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Preoperative magnetic resonance imaging (MRI) allows highly reliable imaging of the mesorectal fascia (mrMRF) and its relationship to the tumor. The prospective multicenter observational study OCUM uses these findings to indicate neoadjuvant chemoradiotherapy (nCRT) in rectal carcinoma. nCRT was indicated in patients with positive mrMRF (≤ 1 mm) in cT4 and cT3 carcinomas of the lower rectal third. A total of 527 patients (60.2%) underwent primary total mesorectal excision, and 348 patients (39.8%) underwent long-term nCRT followed by surgery. The mrMRF was involved in 4.6% of the primary surgery group and 80.7% of the nCRT group. Rates of resections within the mesorectal plane (90.8%), sparing of pelvic nerves on both sides (97.8%), and number of regional lymph nodes (95.3% with ≥ 12 lymph nodes examined) are indicative of high-quality surgery. Resection was classified as R0 in 98.3%, the pathological circumferential resection margin (pCRM) was negative in 95.1%. Patients in the nCRT group had more advanced carcinomas with a significantly higher rate of abdominoperineal excision. Independent risk factors for pCRM positivity were advanced stage (T4), metastatic lymph nodes, resection in the muscularis propria plane, and location in the lower third. The risk classification of rectal cancer patients by MRI seems to be highly reliable and allows the restriction of nCRT to approximately half of the patients with clinical stage II and III rectal carcinoma, provided there is a high-quality MRI diagnostic protocol, high-quality surgery, and standardized examination of the resected specimen.

Background Neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer carries a high risk of adverse effects. The aim of this study was to examine the selective application of nCRT based on patient risk profile, as determined by MRI, to find the optimal range between undertreatment and overtreatment. Study Design In this prospective multicenter observational study, nCRT before total mesorectal excision (TME) was indicated in high-risk patients with involved or threatened mesorectal fascia (≤1 mm), or cT4 or cT3 carcinomas of the lower rectal third. All other patients received primary surgery. Results Of the 1,093 patients, 878 (80.3%) were treated according to the protocol, 526 patients (59.9%) underwent primary surgery, and 352 patients (40.1%) underwent nCRT followed by surgery. The 3-year locoregional recurrence (LR) rate was 3.1%. Of 604 patients with clinical stages II and III, 267 (44.2%) had primary surgery; 337 (55.8%) received nCRT followed by TME. The 3-year LR rate was 3.9%, without significant differences between groups. In patients with clinical stages II and III who underwent primary surgery, 27.3% were diagnosed with pathological stage I. Conclusions The results justify the restriction of nCRT to high-risk patients with rectal cancer classified by pretreatment MRI. Provided that a high-quality MRI diagnosis, TME surgery, and standardized examination of the resected specimen are performed, nCRT, with its adverse effects, costs, and treatment time can be avoided in more than 40% of patients with stage II or III rectal cancer with minimal risk of undertreatment. ( clinicaltrials.gov NCT325649)

Background It is not clear whether all patients with rectal cancer need chemoradiotherapy. A restrictive use of neoadjuvant chemoradiotherapy (nCRT) based on MRI findings for rectal cancer was investigated in this study. Methods This prospective multicentre observational study included patients with stage cT2–4 rectal cancer, with any cN and cM0 status. Carcinomas in the middle and lower third that were 1 mm or less from the mesorectal fascia, all cT4 tumours, and all cT3 tumours of the lower third were classified as high risk, and these patients received nCRT followed by total mesorectal excision (TME). All other carcinomas with a minimum distance of more than 1 mm from the mesorectal fascia and those in the upper third were classified as low risk; these patients underwent TME alone (no nCRT). Patients were followed for at least 3 years. Outcomes were the rates of local recurrence, distant metastasis and survival. Results Among 545 patients included, 428 were treated according to the study protocol: 254 (59·3 per cent) had TME alone and 174 (40·7 per cent) received nCRT and TME. Median follow-up was 60 months. The 3- and 5-year local recurrence rates were 1·3 and 2·7 per cent respectively, with no differences between the two treatment protocols. Patients with disease requiring nCRT had higher 3- and 5-year rates of distant metastasis (17·3 and 24·9 per cent respectively versus 8·9 and 14·4 per cent in patients who had TME alone; P = 0·005) and worse disease-free survival compared with that in patients who did not need nCRT (3- and 5-year rates 76·7 and 66·7 per cent, versus 84·9 and 76·0 per cent in the TME-alone group; P = 0·016). Conclusion Restriction of nCRT to high-risk patients achieved good results.

Introduction of total mesorectal excision (TME) surgery for rectal cancer decreased local recurrence dramatically. Additional neoadjuvant chemoradiation (nCR) is frequently given in UICC II and III tumors based on TNM staging which is of limited accuracy. We aimed to evaluate determination of circumferential margin by magnetic resonance imaging (mrCRM) as an alternative criterium for nCR.Multicenter prospective cohort study which enrolled 642 patients in 13 centers with non-metastasized rectal adenocarcinoma. Patients with T4 tumors or patients with a mrCRM of 1 mm or less were treated by neoadjuvant chemoradiation. All others proceeded directly to surgery when inclusion criteria and no exclusion criteria were met. Quality of TME and accuracy of mrCRM determination were assessed during pathology workup.TME was complete in 381 of 389 patients after surgery without nCR (97.9%) and in 245 of 253 patients (96.8%) after nCR. Negative pathology circumferential margins (pCRM) were seen in 97.4% without nCR and in 89% of patients after nCR. Negative pCRM was predicted by negative mrCRM in 98.3% of rectal cancers. NCR was given to 253 of 642 patients (39.5%). Lymph node count was 23 (range 7-79; median/range) for surgery without nCR and 19 (range 2-56) for surgery after nCR.Surgical quality determined by pathology workup of specimen was very good in this study. Magnetic resonance imaging guided indication for nCR allows to achieve superb results concerning surrogate parameters for good oncological outcome. Thus, use of neoadjuvant chemoradiation with its potential detrimental side effects may be substantially reduced in selected patients.

Survival is an important indicator of outcome quality in rectal carcinoma. The 5-year survival rate is the typical outcome measurement. In patients with neoadjuvant chemoradiation followed by curative surgery, 7 years of follow-up is recommended. Different methods of survival analysis lead to different results. Here, we compared four different methods. The data of 439 patients with rectal carcinoma treated with neoadjuvant chemoradiation followed by curative total mesorectal excision (TME) surgery between 1995 and 2010 were analysed. After stratifying by stage, relative survival (RS), cancer-related survival (CRS), overall survival (OS) and disease-free survival (DFS) were compared. In particular, the 3-year disease-free survival rate was compared to the 5- and 7-year overall survival rates. In the total cohort, the 5-year survival rates ranged from 90% (RS), over 84% (CRS) and 83% (OS) to 72% (DFS). Depending on the stage of disease, the differences between the 5-year survival rates varied between 10 and 32 percentage points. The differences were lowest in UICC stage y0 and highest in UICC stage yIV. The 3-year DFS-rate was always lower (worse) than the 5-year OS rate and higher (better) than the 7-year OS rate, with the exception of stage yIV. Comparisons of survival are only meaningful if the same methods are applied. The 3-year rate of DFS was always worse than the rate of 5-year OS. Therefore, the 3-year rate of DFS appears to be a useful surrogate indicator in rectal carcinoma treatment studies.

For many years, the impact of the surgeon volume on short- and long-term outcome after rectal carcinoma surgery is controversially discussed. Literature and own department data were reviewed in order to clarify the impact of surgeon volume in the current era of total mesorectal excision surgery, multimodal therapy, quality management, and centralization of cancer care. Uni- and multivariate analysis of data from 1,028 patients with solitary rectal carcinoma, treated between 1995 and 2010 at the Department of Surgery, University Hospital, Erlangen, Germany, was performed. Surgeons were subdivided according to the number of operations/year into high- (at least seven/year), medium- (three to six), and low- (less than three) volume surgeons. Of 1,028 patients, 800 (77.8 %) were operated by five high-volume surgeons, 193 (18.8 %) by seven medium-volume surgeons, and 35 (3.4 %) by 12 low-volume surgeons. Surgeon volume was significantly associated with postoperative mortality and the rate of positive pathological circumferential resection margin. In risk-adjusted analysis, after primary surgery, surgeon volume had a significant impact on observed overall survival and disease-free survival, but not on locoregional recurrence. After neoadjuvant radiochemotherapy, only observed overall survival was significantly influenced by surgeon volume. In surgical departments with special interest in rectal carcinoma, surgeon volume has some influence on short- and long-term outcome. Irrespective of this fact, specialization, experience, individual skill, hospital organization, and regular quality assurance are essential prognostic factors ensuring good results in rectal carcinoma surgery.

A cohort study was carried out to analyse quality indicators in the diagnosis and treatment of rectal carcinoma.A total of 2,470 patients with rectal carcinoma treated between 1985 and 2007 at the Department of Surgery, University of Erlangen, were analysed and compared within four time intervals.Most of the indicators analysed from 2004 to 2007 fulfilled the defined target values. The indicators for process quality of surgical treatment and the surrogate indicators of outcome quality in surgery showed excellent results. Comparing this to previous data, it displays the new developments such as introduction of multimodal treatment for high-risk patients. While the rate of locoregional recurrences decreased, no significant improvement in survival was found.Careful analysis of quality indicators is important for both quality management and comparison of treatment results. The progress in diagnosis and treatment requires a continuous update of definitions and target values.

Is it possible to reduce the frequency of neoadjuvant therapy for rectal carcinoma and nevertheless achieve a rate of more than 90% circumferential resection margin (CRM)-negative resection specimens by a novel concept of magnetic resonance imaging (MRI)-based therapy planning?One hundred eighty-one patients from Berlin and Mainz, Germany, with primary rectal carcinoma, without distant metastasis, underwent radical surgery with curative intention. Surgical procedures applied were anterior resection with total mesorectal excision (TME) or partial mesorectal excision (PME; PME for tumours of the upper rectum) or abdominoperineal excision with TME.With MRI selection of the highest-risk cases, neoadjuvant therapy was given to only 62 of 181 (34.3%). The rate of CRM-negative resection specimens on histology was 170 of 181 (93.9%) for all patients, and in Berlin, only 1 of 93 (1%) specimens was CRM-positive. Patients selected for primary surgery had CRM-negative specimens on histology in 114 of 119 (95.8%). Those selected for neoadjuvant therapy had a lower rate of clear margin: 56 of 62 (90%).By applying a MRI-based indication, the frequency of neoadjuvant treatment with its acute and late adverse effects can be reduced to 30-35% without reduction of pathologically CRM-negative resection specimens and, thus, without the danger of worsening the oncological long-term results. This concept should be confirmed in prospective multicentre observation studies with quality assurance of MRI, surgery and pathology.

To obtain data on locoregional recurrence and survival rates in prognostically inhomogeneous pT3 rectal carcinomas we analyzed the data on 853 patients of the Erlangen Registry for Colo-Rectal Carcinomas (ERCRC) and 600 patients of the Study Group for Colo-Rectal Carcinoma (SGCRC), stage I–III, treated by radical surgery alone. The category pT3 was subdivided according to the histological measurement of the maximal tumor invasion beyond the outer border of the muscularis propria: pT3a (up to 5 mm) and pT3b (more than 5 mm). In the ERCRC locoregional recurrence rates were 10.4% (95% confidence interval 6.0–14.6) for pT3a and 26.3% (20.6–31.6) for pT3b (P

Increasingly, data are being accumulated on the influence of intersurgeon variability on outcome after curative surgical treatment of rectal carcinoma. Thus, today the individual surgeon has to be considered as an independent factor influencing locoregional recurrence, as well as survival rates. In general, higher local control and survival can be expected for specialized colorectal surgeons. There are no clear correlations between surgical volume and outcome. Interinstitutional variability in treatment results reflects intersurgeon variability, but analysis is generally more difficult because of a lack of homogeneity with respect to different confounding factors. There are several factors in surgical technique that are important for long-term outcome. Of greatest apparent importance is the adequacy of mesorectal excision (for carcinomas of the middle and lower third, total mesorectal excision; for carcinomas of the upper third, mesorectal excision down to a mesorectal plane 5 cm distal to the gross tumor margin detected by the surgeon in situ). Furthermore, intraoperative local tumor spillage (tumor perforation during mobilization, incision into the tumor), en bloc resection technique, skill, and the extent of regional lymphadenectomy may influence outcome. For quality assurance, detailed operative reports are required, as well as histopathology examinations concerning indicators of surgical oncologic quality discernable from the resection specimens. In future clinical trials of multimodal treatment of rectal cancer, quality assurance of surgery and pathology is necessary for consideration of the surgeon and surgical technique prognostic factors.

The prognosis of solid tumors is predominantly influenced by the anatomic extent before and after initial treatment. It is defined by the TNM/pTNM system and the residual tumor (R) classification as internationally agreed on and published by the International Union Against Cancer (UICC). However, there are several independent factors effective in prognosis in addition to TNM and R. Their identification is the first objective in prognostic factor research. Correctly applied multivariate methods appropriate for the specific situation play a key role. Cooperation between clinical oncologists and experienced medical statisticians is indispensable. Putative new prognostic factors have to be carefully evaluated before they can be accepted for general use in clinical oncology. In the future, we have to focus on the development of prognostic systems. Such systems integrate multiple independent prognostic factors with present staging (TNM, R) to improve the assessment of prognosis.

The value of grading tumor regression after neoadjuvant therapy of rectal carcinoma was evaluated.Analysis was carried out using prospective data of 225 patients with rectal carcinoma treated by neoadjuvant radiochemotherapy followed by radical resection with curative intent. For the histological regression grading, the method of Dworak et al. (1997) was used with a slight modification.After neoadjuvant radiochemotherapy, the most important prognostic factors are pathologically assessed circumferential resection margin, quality of surgery (plane of surgery), and the ypT and ypN classification. In addition, the histological regression grade of primary tumor and regional lymph nodes influence outcome, especially the local recurrence rate.After neoadjuvant therapy, the histological tumor regression grading should be assessed. A regression grading system based on the proposals of Dworak et al. (1997) is recommended.

Purpose: To study the accuracy of different cutoffs for an involved circumferential resection margin (CRM) compared with T and N categories measured by MRI as basis for selective application of neoadjuvant radiochemotherapy (nRCT) in rectal carcinoma. Materials and Methods: In a prospective multicenter observational study involving 153 primarily operated patients, the preoperative results of MRI with pathohistological findings of resected specimens were compared. Results: For a cutoff of ≤1 mm for involvement of the CRM, the accuracy of preoperative MRI was 90.9% (139/153). The negative predictive value was 98.5% (134/136). The four participating departments did not differ significantly. For a cutoff of >2 mm and >5 mm, the rates of false-positive findings increased significantly from 5% to 12% and 35% with a decrease in accuracy to 82% and 62%, respectively. In contrast, the accuracy in predicting T (69.3%) and N categories (61.4%) was much lower. Conclusion: The indication for nRCT should be based on the determination of the minimal distance of the tumor from mesorectal fascia with a cutoff point of >1 mm as measured by MRI. J. Magn. Reson. Imaging 2013;37:1122–1128. © 2013 Wiley Periodicals, Inc.

This study evaluated use of circumferential resection margin status in preoperative MRI (mrCRM) as an indication for neoadjuvant radiochemotherapy (nRCT) in rectal carcinoma patients.In a multicenter prospective study, nRCT was given to patients with carcinoma of the middle rectum with positive mrCRM (≤1 mm), with cT3 low rectal carcinoma, and all patients with cT4 tumors. The short-term endpoints were pathologic pCRM (≤1 mm) as a strong predictor of local recurrence rate and the quality of total mesorectal excision according to the plane of surgery. These endpoints were compared in patients with and without nRCT.Of 230 patients that met the inclusion criteria, 96 (41.7%) received a long course of nRCT and 134 (58.3%) were primarily operated on. The pCRM was positive in 13 of 230 (5.7%) (primarily operated on, 2 of 134 [1.5%]; after nRCT, 11 of 96 [11%]). In 1 of 134 (0.7%) case, the mrCRM was falsely negative. Patients at participating centers varied in terms of preoperative stage but not in pCRM positivity (0%-13%, P = .340). The plane of surgery was mesorectal (good) in 209 of 230 (90.9%), intramesorectal (moderate) in 16 of 230 (7%), and the muscularis propria plane (poor) in 2.2% (5 of 230).Low pCRM positivity and the high quality of mesorectal excision support use of MRI-based nRCT in rectal carcinoma. nRCT was avoidable in 45% of patients with stage II and III disease without significant risk of undertreatment. Preoperative MRI thus allows identification of patients with high risk of local recurrence and use of selective nRCT.

As a result of Japanese reports of improved survival of gastric cancer patients after extended lymph node dissection, a study was undertaken to evaluate factors that might influence these results. The influence of staging was evaluated by stratifying 1085 patients of the National Cancer Center of Japan and grouping them according to the three commonly used systems; UICC's old and new TNM systems (fourth edition) and the system of the Japanese Research Society for the study of Gastric Cancer (JRSGC). No survival difference was found between the stages of the three systems, except for stage II, where the new TNM and the JRSGC differed (p

At present, staging of malignant tumors is based on the anatomical extent of disease defined by the T(umor) N(odes) M(etastasis) classification. The main objective of further efforts in classifying tumors is to identify additional independent prognostic factors and to create mathematical models that may predict disease progression by prognostic grouping. This article summarizes problems, methods and the design of coordinated studies on prognostic grouping.

Inadvertent perforation or incision into rectal carcinoma during surgery may lead to massive dissemination of tumor cells in the operative area. It was observed in 8.7 percent of 1360 radical resections for cure. In time, the incidence could be reduced from 11.0 to 5.2 percent. Intraoperative spillage of tumor cells influences the incidence of local recurrence. In the last period (1982 to 1985) in cases of spillage of tumor cells, local recurrence was seen in 39 percent as opposed to 12.9 percent in perforation or incision of the tumor. Intraoperative tumor-cell spillage has a negative effect on survival rates, reducing the relative five-year survival rate after resection for cure from 70 to 44 percent. It should be recorded in the surgical and pathologic reports and considered in the analysis of treatment results and in selection of patients for adjuvant radiotherapy.

The local recurrence rate is an important indicator in the quality management of rectal carcinoma. The data of the German Study Group for Colorectal Carcinoma (SGCRC) and the Erlangen Registry for Colorectal Carcinoma (ERCRC) were used to demonstrate the influence of different calculation methods on the level of local recurrence rates. The application of uniform definitions, rules and presentations is necessary to enable national and international comparisons. Only 5-year local recurrence rates allow treatment quality to be definitely judged, especially when multimodal treatment was applied.

The TNM/pTNM classification of anatomic extent before treatment is the strongest predictor of outcome in exocrine pancreatic carcinoma. Frequent changes in staging, published by the UICC in 1987, 1997, and 2002, lead to considerable problems.The data on 272 patients with resection of a pancreatic ductal adenocarcinoma between 1978 and 1997 were analyzed.Two hundred sixty-five tumors were assigned to a higher pT category in 1997. Of them, 70 were reassigned to a lower pT category in 2002. No patient fulfilled the criteria of pT4 in 2002. Eighty-seven tumors were assigned to a higher pathologic stage in 1997. In 2002, 151 tumors were assigned to a lower pathologic stage. No patient was assigned to pathologic stage III. The staging systems of 1987 and 1997 are able to identify subgroups of patients with superior prognosis. The staging system of 2002 includes the same 12 patients in stage I as the classification of 1997. However, stage II contains an inhomogeneous group of 193 patients with poor prognosis.Changes in the TNM classification require a conversion of the data. Analysis and comparison of published results are very difficult and sometimes impossible if classification systems change too often. The present classification is well qualified for treatment choice and gives good information on prognosis after resection. It should be unchanged for at least 10 years.

The American Joint Committee on Cancer (AJCC) recently proposed a new staging system for cutaneous melanoma. We tested its practicability and its prognostic value was compared with the currently used TNM classification. The data of 1976 melanoma patients were used for the testing. 1218 patients (61.6%) could be assigned to the proposed pT classification, 136 patients (90.1%) with lymph node metastases and/or in-transit metastases to the proposed pN classification and all 14 patients with distant metastases to the proposed pM classification. Proposed pathological staging was possible for 971 patients (49%). The number of pT1 patients (399 versus 230) and stage I patients (544 versus 393) was distinctly higher in the proposed classification. In proposed stage II and III groups, subgroups with different prognosis could be identified. The new staging system includes more detailed information on clinical and pathohistological findings. Nevertheless, it is practicable and enables more patients with excellent prognosis to be identified.

BACKGROUND It is unclear whether patients with Stage II colon carcinoma should be offered adjuvant chemotherapy. Therefore, the authors analyzed the risk factors of these patients to identify high-risk subgroups who may benefit from such treatment. METHODS The data from 305 patients with Stage II colon carcinoma documented in the Erlangen Registry of Colorectal Carcinoma were analyzed to identify risk factors for distant metastasis and disease-related survival. The patients were divided into two subgroups: those in a low-risk group and those in a high-risk group. The data were then compared with those from 306 patients with Stage II colon carcinoma from the German Study Group for Colorectal Carcinoma (SGCRC). RESULTS Emergency presentation, a primary tumor site in the left colon, pT3 tumors with a depth of invasion of > 15 mm beyond the outer border of the muscularis propria, and pT4 lesions were identified as the major risk factors for Stage II colon carcinoma. On dividing patients into subgroups according to these risk factors, it was found that patients in the high-risk group had a significantly higher risk of distant metastases and a significantly lower disease-related survival rate compared with patients in the low-risk group. On analyzing the SGCRC data, the authors also found a significantly higher rate of distant metastases in the high-risk group, but the disease-related survival rate differed only marginally. CONCLUSIONS Among patients with Stage II colon carcinoma, it is possible to identify a high-risk group of patients who may be candidates for adjuvant chemotherapy. Stratification by the risk factors emergency presentation, tumor site, depth of tumor invasion, and surgical department should be employed in further clinical studies. Cancer 2001;92:1435–43. © 2001 American Cancer Society.

Aims. To recognize possible advantages of the 5th edition of TNM of gastric carcinoma in comparison to the former edition. Methods. Data from Erlangen Cancer Center for 898 patients with gastric carcinoma treated surgically by total or subtotal gastrectomy with en bloc lymphadenectomy were analysed. Results. The prognostic significance of TNM has been improved by the new edition as demonstrated by the likelihood ratio test. In addition, uncertainties of method in the pathological classification of regional lymph-node metastasis inherent in the 4th edition can now be avoided. Conclusion. The changes in the TNM classification introduced by the 5th edition are justified by data from the Erlangen Cancer Center, have methodic advantages in determining the N classification, and lead to an improvement in estimation of outcome.

Introduction: Ductal adenocarcinoma of the pancreas is a highly aggressive tumor with early local spread beyond the pancreas, predominantly to the retroperitoneum, but also with invasion of adjacent great vessels and adjacent organs. Discussion: Anterior extension may lead to perforation of the visceral peritoneum and spread within the peritoneal cavity. Cytology in peritoneal lavage can be positive before any peritoneal metastasis is seen. Invasion of lymphatics and veins as well as perineural invasion are common. The lymph drainage of the pancreas is multidirectional to superior, inferior, anterior, posterior and left lymph nodes. In node-negative cases, isolated tumor cells in the sinus of regional lymph nodes may be found by immunocytochemistry; such findings must be distinguished from micrometastasis. The same applies to isolated tumor cells in bone marrow. Prognosis: The independent prognostic significance of isolated tumor cells in the regional lymph nodes and in the bone marrow remains to be proven. For classification of anatomic extent the new, fifth edition (1997) of the UICC TNM classification should be used. The complex Japanese classification cannot be directly compared with the UICC system. Conclusion: Tumor size and histologic grade influence the extent of spread. Anatomic extent and histologic grade are the strongest predictors of outcome.

Knowledge of a possible correlation between distal polyps found at screening sigmoidoscopy and proximal colonic lesions is important for deciding whether to perform total colonoscopy or not.A prospective analysis of 2439 consecutive patients with colorectal polyps. Of these, 304 were asymptomatic subjects who underwent complete colonoscopy for screening and were found to have adenomatous or hyperplastic polyps in the distal colorectum.Ten (15%) out of 65 patients with distal hyperplastic polyps only and 86 (36%) out of 239 with distal adenomatous polyps were found to have adenomatous polyps in the proximal colon as well (P0.001). The frequency of synchronous proximal adenomas in patients with small (or = 5 mm) or large distal adenomas (5 mm) was comparable (37% and 35%, respectively). However, patients with small distal adenomas had significantly smaller proximal adenomas (P = 0.004) containing less villous component (P = 0.017) than those with large distal adenomas. Neither the patient's age nor the presence of multiple distal adenomas increased the prevalence of proximal adenomas.Hyperplastic polyps found on rectosigmoidoscopy do not indicate a need for a complete colorectal examination, as 15% of patients with distal hyperplastic polyps will have proximal adenomatous polyps, a figure that is comparable with that of asymptomatic patients having no distal polyps, either hyperplastic or adenomatous. When only small distal adenomas are found at screening sigmoidoscopy in asymptomatic persons the decision to do a total colonoscopy should be based on individual considerations, as in such cases only small polyps are to be expected in the proximal colon.

Tumor classification is associated with two inherent problems: (1) to find a compromise between the simplicity needed for a wide application by the medical community and sufficient differentiation and specification required for the presently high differentiation in treatment options and for detailed analysis of treatment results; and (2) to achieve an agreement between the stability necessary for data collection over long periods and the needed continuous inclusion of new proposals that arise by advances in diagnostic and therapeutic methods and the increasing knowledge of prognostic factors. The aim of this report is to inform on the changes and expansions of the international classification of gastric carcinoma during the last few years, to refer to new developments, to point out the relations between established classifications and molecular biology, and to show the future trend in tumor classification.

The anatomic extent of tumor (TNM, pTNM) and, in case of treatment, the residual tumor status following treatment (residual tumor, or R classification) are the strongest predictors for outcome of patients with gastrointestinal cancer. The results of the pTNM and the R classifications depend on the methods used. In particular, the pN classification correlates with the number of nodes examined. The findings of micrometastases or isolated tumor cells in bone marrow should be indicated, and such cases must be analyzed separately from other metastatic cases. The same applies to patients with positive cytology in ascites fluid or peritoneal washings without gross involvement of the peritoneum. For the R classification the additional descriptors (conv), for conventional methods used, and (soph), for sophisticated, are recommended to indicate the methods used for classification. In general, long-term survival can be expected only after R0 resection (resection without residual tumor). The observed 5-year survival after R0 resection is 15% to 40% for esophageal carcinoma. 40% to 75% for gastric carcinoma, and 55% to 60% for colorectal carcinoma; the respective figures for R1 and R2 resections are only about 5% each. In R1 and R2 cases prognosis is determined primarily by the absence or presence of distant metastases, and pT and pN are of minor significance. After R0 resection there is a wide spectrum of prognoses. Careful pTNM classification allows a good estimation of the prognosis and can be considered the gold standard for any analysis of treatment results.

The R classification, adopted in 1987 by the UICC, denotes absence or presence of residual tumor after treatment. Residual tumor may be localized in the area of the primary tumor and/or as distant metastases. R0 corresponds to resection for cure or complete remission. R1 to microscopic residual tumor, R2 to macroscopic residual tumor. The R classification takes into account clinical and pathological findings. A reliable classification requires the pathological examination of resection margins. The R classification has considerable clinical significance, particularly being a strong predictor of prognosis. General and specific procedures for performing pathological R classification on resection specimens of different organs will be described. New methods in R classification comprise imprint cytology, cytolocial examination of ascites, examination of bone marrow biopsy. The importance of these methods will have to be established in the future.

The tumor status following treatment is described by the residual tumor (R) classification: R0, no residual tumor; R1, microscopic residual tumor; R2, macroscopic residual tumor. Residual tumor may be found in the area of primary tumor and its regional lymph nodes and/or at distant sites. The R classification reflects the effects of treatment and influences further treatment planning. Furthermore, the R classification is a strong predictor of prognosis. An acceptable long-term prognosis can be expected only in R0 patients. Although there exist clear correlations between stage and R classification the differences in prognosis of R0 versus R1,2 cannot be explained by differences in stage alone. The prognostic significance of R classification is demonstrated by respective data for non-small cell lung carcinoma, squamous cell carcinoma of oesophagus, gastric carcinoma, ductal adenocarcinoma of the pancreas, colorectal carcinoma, lung and liver metastases.

The purpose of tumour staging for colorectal cancer (CRC) is to help define clinical management, facilitate communication between physicians, provide a basis for stratification and analysis of treatment results in prospective studies, and provide some prognostic information for patients and their families. The World Congresses of Gastroenterology, Digestive Endoscopy, and Coloproctology, Working Party on staging for CRC studied six commonly used systems to review their strengths and weaknesses. Although it was concluded that defining a new staging system was unnecessary, it was recognized that there is a need to define a terminology to describe the full anatomic extent of spread of CRC. Furthermore, we note that there are several additional features, derived from both clinical and pathology information, which have had prognostic significance shown by appropriately constructed multivariate analyses and which can be used to formulate a more accurate prognostic index than that provided by a description of anatomical tumour spread. Thus the Working Party came to two principal conclusions. First, a standard format should be adopted for the collection of the essential data required for prospective studies, and we recommend the 'International Documentation System (IDS) for CRC' for this purpose. Second, a nomenclature which describes the full anatomical extent of tumour spread and residual tumour status in CRC has been defined and should be adopted, from which all currently used staging systems can be derived. We have called this nomenclature the 'International Comprehensive Anatomical Terminology (ICAT) for CRC'. In the event that these recommendations are adopted, we envision that there will be improved clarity in the documentation of treatment outcome for patients with CRC and improved communication of results derived from prospective studies. Furthermore, an acceptance of IDS and ICAT would set the scene to develop a prognostic index for individual patients with CRC by the expansion of anatomical clinicopathology staging information to include additional factors which have independent prognostic significance.

In the last 10 years, 130 patients with early gastric carcinoma were operated on at the Surgical University Clinic of Erlangen. The ulcerous type was the most frequent (85%) and had the best prognosis with a 5-year survival rate of 87% excluding operative mortality, and 100% when agecorrected.

It is possible to make a histopathological diagnosis of colorectal carcinoma from ulcerating lesions by means of forceps biopsy, but this presents problems in polypoid tumours. In order to make the diagnosis of invasive carcinoma, evidence of invasive growth into the submucosa is necessary. In polypoid tumours, this can be done usually only by endoscopic or surgical polypectomy. In addition to histopathological diagnosis, one of the most important tasks for the contemporary pathologist is the exact classification of colorectal tumours. The most important parameters are typing, grading, staging and the R classification, i.e. the assessment of presence or absence of residual tumour following treatment. Typing and grading is done according to the WHO recommendations; the great majority of colorectal carcinomas are adenocarcinomas or mucinous adenocarcinomas. In grading, one can differentiate into either four grades (G1 to 4) or between low and high grade. The internationally accepted TNM/pTNM system, as described in the 4th edition, is used for staging. This system has considerable advantages over the traditional, but often misused Dukes' classification. After treatment, the surgeons and the pathologists must work together to determine the R classification. Typing, grading and staging are of great importance in deciding on the indication for either a limited surgical procedure or a radical resection. Together with the R classification, they decisively influence the indications for post-treatment after surgical therapy. R classification is the most important factor for prognosis after surgical removal of tumours. Following resection for cure, the prognosis is especially affected by the pTNM classification and its corresponding stages. The independent prognostic significance of other clinical, macroscopic and histological findings cannot yet be definitively determined.

In the evolution of rectal cancer, the adenoma-carcinoma sequence is of the greatest importance. In the rectum, we should employ the termcarcinomaonly when the tumor has penetrated the muscularis mucosae and has invaded at least the submucosa. If the invasive growth is limited to the submucosa (early colorectal carcinoma), the prognosis is excellent. The further progression of the tumor is both horizontal and vertical. With increasing vertical growth (penetration), the incidence of lymphatic metastases rises. Lymphatic spread follows certain rules, which are of significance in the selection of surgical procedure. Histological evidence of venous invasion signals the danger of hematogenic dissemination.

In 597 patients with adenocarcinoma or mucinous adenocarcinoma of the rectum, the prognosis after radical resection for cure was investigated. Staging according to the fourth edition of the UICC TNM Classification showed a good correlation to prognosis. By multivariate analysis, various additional independent prognostic factors could be demonstrated. The individual additional prognostic factors are partly of significance in some pTNM defined stages and substages, but not in others. In order to obtain the most detailed knowledge of prognostic factors after radical resection for cure, multivariate analysis of prognostic factors in colorectal carcinoma must be performed not only in separate colonic and rectal groups, but also separately for each of the individual pTNM defined stages and substages.

The purpose of this study was to reevaluate the significance of serum PHI in gastrointestinal cancer at histopathologically defined stages prior to primary treatment. A total of 248 patients with malignant tumors of the gastrointestinal tract and a collective of 42 patients with noncancerous diseases were studied. The results are compared with those obtained with the established markers tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA). Phosphohexose isomerase (PHI) revealed an overall diagnostic sensitivity of 69%, combined with a specificity of 74%. The corresponding data for TPA were found to be 73 and 47% while for CEA 26 and 95% respectively were determined. Even in the early stages of colorectal and esophageal carcinoma, PHI showed a sensitivity of about 60%. A continuous rise of PHI serum levels, correlating well with the extent of the tumor disease, could be detected. In contrast to TPA and CEA, PHI assay can be carried out with a minimum of laboratory efforts, in a short time and at low costs. These findings suggest that serum PHI assay is a useful aid for screening of gastrointestinal cancer, especially esophageal and gastric carcinoma, and a reliable marker for treatment control and follow-up.

Mononuclear cell (MNC) populations in tissue specimens from 11 colorectal adenocarcinomas and 1 mucinous adenocarcinoma were analyzed, applying different monoclonal antibodies (MoAB). Tumor epithelium could be characterized by MoAB VEP9, predominantly binding to mucus secreted by the tumor cells. In approximately 30%-50%, the tumor epithelium also reacted in a patchy pattern with the MoABs OKT10 and OKIa, which define in the peripheral blood activated and HLA-DR expressing cells. T-lymphocytes, as defined by the MoAB 9.6, and T-lymphocyte subpopulations, as characterized by the MoABs OKT4 and OKT8, were found in the intratumoral stroma and in peritumoral inflammatory areas. Quantifying the relative amounts of mononuclear cell subpopulations in the different stroma compartments, a predominance of OKT10- and OKIa-defined and MoAB-S39-reactive cells was observed. NK cells, as labelled by the MoAB Leu-7, were only demonstrated singularly in different areas of the stroma. Nonlymphoid structures such as vessel walls were shown to express antigens recognized by the MoABs OKIa, OKT10, and Leu-7. In some instances, nerve structures were labelled by the MoABs OKIa, OKT10, S39, and Leu-7. Using semiquantitative analysis, no correlation could be obtained between the intratumoral and peritumoral infiltration with T-lymphocytes, T-lymphocyte subpopulations and monocytic cells, and histopathological tumor grading and staging.

The “borderline lesion” of the stomach (severe dysplasia of the protruded type) is nowadays considered to be a true precancerous lesion. Histologically, this lesion is characterized by a proliferation in the area of the glandular neck, combined with severe cellular atypia. Investigation by means of transmission electron microscopy reveals the structure of these cells to be very similar to the structure of cells of an intestinal-cell-type carcinoma of the stomach. In addition to signs for a loss of differentiation of the cells, such as the absence of rough-surfaced endoplasmatic reticulum, mucin granules, and of the polarity of the cells, remarkably frequently luminal bulges and “blebs” developed to various extents can be detected. Morphometric analysis is delineating the tendency of structural features of the borderline lesion to develop toward the gastric cancer cell. These irregularities might be expressions of the beginning of expansive growth and signs pointing to differentiation into malignant neoplasia.

The term early colorectal carcinoma is used for an infiltrating carcinoma with submucosal spread, but no involvement of the muscle coat (muscularis propria). Our experience with 249 such tumours is reported. Lymph node metastases were detected in only 3% of 130 patients subjected to classical surgery. Early colorectal carcinoma represents a cancer stage with an excellent prognosis (age-corrected 10-year survival rate 100%). The survival rates after limited therapeutic procedures (endoscopic polypectomy, local surgical excision, segmental/tubular resection) or after classical radical surgery do not differ significantly provided that certain selection criteria are strictly observed.

A system of classifying colorectal carcinomas into five prognostic groups is described. This classification includes not only tumor spread, regional lymph node involvement, and distant metastases, but also resectability and R-classification (residual tumor or curability). All patients with colorectal tumors can be classified by means of this system. The five prognostic groups differ statistically significantly (p less than 0.01) from one another with respect to age-corrected 5-year survival rates.