Carolyn C. Compton

The American Joint Committee on Cancer: the 7th Edition of the AJCC Cancer Staging Manual and the Future of TNM

The American Joint Committee on Cancer and the International Union for Cancer Control update the tumor–node–metastasis (TNM) cancer staging system periodically. The most recent revision is the 7th edition, effective for cancers diagnosed on or after January 1, 2010. This editorial summarizes the background of the current revision and outlines the major issues revised. Most notable are the marked increase in the use of international datasets for more highly evidenced-based changes in staging, and the enhanced use of nonanatomic prognostic factors in defining the stage grouping. The future of cancer staging lies in the use of enhanced registry data standards to support personalization of cancer care through cancer outcome prediction models and nomograms.

Permanent coverage of large burn wounds with autologous cultured human epithelium

WHEN burns are so extensive that skin grafts obtainable from remaining donor sites are insufficient to provide wound coverage, a new source of autograft must be found. Human epidermal cells from a ...

Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999.

BACKGROUND Under the auspices of the College of American Pathologists, the current state of knowledge regarding pathologic prognostic factors (factors linked to outcome) and predictive factors (factors predicting response to therapy) in colorectal carcinoma was evaluated. A multidisciplinary group of clinical (including the disciplines of medical oncology, surgical oncology, and radiation oncology), pathologic, and statistical experts in colorectal cancer reviewed all relevant medical literature and stratified the reported prognostic factors into categories that reflected the strength of the published evidence demonstrating their prognostic value. Accordingly, the following categories of prognostic factors were defined. Category I includes factors definitively proven to be of prognostic import based on evidence from multiple statistically robust published trials and generally used in patient management. Category IIA includes factors extensively studied biologically and/or clinically and repeatedly shown to have prognostic value for outcome and/or predictive value for therapy that is of sufficient import to be included in the pathology report but that remains to be validated in statistically robust studies. Category IIB includes factors shown to be promising in multiple studies but lacking sufficient data for inclusion in category I or IIA. Category III includes factors not yet sufficiently studied to determine their prognostic value. Category IV includes factors well studied and shown to have no prognostic significance. MATERIALS AND METHODS The medical literature was critically reviewed, and the analysis revealed specific points of variability in approach that prevented direct comparisons among published studies and compromised the quality of the collective data. Categories of variability recognized included the following: (1) methods of analysis, (2) interpretation of findings, (3) reporting of data, and (4) statistical evaluation. Additional points of variability within these categories were defined from the collective experience of the group. Reasons for the assignment of an individual prognostic factor to category I, II, III, or IV (categories defined by the level of scientific validation) were outlined with reference to the specific types of variability associated with the supportive data. For each factor and category of variability related to that factor, detailed recommendations for improvement were made. The recommendations were based on the following aims: (1) to increase the uniformity and completeness of pathologic evaluation of tumor specimens, (2) to enhance the quality of the data needed for definitive evaluation of the prognostic value of individual prognostic factors, and (3) ultimately, to improve patient care. RESULTS AND CONCLUSIONS Factors that were determined to merit inclusion in category I were as follows: the local extent of tumor assessed pathologically (the pT category of the TNM staging system of the American Joint Committee on Cancer and the Union Internationale Contre le Cancer [AJCC/UICC]); regional lymph node metastasis (the pN category of the TNM staging system); blood or lymphatic vessel invasion; residual tumor following surgery with curative intent (the R classification of the AJCC/UICC staging system), especially as it relates to positive surgical margins; and preoperative elevation of carcinoembryonic antigen elevation (a factor established by laboratory medicine methods rather than anatomic pathology). Factors in category IIA included the following: tumor grade, radial margin status (for resection specimens with nonperitonealized surfaces), and residual tumor in the resection specimen following neoadjuvant therapy (the ypTNM category of the TNM staging system of the AJCC/UICC). (ABSTRACT TRUNCATED)

Pancreatic intraepithelial neoplasia: a new nomenclature and classification system for pancreatic duct lesions.

Proliferative epithelial lesions in the smaller caliber pancreatic ducts and ductules have been the subject of numerous morphologic, clinical, and genetic studies; however, a standard nomenclature and diagnostic criteria for classifying these lesion have not been established. To evaluate the uniformity of existing systems for grading duct lesions in the pancreas, 35 microscopic slides with 35 representative duct lesions were sent to eight expert pathologists from the United States, Canada, and Europe. Kappa values for interobserver agreement could not be calculated initially because more than 70 different diagnostic terms were used by the eight pathologists. In several cases, the diagnoses rendered for a single duct lesion ranged from “hyperplasia,” to “metaplasia,” to “dysplasia,” to “carcinoma in situ.” This review therefore demonstrated the need for a standard nomenclature and classification system. Subsequently, during a working group meeting, the pathologists agreed to adopt a single standard system. The terminology pancreatic intraepithelial neoplasia (or PanIN) was selected, and diagnostic criteria for each grade of PanIN were established (http://pathology.jhu.edu/pancreas_panin). This new system was then evaluated by having the eight pathologists rereview the original 35 cases. Only seven different diagnoses were rendered, and kappa values of 0.43, 0.14, and 0.42 were obtained for PanINs 1, 2, and 3 respectively. Cases assigned other diagnoses (e.g., squamous metaplasia) collectively had a kappa value of 0.41. These results show both the potential of the classification system, and also the difficulty of classifying these lesions even with a consistent nomenclature. However, even when there is lack of consensus, having a restricted set of descriptions and terms allows a better understanding of the reasons for disagreement. It is suggested that we adopt and apply this system uniformly, with continued study of its reliability and use, and possibly further refinement. The acceptance of a standard classification system will facilitate the study of pancreatic duct lesions, and will lead ultimately to a better understanding of their biologic importance.

An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms

Invasive pancreatic ductal adenocarcinoma is an almost uniformly fatal disease. Several distinct noninvasive precursor lesions can give rise to invasive adenocarcinoma of the pancreas, and the prevention, detection, and treatment of these noninvasive lesions offers the potential to cure early pancreatic cancers. Noninvasive precursors of invasive ductal adenocarcinoma of the pancreas include pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms. Diagnostic criteria, including a distinct ovarian-type stroma, and a consistent nomenclature are well established for mucinous cystic neoplasms. By contrast, consistent nomenclatures and diagnostic criteria have been more difficult to establish for PanINs and IPMNs. Because both PanINs and IPMNs consist of intraductal neoplastic proliferations of columnar, mucin-containing cells with a variable degree of papilla formation, the distinction between these two classes of precursor lesions remains problematic. Thus, considerable ambiguities still exist in the classification of noninvasive neoplasms in the pancreatic ducts. A meeting of international experts on precursor lesions of pancreatic cancer was held at The Johns Hopkins Hospital from August 18 to 19, 2003. The purpose of this meeting was to define an international acceptable set of diagnostic criteria for PanINs and IPMNs and to address a number of ambiguities that exist in the previously reported classification systems for these neoplasms. We present a consensus classification of the precursor lesions in the pancreatic ducts, PanINs and IPMNs.

Treatment of intrahepatic malignancy with radiofrequency ablation: radiologic-pathologic correlation.

Radiofrequency (RF)‐induced tissue coagulation represents a new approach for the thermal destruction of tumors within the liver. The purpose of the current study was to 1) assess technique safety; 2) determine the extent and evolution of induced cellular damage; and 3) correlate the observed pathologic effects with radiologic studies.

A Better Model of Acute Pancreatitis for Evaluating Therapy

Existing models of acute pancreatitis have limitations to studying novel therapy. Whereas some produce mild self-limited pancreatitis, others result in sudden necrotizing injury. The authors developed an improved model providing homogeneous moderately severe injury by superimposing secretory hyperstimulation on minimal intraductal bile acid exposure. Sprague-Dawley rats (n = 231) received low-pressure intraductal glycodeoxycholic acid (GDOC) at very low (5 or 10 mmol/L) concentrations followed by intravenous cerulein. Cerulein or GDOC alone caused only very mild inflammation. However, GDOC combined with cerulein was uniformly associated with more edema (p less than 0.0005), acinar necrosis (p less than 0.01), inflammation (p less than 0.006), and hemorrhage (p less than 0.01). Pancreatic injury was further increased and death was potentiated by increasing volume and duration of intraductal low-dose GDOC infusion. There was significant morphologic progression between 6 and 24 hours. The authors conclude that (1) combining minimal intraductal bile acid exposure with intravenous hyperstimulation produces homogeneous pancreatitis of intermediate severity that can be modulated at will; (2) the injury is progressive over at least 24 hours with finite mortality rate; (3) the model provides superior opportunity to study innovative therapy.

PERCUTANEOUS RADIOFREQUENCY TISSUE ABLATION : DOES PERFUSION-MEDIATED TISSUE COOLING LIMIT COAGULATION NECROSIS ?

PURPOSE To determine, by decreasing hepatic perfusion during radiofrequency (RF) ablation, whether perfusion-mediated tissue cooling can explain the reduced coagulation observed in in vivo studies compared to that seen with RF application in ex vivo tissue. MATERIALS AND METHODS RF was applied in vivo with use of cooled-tip electrodes to normal porcine liver without (n = 8) and with balloon occlusion of the portal vein (n = 8), celiac artery (n = 3), or hepatic artery (n = 2), and to ex vivo calf liver (n = 10). In vivo trials of vasopressin (0.3-0.6 U/min) infusion during RF application with (n = 10) and without (n = 2) arterial balloon occlusion were also performed. Intraoperative RF was subsequently performed in seven patients with hepatic colorectal metastases with and without portal inflow occlusion. Remote thermometry was performed in four patients. RESULTS RF application (12 minutes) during portal venous occlusion produced larger areas of coagulation necrosis than RF with unaltered blood flow (2.9 cm +/- 0.1 vs 2.4 cm +/- 0.2 diameter; P < .01). With celiac and hepatic artery occlusion, coagulation diameter measured 2.7 cm +/- 0.2 and 2.5 cm +/- 0.1, respectively. Infusion of vasopressin without vascular occlusion reduced coagulation diameter to 1.1 cm. However, different methods of hepatic or celiac arterial balloon occlusion with simultaneous vasopressin infusion produced a mean 3.4 cm +/- 0.2 of necrosis. Coagulation in ex vivo liver was 2.9 cm +/- 0.1 in diameter. Clinical studies demonstrated greater coagulation diameter for metastases treated during portal inflow occlusion (4.0 cm +/- 1.3) than for tumors treated with normal blood flow (2.5 cm +/- 0.8; P < .05). Thermometry documented a 10 degrees C increase compared to baseline at 10 mm and 20 mm from the electrode after 5 minutes of portal inflow occlusion during constant RF application. CONCLUSIONS Perfusion-mediated tissue cooling reduces coagulation necrosis achievable with RF ablation. Reduction of blood flow during RF application increases coagulation in both an animal model and human liver metastases.

Cystic Tumors of the Pancreas

Cystic neoplasms of the pancreas are rare but in the last years more frequently detected. Within a 10-year-period we treated 30 patients, including 8 serous cystadenomas, 6 mucinous cystadenomas, 12 mucinous cystadenocarcinomas, 2 cystic neuro-endocrine tumors and 1 papillary cystic tumor respectively acinar cell cyst-adenocarcinoma. 80% of the patients had symptoms, experienced abdominal pain, weight loss, weakness or abdominal mass. In eight patients the tumors had been misdiagnosed as a pancreatic pseudocyst. The correct type of cystic tumor was diagnosed by preoperative investigations only a few cases. All patients with serous or mucinous cystadenomas are well and without evident recurrence after resection of the tumor. However the survival time of malignant cystic tumors varied strongly. The curative resection of these tumors give patients the chance of long-term survival.

American Joint Committee on Cancer Prognostic Factors Consensus Conference: Colorectal Working Group.

The American Joint Committee on Cancer (AJCC), which regularly reviews TNM staging systems, established a working party to develop recommendations for colorectal carcinoma.