High-grade Intraepithelial Neoplasia Research Articles

Moxifloxacin as a contrast agent of two-photon microscopic imaging for detecting colorectal diseases.

Since two-photon microscopy (TPM) can obtain high-resolution images at cellular and subcellular level and moxifloxacin has multiphoton fluorescence characteristic, our study aimed to explore the feasibility and diagnostic value of moxifloxacin-assisted TPM in different human colorectal diseases, including low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN) and cancer tissues. Excitation power for TPM imaging with and without moxifloxacin was (2.74 ± 0.16) mW and (0.28 ± 0.02) mW, respectively (p < 0.05). Whether labeled with moxifloxacin or not, images of normal, LGIN, HGIN and cancer tissues all reached the strongest signal at 30 μm from the mucosa. Normalized fluorescence intensity of TPM images with moxifloxacin was approximately 10 times stronger than that without moxifloxacin. Fluorescence signal was differed significantly in normal, LGIN, HGIN and cancer tissues with or without moxifloxacin (p < 0.05). Besides, moxifloxacin-assisted TPM could present variant tissue features with different colorectal diseases, such as the crypt opening, glandular structure, adjacent glandular space and fluorescence distribution.

Dilatation of the main pancreatic duct of unknown origin: causes and risk factors of pre-malignancy or malignancy.

A dilatation of the main pancreatic duct (MPD) is mainly due to obstructive causes (pancreatic tumor, chronic pancreatitis) or intraductal papillary mucinous neoplasm (IPMN). This study aims to assess the risk of pre-malignancy or malignancy in case of MPD dilatation with no visible mass nor obstructive calcification on computed tomography scan (CT-scan) in a population operated for it. All patients operated on from November 2015 to December 2019 in our center for a significant dilatation of the MPD without visible obstructive cause on CT-scan were included. Preoperative work-up included at least CT-scan, magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). Primary endpoint was the final pathological diagnosis. Secondary endpoints were predictive factors of malignancy. 101 patients were included, mean age 68years-old. Final pathological data were pancreatic adenocarcinoma (n = 2), IPMN with high-grade dysplasia (n = 37), high-grade Pancreatic Intraepithelial Neoplasia (PanIN) (n = 2) (total of pre-malignant or malignant lesions: n = 41), neuroendocrine tumor (n = 6), IPMN with low-grade dysplasia (n = 45), low-grade PanIN (n = 5), chronic pancreatitis (n = 3), and benign stenosis (n = 1). On preoperative explorations, the median diameter of MPD was 7mm [3-35]. MRI and/or EUS showed intraductal material, nodule, or cyst in 22, 32, and 52 patients, respectively; 22 patients without nodule visible on MRI or EUS had still a pre-malignant or malignant lesion. In multivariate analysis, predictive factors forpre-malignancy or malignancy were symptoms before surgery (p = 0.01), MPD dilatation without downstream stenosis (p = 0.046), and the presence of nodule (p = 0.009). A dilatation of the MPD without detectable mass or obstructive calcification on CT-scan was associated with a pre-malignant or malignant lesion in 41 patients. Symptoms before surgery, MPD dilatation without duct narrowing, and the presence of nodules on MRI/EUS were associated with the risk of pre-malignancy ormalignancy.

Association of P16, Ki-67, and CD44 expression in high-grade squamous intraepithelial neoplasia and squamous cell carcinoma of the cervix.

Stem cells exist in niches in the cervical tissue at squamocolumnar junction, which when infected with HR-Human Papilloma Virus undergo malignant transformation to cancer stem cells and have a role in carcinogenesis and metastasis. The expression of CD44, P16, and Ki67 in high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC) is assessed in this study. Twenty-six cases each of normal cervix, HSIL, and SCC of cervix cases were subjected to immunohistochemistry markers; p16, Ki-67, and CD44. The association of expression of these markers between normal, HSIL, SCC cervix, and clinic-pathological parameters was statistically analyzed. P < 0.05 was considered significant. Of 26 cases of HSIL, 61.5%, 7.7%, and 30.8% cases were positive, ambiguous, and negative respectively for p16 expression. About 11.5%, 53.8%, and 34.6% of cases were strongly positive, positive, and weakly positive, respectively, for Ki-67 expression. About 42.3%, 42.3%, and 15.4% cases were strongly positive, positive, and weakly positive, respectively, for CD44 expression. Among 26 cases of SCC of the cervix 92.3% and 7.7% were positive and ambiguous respectively. About 73.1% and 26.9% of cases were strongly positive and positive, respectively, for Ki-67 expression. 65.4%, 30.8%, and 3.8% of cases were strongly positive, positive, and weakly positive, respectively, for CD44 expression. p16, Ki-67, and CD44 expression between the three groups were statistically significant. p16 expression versus FIGO stage including lymph node involvement and CD44 expression versus lymph node involvement in carcinoma cervix was statistically significant. Expression of p16, Ki-67, and CD44 increases as the lesion progress from normal to HSIL to carcinoma cervix. p16 and CD44 expression increase with lymph node involvement. P16 expression was maximum in Stage II than Stage III.

Diagnostic Value of Serum Pepsinogen Ⅰ/Pepsinogen Ⅱ Combined with Tumor Markers for Helicobacter pylori-Positive Early-Stage Gastric Cancer

To investigate the diagnostic value of serum pepsinogen (PG) Ⅰ/PGⅡ combined with tumor markers for Helicobacter pylori ( Hp)-positive early-stage gastric cancer. A retrospective study was conducted with the clinical data of 109 patients with gastric cancer (the gastric cancer group), 115 patients with chronic atrophic gastritis (the benign group), 112 cases of low-grade intraepithelial neoplasia (the low grade group), 109 cases of high-grade intraepithelial neoplasia (the high grade group), and 104 healthy subjects who underwent the relevant screening tests as part of their general physical examination (the healthy group). All the subjects were admitted to or received care at our hospital between May 2018 and April 2021. The levels of serum PGⅠ, PGⅡ, carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724), and Hp infection status were examined. The findings for these indicators were compared among the groups, and the differences in serum indicators in Hp-positive and Hp-negative patients were compared. The diagnostic value of serum PGⅠ/PGⅡ combined with tumor markers for Hp-positive early-stage gastric cancer was assessed with receiver operating characteristic (ROC) curve. The serum levels of PGⅠ and PGⅠ/PGⅡ decreased in successive order in the healthy group, the benign group, the low grade group, the high grade group, and the gastric cancer group ( P<0.05). The serum levels of PGⅡ, CEA, CA199, and CA724 in the gastric cancer group, the high grade group, and the low grade group were all higher than those in the healthy group and the benign group ( P<0.05). The Hp-positive rates of the gastric cancer group, the high grade group, the low grade group and the benign group were higher than that of the healthy group ( P<0.01). The levels of serum PGⅠ, PGⅡ, CEA, CA199, and CA724 of the Hp-positive subjects of the healthy group, the benign group, the low grade group, the high grade group, and the gastric cancer group were higher than those of the Hp-negative subjects ( P<0.05), while their PGⅠ/PGⅡ levels were always lower than those of the Hp-negative persons ( P<0.05). The specificity and area under the curve ( AUC) of serum PGⅠ/PGⅡ, CEA, CA199, and CA724 in the combined diagnosis of Hp-positive early-stage gastric cancer were higher than those of each indicator used alone in diagnosis ( P<0.05). In the gastric cancer group, the proportion of patients with PGⅠ/PGⅡ>2.32 was lower in the Hp-positive patients than that in the Hp-negative patients ( P<0.05), while the proportions of patients with CEA>66.99 ng/mL, CA199>110.35 U/mL, and CA724>44.20 U/mL were higher in the Hp-positive patients than those in the Hp-negative patients ( P<0.05). Testing PGⅠ/PGⅡ in combination with CEA, CA199, and CA724 results in better diagnostic value for Hp-positive early-stage gastric cancer.

Hysterectomy through Minimally Invasive Surgery for Cervical High-grade Intraepithelial Neoplasia: Reassessment of the Specimens' Eligibility for Histological Examination.

The objective was to investigate the microscopic artifacts made in the uterus of cervical high-grade squamous intraepithelial lesion (HSIL) resected by hysterectomy through minimally invasive (H-MI) procedures and to verify whether these specimens are suitable for histopathological assessment. This single-center retrospective study analyzed 28 patients with cervical HSIL, consisting of 21 premenopausal and seven postmenopausal women, who underwent H-MI. The proportion of the cervical mucosa covered by intact surface epithelium (residual ratio [RR]) was measured on microscopically. Surgical margin's status was also verified. All cases developed detachment of the cervical surface epithelium to a varying extent. The RR was significantly higher in the premenopausal patients (median: 75.5%) than in the postmenopausal patients (median: 37.6%). Among the premenopausal patients, the RR was lower in the cases on whom uterine manipulator (UM) was used (median: 70.5%) than in the cases without UM use (median 92.7%). Among the 21 cases whose resected uterus contained HSIL, the vaginal resection margin was not assessable in three (14.2%) of the seven postmenopausal cases due to the artifact. Although transvaginal manipulation of the uterus causes detachment of the cervical surface epithelium, H-MI for cervical HSIL provides an acceptable specimen for histological assessment in premenopausal patients, even if UM is used. In postmenopausal women, H-MI easily develops artifactual loss of cervical surface epithelium, sometimes providing an unfavorable specimen for microscopic assessment.

Oral higher dose prednisolone to prevent stenosis after endoscopic submucosal dissection for early esophageal cancer.

Esophageal stenosis is one of the main complications of endoscopic submucosal dissection (ESD) for the treatment of large-area superficial esophageal squamous cell carcinoma and precancerous lesions (≥ 3/4 of the lumen). Oral prednisone is useful to prevent esophageal stenosis, but the curative effect remains controversial. To share our experience of the precautions against esophageal stenosis after ESD to remove large superficial esophageal lesions. Between June 2019 and March 2022, we enrolled patients with large superficial esophageal squamous cell carcinoma and high-grade intraepithelial neoplasia experienced who underwent ESD. Prednisone (50 mg/d) was administered orally on the second morning after ESD for 1 mo, and tapered gradually (5 mg/wk) for 13 wk. In total, 14 patients met the inclusion criteria. All patients received ESD without operation-related bleeding or perforation. There were 11 patients with ≥ 3/4 and < 7/8 of lumen mucosal defects and 1 patient with ≥ 7/8 of lumen mucosal defect and 2 patients with the entire circumferential mucosal defects due to ESD. The longitudinal extension of the esophageal mucosal defect was < 50 mm in 3 patients and ≥ 50 mm in 11 patients. The esophageal stenosis rate after ESD was 0% (0/14). One patient developed esophageal candida infection on the 30th d after ESD, and completely recovered after 7 d of administration of oral fluconazole 100 mg/d. No other adverse events of oral steroids were found. Oral prednisone (50 mg/d) and prolonged prednisone usage time may effectively prevent esophageal stricture after ESD without increasing the incidence of glucocorticoid-related adverse events. However, further investigation of larger samples is required to warrant feasibility and safety.

High-grade vaginal intraepithelial neoplasia and recurrence risk: analysis of an Italian regional referral center series.

The main aim of this study was to investigate the long-term risk of disease recurrence in women treated for high-grade vaginal intraepithelial neoplasia (HG-VaIN). We conducted a retrospective analysis on a cohort of 82 women diagnosed with HG-VaIN between 2010 and 2021 at the "Regional Referral Center for Prevention, Diagnosis and Treatment of HPV-related Genital Disorders", Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. All women underwent either ablative treatment (CO2 laser ablation or electrocoagulation) or cold-knife excision. In our series, the recurrence rate following treatment was 17%. The 5-year cumulative probability of recurrence was 30.4% and the median time to recurrence was 15.5months. None of the patients progressed to invasive vaginal cancer during follow-up. A concomitant cervical or vulvar intraepithelial lesion was significatively associated with an increased risk of recurrence (p = 0.006). The results of our study suggest that women with HG-VaIN are at high risk of developing disease recurrence after treatment, especially patients with a concomitant cervical or vulvar intraepithelial lesion. In these women strict monitoring is mandatory to obtain an early identification of recurrence.

101. Effect of Human Papillomavirus Vaccine to Interrupt Recurrence of Vulvar and Anal Neoplasia (VIVA): A Randomized, Placebo-Controlled Trial

Abstract Background Anal and vulvar high-grade intraepithelial lesions (HSIL) often recur after primary treatment, with 30%-50% recurrence in the 5-years following treatment. Treatment for recurrent lesions can be uncomfortable, debilitating, and costly. The VIVA trial evaluated the effects of the nonavalent human papillomavirus (HPV) vaccine (9vHPV) on recurrent anal or vulvar HSIL. Methods We conducted a randomized, double-blinded, placebo-controlled trial of the 9vHPV in vaccine-naïve persons aged 27-69 years who were previously treated for anal or vulvar HSIL and HSIL-free at enrollment. Participants had high-resolution anoscopy or vulvoscopy at screening, month 18 and 36 visits. Eligible participants were randomly assigned (1:1) to receive 9vHPV or placebo on day 1, month 2 and 6. We hypothesized that 9vHPV leads to a 50% reduction of HSIL recurrence. The primary endpoint was anal or vulvar HSIL recurrence, which was assessed in the intent-to-treat (ITT) population. Results Between July 2017 and December 2021, 187participants (99 cis-men, 86 cis-women, 2 transgender persons) with a history of anal (104, 56%) or vulvar (83, 44%) HSIL enrolled in the trial. 181 (97%) participants were included in the ITT analysis. Median age was 55 years (IQR 48-63); 71 out of 181 participants (39%) had well-controlled HIV infection. The DSMB recommended stopping the study early because it met specified futility boundaries at interim analysis. Predictive power to show a significant difference in the primary endpoint was 6.4% should the study continue to accrue. With 46% of planned information accrued, the vaccine was not significantly more efficacious than the placebo in preventing recurrent HSIL, with 15 cases in the 9vHPV arm versus 18 cases in placebo (incidence 9.1 versus 10.0/100 person-years; p= 0.83 by log-rank test). We found no differences in HSIL recurrences among vaccine versus placebo recipients by anatomical site or HIV status. The 9vHPV was safe and well-tolerated. Kaplan-Meier Curve for overall high-grade squamous intra-epithelial neoplasia (HSIL) recurrences for nonavalent-HPV vaccine vs placebo recipients Conclusion We found no benefit of the 9vHPV vaccine for prevention of recurrent anal or vulvar HSIL. Our study underlines the importance of HPV prevention with prophylactic HPV vaccines and the need for novel therapeutic vaccines and antivirals to manage prevalent HSIL that have a high potential to recur. Disclosures Denise Galloway, PhD, Merck: Grant/Research Support Anna Wald, MD, MPH, Aicuris: Advisor/Consultant|Auritec: Advisor/Consultant|Crozet: Advisor/Consultant|DXNow: Advisor/Consultant|GSK: Grant/Research Support|Merck: Advisor/Consultant|sanofi: Grant/Research Support|VIR: Advisor/Consultant|X-Vax: Advisor/Consultant.

Pagetoid Squamous Intraepithelial Neoplasia of the Vulva as a Mimicker of Vulvar Extramammary Paget Disease: Two Cases with Basal Layer Sparing.

Human papillomavirus-associated vulvar intraepithelial neoplasia (high-grade squamous intraepithelial neoplasia [HSIL] or VIN of usual type) is a lesion characterized by atypia extending from the basal layer to the upper epidermis. There are only rare reports of vulvar intraepithelial morphology exhibiting a pagetoid pattern of intraepithelial dissemination. We herein report two cases of vulvar HSIL in which a pagetoid pattern of spread and a largely uninvolved basal layer represented a diagnostic pitfall for extramammary Paget disease. Nuclear atypia reminiscent of HSIL in addition to expression of p16, KRT5/6, and p40 were however in favor of pagetoid HSIL. Although there is morphological and immunohistochemical overlap between these two entities, an accurate diagnosis is important, since an erroneous diagnosis of vulvar extramammary Paget disease may lead to an extensive workup comprising radiological imaging, colonoscopy, and cystoscopy.

Intercourse dysfunction following surgery for extensive high-grade vaginal intraepithelial neoplasia with concurrent microinvasive vaginal carcinoma

Despite the growing interest on the clinical importance of vaginal intraepithelial neo- plasia (VAIN), its natural history, preferred method of treatment and risk of progression and recurrence are not completely understood due to its rarity. We present in our paper an interesting case of a 45 years old woman who was diagnosed after biopsy with VAIN3 and a small focus of microinvasive vaginal carcinoma. Due to the important local extension of the lesion and taking into account that the patient had completed childbearing we decided to perform total abdominal hysterectomy and col- pectomy. The patient underwent adjuvant chemo and radiation therapy. The recovery was uneventful, but following surgery the patient experienced, as expected, vaginal intercourse impairment. The patient remains disease- free 13 months post surgery.

Study protocol for artificial intelligence-assisted sponge cytology as pre-endoscopy screening for early esophegeal squmaous epithelial lesions in China

BackgroundEndoscopic screening is the widely accepted screening strategy for esophageal squmaous cell carcinoma (ESCC). However, massive endoscopic screening is expensive and not cost-efficient, and novel pre-endoscopy detection used as a preliminary screening method arouses new concerns. We are planning to launch an artificial intelligence (AI) assisted sponge cytology for detecting esophageal squmaous high-grade intraepithelial neoplasia (HGIN) and above lesions. The aim of this trail is to investigate the efficiency of AI-assisted sponge cytology in population-based screening of early esophageal squmaous epithelial lesions.MethodsThe study will be prospectively conducted in five regions with a high prevalence of ESCC. AI-assisted sponge cytology and endoscopic examination will be sequentially performed. Based on our previous data, at least 864 patients with esophageal HGIN and above lesions are needed to achieve enough statistical power. And, a calculated 112,500 individuals with high risks of ESCC will be recruited. In the first stage, each 24,000 participants who meet the inclusion criteria will be recruited on a voluntary basis. Setting pathological results as standard reference, diagnostic threshold and according performance of AI-assisted detection will be evaluated. A prediction model will be constructed by co-analyzing cytological results and relevant risk factors. Then, an external validation cohort will be used for validation of the model efficiency. Also, cost-efficiency analysis will be performed. This study protocol was registered on chineseclinicaltrial.gov (ChiCTR1900028524).DiscussionOur study will determine whether this AI-assisted sponge cytology can be used as an effective pre-endoscopy detection tool for large-scale screening for ESCC in high-risk areas.

Expected value of artificial intelligence in gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

This ESGE Position Statement defines the expected value of artificial intelligence (AI) for the diagnosis and management of gastrointestinal neoplasia within the framework of the performance measures already defined by ESGE. This is based on the clinical relevance of the expected task and the preliminary evidence regarding artificial intelligence in artificial or clinical settings. MAIN RECOMMENDATIONS:: (1) For acceptance of AI in assessment of completeness of upper GI endoscopy, the adequate level of mucosal inspection with AI should be comparable to that assessed by experienced endoscopists. (2) For acceptance of AI in assessment of completeness of upper GI endoscopy, automated recognition and photodocumentation of relevant anatomical landmarks should be obtained in ≥90% of the procedures. (3) For acceptance of AI in the detection of Barrett's high grade intraepithelial neoplasia or cancer, the AI-assisted detection rate for suspicious lesions for targeted biopsies should be comparable to that of experienced endoscopists with or without advanced imaging techniques. (4) For acceptance of AI in the management of Barrett's neoplasia, AI-assisted selection of lesions amenable to endoscopic resection should be comparable to that of experienced endoscopists. (5) For acceptance of AI in the diagnosis of gastric precancerous conditions, AI-assisted diagnosis of atrophy and intestinal metaplasia should be comparable to that provided by the established biopsy protocol, including the estimation of extent, and consequent allocation to the correct endoscopic surveillance interval. (6) For acceptance of artificial intelligence for automated lesion detection in small-bowel capsule endoscopy (SBCE), the performance of AI-assisted reading should be comparable to that of experienced endoscopists for lesion detection, without increasing but possibly reducing the reading time of the operator. (7) For acceptance of AI in the detection of colorectal polyps, the AI-assisted adenoma detection rate should be comparable to that of experienced endoscopists. (8) For acceptance of AI optical diagnosis (computer-aided diagnosis [CADx]) of diminutive polyps (≤5 mm), AI-assisted characterization should match performance standards for implementing resect-and-discard and diagnose-and-leave strategies. (9) For acceptance of AI in the management of polyps ≥ 6 mm, AI-assisted characterization should be comparable to that of experienced endoscopists in selecting lesions amenable to endoscopic resection.

The psychological impact of esophageal cancer screening on anxiety and depression in China.

The psychological impact of screening is unclear and has been ignored. This study aimed to evaluate the psychological impact of esophageal cancer (EC) screening on anxiety and depression in China. A multicenter, population-based study in five high-risk regions of EC was conducted from 2019 to 2020. Residents were recruited and underwent endoscopic screening and then were diagnosed with normal, esophagitis, low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN) and EC. Subjects who did not participate in the screening were referred to as the control group. We surveyed their anxiety and depression levels at baseline and after endoscopy and informed them of different pathological results to evaluate the psychological impact of the screening process. A total of 2,337 subjects completed all surveys in the screening process (normal: 355, esophagitis: 1,713, LGIN: 213, HGIN: 43 and EC: 13), with 63 controls. The levels of anxiety and depression of screeners were significantly higher than those of controls (P < 0.001). The fluctuation of anxiety and depression showed a "V" pattern in the screening process. The prevalence of anxiety symptoms at baseline, after endoscopy and after knowing the pathological results was 5.6, 0.3, and 3.2%, respectively (P < 0.001), and the corresponding prevalence of depression was 3.6, 0.2, and 2.1%, respectively (P < 0.001). With the aggravation of pathological results, the levels of anxiety and depression increased significantly (P < 0.001), especially in patients informed of HGIN (16.3 and 9.3%) and EC (23.1 and 30.8%). Participation in endoscopic screening may bring short-term adverse psychological effects, especially at baseline and knowing the pathological results. More attention should be given to participants waiting for endoscopic screening. The method of informing the screening results of HGIN and EC should be improved. Further precise screening is needed to concentrate on high-risk groups to reduce the psychological impact of screening.

Focal pancreatic parenchyma atrophy is a harbinger of pancreatic cancer and a clue to the intraductal spreading subtype

Background/ObjectivesRadiological evidence of focal pancreatic parenchymal atrophy (FPPA) may presage early pancreatic ductal adenocarcinoma (PDAC) development. We aimed to clarify the incidence of FPPA and the clinicopathological features of PDAC with FPPA before diagnosis. MethodsData on endoscopic ultrasound-guided fine-needle biopsies and surgical samples from 170 patients with pancreatic cancer histologically diagnosed between 2014 and 2019 were extracted from the pathology database of Komagome Hospital and Juntendo University hospital and retrospectively evaluated together with 51 patients without PDAC. ResultsFPPA was identified in 47/170 (28%) patients before PDAC diagnosis and in 2/51 (4%) patients in the control group (P < 0.01). The median duration from FPPA detection to diagnosis was 35 (interquartile range [IQR]:16–63) months. In 24/47 (51%) patients with FPPA, the atrophic area resolved.The lesion was in the head and body/tail in 7/40 and 67/56 of the patients with (n = 47) and without FPPA (n = 123), respectively (P < 0.001). Histopathologically confirmed non-invasive lesions in the main pancreatic duct and a positive surgical margin in the resected specimens occurred in 53% vs. 21% (P = 0.078) and 29% vs. 3% (P = 0.001) of the groups, respectively. The PDAC patients with FPPA accompanied by a malignant pancreatic resection margin had high-grade pancreatic intraepithelial neoplasia. ConclusionsFPPA occurred in 28% of the PDAC group at 35 months prediagnosis. The FPPA area resolved before PDAC onset. Benchmarking previous images of the pancreas with the focus on FPPA may enable prediction of PDAC. PDAC with FPPA involves widespread high-grade pancreatic intraepithelial neoplasia requiring a wide surgical margin for surgical excision.

Hepatobiliary and Pancreatic: An unusual cause of biliary obstruction.

A 41-year-old man, with no relevant personal history, presented with postprandial fullness, nausea, and weight loss in the last 2 years. On physical examination, he had mild jaundice. Laboratory examination revealed conjugated hyperbilirubinemia (total bilirubin 3.62 mg/dL, conjugated bilirubin 2.60 mg/dL) and cytocholestasis with cholestatic predominance (AST 102 U/L, ALT 144 U/L, FA 330 U/L, GGT 681 U/L). An abdominal computed tomography followed by magnetic resonance cholangiopancreatography (MRCP) showed common bile duct (CBD) stenosis, without mural thickening or intraluminal mass, and intrahepatic and extrahepatic duct dilation. There were no lesions in the hepatic or pancreatic parenchyma (Fig. 1). Endoscopic retrograde cholangiopancreatography (ERCP) showed a heterogeneous filling defect in the distal half of the CBD with upstream dilatation. Biliary sphincterotomy and exploration with a balloon were performed, and tumor tissue fragments with a villous appearance and necrotic areas were obtained. Cholangioscopy allowed the identification of a friable villous vegetative lesion in the middle third of the CBD leading to luminal narrowing (Fig. 2). Biopsies revealed an intraductal tubulopapillary neoplasm with high-grade dysplasia and focal transformation into adenocarcinoma (ADC). Staging exams excluded lymph node or distant metastasis, and, after multidisciplinary discussion, the patient underwent Whipple's cephalic pancreatoduodenectomy with hepaticojejunostomy. The anatomopathological examination of the surgical specimen showed a moderately differentiated ADC in intestinal-type intraductal papillary neoplasm of the bile duct (IPNB) (pT1N0R0) (Fig. 2). There was no indication for adjuvant chemotherapy, but clinical, analytical, and imaging surveillance was recommended. After 1 year of follow-up, the patient remains asymptomatic. IPNBs are rare neoplasms arising from the bile duct considered to be an important precursor of cholangiocarcinoma. They are commonly found in Far East Asia where hepatolithiasis and clonorchiasis are endemic. IPNBs can occur anywhere in the extrahepatic or intrahepatic bile ducts and microscopically are classified into four types: pancreaticobiliary, intestinal, gastric, and oncocytic. Most cases show at time of diagnosis high-grade intraepithelial neoplasia or invasive carcinoma. IPNBs secrete mucin and induce biliary obstruction and dilation, but do not have a typical clinical or imaging presentation, making their early diagnosis a clinical challenge. The major treatment is surgical resection with a better prognosis compared to cholangiocarcinoma.

Vulvar High-Grade Squamous Intraepithelial Lesions Treated with Imiquimod: Can Persistence of Human Papillomavirus Predict Recurrence?

Simple SummaryVulvar high-grade intraepithelial lesion (vulvar HSIL) is a premalignant vulvar condition that requires intervention, usually surgery. It recurs frequently, and its treatment involves repeated disfiguring surgeries. Vulvar HSIL is associated with human papillomavirus. Imiquimod is a medical treatment option currently attracting attention because vulvar high-grade intraepithelial neoplasia is frequent in young women with multiple vulvar lesions. Few studies have evaluated the long-term effects of the response to imiquimod and the association of human papillomavirus with response and recurrence. We describe a retrospective (with cases already treated) study designed to determine the long-term response to imiquimod in patients with vulvar HSIL, and also to analyze the role of human papillomavirus (HPV), and different HPV types, in the persistence or recurrence of vulvar HSIL after imiquimod treatment.Objectives: Vulvar high-grade squamous intraepithelial lesion (vulvar HSIL) or vulvar intraepithelial neoplasia (VIN) is a premalignant condition that can progress to carcinoma. Imiquimod is a topical drug with high effectiveness and low morbidity. We aimed (1) to assess the long-term response to imiquimod in a cohort of patients with vulvar HSIL and (2) and to analyze the role of HPV determined in pre- and post-imiquimod treatment biopsies in the persistence or recurrence of vulvar HSIL. Design: Retrospective study between 2011 and 2022. Setting: Referrals from the primary care area of Baix Llobregat treated in the gynecology department of a university hospital in Barcelona, Spain. Population: 20 women with vulvar HSIL treated with imiquimod. Methods: The inclusion criteria were vulvar HSIL, vulvar HPV determination by pre- and post-treatment biopsy, acceptance of medical treatment, at least one follow-up and 4 weeks of treatment. Main outcome measures: Histological diagnosis of vulvar HSIL with pre- and post-imiquimod HPV determination. Response to treatment (complete, partial, no response, recurrence). Results: After imiquimod, 10 (50%) and 6 (30%) cases had complete and partial responses, respectively. Another 4 cases (20%) did not respond. Before treatment, 19 (95%) cases were positive for vulvar HPV (16 cases had HPV type 16). After treatment, 10 cases (50%) were positive for HPV (8 cases with HPV type 16): 2 cases (20%) with a complete response, 5 cases (83.3%) with a partial response and 3 cases (75%) with no response. Eight of the 10 HPV-negative cases (80%) post-treatment showed a complete response. HPV type 16 was present in 16 cases (84.2%) pre-treatment and in 8 cases (80%) post-treatment. Ten patients underwent additional treatments following a partial response, no response or recurrence. The 2 HIV and 3 immunosuppressed patients treated with imiquimod showed a partial response and required additional treatment. All these patients were HPV-positive pre- and post-treatment (100%). Response to imiquimod was associated with post-treatment vulvar HPV positivity (p = 0.03). The median time to a complete response in HPV-negative cases was 4.7 months versus 11.5 months in HPV-positive cases post-imiquimod treatment. Recurrence of vulvar HSIL was observed in 7 patients (35%), with a median time to recurrence of 19.7 months (range 3.2–32.7). Recurrence was experienced in 10% of cases with a complete response, in 4/6 (66.6%) cases with a partial response, and in 2/4 (50%) women with no response. Four of the 7 recurrent cases (57%) were infected with HIV or immunosuppressed. Six (85%) of the recurrent cases were HPV-positive post-treatment (all were HPV type 16). Four (30.7%) of the non-recurrent cases were HPV-positive post-treatment with imiquimod (p = 0.05), two of which were HPV type 16 (50%). Conclusions: Imiquimod effectively treats vulvar HSIL. Cases with a complete response showed less HPV positivity post-treatment than partial or non-response cases. Recurrences were more frequent in those with a partial or no response to imiquimod, and in immunosuppressed patients. In recurrent cases, 85% were HPV-positive post-treatment, while 30.7% of non-recurrent cases were HPV-positive. HPV positivity in the post-treatment biopsy suggests the need for stricter follow-up of patients.

Preoperative evaluation of endoscopic submucosal dissection for early gastric cancer.

Objective:To retrospectively analyze the preoperative endoscopic evaluation of the size, nature, and depth of lesions in endoscopic submucosal dissection (ESD) for early gastric cancer and precancerous lesions, determine whether the lesions can be completely resected, and reduce the risk of additional surgery after ESD.Methods:A total of 114 patients with high-grade intraepithelial neoplasia(HGIN) and early gastric cancer treated with ESD in Hebei General Hospital from January 2016 to April 2021 were enrolled in this study. The lesions were evaluated preoperatively according to the endoscopic findings of white light, magnifying endoscopy, endoscopic features of narrow band imaging, and preoperative pathology. Lesion size, positive resection margin, lesion depth, and vascular invasion of postoperative pathology were used as criteria.Results:There were 121lesions in 114 patients. The coincidence rates of preoperative and postoperative pathology were 87.21% (75/86) for HGIN and 92.1% (35/38) for adenocarcinoma. There was no significant difference in the coincidence rate between preoperative pathological evaluation and postoperative pathology among the 3 lesions (χ2 = 10.614, P = .005). The type and malignancy of the lesion were not related to its location or size. Magnifying endoscopy combined with narrow-band imaging showed that HGIN and early gastric cancer had clear borders, irregular microvessels, and irregular surface microarchitecture on endoscopic features. Lesions > 3 cm, surface ulcers and spontaneous bleeding may be risk factors for deeper lesions.Conclusion:ESD is not only a method for the treatment of early gastric cancer and precancerous lesions, but is also an important method for definite pathological diagnosis. Accurate preoperative assessment of lesion type, lesion extent and depth of invasion is helpful to improve the complete resection rate of ESD and reduce the risk of additional surgery.

Clinical outcomes of laser vaporization for vaginal intraepithelial neoplasia – A 20-year retrospective review

ObjectivesThe purpose of our study is to evaluate clinical outcomes of CO2 laser vaporization in patients with high-grade vaginal intraepithelial neoplasia (VAIN), and analyze potential risk factors for unfavourable outcome. Study designA retrospective cohort study was carried out on all patients with high-grade VAIN treated by laser vaporization from Jan 2001 to Dec 2020 in a gynae-oncology training centre in Hong Kong. ResultsA total of 116 women underwent laser therapy for high-grade VAIN during the study period and the median follow-up time was 49.5 months. Disease regression was achieved in 75% of patients after first laser treatment. However, 23% of them had disease recurrence after initial regression. Regression rate declined significantly at subsequent laser treatment for disease persistence or recurrence, from 75% after the first laser, to 52.9% after the second laser and 26.5% after the third or more laser (p < 0.001). Eleven patients (9.4%) had disease progression to cancer during subsequent follow-ups. VAIN 3 was the only independent risk factor for unfavourable outcome after multivariable logistic regression (OR = 2.86, 95% CI 1.16–7.06, p = 0.023). ConclusionCO2 laser vaporization is a safe and effective treatment modality for high-grade VAIN, but with high recurrence rate. Patients should be carefully counselled about treatment failure, recurrence risk, and the need for long-term surveillance for any progression to cancer. Alternative treatment modalities should be considered in patients who failed to regress after two episodes of laser treatment.

O-Glycosylating Enzyme GALNT2 Predicts Worse Prognosis in Cervical Cancer.

Identification of novel biomarkers is helpful for the diagnosis and treatment of cervical cancer. Mucin glycosylating enzyme GALNT2 modulates mucin O-glycosylation, and has been revealed as a regulator of tumorigenesis in various cancers. However, the expression pattern of GALNT2 in cervical cancer is still unclear. In this study, we demonstrated that the mRNA expression and protein level of GALNT2 were increased in cervical high-grade intraepithelial neoplasia and tumor tissues compared with normal cervix tissues. Kaplan-Meier plotter showed that overexpression of GALNT2 was associated with worse overall survival in TCGA cohort (p < 0.001, HR = 2.65, 95% CI = 1.62–4.34) and poor disease free survival in GSE44001 cohort (p = 0.0218, HR = 2.15, 95% CI = 1.14–4.06). In addition, GSEA analysis showed that various immune-related pathways were closely related to the expression of GALNT2 in cervical cancer. Moreover, co-expression of GALNT2 and IL1A, IL1B, IL11, CXCL1, CXCL2, CXCL5, CXCL6, CXCR1, or CCR3 predicted poor overall survival, and the expression of GALNT2 also affected the prognostic value of CD47, CD274, CD276, CSF1R, TNFSF9, and TNFSF11 in cervical cancer patients. These findings suggest that GALNT2 might be used as a prognostic biomarker in cervical cancer.

Differential effects of omega-3 PUFAS on tumor progression at early and advanced stages in TRAMP mice.

In vitro studies evidenced antitumor effects of omega-3 polyunsaturated fatty acids ([n-3]PUFAs), but their effects on prostate cancer (PCa) remain controversial in epidemiological studies. Here we investigated whether an (n-3) PUFA-enriched diet affects tumor progression in transgenic adenocarcinoma of the mouse prostate (TRAMP), at early (12 weeksage) and advanced stages (20 weeksage). TRAMP mice were fed with standard rodent diet (C12, C20) or (n-3) PUFA-enriched diet containing 10% fish oil (T12, T20). A group of 8 weeksage animals fed standard diet was also used for comparison (C8). The ventral prostate was processed for histopathological and immunohistochemical analyses and serum samples submitted to biochemical assays. At early stages, (n-3) PUFA increased the frequency of normal epithelium (3.8-fold) and decreased the frequency of high-grade intraepithelial neoplasia (3.3-fold) and in situ carcinoma (1.9-fold) in the gland, maintaining prostate pathological status similar to C8 group. At advanced stages, 50% of the animals developed a large primary tumor in both C20 and T20, and tumor weight did not differ (C20: 2.2 ± 2.4; T20: 2.8 ± 2.9 g). The ventral prostate of T12 and of T20 animals that did not develop primary tumors showed lower cell proliferation, tissue expressions of androgen (AR) and glucocorticoid (GR) receptors, than their respective controls. For these animals, (n-3) PUFA also avoided an increase in the number of T-lymphocytes, collagen fibers, and αSMA immunoreactivity, and preserved stromal gland microenvironment. (n-3) PUFA also lowered serum triglycerides and cholesterol, regulating the lipid metabolism of TRAMP mice. (n-3) PUFAs had a protective effect at early stages of PCa, delaying tumor progression in TRAMP mice, in parallel with reductions in cell proliferation, AR, and GR and maintenance of the stromal compartment of the gland. However, (n-3) PUFAs did not prevent the development of primary tumors for the T20 group, reinforcing the need for further investigation at advanced stages of disease.