grades (P = 0.772). Portal vein invasion, poor differentiation and lymph node metastasis were considered independent risk factors for OS and RFS, while BilIN was not. Subgroup analysis showed no significant difference in long-term survival between the lymph node metastasis subgroup, or between the portal vein invasion subgroup. CONCLUSION: For pCCA patients underwent curative resection, residual BilIN at resection margin is acceptable. Additional resection is not necessary for such patients to achieve absolute R0 margin.

[Development and validation of predictive models for esophageal squamous cell carcinoma and its precancerous lesions using terminal motif analysis in circulating cell-free DNA].

Objectives: To develop and validate predictive models for esophageal squamous cell carcinoma (ESCC) using circulating cell-free DNA (cfDNA) terminal motif analysis. The goal was to improve the non-invasive detection of early-stage ESCC and its precancerous lesions. Methods: Between August 2021 and November 2022, we prospectively collected plasma samples from 448 individuals at the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences for cfDNA extraction, library construction, and sequencing. We analyzed 201 cases of ESCC, 46 high-grade intraepithelial neoplasia (HGIN), 46 low-grade intraepithelial neoplasia (LGIN), 176 benign esophageal lesions, and 29 healthy controls. Participants, including ESCC patients and control subjects, were randomly assigned to a training set (n=284) and a validation set (n=122). The training cohort underwent z-score normalization of cfDNA terminal motif matrices and a selection of distinctive features differentiated ESCC cases from controls. The random forest classifier, Motif-1 (M1), was then developed through principal component analysis, ten-fold cross-validation, and recursive feature elimination. M1's efficacy was then validated in the validation and precancerous lesion sets. Subsequently, individuals with precancerous lesions were included in the dataset and participants were randomly allocated to newly formed training (n=243), validation (n=105), and test (n=150) cohorts. Using the same procedure as M1, we trained the Motif-2 (M2) random forest model with the training cohort. The M2 model's accuracy was then confirmed in the validation cohort to establish the optimal threshold and further tested by performing validation in the test cohort. Results: We developed two cfDNA terminal motif-based predictive models for ESCC and associated precancerous conditions. The first model, M1, achieved a sensitivity of 90.0%, a specificity of 77.4%, and an area under the curve (AUC) of 0.884 in the validation cohort. For LGIN, HGIN, and T1aN0 stage ESCC, M1's sensitivities were 76.1%, 80.4%, and 91.2% respectively. Notably, the sensitivity for jointly predicting HGIN and T1aN0 ESCC reached 85.0%. Both the predictive accuracy and sensitivity increased in line with the cancer's progression (P＜0.001). The second model, M2, exhibited a sensitivity of 87.5%, a specificity of 77.4%, and an AUC of 0.857 in the test cohort. M2's sensitivities for detecting precancerous lesions and ESCC were 80.0% and 89.7%, respectively, and it showed a combined sensitivity of 89.4% for HGIN and T1aN0 stage ESCC. Conclusions: Two predictive models based on cfDNA terminal motif analysis for ESCC and its precancerous lesions are developed. They both show high sensitivity and specificity in identifying ESCC and its precancerous stages, indicating its potential for early ESCC detection.

Carcinoma in situ within the bladder trigone with an isolated metastasis to the prostate without involvement of prostatic urethra: a unique case report.

BACKGROUND: Carcinoma in situ of the bladder is a high-grade cancer that originates in the superficial layer of the bladder. It has the potential to invade nearby organs, and it can spread through blood and lymphatic circulation to distant parts of the body. CASE PRESENTATION: A 58-year-old non-smoker male presented with gross and microscopic hematuria. His family history included his father's recent bladder cancer. Initial investigations showed hematuria, inflammation, negative urine culture, digital rectal examination revealed an enlarged right lobe of the prostate, and an elevated Prostate-Specific Antigen level. Histopathological examination of samples taken from the bladder mucosa and the prostate confirmed urothelial carcinoma in situ in the bladder and prostate. Further evaluation revealed no other metastasis. The tumor was classified as T4aN0M0. The patient underwent radical cystoprostatectomy and histopathological examination showed that the tumor invading the muscularis propria of the bladder as well as the prostatic glands, but no malignancy was found in prostatic urethra and other areas. The patient was discharged three weeks post-operation and completed on adjuvant chemotherapy consisting of Gemcitabine, and Cisplatin to prevent of relapse. The patient is currently in a good healthy. CONCLUSION: The occurrence of bladder cancer metastasizing to the prostate without involving the prostatic urethra is uncommon and requires precise diagnostic techniques for accurate tumor classification. Early management is advised to enhance the prognosis for the patient.

Oncologic Outcomes for Squamous Cell Carcinoma In Situ With a Clinically Resolved Biopsy Site Managed by Watchful Waiting.

BACKGROUND: Treatment option decisions for low-risk squamous cell carcinoma in situ (SCCIS) are hampered by a paucity of management-type-specific outcomes data. OBJECTIVE: Describe SCCIS tumor outcomes managed by watchful waiting and risk factors associated with poor cancer outcomes. MATERIALS AND METHODS: Retrospective cohort study. Setting: Single academic hospital in a rural setting. Patients: Adults with SCCIS diagnosed between January 01, 2014, and December 31, 2016. Main Outcomes and Measures: Hazard ratios (HRs) for local recurrence (LR), nodal metastases (NM), distant metastases (DM), and disease-specific death (DSD). RESULTS: A total of 411 consecutive SCCIS tumors that were considered clinically resolved at follow-up and managed with watchful waiting were included. Seventeen tumors recurred locally. No instances of NM, DM, or DSD were identified. Multivariate analysis found that solid-organ transplant recipient status conferred the highest risk of local recurrence [HR, 9.979 (95% CI, 2.249-39.69)]. Additional risk factors predicting LR include anatomic location on the vermilion lip or ear [HR, 9.744 (95% CI, 1.420-69.28)], anatomic location on the head and neck [HR, 6.687 (95% CI, 1.583-36.15)], and a biopsy with tumor extending to the deep edge [HR, 6.562 (95% CI, 1.367-39.04)]. CONCLUSION: Watchful waiting for SCCIS with a clinically resolved biopsy site has a local recurrence rate of 4%.

Is routine histopathological analysis of hemorrhoidectomy specimens necessary? A systematic review and meta-analysis.

BACKGROUND: Hemorrhoidectomy is a common procedure used to treat symptomatic hemorrhoids. However, the necessity and cost-effectiveness of routinely conducting histopathological analysis on excised tissue samples are uncertain. METHODS: A systematic review was conducted using MEDLINE and EMBASE up to December 2023 for studies assessing the histopathological outcomes of hemorrhoidectomy specimens. Meta-analysis was performed on articles with combinable results to determine the pooled proportions of cancer and anal intraepithelial neoplasia (AIN) using the random effects model. RESULTS: From 2974 initial search results, 12 studies were included in the review, with 48,365 resected specimens from hemorrhoidectomy. Among these, there were 11 retrospective studies and one prospective study. A meta-analysis of 11 studies revealed that the prevalence of anal cancer was low, at 0.13% (95% CI: 0.05%-0.31%). The prevalence of anal cancer and AIN combined was 1.16% (95% CI: 0.53%-2.52%). CONCLUSION: This literature review estimated the probability of malignancy detection in hemorrhoid specimens sent for histopathological evaluation. The low incidence of malignant findings implies that routine analysis of hemorrhoidectomy samples may not be cost-effective. However, existing studies have yet to establish definitive risk factors for abnormal histological diagnoses to aid in the selection of specimens for selective histopathology.

Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial.

PURPOSE: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up. MATERIALS AND METHODS: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence-free (HGRF). RESULTS: One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease. CONCLUSIONS: At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer.

Does serous tubal intraepithelial carcinoma (STIC) metastasize? The clonal relationship between STIC and subsequent high-grade serous carcinoma in BRCA1/2 mutation carriers several years after risk-reducing salpingo-oophorectomy.

OBJECTIVE: The majority of high-grade serous carcinomas (HGSC) of the ovary, fallopian tube, and peritoneum arise from the precursor lesion called serous tubal intraepithelial carcinoma (STIC). It has been postulated that cells from STICs exfoliate into the peritoneal cavity and give rise to peritoneal HGSC several years later. While co-existent STICs and HGSCs have been reported to share similarities in their mutational profiles, clonal relationship between temporally distant STICs and HGSCs have been infrequently studied and the natural history of STICs remains poorly understood. METHODS: We performed focused searches in two national databases from the Netherlands and identified a series of BRCA1/2 germline pathogenic variant (GPV) carriers (n = 7) who had STIC, and no detectable invasive carcinoma, at the time of their risk-reducing salpingo-oophorectomy (RRSO), and later developed peritoneal HGSC. The clonal relationship between these STICs and HGSCs was investigated by comparing their genetic mutational profile by performing next-generation targeted sequencing. RESULTS: Identical pathogenic mutations and loss of heterozygosity of TP53 were identified in the STICs and HGSCs of five of the seven patients (71%), confirming the clonal relationship of the lesions. Median interval for developing HGSC after RRSO was 59 months (range: 24-118 months). CONCLUSION: Our results indicate that cells from STIC can shed into the peritoneal cavity and give rise to HGSC after long lag periods in BRCA1/2 GPV carriers, and argues in favor of the hypothesis that STIC lesions may metastasize.