Hema Mahajan

Endoscopic mucosal resection for large serrated lesions in comparison with adenomas: a prospective multicentre study of 2000 lesions

Objective Endoscopic mucosal resection (EMR) is effective for large laterally spreading flat and sessile lesions (LSLs). Sessile serrated adenomas/polyps (SSA/Ps) are linked to the relative failure of colonoscopy to prevent proximal colorectal cancer. We aimed to examine the technical success, adverse events and recurrence following EMR for large SSA/Ps in comparison with large conventional adenomas. Design Over 74 months till August 2014, prospective multicentre data of LSLs ≥20 mm were analysed. A standardised dye-based conventional EMR technique followed by scheduled surveillance colonoscopy was used. Results From a total of 2000 lesions, 323 SSA/Ps in 246 patients and 1527 adenomas in 1425 patients were included for analysis. Technical success for EMR was superior in SSA/Ps compared with adenomas (99.1% vs 94.5%, p<0.001). Significant bleeding and perforation were similar in both cohorts. The cumulative recurrence rates for adenomas after 6, 12, 18 and 24 months were 16.1%, 20.4%, 23.4% and 28.4%, respectively. For SSA/Ps, they were 6.3% at 6 months and 7.0% from 12 months onwards (p<0.001). Following multivariable adjustment, the HR of recurrence for adenomas versus SSA/Ps was 1.7 (95% CI 0.9 to 3.0, p=0.097). Subgroup analysis by lesion size revealed an eightfold increased risk of recurrence for 20–25 mm adenomas versus SSA/Ps, but no significantly different risk between lesion types in larger lesion groups. Conclusion Recurrence after EMR of 20–25 mm LSLs is significantly less frequent in SSA/Ps compared with adenomatous lesions. SSA/Ps can be more effectively removed than adenomatous LSLs with equivalent safety. Ensuring complete initial resection is imperative for avoiding recurrence. Trial registration number ClinicalTrials.gov NCT01368289.

Characteristics of HER2-positive breast cancer diagnosed following the introduction of universal HER2 testing

The aim of this study was to determine the impact of universal HER2 testing on the clinico-pathologic profile of HER2+ breast cancer. Data were extracted from breast cancer pathology reports spanning two periods: before (2003/4, n = 379), and after (2008/9, n = 560) the introduction of universal testing. In 2003/4, 43.3% of breast cancers were tested for HER2 with 16% of tested cases HER2+. In 2008/9, 98.4% of cases were tested with 14.7% HER2+. In 2008/9, HER2+ status was associated with younger age, higher grade, increased tumour size, lymph node involvement, negative oestrogen and/or progesterone receptor status. HER2+ cases diagnosed in 2003/4 were not significantly different in respect of these features. The rate of HER2+ breast cancer amongst screen detected cases in 2008/9 was 8.3%. The phenotype of HER2+ breast cancer was stable following the introduction of universal testing. The overall rate of HER2+ breast cancer was influenced by screen detection.

Usefulness of smears in intra-operative diagnosis of newly described entities of CNS

The recent edition of World Health Organisation (WHO) Classification of Tumours of the Central Nervous System has incorporated a substantial number of important changes. It has recognised several new entities, many of which are rare. Intra‐operative diagnosis of these tumours can be difficult with the freezing artefact that often cripples brain frozen sections. In many instances intra‐operative smears are extremely useful adjuvants in neuropathological diagnosis. In this article, we describe intra‐operative smear findings of three of the newly described tumours. Their characteristic cytologic features are illustrated along with differentiating features from the common mimics, together with a general approach to brain smears. The entities we discuss here are papillary glioneuronal tumour, papillary tumour of the pineal region and angiocentric glioma. All three tumours share at least focal pseudo‐papillary/vasculocentric architecture. Smears from papillary glioneuronal tumour demonstrated dual population of cells in a neuropil background, whereas papillary tumour of the pineal region and angiocentric glioma comprise a single population of cells. These two tumours can further be differentiated based on their cell morphology and background.

Intraoperative sentinel lymph node assessment in breast cancer: a comparison of rapid diagnostic method based on CK19 mRNA expression and imprint cytology

Sentinel lymph node biopsy in breast cancer is a routine technique for staging the axilla. The two most common methods of intraoperative histopathological assessment, imprint cytology and frozen section, are hampered by poor sensitivity and lack standardized methodology. The one‐step nuclei acid amplification (OSNA) assay is a rapid quantification of cytokeratin 19 mRNA. This prospective study compared an existing intraoperative imprint cytology protocol with the OSNA system.

IFN-λ3, not IFN-λ4, likely mediates IFNL3–IFNL4 haplotype–dependent hepatic inflammation and fibrosis

Genetic variation in the IFNL3–IFNL4 (interferon-λ3–interferon-λ4) region is associated with hepatic inflammation and fibrosis. Whether IFN-λ3 or IFN-λ4 protein drives this association is not known. We demonstrate that hepatic inflammation, fibrosis stage, fibrosis progression rate, hepatic infiltration of immune cells, IFN-λ3 expression, and serum sCD163 levels (a marker of activated macrophages) are greater in individuals with the IFNL3–IFNL4 risk haplotype that does not produce IFN-λ4, but produces IFN-λ3. No difference in these features was observed according to genotype at rs117648444, which encodes a substitution at position 70 of the IFN-λ4 protein and reduces IFN-λ4 activity, or between patients encoding functionally defective IFN-λ4 (IFN-λ4–Ser70) and those encoding fully active IFN-λ4–Pro70. The two proposed functional variants (rs368234815 and rs4803217) were not superior to the discovery SNP rs12979860 with respect to liver inflammation or fibrosis phenotype. IFN-λ3 rather than IFN-λ4 likely mediates IFNL3–IFNL4 haplotype–dependent hepatic inflammation and fibrosis.

The histological features of intestinal spirochetosis in a series of 113 patients.

A multicenter retrospective review of cases diagnosed as spirochetosis was performed to determine the presenting symptoms and histological changes. A total of 113 cases were retrieved from the archives, consisting of 97 colorectal specimens and 16 appendices. In only 25 cases was the presenting symptom recorded as diarrhea. Of the colorectal specimens, 87 (90%) showed no mucosal abnormality (apart from the spirochetes); the other 10 showed mucosal inflammation but 6 of them had a diagnosis of another inflammatory disease process accounting for the inflammatory changes. Five appendices showed acute appendicitis; the other 11 were unremarkable. It is concluded that spirochetosis in an unselected general population is unlikely to be of pathological significance. Furthermore, if spirochetosis is observed in an inflamed biopsy, it is most likely to be an incidental finding.

Wide-field endoscopic mucosal resection versus endoscopic submucosal dissection for laterally spreading colorectal lesions: a cost-effectiveness analysis

Objective To compare the cost-effectiveness of endoscopic submucosal dissection (ESD) and wide-field endoscopic mucosal resection (WF-EMR) for removing large sessile and laterally spreading colorectal lesions (LSLs) >20 mm. Design An incremental cost-effectiveness analysis using a decision tree model was performed over an 18-month time horizon. The following strategies were compared: WF-EMR, universal ESD (U-ESD) and selective ESD (S-ESD) for lesions highly suspicious for containing submucosal invasive cancer (SMIC), with WF-EMR used for the remainder. Data from a large Western cohort and the literature were used to inform the model. Effectiveness was defined as the number of surgeries avoided per 1000 cases. Incremental costs per surgery avoided are presented. Sensitivity and scenario analyses were performed. Results 1723 lesions among 1765 patients were analysed. The prevalence of SMIC and low-risk-SMIC was 8.2% and 3.1%, respectively. Endoscopic lesion assessment for SMIC had a sensitivity and specificity of 34.9% and 98.4%, respectively. S-ESD was the least expensive strategy and was also more effective than WF-EMR by preventing 19 additional surgeries per 1000 cases. 43 ESD procedures would be required in an S-ESD strategy. U-ESD would prevent another 13 surgeries compared with S-ESD, at an incremental cost per surgery avoided of US

Comparison of the histopathological effects of two electrosurgical currents in an in vivo porcine model of esophageal endoscopic mucosal resection

210 112. U-ESD was only cost-effective among higher risk rectal lesions. Conclusion S-ESD is the preferred treatment strategy. However, only 43 ESDs are required per 1000 LSLs. U-ESD cannot be justified beyond high-risk rectal lesions. WF-EMR remains an effective and safe treatment option for most LSLs. Trial registration number NCT02000141.

Fine needle aspiration biopsy cytology of phyllodes tumour and fibroadenoma: A cytomorphological study of 104 cases

BACKGROUND AND STUDY AIMS Stricture formation is the main limitation of endoscopic resection in the esophagus. The optimal electrosurgical current (ESC) for endoscopic resection in the esophagus and other gastrointestinal sites is unknown. There may be a relationship between the type of ESC used and the development of post-procedure esophageal stricture. Unlike the low power coagulating current (LPCC), the microprocessor-controlled current (MCC), which alternates between short pulse cutting and coagulation, avoids high peak voltages that are thought to result in deep thermal injury. The aim of this study was to determine the histopathological variables associated with these two commonly employed ESCs used for esophageal endoscopic resection. METHODS Standardized endoscopic resection of normal mucosa by band mucosectomy was performed by a single endoscopist in 12 adult pigs. The procedures were randomized 1 : 1 to either LPCC (ERBE 100 C at 25 W) or MCC (ERBE Endocut Q, Effect 3). Necropsy and esophagectomy were performed at 72 hours after the procedure. Two histopathologists, who were blinded to the ESC allocation, independently assessed the presence and depth of ulceration, necrosis and inflammation. RESULTS A total of 45 resections were analyzed. In the LPCC and MCC groups, ulceration extending into the muscularis propria was present in 9/24 (37.5 %) and 1/21 (4.8 %) resected specimens, respectively (P = 0.04). Necrosis extending into the muscularis propria was present in 13/24 (54.1 %) and 1/21 (4.8 %) resected specimens, respectively (P = 0.002). One case of microperforation with muscularis propria injury was noted in the LPCC group compared with none in the MCC group. The quantified mean depth of ulceration, necrosis, and acute inflammation was significantly greater in the LPCC group.  CONCLUSIONS In an in vivo porcine survival model of esophageal endoscopic mucosal resection, the use of MCC resulted in significantly less deep thermal ulceration, necrosis, and acute inflammation compared with LPCC. MCC should be used in preference over LPCC for esophageal endoscopic resection.

57. Uterine endometrial adenocarcinoma with an unusual immunoprofile – A case report

The cytomorphological features in the distinction between phyllodes tumour (PT) and fibroadenoma (FA) on fine needle aspiration biopsy (FNAB) remains challenging because of the biphasic nature of these lesions and the rarity of PT.