Polyp Neoplasia Research Articles

Announcing the winner of the John J. Sciarra IJGO Prize Paper Award for 2021

The editors of the International Journal of Gynecology & Obstetrics (IJGO) are pleased to announce the winner of the prize paper award for the best clinical research paper from a low- or middle-income country published in IJGO during 2021. The winning paper is: Tang X, Guo C, Liu S, Guo J, Hua K and Qiu J. A novel prognostic nomogram utilizing the 2018 FIGO staging system for cervical cancer: A large multicenter study. Int J Gynecol Obstet 2021;155:86–94. https://doi.org/10.1002/ijgo.13644. It was published in the October 2021 issue of IJGO. This award brings with it a stipend of £800, a certificate of recognition, and complimentary access to IJGO for a period of 1 year from the date the prize is awarded. All clinical research articles submitted to the IJGO from low- and middle-income countries that were published in 2021 were considered for this prize. The paper was chosen from 95 qualifying articles. Selection and review were undertaken by the editors, and the Editorial Board of IJGO endorsed the decision. The winning paper by Tang et al. evaluated the prognostic performance of the revised 2018 FIGO staging system for cervical cancer in a multicentre study across four sites. In 3238 patients with cervical cancer, 1841 (almost 60%) were re-staged. Almost one third of these were re-staged due to tumor size, approximately 30% due to lymph node metastasis, and one third due to the inconsistency between the pre-operative and post-operative assessments. They concluded that the 2018 FIGO staging system was a better reflection of the survival of cervical cancer patients. This very important work also allowed the group to establish a nomogram that allowed them to predict the prognosis of cervical cancer more accurately. Additional papers that are worthy of special recognition are awarded an honorable mention. While the honorable mention recognition does not include a financial award, each author receives a certificate of recognition and a letter of commendation from the editors of IJGO. The IJGO Prize Paper Award was established in 1998 for the purpose of encouraging investigators, especially young scientists, from low- and middle-income countries to submit their best clinical research articles for publication in the journal. IJGO is the official publication of FIGO (International Federation of Gynecology and Obstetrics), the primary international organization for the specialty of obstetrics and gynecology. FIGO is dedicated to enhancing the health care of women worldwide. HONORABLE MENTIONS 2021 The following 11 papers receive an honorable mention: China Li Y, Wang H, Zhang Y, et al. Correlation between multi-type human papillomavirus infections and viral loads and the cervical pathological grade. Int J Gynecol Obstet. 2020;152:96–102. https://doi.org/10.1002/ijgo.13406 Wang X, Zhang C, Li X, Qi H, Liu Q, Lei J. Safety and efficacy of titrated oral misoprostol solution versus vaginal dinoprostone for induction of labor: a single-center randomized control trial. Int J Gynecol Obstet. 2021;154:436–443. https://doi.org/10.1002/ijgo.13546 Brazil Laporte M, Becerra A, Castro L, Veiga N Jr, Espejo-Arce X, Bahamondes L. Evaluation of clinical performance when intrauterine devices are inserted by different categories of healthcare professional. Int J Gynecol Obstet. 2021;152:196–201. https://doi.org/10.1002/ijgo.13396 Barbieri MM, Herculano TB, Dantas Silva A, Bahamondes L, Juliato CRT, Surita FG. Acceptability of ENG-releasing subdermal implants among postpartum Brazilian young women during the COVID-19 pandemic. Int J Gynecol Obstet. 2021;154:106–112. https://doi.org/10.1002/ijgo.13663 Turkey Karakas LA, Atilgan AO, Akilli H, Kuscu UE, Haberal A, Ayhan A. Nulliparity and postmenopausal status are independent factors of malignancy potential of endometrial intraepithelial neoplasia in polyps. Int J Gynecol Obstet. 2021;152:433–438. https://doi.org/10.1002/ijgo.13448 Iran Ghotbizadeh Vhdani F, Nasiri Khormoji N, Eftekhar N, et al. A double-blind randomized trial on subendometrial injection of vasopressin to control bleeding in postpartum hysterectomy due to abnormally invasive placenta. Int J Gynecol Obstet. 2021;153:228–233. https://doi.org/10.1002/ijgo.13440 South Africa Budhram S, Vannevel V, Botha T, et al. Maternal characteristics and pregnancy outcomes of hospitalized pregnant women with SARS-CoV-2 infection in South Africa: An International Network of Obstetric Survey Systems-based cohort study. Int J Gynecol Obstet. 2021;155:455–465. https://doi.org/10.1002/ijgo.13917 Goldman B, Naidoo T. Formal training in cardiotocograph interpretation of healthcare practitioners improves interpretation: a prospective descriptive analytical study in a resource constrained setting. Int J Gynecol Obstet. 2021;153:527–532. https://doi.org/10.1002/ijgo.13513 Kenya Gwako GN, Obimbo MM, Gichangi PB, Kinuthia J, Gachuno OW, Were F. Association between obstetric and medical risk factors and stillbirths in a low-income urban setting. Int J Gynecol Obstet. 2021;154:331–336. https://doi.org/10.1002/ijgo.13528 Egypt Abdallah A, Khairy M, Tawfik M, et al. Role of first-trimester three-dimensional (3D) power Doppler of placental blood flow and 3D placental volume in early prediction of pre-eclampsia. Int J Gynecol Obstet. 2021;154:466–473. https://doi.org/10.1002/ijgo.13572 Malaysia Goh YP, Tan PC, Hong JGS, Sulaiman S, Omar, SZ. Combined massage and warm compress to the perineum during active second stage of labor in nulliparas: a randomized trial. Int J Gynecol Obstet. 2021;155:532–538. https://doi.org/10.1002/ijgo.13613

Prevalence of neoplasia in solitary and multiple esophago-gastrointestinal polyps: 5 years retrospective histopathological study.

The increasing use of endoscopy has led to more discernable abnormalities in the stomach, including polyps. Gastric polyps encompass a spectrum of pathologic conditions that can vary in histology, neoplastic potential, and management. Despite their high prevalence, there is a paucity of literature to support management and treatment decisions for endoscopists. The goal of this review is to summarize clinical, endoscopic, and histopathologic features of various polyps, review syndromes associated with such polyps and provide management recommendations. The present study was carried out for analyzing and comparing the prevalence of neoplasia in polyps (Solitary and multiple) removed endoscopically from the esophagus, stomach, and bowel undergoing screening. Five years retrospective study was done on patients who underwent endoscopy procedures including Oesophagogastroduodenoscopy (OGD) and colonoscopybetween June 2015 and March 2019 in Faruk Medical City Hospital, Sulaimani City. Age and sex of patients, site of occurrence, number of polyps (solitary or multiple), and polyps' histologic type of 369 cases were analyzed in this study. Regarding solitary polyps, out of 279 polyps, 155 were neoplastic (55%) and 124 were non-neoplastic polyps, while multiple polyps, out of a total of 90 cases, 68 were neoplastic (75%) and 22 were non-neoplastic. More than 78% of patients were above the age of 40 years. Tubular adenoma was the most commonly diagnosed polyp. Large bowel was the most commonly involved site and left-sided polyps outnumbered right-sided ones with the sigmoid colon being the most commonly involved site. Screening programs including endoscopy, especially the colon for detecting polyps and particularly the colorectal region can be helpful to reduce morbidity and mortality of patients.

Nulliparity and postmenopausal status are independent factors of malignancy potential of endometrial intraepithelial neoplasia in polyps.

To estimate the risk of concurrent endometrial cancer in endometrium when endometrial intraepithelial neoplasia (EIN) is found within an endometrial polyp and to identify the possible predictive factors for concurrent endometrial cancer. Histopathologic data of women who underwent hysteroscopy for resection of endometrial polyps at Ankara Baskent University Hospital, between 2011 and 2019 were screened. Patients whose polypectomy report was EIN in a polyp, and who had a final report of the hysterectomy specimen were included. Patients were divided into two groups according to the presence of concurrent cancer in the hysterectomy material: group 1, concurrent cancer present and group 2, concurrent cancer absent. Statistical analyses were performed using SPSS. A total of 4125 women underwent hysteroscopy for the resection of endometrial polyps. Of those women, 161 (3.9%) were diagnosed as having EIN and 115 met the criteria. The rate of concurrent endometrial cancer was 28.6% (33/115). According to multivariate analysis, nulliparity (odds ratio [OR] 0.38; 95% confidence interval [CI] 1.04-3.67; p=0.036) and postmenopausal status (OR 0.64; 95% CI 0.42-0.98; p=0.042) were found to be independent factors significantly associated with concurrent endometrial cancer. The incidence of concurrent cancer is higher in postmenopausal or nulliparous women when EIN is detected in a polyp.

776 NOVEL METHOD TO ASSESS COLD SNARE POLYPECTOMY QUALITY FOR 1-10 MM COLORECTAL POLYPS – MEASURING THE MINIMUM EXTENT OF A HEALTHY RESECTION MARGIN

Measuring quality of polypectomy in clinical practice remains a challenge. We examined the extent of a normal healthy tissue margin around neoplastic tissue of the resected polyp specimen as a potential quality marker for polypectomy. Prospective single center study in patients who underwent an elective outpatient colonoscopy with non-cautery (cold) polyp resection between July 2017 and September 2019. All non-fragmented polyps were included in the analysis. Patient and polyp characteristics, and resection methods were prospectively documented on predefined case report forms. To control for snare type, all snares were rotated monthly (one snare type each month). The healthy margin was defined as the difference between the resected specimen size and the neoplasia size (serrated or adenomatous; measured by the pathologist) divided by two. We assessed the healthy margin across endoscopists, by type of snare (dedicated cold snare vs standard snare), and by polyp characteristics. 561 patients (mean age 65) with 1724 polyps were included in the analysis. The mean size as estimated by the endoscopist was 4.0 mm (median 4 mm). This estimate was approximately 50% greater than the measured neoplasia size of 2.6 mm (median 2.0 mm). The healthy margin varied across endoscopists from 0.8 to 1.4 mm (p<0.001), with an almost 2-fold variation in the proportions of polyps with a minimum helathy margin of ≥1 mm (29% to 57%, (p<0.001). Attending-gastroenterologists resected polyps with a wider margin than trainees (p<0.001). Dedicated cold snares achieved a larger resection margin than standard snares (1.4 vs 1.0 mm, p<0.001), and removed a greater proportion of polyps with a margin ≥1mm (56% vs 39%, p<0.001). There was no difference in the extent of the healthy margin by polyp size, proximal location, or histology. The study examined the healthy tissue margin surrounding polyp neoplasia as a potentially novel quality marker for polyp resection. The margin varied two-fold across endoscopists, in particular between attendings and trainees, and was larger when dedicated cold snares were used. The findings encourage future validation of this new measure.Figure 1Variation of mean minimum healthy margin across endoscopistsView Large Image Figure ViewerDownload Hi-res image Download (PPT)

Implementation of real-time probe-based confocal laser endomicroscopy (pCLE) for differentiation of colorectal polyps during routine colonoscopy.

Background and aims Probe-based confocal laser endomicroscopy (pCLE) is used to differentiate between neoplastic and non-neoplastic colorectal polyps during colonoscopy. We aimed to assess the accuracy of two endoscopists starting to use real-time pCLE for differentiation of colorectal polyps and to determine the negative predictive value (NPV) for neoplasia in polyps ≤ 5 mm. Methods Patients undergoing colonoscopy in a tertiary hospital were included in this prospective trial. After a training session, two colonoscopists assessed 50 polyps between August 2012 and April 2014. They sequentially used narrow-band imaging (NBI) and real-time pCLE to differentiate non-adenomatous, adenomatous, and carcinomatous polyps during colonoscopy. Histologic diagnosis by a gastrointestinal pathologist was the gold standard. Results were compared to post-hoc pCLE by a panel of gastroenterologists and pathologists. Results The accuracy of real-time pCLE was 76 %, compared to 73 % for NBI, and was not significantly different between the first 50 cases (74 %) and the last 50 cases (78 %, P = 0.64). The accuracy in polyps > 5 mm was 87 % versus 59 % in polyps ≤ 5 mm ( P = 0.04) and increased from 45 % (13/29) in poor quality images to 86 % (44/51) in fair quality images and 95 % (19/20) in good quality images ( P < 0.01). The post-hoc pCLE accuracy was 62 %. The NPV for polyps ≤ 5 mm was 58 % for real-time pCLE and 54 % for post-hoc pCLE. Conclusion Although a fair accuracy of real-time pCLE for differentiation of colorectal polyps can be achieved within 50 cases, low NPV and difficulty in obtaining high-quality pCLE images hamper implementation in routine clinical practice.

Safety of cold polypectomy for &lt; 10 mm polyps at colonoscopy: a prospective multicenter study

Cold polypectomy techniques (without electrocautery) by means of biopsy forceps or snare are widely adopted for the removal of subcentimetric polyps. However, few data are available on the safety of this approach. The aim of this study was to assess the safety of cold polypectomy for subcentimetric polyps, as well as the rate of advanced neoplasia in these lesions. In a prospective multicenter trial, consecutive patients with at least one < 10-mm polyp at colonoscopy were prospectively included. All of the < 10-mm polyps detected within the study period were removed by cold polypectomy. The rates of immediate or delayed bleeding and other complications were assessed at 7 and 30 days after cold polypectomy by telephone calls. The rate of advanced histology was also assessed. Predictive variables of postpolypectomy bleeding or advanced neoplasia were identified by multivariate analysis. A total of 1015 < 10-mm polyps in 823 patients (15.5 % on antiplatelet agents) were removed. Of these, 822 (81 %) were ≤ 5 mm and 193 (19 %) were 6 - 9 mm. Immediate postpolypectomy bleeding occurred in 18 patients, corresponding to a per-patient and per-polyp bleeding rate of 2.2 % (95 % confidence interval [CI] 1.2 % - 3.2 %) and 1.8 % (95 %CI 1 % - 2.6 %), respectively. Therapy with antiplatelet agents (odds ratio [OR] 4; 95 %CI 1.5 - 10.6) and larger polyp size (OR 2; 95 %CI 1.1 - 6.9) were independent predictors of bleeding. Bleeding was successfully treated by endoscopic hemostasis in all cases and required no further medical intervention. Advanced neoplasia prevalence in polyps ≤ 5 mm was as high as 8.7 %. The results from this study showed the high safety of a cold polypectomy approach for subcentimetric polyps. This was due to the low rate of postpolypectomy bleeding and to the high efficacy of endoscopic hemostasis in its treatment. The high rate of advanced neoplasia in polyps ≤ 5 mm should prompt some caution on the management of these lesions following detection at computed tomography colonography or colon capsule endoscopy.

Hyperplastic polyps, serrated adenomas, and the serrated polyp neoplasia pathway

It was previously though that adenomas gave rise to colorectal cancers and that other polyps were harmless. Serrated polyps—hyperplastic polyps, serrated adenomas, and sessile serrated adenomas—show distinct patterns of genetic and epigentic mutation that suggest their role in an alternative pathway of colorectal cancer development. In parallel with these findings are improved demographic and histologic data that also indicate that a subset of serrated polyps are precursors of cancer.

Comparison of Microsatellite Instability, CpG Island Methylation Phenotype, BRAF and KRAS Status in Serrated Polyps and Traditional Adenomas Indicates Separate Pathways to Distinct Colorectal Carcinoma End Points

The aim of this study was to compare BRAF and KRAS, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI) status in each of the histologic categories, including end-point carcinomas with residual adenoma, of the serrated polyp neoplasia pathway and the traditional (nonserrated) adenoma-carcinoma sequence. Deoxyribonucleic acid (DNA) was extracted from the selected samples and assayed for BRAF, KRAS2 codon12, 13, CIMP using markers hMLH1, MGMT, MINT1, MINT2, p16, and MSI using an assay for BAT25 and BAT26. A BRAF mutation was present in 82% of serrated carcinomas (SCas), 62% of serrated adenomas (SAs), 83% of serrated polyps with abnormal proliferation (SPAPs-syn. sessile serrated adenoma [SSA]), 76% of microvesicular serrated polyps (MVSPs), and was not found in any of the histologic categories of the traditional adenoma-carcinoma sequence. KRAS2 mutations were found in 43% of the goblet cell serrated polyp (GCSP) category, 13% of MVSPs, 7% of SPAPs, and 24% of SAs; in 26% of large traditional adenoma (lTAs) compared with small traditional adenomas (sTAs) (0/30; P<0.005) and in 37.3% of traditional carcinomas (TCa). CIMP-H (>1 marker positive) was significantly more frequent in SPAP, SA, and SCa compared with MVSP (P<0.05); CIMP-H was present in 10% of sTAs but was found more frequently in lTA (44.4%; OR 7.2; P=0.007) and TCa (38.9%; OR 5.8; P=0.007). Higher CIMP levels (4 or more markers positive) were significantly more frequent in advanced categories of the serrated pathway (SAs [31%] and SCas [30%]) compared with lTAs [0%] and TCAs [3.4%] (OR 12.2; P=0.02). MSI-H was identified only in the adenocarcinoma component of SCas (9/11) or in the contiguous SAs (3/7). The findings indicate that a BRAF mutation is a specific marker for a serrated polyp pathway that has its origin in a hyperplastic polyp (MVSP) and a potential end point as MSI carcinoma. CIMP-High (CIMP-H) develops early in this sequence and MSI-H develops late. The data provided a less complete picture of a second serrated pathway, identified by a KRAS2 mutation in SAs, but showed that the progressive stages of both iterations of the serrated neoplasia pathway are separate and distinct from those of the traditional adenoma-carcinoma sequence.

Microsatellite Instability in Interval Colon Cancers

Colon cancers that develop after a complete colonoscopy may be the result of "failure of colonoscopy" or rapid tumor growth. Tumors that develop via the mismatch repair gene pathway demonstrate rapid tumor growth. The aim of this study was to determine if interval colon cancers were more likely than noninterval cancers to result from the loss of function of mismatch repair genes and hence demonstrate microsatellite instability (MSI). We searched our institution's cancer registry for interval cancers, defined as colon cancers that developed within 5 years of a complete colonoscopy. These were frequency matched in a 1:2 ratio by age and sex to patients with noninterval cancers (defined as colon cancers diagnosed on a patient's first recorded colonoscopy). Archived cancer specimens for all subjects were retrieved and tested for MSI. Of the 993 colon cancers diagnosed during the study period, 51 (5.1%) were identified as an interval cancer, and 112 subjects with noninterval cancer served as a comparison group. Study subjects were almost all men. MSI was found in 30.4% of interval cancers compared with 10.3% of noninterval cancers (P = .003). After adjusting for age, interval cancers were 3.7 times more likely to show MSI than noninterval cancers (95% confidence interval, 1.5-9.1). This association was strongest for tumors located in the distal colon (odds ratio, 17.5; P = .008). No difference in TNM stage at diagnosis, histologic type or grade, or 5-year survival was found between groups. Interval colon cancers were almost 4 times as likely as noninterval colon cancers to be associated with mismatch repair gene dysfunction.

BRAF and KRAS Mutations in hyperplastic polyps and serrated adenomas of the colorectum: relationship to histology and CpG island methylation status.

The aim of this study was to test the hypothesis that mutations of the oncogenes BRAF or KRAS are early events in the putative serrated polyp neoplasia pathway and more advanced pathology is associated with acquired mutator and suppressor gene inactivation by CpG island methylation of promoter regions. We assayed 79 sporadic hyperplastic polyps (HPs) classified according to the schema of Torlakovic et al and 25 serrated adenomas (SAs) for BRAF and KRAS mutations and related the findings to histologic characteristics and CpG island methylation phenotype (CIMP). Mutations at exon 15, codon 599, of BRAF were assayed using an allele-specific PCR (AS-PCR) technique and confirmed in a sample of AS-PCR- positive cases by direct sequencing of exon 15. AS-PCR-negative HPs and SAs were also sequenced on exon 15 and exon 11 to detect additional mutations. PCR-RFLP was used to assay KRAS codon 12 and 13 mutations, and these mutations were further validated by direct sequencing of the KRAS gene. BRAF599 mutations were identified in a total of 55 HPs (69.6%) and KRAS mutations in a total of 13 (16.5%). BRAF599 mutations occurred with similar frequencies among microvesicular serrated polyp (76.3%) and serrated polyp with abnormal proliferation (82.1%) subtypes but less frequently in goblet cell serrated polyps (23.1%). Conversely, KRAS mutations were most frequent in goblet cell serrated polyp (46.2%) and less frequent in microvesicular serrated polyp (13.2%) and serrated polyp with abnormal proliferation (7.1%). BRAF599 and KRAS mutations were present in 15 (60.0%) and 7 (28.0%) of SAs, respectively. BRAF 599 mutation and KRAS were mutually exclusive findings in the polyps studied and one or the other occurred in 68 of 79 (86.1%) HPs and 22 of 25 (88.0%) SAs. CpG island methylation involving 2 or more genes (CIMP-H) was present in 80.0% of SAs, 75% serrated polyp with abnormal proliferations, 47.4% of microvesicular serrated polyps, and 15.4% of goblet cell serrated polyps. SAs were significantly more likely to be CIMP-H than HPs (odds ratio 3.7; 95% confidence interval, 1.27-10.86; P = 0.017). A similar high frequency of KRAS or BRAF mutations across the histologic spectrum of the serrated polyps assayed suggests that these are early events in the serrated polyp neoplasia pathway. In contrast, the association of higher levels of CpG island methylation with more advanced histologic changes suggests that CpG island methylation plays a role in serrated polyp progression toward colorectal carcinoma.

Hyperplastic Polyps, Serrated Adenomas, and the Serrated Polyp Neoplasia Pathway

Hyperplastic Polyps, Serrated Adenomas, and the Serrated Polyp Neoplasia Pathway