T1a Adenocarcinoma Research Articles

Incidental Gallbladder Carcinoma in Gallbladder Polyps: Challenges of Gallbladder Malignancy for an Endemic Population.

BackgroundGallbladder polyps are considered pre-malignant lesions of gallbladder carcinoma. This study aims to highlight the role of early cholecystectomy in the management of gallbladder polyps in an endemic population.MethodsA retrospective analysis of 2,076 lap cholecystectomy procedures performed at the Department of Surgical Gastroenterology at a tertiary referral centre in Northern India was conducted and incidental malignancy in gallbladder polyps analysed. The 8th edition of the American Joint Committee on Cancer for tumour-node-metastasis (TNM) staging of gallbladder carcinoma was used.ResultsOf 54 patients with gallbladder polyps, 53 had benign histology and one had malignant cells in the lamina propria suggestive of T1a adenocarcinoma. The patient with the malignant polyp was older (57 years old) than the patients in the non-cancer group, which had a mean age of 45 (P = 0.039). The size of the malignant polyp was approximately 4 mm, significantly smaller than the average 7.9 mm size of the benign polys (P = 0.031).ConclusionCholecystectomy needs to be considered early in the management of small-sized gallbladder polyps, particularly in areas endemic for gallbladder carcinoma.

The real risk of nodal disease in T1 oesophageal adenocarcinoma

Lymph node status is regarded as an important factor in the prognosis of oesophageal cancer. T1 oesophageal adenocarcinoma management has to include endoscopic management as part of the algorithm. We reviewed the literature to assess the true risk of lymph node metastasis in patients with T1 oesophageal adenocarcinoma. Medline, Embase, PubMed and Cochrane where searched for manuscripts in English reviewing lymph node metastasis in superficial (T1) oesophageal adenocarcinoma. The main outcome was probability of lymph node metastasis in T1a and T1b oesophageal adenocarcinoma. Secondary outcome was the rate of lymph node metastasis of submucosal involvement of T1b (SM1, SM2 and SM3). There were 38 studies identified. 22 studies were excluded due to low lymph node yield (<15) or insufficient statistical analysis. For the 16 remaining studies, a total of 1382 cases were included: T1a adenocarcinoma (533 patients) with 11 (2%) node positive and T1b adenocarcinoma (849 patients) with 189 (22%) node positive. Subgroup analysis of T1b lesions was available in 8 reports (365 patients). Node positivity for SM1, SM2 and SM3 was 19.9%, 20.2% and 32.9%, respectively. T1a disease on endoscopic mucosal resection (EMR) demonstrates a 2% nodal metastasis rate, T1b disease a rate of 22%. T1a disease may be safely treated by EMR. T1a disease appears suitable for endoscopic therapy; however, T1b disease presents a high rate of nodal metastasis.

Lymph node metastasis in Chinese patients with clinical T1 non-small cell lung cancer: A multicenter real-world observational study.

BackgroundApproximately 8.3–15.9% of patients with clinical stage I non‐small cell lung cancer are subsequently shown to have lymph node metastasis. However, the clinical characteristics of patients with lymph node metastasis in China are not fully understood.MethodsThis is a multicenter retrospective analysis of pathological T1 non‐small cell lung cancer patients who underwent surgical resection from 2 January 2014 to 27 December 2017. Clinical and pathological information was collected with the assistance of the Large‐scale Data Analysis Center of Cancer Precision Medicine‐LinkDoc database. The clinical and pathological factors associated with lymph node metastasis were analyzed by univariate and multivariate logistic regression.ResultsA total of 10 885 participants (51.6% women; 15.3% squamous cell carcinoma) were included in the analysis. The median age was 60.0 years (range 12.9–86.6 years). A total of 1159 patients (10.6%) had metastases in mediastinal nodes (N2), and 640 patients (5.9%) had metastasis in pulmonary lymph nodes (N1). Most patients had T1b lung cancer (4766, 43.8%). Of the patients, 3260 (29.9%) were current or former smokers. The univariate and multivariate analyses showed that younger age, squamous cell carcinoma, poor differentiation, larger tumor size, carcinoembryonic antigen level ≥5 ng/mL, and vascular invasion (+) were significantly associated with higher percentages of lymph node metastases (P < 0.001 for all).ConclusionThis real‐world study showed the significant association of lymph node metastasis with age, tumor size, histology and differentiation, carcinoembryonic antigen levels, and status of vascular invasion. Female patients with T1a adenocarcinoma in the right upper lobe barely had lymph node metastasis.

VLE for Identification of Subsquamous T1a Esophageal Adenocarcinoma

Barrett's Esophagus (BE) is detected using White Light Endoscopy (WLE) or narrow band imaging (NBI) during esophagogastroduodenoscopy (EGD). Subsquamous disease is often not visualized using traditional WLE or NBI, presenting a challenge when surveying and treating patients with BE. Newer technologies, such as volumetric laser endomicroscopy (VLE), allow for visualization of abnormalities perhaps not identified by traditional endoscopic imaging modalities. Herein, we present a case of subsquamous adenocarcinoma of the esophagus successfully identified using the NvisionVLE® Imaging System allowing for targeted, curative endoscopic mucosal resection (EMR). A 68-year-old male with history of short segment BE and T1a adenocarcinoma 1cm from the gastroesophageal junction status post successful EMR followed by radiofrequency ablation (RFA) was found to have subsequent surveillance biopsies showing intramucosal cancer (IMC) despite no residual mucosal abnormalities, triggering referral to a tertiary care center. EGD was performed and WLE, NBI, and the NvisionVLE® Imaging System initially revealed no significant abnormalities, including no obvious residual BE. However, upon reviewing VLE data prior to subsequent surveillance endoscopy, subsquamous regions of suspicion were identified approximately 1cm proximal to the original BE segment. EGD was performed and the area identified on review of VLE data showed slight discoloration of the mucosa using NBI. Cautery marks were placed on both sides as landmarks and VLE was then performed re-confirming the suspicious abnormal subsquamous glandular structures and relation of cautery marks. VLE-targeted EMR was performed. Pathology confirmed subsquamous T1 adenocarcinoma with negative margins. Surveillance biopsies from within the prior BE segment length were negative for BE, dysplasia, or cancer. Patients with adenocarcinoma or dysplasia on random biopsies, with no suspicious lesion under WLE or NBI can present a challenge. However, with use of the NvisionVLE® Imaging System, subsquamous abnormalities can be identified as shown in our patient. The precise localization allows for complete and curative therapy, unachievable by older technologies. More research is needed to prove the broader impact of Advanced Optical Coherence Tomography in the management of BE related dysplasia and cancer, however, the results in our patient show its potential impact on BE patients, especially with subsquamous disease.1760_A Figure 1. VLE imaging showing subsquamous areas of suspicion1760_B Figure 2. EGD image with cautery marks outlining area identified on VLE1760_C Figure 3. Pathology slides confirming subsquamous T1a adenocarcinoma

PS02.093: LYMPH NODE METASTASES IN T1 OESOPHAGEAL ADENOCARCINOMA: WHAT IS THE REAL RISK IN EARLY OESOPHAGEAL CANCER?

Abstract Background Lymph node status is regarded as the most important factor for prognosis for oesophageal cancer. T1 oesophageal adenocarcinoma management has shifted from oesophagectomy only to include endoscopic management as part of the algorithm, with some bodies (National Comprehensive Cancer Network (NCCN) 2016) recommending it for management of T1a disease and selected T1b disease. We reviewed the literature to assess the true risk of lymph node metastasis in patients with T1 oesophageal adenocarcinoma. Methods Medline, Embase, Pubmed and Cochrane where searched for manuscripts in english reviewing the lymph node metastasis in superficial (T1) oesophageal adenocarcinoma. The main outcome was reviewing the risk of lymph node metastasis in T1a and T1b oesophageal adenocarcinoma. Secondary outcomes looked at the rate of lymph node metastasis for T1b cancers based on degree of submucosal involvement (SM1, SM2 and SM3). Studies were excluded if neo-adjuvant chemotherapy or radiotherapy were received and if the surgical lymph node yield was &lt; 15 lymph nodes. Results 38 Studies were identified. 22 studies were excluded due to low lymph node yield (&lt; 15) or insufficient statistical analysis. For the 16 studies, a total of 1422 cases were included. 533 patients had T1a adenocarcinoma with 11 patients demonstrating positive lymph nodes (2%). 849 had T1b adenocarcinoma with 189 patients demonstrating positive lymph nodes (22%). Eight Studies did subgroup analysis of T1b lesions with a total of 365 patients identified. The rate of lymph node positivity for SM1, SM2 and SM3 was 17.9%, 16.6% and 29.6% respectively. Conclusion Early oesophageal adenocarcinoma (T1) is increasing in prevalence due to surveillance of pre-malignant conditions (Barrett's Oesophagus). Recently some bodies recommend the use of endoscopic mucosal resection as first line therapy for T1a disease. It is important to inform our patients the risk of lymph node metastasis is low but significant (2%). Given in specialised units, oesophagectomy can be performed with low mortality (&lt; 1%) and morbidity with good quality of life it is justifiable to recommend oesophagectomy or endoscopic management in patients who are fit enough for surgery. For T1b disease an oesophagectomy is the gold standard of treatment given the significant risk of lymph node positivity (22%). Disclosure All authors have declared no conflicts of interest.

Esophagectomy versus endoscopic resection for patients with early-stage esophageal adenocarcinoma: A National Cancer Database propensity-matched study

ObjectivesEndoscopic resection has been rapidly adopted in the treatment of early-stage esophageal tumors. We compared the outcomes after esophagectomy or endoscopic resection for stage T1a adenocarcinoma. MethodsWe queried the National Cancer Database for patients with T1a esophageal adenocarcinoma who underwent esophagectomy or endoscopic resection and generated a balanced cohort with 735 matched pairs using propensity-score matching. We then performed a multivariable Cox regression analysis on the matched and unmatched cohorts. ResultsWe identified 2173 patients; 1317 (60.6%) underwent esophagectomy, and 856 (39.4%) underwent endoscopic resection. In the unmatched cohort, patients who underwent esophagectomy were younger, more often not treated in academic settings, and more likely to have comorbidities (30.4% vs 22.5%, P = .002). They had longer hospital stays and more readmissions than patients who underwent endoscopic resection. Factors positively affecting overall survival were younger age, resection at an academic medical center, and lower Charlson–Deyo comorbidity score. In the matched cohort, patients who underwent esophagectomy had longer hospital stays and were more likely to be readmitted within 30 days (7.0% vs 0.6%, P < .001). When a time period–specific partition was applied, endoscopic resection had a lower death hazard 0 to 90 days after resection (hazard ratio, 0.15; P = .003), but this was reversed for survival greater than 90 days (hazard ratio, 1.34; P = .02). ConclusionsIn patients with early-stage esophageal adenocarcinoma, survival appears equivalent after endoscopic resection or esophagectomy, but endoscopic resection is associated with shorter hospital stays, fewer readmissions, and less 90-day mortality. In patients surviving more than 90 days, esophagectomy may provide better overall survival.

Current Concepts in Treatment of Barrett’s Esophagus With and Without Dysplasia

BackgroundAround 10–15% of patients with gastroesophageal reflux disease will develop Barrett’s esophagus (BE). The development of novel endoscopic modalities has changed the management of BE in the last decade. AimThe aim of this study was to review the current evidence for the treatment of BE with and without dysplasia. ResultsIn patients with BE without dysplasia, antireflux surgery should not be suggested as a modality to prevent the malignant transformation of BE, but its indications should be the same as for other patients with gastroesophageal reflux. Endoscopic surveillance at intervals of 3–5 years is recommended for these patients. For patients with BE with low-grade dysplasia, radiofrequency ablation (RFA) is the preferred treatment modality, while endoscopic surveillance every 12 months is an acceptable alternative in patients with life-limiting comorbidities. For most patients with BE and high-grade dysplasia, RFA is the preferred treatment strategy. Patients with intramucosal adenocarcinoma (T1a), should be treated with EMR followed by ablative therapy, in order to eradicate the remaining intestinal metaplasia. Endoscopic resection may be suitable for low-risk T1b tumors (well-differentiated, without lymphovascular invasion, and with superficial submucosal invasion); however, further data are necessary to better risk stratify this group. ConclusionsPatients with BE without dysplasia should undergo endoscopic surveillance every 3–5 years. Endoscopic ablative therapy (RFA) is the preferred treatment modality for dysplastic BE. Patients with T1a adenocarcinoma should be treated with EMR followed by ablative therapy. Low-risk T1b tumors may be suitable for endoscopic resection.

Endoscopic Treatment of High-Grade Dysplasia and Early Esophageal Cancer.

The emergence of novel endoscopic modalities has challenged the role of surgery for patients with Barrett's esophagus (BE) and high-grade dysplasia (HGD) or early esophageal adenocarcinoma. The aim of this study was to review the available evidence of the endoscopic treatment of HGD and early esopahgeal adenocarcinoma. For most patients with BE and HGD, endoscopic ablative therapy is the preferred treatment strategy. Patients with intramucosal adenocarcinoma (T1a) should be treated with endoscopic mucosal resection (EMR) followed by ablative therapy, in order to eradicate the remaining intestinal metaplasia. The best approach to treatment of adenocarcinoma with submucosal invasion (T1b) remains elusive. Endoscopic resection may be suitable for low-risk T1b tumors (well differentiated, without lymphovascular invasion and with superficial submucosal invasion); however, further data are necessary to better risk stratify this group. Careful endoscopic surveillance is recommended following complete eradication of intestinal metaplasia to detect recurrent disease. Patients with BE and HGD should undergo endoscopic ablative therapy. Patients with T1a adenocarcinoma should be treated with EMR and subsequent ablation of the entire BE segment. Low-risk T1b tumors may be suitable for endoscopic resection.

Multidisciplinary treatment of T1a adenocarcinoma in Barrett’s esophagus: contemporary comparison of endoscopic and surgical treatment in physiologically fit patients

Previous reports comparing endoscopic therapy (ET) and surgical therapy (ST) have predominantly assessed patients with high-grade dysplasia. The study aim was to compare ET to ST in physiologically fit patients with cT1a adenocarcinoma (EAC). Review of two prospective databases yielded 100 patients presenting with clinical cT1a EAC between 2000 and 2013. Only physiologically fit patients who were candidates for either treatment were analyzed. Presenting patient characteristics were similar between ET (n=36) and ST groups (n=49). Surgical patients were less likely to be staged with EMR (43 vs 100%) and were associated with mass lesions >1cm at EGD (p=0.01), multifocal EAC (p=0.03), and positive margins for EAC on EMR (p<0.05). On multivariate analysis, only multifocal HGD was an independent factor for surgery. Following esophagectomy, R0 resection rates for Barrett'sesophagus and cancer were 100%. Incidence of surgery decreased over the study period from 85 to 25%. All ET patients had EMR, and 28 patients underwent additional ablative therapies for Barrett'sesophagus. Following ET, eradication rates of EAC, dysplasia, and BE were 92, 81, and 53%, respectively. Morbidity rates were comparable between groups (ST 51% vs ET 39%, p=0.31). In-hospital mortality rate was zero in each group. Recurrence rates in ST and ET group were 2 and 11% (p=0.08). In the ET group, two patients with endoluminal cancer recurrence after complete eradication underwent esophagectomy. Age-adjusted overall survival was comparable. In high-volume esophageal centers, ST and ET provide equally safe and effective treatment for cT1a EAC in medically fit patients. While the results of this study provide a historical perspective and clearly demonstrate an evolution toward ET over time, the appropriate treatment modality is best selected in a multidisciplinary fashion with EMR providing the most accurate staging. In endoscopically treated patients, indefinite endoscopic follow-up required, however, standardized long-term follow-up protocols are needed.

Standardised reporting protocol for endoscopic resection for Barrett oesophagus associated neoplasia: expert consensus recommendations

Endoscopic resection (ER) is considered the therapy of choice for intraepithelial neoplasia associated with visible lesions and T1a adenocarcinoma. Pathologists are bound to encounter specimens collected via these techniques more frequently in their practice. A standardised protocol for handling, grossing, and assessing ER specimens should be adopted to ensure that all prognostic information and characteristics influencing treatment are included in reports (see Supplementary Video Abstract, http://links.lww.com/PAT/A22). The entire specimen should be appropriately oriented, processed and assessed. An ER specimen will commonly show intraepithelial neoplasia or invasive carcinoma. There are essential features that should be recorded if invasive carcinoma is found as they dictate further management and follow-up. These features are the margin status, depth of invasion, degree of differentiation and presence or absence of lymphovascular invasion. Important features such as duplication of muscularis mucosae should be recognised to avoid misinterpretation of depth of invasion. Key diagnostic and prognostic elements that are essential for optimal clinical decisions have been included in the reporting format proposed by the Structured Pathology Reporting committee of the Royal College of Pathologists of Australasia (RCPA).

Tu1320 Multidisciplinary Treatment of T1a Adenocarcinoma in Barrett's Esophagus: Contemporary Comparison of Endoscopic and Surgical Treatment

Endoscopic therapy for T1a adenocarcinoma (EAC) in Barrett's esophagus (BE) has become an accepted alternative to esophagectomy. There are no generally accepted guidelines regarding best treatment and no contemporary comparison of endoscopic therapy to surgical treatment.

Management of Early‐stage Esophageal Neoplasia (MESEN) Consensus

Treatment of esophageal adenocarcinoma often involves surgical resection. Newer technologies in interventional endoscopy have led to a substantial paradigm shift in the management of early-stage neoplasia in Barrett's esophagus comprising high-grade dysplasia (HGD), intramucosal carcinoma, and, in some cases, submucosal carcinoma. However, there has been no consensus regarding the indications for esophageal preservation in these cases. In this work, consensus guidelines were established for the management of early-stage esophageal neoplasia considering clinically relevant aspects (age, comorbidities, and social environment) in each scenario. Seventeen experts were invited to participate based on their background and clinical expertise at high-volume centers. A questionnaire was created that included four clinical scenarios covering a wide range of situations within HGD and/or early esophageal neoplasia, particularly where controversies are likely to exist. Each of the clinical scenarios was open to discussion subdivided by patient age (20, 50, and 80 s). For each clinical scenario an expert was chosen to defend that position. Each defense triggered a subsequent discussion during a consensus meeting. Conclusions of that discussion together with an accompanying literature analysis allowed experts to confirm or change their original choices and served as the basis for the recommendations stated in this article. There was 100 % consensus supporting esophageal preservation in patients with HGD, independent of patient age or Barrett's length. In patients with T1a adenocarcinoma, consensus for preservation was not reached (65 %) for young and middle-aged individuals but was supported for elderly patients (100 %). For T1b adenocarcinoma, consensus was reached for surgical resection (90 %), leaving organ preservation for patients with very low risk of nodal invasion or poor surgical candidates. Advances in endoscopic imaging and therapy allow for organ preservation in most settings of early-stage neoplasia of the esophagus, provided that the patient understands the implications of this decision.

Expert pathology review and endoscopic mucosal resection alters the diagnosis of patients referred to undergo therapy for Barrett’s esophagus

Endoscopic therapy has emerged as an alternative to surgical esophagectomy for the management of Barrett's esophagus (BE)-associated neoplasia. Accurate pretreatment staging is essential to ensure an appropriate choice of therapy and optimal long-term outcomes. This study aimed to assess the frequency with which expert histopathologic review of biopsies combined with endoscopic mucosal resection (EMR) would alter the pretreatment diagnosis of BE-associated neoplasia. Patients referred to the Vanderbilt Barrett's Esophagus Endoscopic Treatment Program (V-BEET) were retrospectively identified. Demographic, histopathologic, and endoscopic data were extracted from the medical record. For this study, 29 subjects referred for endoscopic staging of BE fulfilled the entry criteria. The referral diagnosis was low-grade dysplasia (LGD) in 3 % (1/29), high-grade dysplasia (HGD) in 62 % (18/29), intramucosal adenocarcinoma (T1a) adenocarcinoma in 17 % (5/29), and invasive adenocarcinoma in 17 % (5/29) of the subjects. Expert histopathologic review of available referral biopsy specimens altered the diagnosis in 33 % (5/15) of the cases. Further diagnostic staging with EMR showed BE without dysplasia in 10 % (3/29), LGD in 14 % (4/29), HGD in 34 % (10/29), T1a adenocarcinoma in 28 % (8/29), and invasive adenocarcinoma in 14 % (4/29) of the patients. The combination of expert histopathologic review and EMR altered the initial diagnosis for 55 % (16/29) of the subjects, with 56 % (9/16) upstaged to more advanced disease and 44 % (7/16) downstaged to less advanced disease. The practice of combined expert histopathologic review and EMR alters the pretreatment diagnosis for the majority of patients with BE-associated neoplasia. Caution is advised for those embarking on endoscopic or surgical treatment for BE-associated neoplasia in the absence of these staging methods.

Sa1569 Endoscopic Therapy for Superficial Adenocarcinoma of Esophagus

Endoscopic mucosal resection (EMR) and ablation (radiofrequency ablation [RFA] and cryotherapy) are increasingly being utilized alone or in combination for treatment of Barrett's esophagus with high grade dysplasia (HGD). In our experience, diagnostic EMR frequently upstages pathology to adenocarcinoma. Given a very low rate of lymph node metastasis, endoscopic therapy has become an accepted treatment option for T1a adenocarcinoma of the esophagus with low-risk features. We sought to review our experience of endoscopic management of T1a adenocarcinoma of the esophagus.

A Prospective, Randomized Trial Comparing Conventional Transurethral Prostate Resection With PlasmaKinetic® Vaporization of the Prostate: Physiological Changes, Early Complications and Long-Term Followup

We compared standard transurethral prostate resection with bipolar PlasmaKinetic prostate vaporization for bladder outflow obstruction using a Gyrus PlasmaKinetic Plasma V bar. A total of 160 men were enrolled in a prospective, randomized trial. Those at higher risk for cancer were excluded by prostate specific antigen and digital rectal examination with or without transrectal ultrasound biopsy. A total of 81 men underwent prostate vaporization and 79 underwent transurethral prostate resection. Preoperative International Prostate Symptom Score and quality of life score, uroflowmetry, post-void residual urine and transrectal ultrasound prostate volume were recorded. Preoperative and postoperative serum hemoglobin, hematocrit and sodium were measured. Perioperative fluid absorption was calculated using weighing on table and blood loss using the Hemocue system. Longer followup of International Prostate Symptom Score and quality of life score, uroflowmetry and post-void residual urine was available in 149 men, including 76 who underwent prostate vaporization and 73 who underwent transurethral prostate resection. Data were analyzed using the 1 or 2-sample t and chi-square tests. The 2 groups were comparable in all preoperative parameters. Perioperative fluid absorption, intraoperative blood loss, preoperative and postoperative serum hematocrit, and sodium changes were not statistically different. Mean resection time was 4 minutes shorter for transurethral prostate resection (28.5 vs 32.6 minutes, p = 0.08). Patients with transurethral prostate resection showed a greater hemoglobin decrease (1.39 vs 0.8 gm/dl, p = 0.002) and required more irrigation postoperatively (28.3 vs 20.4 l, p = 0.001). Four patients with transurethral prostate resection required transfusion compared with none who underwent prostate vaporization. After transurethral prostate resection hospital stay was longer (3.36 vs 3.02 days, p = 0.03). Cancer was detected in 8 patients with transurethral prostate resection (10%), of whom 7 are under prostate specific antigen surveillance and 1 received radical radiotherapy. Mean long-term followup was 258 days (range 82 to 884). Prostate vaporization and transurethral prostate resection were equally effective at followup, as evidenced by changes in maximum urine flow, International Prostate Symptom Score, quality of life score and post-void residual urine. The 2 operations are highly effective in experienced hands. PlasmaKinetic prostate vaporization resulted in less postoperative bleeding and a slightly shorter hospital stay. The lack of a histological specimen with this version of PlasmaKinetic prostate vaporization may mean that clinically significant cancers are missed.

Neuroendocrine stains and proliferative indices of prostatic adenocarcinomas in transurethral resection samples.

To determine whether the quantification of certain neuroendocrine and proliferative markers would help in the prognostic evaluation of prostatic adenocarcinomas obtained during transurethral resection of the prostate (TURP). Samples from two groups of patients with prostate cancer were examined. One group comprised 23 patients, of whom 12 were stage IV and 11 stage III, all with Gleason scores of > or = 7; this group was designated as high-grade, high-stage (HGHS). The second group comprised 10 consecutive patients with stage T1a adenocarcinoma of the prostate with Gleason scores of < or = 6, designated as low-grade, low-stage (LGLS) tumours. Tumour tissue from each TURP was stained with MIB-1 (an indicator of cell proliferation), neuron-specific enolase (NSE), chromogranin A (ChA) and synaptophysin (Syn), and 1000 cells counted to determine the percentages of positive cells in both benign and malignant tissue. The percentage of MIB-1-positive cells was designated as the proliferative index (PI). Patients were clinically followed to evaluate tumour progression, documented by rising prostate-specific antigen (PSA) levels, X-ray evidence of recurrent or metastatic carcinoma, or tissue biopsy showing malignancy. The mean number of neuroendocrine cells (NEC) for each marker and the mean PI were greater in the HGHS tumours than in the LGLS tumours or surrounding benign tissue of either group (P < 0.01). The LGLS tumours were remarkable for a having mean PI of about twice that of the benign tissue (2.9 and 1.3, respectively, P < 0.01); the NEC in these cases were more frequent in the benign than in the malignant tissue. There was no significant difference between the mean PIs and the mean percentages of NEC in the 14 HGHS tumours that progressed and the nine HGHS tumours that did not (P values 0.37-0.96). Although the PI assessed by MIB-1 and the number of NEC-positive cells were much higher in HGHS than LGLS tumours, this finding did not appear to have independent prognostic significance. The significance of the higher PI in LGLS tumours than in corresponding benign tissue is uncertain; LGLS tumours had fewer NEC than the surrounding benign tissue. The quantification of any of these four markers (MIB-1, NSE, ChA, Syn) was not prognostically helpful in these groups of cancers present in TURP specimens.