TNM staging of colorectal cancer should be reconsidered by T stage weighting

AIM:To verify that the T stage has greater weight than the N stage in the staging of colorectal cancer.METHODS:Open data from the Surveillance,Epidemiology,and End Results program were reviewed and analyzed according to the T stage,N stage,and patients’observed survival(OS).The relative weights of the T and N stages were calculated by multiple linear regressions based on their impact on survival.Risk scores for25 TN categories were then calculated from the T and N stage relative weights,and a rearranged tumor node metastasis(TNM)staging system was proposed via a cluster analysis of the TN scores.RESULTS:Both T and N stages significantly affect the OS of patients with colorectal cancer.Moreover,the T stage has greater weight than the N stage in the TNM staging system of colorectal cancer.For colon cancer,the relative T and N stage weights were 0.58 and 0.42,respectively,and for rectal cancer,the relative T and N stage weights were 0.61 and 0.39,respectively.On the basis of cluster analysis of the TN scores,T1N1a was classified to stageⅠ,and T2N1a-1b and T1N1b-2a were classified to stageⅡin our revised TNM staging system for both colon and rectal cancer.For colon cancer,T4bN0 was classified to stageⅢa,but for rectal cancer,it was classified to stageⅢb.CONCLUSION:As the T stage affects colorectal cancer survival more significantly than the N stage,the TNM staging should be revised by relative T stage weight.     

TNM staging, molecular staging and prognostic factors of rectal cancer]

Pathologic evaluation of the resected specimen is a critical component when managing the patients with rectal cancer, from initial diagnosis through definitive treatment. The best estimation of prognosis in rectal cancer is related to the anatomic extent of disease determined by pathology. Although a large number of staging system has been developed for rectal cancer over the years, use of TNM staging system of the AJCC (American Joint Committee on Cancer) and the UICC (International Union Against Cancer) are gaining popularity among the colorectal surgeons. Multiple genetic alterations are the prerequisite for carcinogenesis including rectal cancer. Although numerous molecular markers are investigated in relation to prognosis or response to therapy of rectal cancer, those molecular markers could not provide sufficient evidence for the incorporation of available prognostic biomarkers into clinical practice. In this article, the evolution of staging system of rectal cancer and its prognostic relevance are reviewed comprehensively.     

Gastrointestinal TNM cancer staging by endosonography

St. Mark's Hospital     

Integration of genetic signature and TNM staging system for predicting the relapse of locally advanced colorectal cancer

Purpose  

To identify potential genetic markers in treated stage II–III colorectal cancer patients and predict 3-year tumor relapse using statistical models based on important clinical factors and significant genetic markers.     

前列腺癌临床分期方法与术后病理分期一致性比较

目的　探讨前列腺癌临床分期方法预测病理分期对选择治疗、判断疗效和评估预后的意义。　方法　对 34例局限性前列腺癌患者术前根据血清前列腺特异性抗原 (PSA)、穿刺后Gleason评分、阳性穿刺针数百分率、直肠指诊和MRI检查进行临床分期 ,与前列腺癌根治术后病理分期进行比较 ,评价其诊断性实验结果。　结果　 34例术后病理诊断B期 2 0例 (5 8 8% ) ,C期 12例(35 3% ) ,D期 2例 (5 9% )。其中血清PSA、Gleason评分、阳性穿刺百分率、直肠指诊和MRI分期对术后病理分期的诊断一致性有显著相关性 (P <0 0 1)。每种临床分期对病理分期的诊断一致性偏低或偏高 ,其敏感性高于 90 0 % ,其中MRI的特异性为 71 4 % ,对前列腺内肿瘤 (B期 )的预测为80 9% ;血清PSA、阳性穿刺百分率和MRI对浸润前列腺包膜及包膜外肿瘤 (C期 )的预测为 90 9%。阳性穿刺百分率的准确性为 82 4 %。　结论　血清PSA、Gleason评分、穿刺阳性针数百分率、直肠指诊和MRI可初步预测前列腺癌的病理分期 ,综合多种临床分期方法能较准确预测前列腺癌的病理分期 ,选择合理的治疗方法。     

Sex differences in epidemiological, clinical and pathological characteristics of colorectal cancer

Sex significantly influences the clinical and pathological characteristics of colorectal cancer (CRC). These include differences in incidence and mortality rates, clinical presentations including age, emergency surgery for complications from CRC, screening participation rates, site, stage and treatment utilization, histopathology and survival. Environmental, behavioral and biological factors contribute to the differential risk. Recent advances in the molecular biology of CRC, specifically in microsatellite status, estrogen hormone and estrogen receptor β, have led to greater understanding of the effect of estrogen in colorectal carcinogenesis. Estrogen may preferentially protect against microsatellite unstable cancers through its effect on selected molecular targets; however, the exact pathways have not been elucidated. Recognition of important sex disparities in these areas may lead to the implementation of specific measures to diminish these differences and facilitate equitable distribution of health resources. Identifying specific molecular targets on CRC that interact with estrogen may stimulate research to improve the overall outcomes of all patients with CRC.     

超声小探头对结直肠癌术前分期诊断的初步研究

目的：超声小探头（ultrasonic miniprobe,UMP）应用于结、直肠癌术前分期的准确性及可行性。方法：对50例结、直肠癌患者做UMP检查,对准病灶进行全瘤扫描,择最佳影像冻结、摄片,退出UMP,最后做活组织检查,全部病例均行根治术,癌周淋巴结分组编号、装瓶、送病理检查。结果：本组UMP对50例结、直肠浸润深度（T分期）与术后病理浸润深度对比,其准确率T1－T4期分别为75％,80％,88％及67％,T分期的总准确率为84％（P＜0．01）,过高分期5例（10％）,过低分期3例（6％）;N分期,UMP诊断阳性淋巴结（n=22),术后病理（n=28),准确率795,UMP诊断阴性淋巴结（n＝20）,术后病理（n＝22）,准确率91％,总准确率84％（42／50）,敏感性79％,特异性为91％（P＜0．01）。结论：（1）UMP是当前应用于结、直肠癌术前TNM分期最有实用价值的方法之一。肿瘤狭窄患者适应术前分期检查。（2）UMP系高频超声频探头,由于超声穿透深度的限制。对远处转移的M分期是不可能的。（3）UMP对浸润深度及处淋巴结转移有一定的参考价值。并应结合其它影像检查如腹部B超、CT等,扬长弃短,相辅相成,以提高术前分期的准确性及完整性。     

慢性乙型肝炎临床与病理分级,分期的对比分析

目的评价１９９５年《病毒性肝炎防治方案（试行）》有关临床分度与病理分级、分期的一致性。方法对２６６例慢性乙型肝炎患者的临床表现、血清生化指标和临床分度的结果与病理分级、分期进行对比分析。结果临床症状的轻重和某些异常体征与病理分级显著相关（χ２分别为５２１５和２７８２，Ｐ＜０．０５）；血清总胆红素、白蛋白、白蛋白／球蛋白比值和凝血酶原活动度等的异常程度对判断轻度和重度慢性肝炎有较大的参考价值，而血清丙氨酸转氨酶和γ球蛋白水平与病理诊断并不符合；所有血生化指标的分度标准对病理重度慢性肝炎的漏诊率较高。慢性肝炎肝组织的炎症活动程度与纤维化程度显著相关（χ２＝３６２３７，Ｐ＜０．００１），而与ＨＢｅＡｇ阳性与否无明显关系（χ２＝６６５，Ｐ＞０．０５）。结论对１９９５年《病毒性肝炎防治方案（试行）》中的临床分度的标准应作适当的调整     

Molecular staging of colorectal cancer

PURPOSE. Multiple attempts have been made to improve the clinical/pathologic staging system of Dukes to focus adjuvant therapy decisions. The purpose of this study was to determine whetherK-ras mutational status of regional nodes in patients with Dukes B₂ colorectal cancer could be used to stage their disease more accurately. METHODS: Using formalin-fixed, paraffin-embedded archival material, tumor samples were screened forK-ras mutations using a mutation-specific polymerase chain reaction method, followed by gel electrophoresis in a 96-well array. Patients with Dukes B₂ tumors that have mutations in codon 12 or 13 of theK-ras gene were identified. RESULTS: Mutational analysis of the lymph nodes from these patients revealed an 80 percent (16/20) incidence of the same mutations in regional lymph nodes. None of the four patients with mutation-free nodes developed recurrence compared with 37.5 percent (6/16) withK-ras positive lymph nodes. CONCLUSIONS: The data suggest that patients with Dukes B₂ colorectal cancers that have mutations in codon 12 or 13 of theK-ras gene are at high risk for the development of nodal metastases. Mutational analysis of the lymph nodes identifies high-risk patients who should be considered for adjuvant chemotherapy. Therefore,K-ras mutational analysis should be considered for molecular staging of colorectal cancer.This work was done at the Ferguson-Blodgett Digestive Disease Institute, Grand Rapids, Michigan.Financial support came from the Ferguson-Blodgett Foundation.Read at the meeting of The American Society of Colon and Rectal Surgeons, Philadelphia, Pennsylvania, June 22 to 26, 1997.     

Problems of staging colorectal cancer

Summary A total of 2994 cases of previously untreated colorectal carcinomas taken from the database of the International Cancer Patient Data Exchange Sytem of the UICC were analyzed. The objective was to compare pretherapeutic and postsurgical data and to investigate the impact of missing information on the quality of tumor staging under routine conditions. In clinical staging, a higher percentage of items were marked unknown in the questionnaires than in histopathological staging. The clinical and postoperative assessment of TNM stages Ib, II, and III frecuently diverged, indicating a low precision for clinical staging. Fistulae were rarely observed in either colon or rectum carcinoma.Authors for the International Cancer Patient Data Exchange System of the UICC. Members of the following institutions are cooperating in the ICPDES: Duke Comprehensive Cancer Center, Durham, NC (until 1983; Director; W.W. Shingleton; Representative for the ICPDES: E. Cox), University of Texas M.D. Anderson Hospital, Houston, TX (C.A. LeMaistre; UICC/CICA Coordinator for the ICPDES and International Data Center V.F. Guinee), Mayo Comprehensive Cancer Center, Rochester, MN (until 1983, C.G. Moertel; W.F. Taylor, H. Golenzer), Memorial Sloan-Kettering Cancer Center, New York, NY (P. Marks; S. Bretsky), Roswell Park Memorial Institute, Buffalo, NY (G.P. Murphy; W.W. Lane), Institut Jules Bordet, Bruxelles (W. Mattheiem), Fondation Bergonié, Bordeaux (C. Lagarde; M. Durand). Tumorzentrum Heidelberg/Mannheim (Ch. Herfarth; G. Wagner, G. Pfaff), Westdeutsches Tumorzentrum Essen (C.G. Schmidt, R. Pfeiffer), Országos Onkologiai Intézet, Budapest (S. Eckhardt, Z. Péter); Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano (U. Veronesi; N. Cascinelii, R. Bufalino), Nederlands Kankerinstituut, Amsterdam (F. Cleton; E. Hamersma, European Data Center: R Zewuster), Rotterdamsch Radio—Therapeutisch Instituut (D. M. van der Veldt; J. W. van der Velden), All — Union Cancer Research Center of the USSR Academy of Medical Sciences, Moscow (N.N. Blokhin; I.V. Vardomskaya), Mount Vernon Hospital, Northwood, Middlesex (since 1982, P. Strickland; S. Dische), Cancer Institute, Chinese Academy of Medical Sciences, Beijing (since (1983, You-Hui Zhang; Jian-Zhang Wang). Our thanks to Prof. Dr. E. Weber, Heidelberg, for his support in the Biplot analysis     

Usefulness of endoscopic ultrasonography in preoperative TNM staging of gastric cancer

AIM:To evaluate the value of endoscopic ultrasono-graphy (EUS) in the preoperative TNM staging of gastriccancer.METHODS :Forty-one patients with gastric cancer(12 early stage and 29 advanced stage) provedby esophagogastroduodenoscopy and biopsiespreoperatively evaluated with EUS according to TNM(1997) classification of International Union ContreleCancer (UICC).Pentax EG-3630U/Hitachi EUB-525 echoendoscope with real-time ultrasound imaging linearscanning transducers (7.5 and 5.0 MHz) and Dopplerinformation was used in the current study.EUS stagingprocedures for tumor depth of invasion (T stage) wereperformed according to the widely accepted five-layerstructure of the gastric wall.All patients underwentsurgery.Diagnostic accuracy of EUS for TNM stagingof gastric cancer was determined by comparingpreoperative EUS with subsequent postoperativehistopathologic findings.RESULTS:The overall diagnostic accuracy of EUS inpreoperative determination of cancer depth of invasionwas 68.3% (41128) and 83.3% (12110),60% (20112),100% (5/5),25% (4/1) for T1,T2,T3,and T4,respectively.The rates for overstaging and understagingwere 24.4% (41/10),and 7.3% (41/3),respectively.EUStended to overstage T criteria,and main reasons foroverstaging were thickening of the gastric wall due toperifocal inflammatory change,and absence of serosallayer in certain areas of the stomach.The diagnosticaccuracy of metastatic lymph node involvement or Nstaging of EUS was 100% (17/17) for NO and 41.7%(24/10) for N ,respectively,and 66% (41/27) overall. Misdiagnosing of the metastatic lymph nodes was relatedto the difficulty of distinguishing inflammatory lymphnodes from malignant lymph nodes,which imitate similarecho features.Predominant location and distribution oftumors in the stomach were in the antrum (20 patients),and the lesser curvature (17 patients),respectively.Three cases were found as surgically unresectable (T4 N ),and included as being correctly diagnosed by EUS.     

Endoscopic ultrasound in the preoperative staging of gastric cancer: correlation with the surgical and/or pathological findings

BACKGROUND: Gastric adenocarcinoma is the major cause of death by cancer in Brazil. For the planning of the treatment and evaluation of the prognosis, the preoperative staging according to the TNM classification is very important. AIM: To evaluate the results of endoscopic ultrasound for the T and N categories. METHODS: We examined 30 patients with gastric adenocarcinoma in the period of 1 year. We used a Olympus GIF UM-20. After positioning in the third portion of the duodenum, we started to evaluate the lymph node stations 16, 13, 12, 6, 5, 4, 3, 8, 7, 9, 10, 11, 1 and 2, using the frequency of 7.5 MHz. The depth of the tumor in the gastric wall was evaluated with the frequencies of 7.5 and 12 MHz. The results T and N were compared with the conclusive findings. In the unresectable cases, the correlation was made by the macroscopic findings. RESULTS: We performed 16 total gastrectomies, 7 subtotal gastrectomies, 5 exploratory laparotomies and 2 laparoscopies. For T category, endoscopic ultrasound results were correct in 25/30 cases (83.3%). All the other 16.7% were overestimated. The accuracy varied from 90% to 96.7% according to the subcategories T1 to T4. For the N category, endoscopic ultrasound results were correct in 23/30 cases (76.7%). Sixteen point six percent were underestimated and 6.7% overestimated. The accuracy varied from 76.7% to 90%, in agreement with the subcategories N1 to N3. CONCLUSION: There was a clear correlation between endoscopic ultrasound and the surgical and pathological findings in the evaluation of T and N categories in patients with gastric adenocarcinoma.     

Accuracy of TNM staging in colorectal cancer: a review of current culprits,the modern role of morphology and stepping-stones for improvements in the molecular era

Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide. Survival is largely stage-dependant, guided by the tumor–node–metastases (TNM) system for TNM assessment. Histopathological evaluation, including assessment of lymph node status, is important for correct TNM staging. However, recent updates in the TNM system have resulted in controversy. A continued debate on definitions resulting in potential up- and downstaging of patients, which may obscure survival data, has led the investigators to investigate other or alternative staging tools. Consequently, additional prognostic factors have been searched for using the regular light microscopy. Among the factors evaluated by histopathology include the evaluation of tumor budding and stromal environment, angiogenesis, as well as involvement of the immune system (including the ‘Immunoscore’). We review the current role of histopathology, controversies in TNM-staging and suggested alternatives to better predict outcome for CRC patients in the era of genomic medicine.     

Anatomical considerations in TNM staging and therapeutical procedures for low rectal cancer

BACKGROUND: Separation of the mesoderm-derived muscular structures and the endoderm-derived structures of the hindgut and reclassification of their involvement based on their embryological origin may be of clinical importance in providing anatomical support for a more standardized perineal resection during abdominoperineal resection. The aim of this study was to utilize magnetic resonance images and histological studies of fetal and neonatal specimens to redefine the T3/T4 distinction by reassessment of the intersphincteric plane and the pelvic diaphragm as they pertain to cancer infiltration and as part of the embryological development of the pelvic floor muscles and their connective tissue compartments. MATERIALS AND METHODS: Pelvic floor anatomy was studied in seven newborn children and 120 embryos and fetuses. Anatomical data were completed by magnetic resonance imaging in 82 patients with T3 and T4 rectal cancers (64 T3, 18 T4; 35 women and 47 men) undergoing neoadjuvant chemoradiation for locally advanced (T3 or T4) rectal cancers. RESULTS: Clear demarcation between mesodermal and endodermal structures of the pelvic floor, which is equally evident in plastinated sections and magnetic resonance images, is already visible in early fetal stages. There is a constitutive overlap between the endoderm- and the ectoderm-derived components of the pelvic floor. CONCLUSION: Our data suggest that the current classification of rectal cancer staging is confusing, where the routinely used TNM classification system unnecessarily differentiates between embryologically identical muscular structures. Tumor spread along the musculature of the hindgut beyond the dentate line could possibly explain the occasional involvement of lymph nodes outside the conventional mesorectum.