A simplified prognostic system for resected pancreatic neuroendocrine neoplasms

Background:

A number of prognostically relevant clinicopathological variables have been proposed for pancreatic neuroendocrine neoplasms. However, a standardized prognostication system has yet to be established for patients undergoing potentially curative tumour resection.

Methods:

We examined a prospectively maintained, single-institution database to identify patients who underwent potentially curative resection of non-metastatic primary pancreatic neuroendocrine neoplasms. Patient, operative and pathological characteristics were analysed to identify variables associated with disease-specific and disease-free survival.

Results:

Between 1991 and 2007, 43 patients met inclusion criteria. After a median follow-up of 68 months, 5-year disease-specific survival was 94% and 5-year disease-free survival was 72%. Tumours sized ≥5 cm and vascular invasion were associated with worse disease-specific survival. Tumours sized ≥5 cm, nodal metastases, positive resection margins and perineural invasion were associated with worse disease-free survival. A scoring system consisting of tumour size ≥5 cm, histological grade, nodal metastases and resection margin positivity (SGNM) permitted stratification of disease-specific (P= 0.006) and disease-free (P= 0.0004) survival. This proposed scoring system demonstrated excellent discrimination of individual disease-specific and disease-free survival outcomes as reflected by concordance indices of 0.814 and 0.794, respectively.

Conclusions:

A simple scoring system utilizing tumour size, histological grade, nodal metastases and resection margin status can be used to stratify outcomes in patients undergoing resection of primary pancreatic neuroendocrine neoplasms.     

Routine Evaluation of the Distal Colon Remnant Before Hartmann’s Reversal is Not Necessary in Asymptomatic Patients

Background  

Reversal of Hartmann’s is a common surgical procedure. Routine preoperative evaluation of the distal colonic/rectal remnant (DCRR) with contrast and/or endoscopic studies is frequently performed despite lack of evidence to support this practice. We hypothesize that asymptomatic patients can safely undergo Hartmann’s reversal without preoperative DCRR evaluation.     

Proliferation, hyperplasia, neogenesis, and neoplasia in the islets of Langerhans

Pancreatic disease is responsible for significant morbidity and mortality as a result of pancreatic carcinoma and diabetes mellitus. Regulation of endocrine cell mass is thought to have a central role in the pathogenesis of both these diseases. Islet cell proliferation, hypertrophy, neogenesis, and apoptosis are the main determinants of endocrine cell mass in the pancreas, and their understanding has been improved by new clues of their genetic and molecular basis. Beta cells have attracted most research interest because of potential implications in the treatment of diabetes mellitus and hypoglycemic disorders. The processes that operate during pancreatic adaptation to a changing hormonal milieu are important in pancreatic carcinogenesis. There is evidence that somatostatin and its receptors are fundamental regulators of endocrine cell mass and are involved in islet tumorigenesis.     

Simultaneous assessment of pulsating and total blood in inflammatory skin lesions using functional diffuse reflectance spectroscopy in the visible range

We present a simple and cost-effective optical technique for the simultaneous assessment of pulsating and total blood noninvasively in an inflammatory skin lesion. Acquisitions of diffuse reflectance spectra in the visible range at 6 Hz are used to trace the oscillating components of reflectance. Measurements on erythematous lesions from a UV insult show slow changing signal at about 0.1 Hz and heart-driven regular oscillations at about 1 Hz simultaneously. The results demonstrate the potential of the technique in monitoring both pulsating and steady components of the blood in inflammatory lesions of the skin.     

Wavelength effects on contrast observed with reflectance in vivo confocal laser scanning microscopy

Background/purpose: The ability to optically section live biological tissue in vivo with laser light is made possible by confocal laser scanning microscopy (CLSM). In this work, the effects of changing the wavelength of incident light used for CLSM imaging of human skin are reported and analyzed.
Methods: Optical phantoms and the skin of eight human volunteers were imaged using CLSM systems having three different incident light wavelengths (405, 785, and 830 nm).
Results: Qualitative and quantitative differences were observed between images obtained at each wavelength, despite the proximity of the two near infrared 785 and 830 nm wavelengths. Furthermore, the penetration depth achieved with the 405 nm CLSM permitted imaging into the papillary dermis.
Conclusion: The laser wavelength used in CLSM reflectance imaging is important to properly understand and resolve different biological structures within human skin.     

Metaphase and interphase cytogenetics in fibroadenomas of the breast

Short-term cultures of fifty-two samples of fibroadenomas were cytogenetically analyzed. Thirty-three of the successfully karyotyped fibroadenomas were further investigated for the presence of amplifications in the CCND1, c-MYC and HER/2-neu genes by means of FISH analysis. Compared to carcinomas, fibroadenomas seem to have less complex cytogenetic rearrangements and limited alterations on HER-2/neu, CCND1 and c-MYC loci. A cytogenetic subgroup of fibroadenomas with hyperdiploid karyotypes and only numerical changes was observed. Amplification of CCND1 seems to play a more substantial role in benign tumor progression. These findings confirm that fibroadenomas do have genetic alterations and support the hypothesis that a fibroadenoma subset displays changes also found in carcinomas, thus indicating that patients belonging to this group might have an increased risk for subsequent breast cancer.     

Discrepancies in current practice of pathological evaluation of sentinel lymph nodes in breast cancer. Results of a questionnaire based survey by the European Working Group for Breast Screening Pathology

AIMS: To evaluate aspects of the current practice of sentinel lymph node (SLN) pathology in breast cancer via a questionnaire based survey, to recognise major issues that the European guidelines for mammography screening should address in the next revision. METHODS: A questionnaire was circulated by mail or electronically by the authors in their respective countries. Replies from pathology units dealing with SLN specimens were evaluated further. RESULTS: Of the 382 respondents, 240 European pathology units were dealing with SLN specimens. Sixty per cent of these units carried out intraoperative assessment, most commonly consisting of frozen sections. Most units slice larger SLNs into pieces and only 12% assess these slices on a single haematoxylin and eosin (HE) stained slide. Seventy one per cent of the units routinely use immunohistochemistry in all cases negative by HE. The terms micrometastasis, submicrometastasis, and isolated tumour cells (ITCs) are used in 93%, 22%, and 71% of units, respectively, but have a rather heterogeneous interpretation. Molecular SLN staging was reported by only 10 units (4%). Most institutions have their own guidelines for SLN processing, but some countries also have well recognised national guidelines. CONCLUSIONS: Pathological examination of SLNs throughout Europe varies considerably and is not standardised. The European guidelines should focus on standardising examination. They should recommend techniques that identify metastases > 2 mm as a minimum standard. Uniform reporting of additional findings may also be important, because micrometastases and ITCs may in the future be shown to have clinical relevance.     

Consistency achieved by 23 European pathologists from 12 countries in diagnosing breast disease and reporting prognostic features of carcinomas

 A detailed analysis of the consistency with which pathologists from 12 different European countries diagnose and classify breast disease was undertaken as part of the quality assurance programme of the European Breast Screening Pilot Network funded by the Europe against Cancer Programme. Altogether 107 cases were examined by 23 pathologists in 4 rounds. Kappa (κ) statistics for major diagnostic categories were: benign (not otherwise specified) 0.74, atypical ductal hyperplasia (ADH) 0.27, ductal carcinoma in situ (DCIS) 0.87 and invasive carcinoma 0.94. ADH was the majority diagnosis in only 2 cases but was diagnosed by at least 2 participants in another 14, in 9 of which the majority diagnosis was benign (explaining the relatively low κ for this category), DCIS in 4 (all low nuclear grade) and invasive carcinoma (a solitary 1-mm focus) in 1. The histological features of these cases were extremely variable; although one feature that nearly all shared was the presence of cells with small, uniform, hyperchromatic nuclei and a high nucleo-cytoplasmic ratio. The majority diagnosis was DCIS in 33 cases; κ for classifying by nuclear grade was 0.38 using three categories and 0.46 when only two (high and other) were used. When ADH was included with low nuclear grade DCIS there was only a slight improvement in κ. Size measurement of DCIS was less consistent than that of invasive carcinoma.The majority diagnosis was invasive carcinoma in 57 cases, the size of the majority being 100% in 49. The remainder were either special subtypes (adenoid cystic, tubular, colloid, secretory, ductal/medullary) or possible microinvasive carcinomas. Subtyping was most consistent for mucinous (κ, 0.92) and least consistent for medullary carcinomas (κ, 0.56). Consistency of grading using the Nottingham method was moderate (κ=0.53) and consistency of diagnosing vascular invasion, fair (κ=0.38). There was no tendency for consistency to improve from one round to the next, suggesting that further improvements are unlikely without changes in guidelines or methodology.