Gritti-Stokes (through-knee) amputation: should it be reintroduced?

BACKGROUND: When there is doubt about perfusion in the distal part of the leg and around the ankle, an above-knee amputation (AKA) site has been the most commonly selected to assure primary wound healing. METHODS: The Gritti-Stokes amputation (GSA), a modified through-knee amputation, seems to have value for selected patients, according to a literature review and our success in a small group of patients. We have investigated the proportion of patients who have had AKA and who might have been suitable candidates for GSA. RESULTS: In a retrospective study of 66 patients who had had AKA, at least one third could have been considered for a GSA and might have benefitted from this procedure. This suggests that some consideration should be given to the reintroduction of the Gritti-Stokes operation. CONCLUSION: Our expectation is that patients so treated could achieve a high proportion of primary wound healing, an end-bearing stump, and more rapid rehabilitation than found in patients undergoing the classic AKA.

College of American Pathologists Conference XXXV: solid tumor prognostic factors-which, how and so what? Summary document and recommendations for implementation. Cancer Committee and Conference Participants.

The College of American Pathologists convened a prognostic factor conference in June 1999 to consider prognostic and predictive factors in breast, colon, and prostate cancer, and to stratify these factors into categories reflecting the strength of published evidence. Because so little progress in prognostic factor clinical utility has been made in the last 5 years, the conference participants focused their attention on decreasing variation in methods, interpretation, and reporting of these factors so that greater clarity of value could be achieved. The conference was organized to promote discussion, broad input, and future planning. An initial plenary session provided an overview of the status of tumor marker research, the impact of variation in medicine and pathology, and statistical issues related to prognostic factor research. In working group sessions for each cancer type, participants interactively evaluated and refined the documents created by the expert panels. A second plenary session dealt with issues common to all 3 groups, including the problem of micrometastases in lymph nodes in these sites; statistical issues that arose during the breakout discussions; and issues of variation in methods, interpretation, and reporting of immunohistochemical assays. A faculty session brainstormed strategies that could be used to implement the changes recommended. This session included invited representatives of the Food and Drug Administration, Health Care Financing Administration, Centers for Disease Control and Prevention, National Cancer Institute, American Joint Committee on Cancer, and International Union Against Cancer. Cancer site and general recommendations were presented and discussed during a final session to achieve consensus of the conference participants and to address feasibility of implementation of these recommendations. A final discussion focused on future initiatives that might lead to implementation of the changes proposed in the conference by the various organizations represented. This report summarizes the general conference recommendations, cancer working group recommendations, and plans for implementation of the recommendations.

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)

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

BACKGROUND: The American Joint Committee on Cancer (AJCC), which regularly reviews TNM staging systems, established a working party to develop recommendations for colorectal carcinoma. METHODS: A multidisciplinary consensus conference using published literature developed an arbitrary classification system of prognostic marker value (Category I, IIA, IIB, III, and IV), which forms the framework for this report. RESULTS: The working party concluded that several T categories should be subdivided: pTis into intraepithelial carcinoma (pTie) and intramucosal carcinoma (pTim); pT1 into pT1a and pT1b corresponding to the absence or presence of blood or lymphatic vessel invasion, respectively; and pT4 into pT4a and pT4b according to the absence or presence of tumor involving the surface of the specimen, respectively. The working party also recommended that TNM groups be stratified based on the presence or absence of elevated serum levels of carcinoembryonic antigen (CEA) (>/= 5 ng/mL) on preoperative clinical examination. In addition, the working party also concluded that carcinoma of the appendix should be excluded from the colorectal carcinoma staging system because of fundamental differences in natural history. CONCLUSIONS: The TNM categories and stage groupings for colorectal carcinoma published in the current AJCC manual have clinical and academic value. However, a few categories require subdivision to provide increasing discrimination for individual patients. The serum marker CEA should be added to the staging system, whereas multiple other factors should be recorded as part of good clinical practice. Although many molecular and oncogenic markers show promise to supplement or modify the current staging systems eventually, to the authors' knowledge none have yet been evaluated sufficiently to recommend their inclusion in the TNM system.

American Joint Committee on Cancer prognostic factors consensus conference.

BACKGROUND: The American Joint Committee on Cancer (AJCC) published the 1st edition of the Cancer Staging Manual in 1977 and began using T (tumor extent), N (regional lymph node status), and M (the presence or absence of distant metastasis) in an organized staging scheme to express the extent of disease in a number of cancer sites. The goal of this program has been to provide physicians and others with a useful methodology to plan treatment, project prognosis, and measure outcome end results. Until recent years, this system has incorporated only elements of anatomic extent of the tumors determined by clinical and pathologic methods. At the present time an increasing number of nonanatomic cancer prognostic factors are being identified and studied. Some of these factors currently are being used for outcome predictions and treatment decisions. METHODS: To begin the process of identifying and validating these prognostic factors to refine the present TNM system, the AJCC convened a Prognostic Factors Consensus Conference to evaluate the roles of biologic, genetic, molecular, and other nonanatomic factors in staging cancer. Working groups were appointed for carcinomas of the breast, colorectum, prostate, and ovary and experts in each of these areas were invited to participate. Emphasis was placed on evaluating existing data and the correlation of these data with survival. RESULTS: None of the groups believed that there were sufficient data at the present time to merit incorporation of serum markers into the TNM system for the four tumors under consideration, although this soon might become possible in prostate carcinoma after the evaluation of survival data from multiple institutions. Recommendations were made regarding the emerging sentinel lymph node technique, the need for an increased use of histopathology in the staging of breast and ovarian carcinomas, and the use of additional histologic staining techniques for the detection of "micrometastases" in lymph nodes. A number of additional recommendations were made for changes to the TNM system that did not involve serum markers and other nonanatomic cancer prognostic factors. CONCLUSIONS: These recommendations are presented for the purpose of discussion and evaluation and do not yet represent formal proposals for a change in the AJCC TNM system of staging.

College of American Pathologists Conference XXVI on clinical relevance of prognostic markers in solid tumors. Report of the Colorectal Cancer Working Group.

The College of American Pathologists Conference XXVI in June 1994 was devoted to a discussion of the clinical relevance of prognostic factors in three solid tumors (breast, prostate, and colorectal). The group considering prognostic factors for adenocarcinoma of the large gut consisted of 15 pathologists, investigators, and surgeons. The group concluded that only a few items are well supported in the existing literature and can be recommended for routine clinical use at this time (pathologic TNM information and stage, tumor type, tumor grade, extramural venous invasion, and preoperative serum carcinoembryonic antigen level). According to the classification system used at the conference, these markers warrant categorization as important prognostic factors (category I). A few factors should be considered as potentially useful after further study (category II). Furthermore, the group agreed that all other current measurements of so-called prognostic factors do not warrant the same recognition of importance, either because they have been studied insufficiently or studies have demonstrated that they do not contribute to prognostication. These additional items were placed in category III. It was also concluded that the statistical methods used to identify and validate prognostic markers, as well as their integration into single statements of prognosis need further national evaluation and standardization.

The association between melanoma, lymphoma, and other primary neoplasms.

BACKGROUND AND OBJECTIVE: Reports of multiple primary tumors are not new. However, we have noted a disproportionate number of patients with melanoma in whom lymphoma develops and wanted to define the incidence of this association. DESIGN: All 664 patients with melanoma treated at Yale-New Haven Hospital, Conn, during the 5-year period from 1986 to 1991 were reviewed. The incidence of all the associated malignant neoplasms among our patients with melanoma was compared with the incidence that would be expected in the normal population adjusted for age, race, and sex. RESULTS: Among the 664 patients, 54 (8.1%) had one or more additional malignant neoplasms. Of the 10 different malignant tumor types recorded, lymphomas were the most prevalent. This incidence of lymphoma among the melanoma patients was 12 of 664, resulting in an incidence of 548 per 100,000 population, 16 times higher (P < .0125) than the expected incidence (34 per 100,000) when adjusted for age, sex, and race. CONCLUSIONS: The incidence of a second malignant neoplasm in our patients with melanoma was 8.1%. Lymphoma was a particularly common type of second malignancy, showing an incidence more than 16-fold higher than that expected in the normal population. It is particularly important, from a clinical point of view, to be aware of this when clinically palpable lymph nodes develop in areas not normally the site of regional lymphatic drainage of the primary melanoma.

PYY inhibition of VIP-stimulated ion transport in the rabbit distal ileum.

Vasoactive intestinal polypeptide (VIP) is the pathophysiologic mediator of several small intestinal hypersecretion states. VIP exerts its effect by binding mucosal receptors and ultimately increasing intracellular levels of cAMP. Peptide YY (PYY), a GI hormone concentrated in the distal ileum and colon, has been demonstrated to decrease VIP-mediated secretion in the colon through a specific Y4 mucosal receptor. Characterization of PYY's effect on VIP-stimulated small intestinal secretion may provide a basis for future therapeutic interventions. We hypothesized that ion transport in the small intestine is mediated through a novel Y receptor subtype. We performed Ussing chamber ion transport studies on rabbit ileum using VIP, PYY, and other pancreatic polypeptide (PP)-fold peptides in order to specifically examine: (1) the effects of VIP and PYY on basal and VIP-stimulated short circuit current (Isc), and (2) the changes in VIP-stimulated Isc in response to NPY, PP, leucine31,proline31 neuropeptide Y fragment, ([Leu31,Pro34]NPY) and the carboxy-terminal fragment of NPY (NPY13-36). VIP increased basal Isc in a concentration-dependent manner, while PYY decreased basal Isc. Graded concentrations of PYY decreased VIP-stimulated increases in Isc. PYY added prior to VIP had no effect on VIP-stimulated increases in ISC. Inhibition of VIP-stimulated Isc increases was seen with NPY, but not with [Leu31,Pro34]NPY, PP, or NPY13-36. This distinct pattern of binding affinity characterizes a novel Y receptor subtype. Additionally, increases in Isc by VIP despite pretreatment with PYY suggests that VIP-stimulated ion transport is mediated through mechanisms other than increases in cAMP.

Inhibition of VIP-stimulated ion transport by a novel Y-receptor phenotype in rabbit distal colon.

Neurocrine, endocrine, and paracrine regulators are critical to the control of colonic secretion. These studies have investigated the inhibition of vasoactive intestinal polypeptide (VIP)-stimulated ion transport by peptide YY (PYY) and other Y-class effectors in rabbit distal colonic mucosa mounted in Ussing chambers. PYY decreased basal short-circuit current (Isc) but did not significantly change either basal Na+ or Cl- flux. PYY inhibited VIP-stimulated increases in Isc by up to 86% and abolished VIP-induced Cl- secretion. PYY decreased VIP-generated increases in Isc by a tetrodotoxin-insensitive mechanism. PYY inhibited cholera toxin-stimulated as well as forskolin-stimulated increases in Isc but failed to alter stimulation by 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP). PYY decreased VIP-stimulated increases in tissue cAMP by 88% and forskolin-stimulated increases by 84%. PYY, neuropeptide Y (NPY), (Leu31,Pro34)-NPY, and pancreatic polypeptide (PP) all demonstrated potent inhibition of VIP-stimulated increases in Isc. PYY-(13-36) demonstrated little effect on VIP stimulation. Thus the rabbit distal colon possesses a novel Y-class receptor phenotype that demonstrates high affinity for all three PP-fold peptides, NPY, PYY, and PP.

Multiple prognostic factors and outcome analysis in patients with cancer. Communication from the American Joint Committee on Cancer.

The authors report the establishment of a new Committee of the American Joint Committee on Cancer that has two objectives as follows: (1) to review the methods available to estimate outcome and (2) to study certain tumors to determine whether an expanded list of prognostic factors can be formulated into new prognostic systems that will have scientific value and clinical utility for treatment selection and staging.