Staging gastrointestinal cancer as a precondition for multimodal treatment

Staging gastrointestinal cancer is useful only if it has an impact on treatment. When applying modern multimodal therapies (i.e., neoadjuvant, adjuvant, or additive treatment), meticulous staging is mandatory. Preoperative staging should include all relevant prognostic factors. If possible, modern cellular biology-related parameters should also be investigated, although their validity has not yet been analyzed properly. Using such modern techniques as endoluminal ultrasonography or video-laparoscopy, a preoperative diagnostic accuracy of 85% can be achieved, providing a sound foundation for therapeutic decisions. Assessment by TNM staging (UICC) and surgical resection without residual tumor (UICC/R0) are crucial, as it has been shown by multivariate analyses that these factors have the most impact on prognosis. Postoperative staging is mainly done by pathohistologic evaluation of the surgical specimen. It is the basis for any postoperative adjuvant or additive therapy. In this paper the diagnostic methods and their validity are discussed in relation to the various gastrointestinal tumors.

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Resumen La estadificación del cáncer gastrointestinal es de utilidad solamente si tiene un impacto sobre el tratamiento. Al aplicar las modernas terapias multimodales, es decir el tratamiento neoadyuante, coadyuvante o aditivo, aparece mandatorio realizar una noticulosa estadificación. La estadificación preoperatoria debe meluir la totalidad de los factores de pronóstico. Si posible, se leben investigar los modernos parámetros de biologia celular, unique su validez todavia no ha sido debidamente analizada. Utilizando modernas técnicas tales como el ultrasonido endolusinal o la videolaparoscopia, se puede lograr una validez diagnostica preoperatoria del orden del 85%, lo cual aporta un sólido undamento para la toma de decisiones terapéuticas. Es crucial la optima valoración del estadío TNM (UICC) y de la resección quirúrgica libre de tumor residual (UICC/R0), puesto que en nodos los análisis multivariados han demostrado tener el mayor impacto sobre el pronóstico. La estadificación preoperatoria consiste fundamentalmente en la exacta evaluación histopatologica del espécimen quirúrgico. Esta es la base para definir la cerapia postoperatoria coadyuvante o aditiva.

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Résumé Le bilan d'extension des cancers digestifs est utile seulement si les résultats influencent le traitement. Afin d'appliquer les modalités thérapeutiques modernes, c'est-à-dire, néoadjuvantes, adjuvantes ou additives, un bilan préopératoire méticuleux est nécessaire. Le bilan préopératoire devrait relever tous les facteurs pronostiques pertinents. Si possible, les paramètres de la biologie cellulaire moderne, bien que leur validité n'a pas encore été analysée avec précision, devraient être également mesurés. Avec des techniques modernes telles l'échoendoscopie et la vidéolaparoscopie, un diagnostic préopératoire exact peut être établi chez environ 85% des patients, semblant donner une base solide pour la décision thérapeutique. La meilleure évaluation du stade TNM (UICC) et la résection sans tumeur résiduelle (UICC/RO) semblent essentielles, puisque ce sont ces facteurs qui ont été démontrés comme les meilleurs éléments pronostiques par l'analyse multivariée. Le bilan postopératoire est la meilleure évaluation histopathologique possible de la pièce chirurgicale. Ceci jette la base de toute thérapeutique néoadjuvante ou additive. Dans cet article, les méthodes diagnostiques actuelles et leur validité sont discutées pour la plupart des tumeurs digestives.

     

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胃癌主要治疗手段是外科手术。正确的术前分期对指导选择手术适应证及制定综合治疗方案具有重要的临床意义。目前 ,胃癌术前检查方法包括胃镜、Ｂ超、ＣＴ、超声内镜、腹腔镜和腹腔镜超声等 ,各种方法对术前分期均有一定意义。现作综述如下。1　胃镜　　胃镜不但适用于判定胃粘膜病变的大小、部位 ,还可以进行活检明确组织学类型 ,但因其较难确定肿瘤浸润胃壁的深度 ,故多数学者认为胃镜不适于胃癌术前分期。但有学者通过大量胃镜表现与病理组织学对照研究 ,认为根据胃镜表现判断肿瘤浸润深度是可能的。 1996年 ,Ｈｉｄｅｏ等[1] 对 10 8例…     

胃癌术前分期与外科综合治疗

1881年Billroth首次成功施行了胃癌切除术，迄今已120余年，外科手术仍被认为是胃癌治疗的最主要手段。目前，早期胃癌的治疗发生了很大变化。即提出缩小胃切除和淋巴结清扫范围的手术：进展期胃癌的治疗则已向“手术加围手术期化疗”的模式转变。正确的胃癌术前分期对选择合理的外科综合治疗方案具有重要的指导意义．本文就术前分期的研究进展及其临床意义和胃癌外科综合治疗的现状作一阐述。     

Preoperative chemotherapy for unresectable gastric cancer

Even with extended surgery, including systematic lymphadenectomy of the lymph node compartment II, only half of the patients with locally advanced gastric cancer (LAGC), which comprises stages IIIA, IIIB, and IV, undergo a macroscopic and microscopic tumor-free resection (i.e., R0 resection, according to UICC 1987/AICC 1988). An improvement of this situation is best accomplished by preoperative treatment modalities to increase the R0 resection rate and by preoperative and postoperative treatment to reduce local recurrences and distant metastases. For LAGC, which includes approximately two-thirds of patients with locoregionally confined tumors, preoperative chemotherapy (CTx) represents a promising approach. Among a group of patients with surgically or clinically staged unresectable LAGC, approximately half underwent R0 resection after down-staging induced by active modern CTx. The long-term survival of these patients seems to be improved. Even in patients who had primarily unresectable tumors as defined by an explorative laparotomy, the long-term survival was about 20% after preoperative CTx and subsequent surgery. Based on these experiences, randomized trials investigating preoperative CTx versus surgery alone are clearly needed to define whether such an approach has an impact on R0 resection rates and survival of patients with LAGC. Preconditions for such trials are clinical staging procedures, including endoscopic ultrasonography (T category) and surgical laparoscopy plus lavage (excluding peritoneal carcinomatosis), and a standardized surgical procedure.

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Resumen Aun con cirugía extensa que incluya la linfadenectomía sistemática de los ganglios del compartimiento II, en sólo la mitad de los pacientes con cáncer gástrico localmente avanzado (CGLA) que comprende los estados IIIA/IIIB/IV, se logra una resección macrosópica y microscópica libre de tumor, o sea RO según la UICC 1987/AICC 1988. Lo anterior puede ser superado, en el mejor de los casos, mediante terapia preoperatoria orientada a incrementar la tasa de resección RO y mediante tratamiento preoperatorio/postoperatorio orientado a reducir las tasas de recurrencia local y de metástasis distantes. Para el CGLA, que incluye aproximadamente 2/3 partes de los pacientes con tumores confinados local-regionalmente, la quimioterapia preoperatoria (CTx) representa un aproche promisorio. En el CGLA definido clinica o quirúrgicamente como no resecable, aproximadamente la mitad de los pacientes pudieron ser sometidos a resección RO en virtud de su mejoría mediante moderna CTx. La sobrevida a largo plazo de estos pacientes parece ser mejor. Aun en los pacientes que tenían tumores primariamente no rescables según hallazgos en la laparotomía exploratoria, la sobrevida a largo plazo fue de alrededor de 20% después de CTx preoperatoria y cirugía subsiguiente. Con base en estas experiencias, los ensayos randomizados que investigan la CTx preoperatoria versus la cirugía sola aparecen como una clara necesidad para definir si tal aproche efectivamente logra un impacto sobre las tasas de resección R0 y sobre la sobrevida de los pacientes con CGLA. Las condiciones para realizar tales ensayos incluyen los procedimientos de estadificación como la ultrasonografia endoscópica (para categorizar T) y la laparoscópica quirúrgica — lavado (para excluir carcinomatosis peritoneal) y un procedimiento quirúrgico estandarizado.

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Résumé Même lorsque l'on réalise une lymphadénecomie étendue systématique du compartiment II, seulement 50% des patients ayant un cancer gastrique local (CGL) de stades IIIA/IIIB/IV auront en fait une résection sans laisser de tumeur macroscopique ou microscopique (e'est à dire RO selon l'UICC 1987/AICC 1988). Une amélioration de cette situation est à espérer si l'on arrive à réaliser un traitement préopératoire capable d'augmenter le nombre de résections RO et à réaliser un traitement pré- et postopératoire efficace dans la réduction des réidives locales et à distance. En ce qui concerne les CGL, représentant environ deux-tiers des patients ayant des tumeurs sans invasion à distance, la chimiothérapie préopératoire semble pleine de promesses. Chez les patients ayant une tumeur évaluée comme non résécable soit chirurgicalement soit cliniquement, à peu près la moitié semblent pouvoir avoir une résection évaluée RO après une amélioration du stade grâce à une chimiothérapie active moderne. La survie à long terme de ces patients semble améliorée. Même chez les patients ayant une tumeur gastrique considérée comme non résecable par une laparotomie exploratrice en premier lieu, ont eu une survie de 20% après une telle chimiothérapie suivie de chirurgie. Basés sur ces données, on a besoin d'essais thérapeutiques randomisés comparant la chimiothérapie préopératoire et la chirurgie seule pour définir si une telle attitude a récllement un impact sur le taux de résection RO et la survie chez le patient ayant une CGL. Les conditions préalables d'un tel essai comportent un moyen valable de faire le bilan préopératoire exact avec notamment un bilan échoendoscopique pour la catégorie (T) et une laparoscopie avec lavage (pour exclure la carcinose) ainsi qu'un procédé chirurgical standardisé.

     

The role of staging laparoscopy for multimodal therapy of gastrointestinal cancer

Background: This prospective study was conducted to evaluate the accuracy and the therapeutic relevance of staging laparoscopy. Methods: Between June 1993 and February 1997 staging laparoscopy was performed in 389 patients with various neoplasms. Additionally, 144 selected patients of this group were examined with laparoscopic ultrasound using a semiflexible ultrasound probe (7.5 MHz). Results: Compared to conventional imaging methods, laparoscopy and laparoscopic ultrasound improved the accuracy of staging in 158 of 389 patients (41%). Statistical subgroup analysis of 131 patients with gastric cancer showed that the accuracy of staging laparoscopy in the detection of distant metastases (68%) was significantly higher (p < 0.01) than that of ultrasound (63%) or computed tomography (58%). In the whole group, laparoscopy alone disclosed intraabdominal tumor dissemination or nonresectable disease in 111 patients. Laparoscopic ultrasound displayed additional metastases—i.e., liver metastases (n = 9), M1 lymph nodes (n = 15), or nonresectable tumors (n = 6) in 30 patients. Although metastastic disease was suggested by preoperative imaging, benign lesions were found in five patients with laparoscopy and in a further 12 patients with ultrasonography. The findings of staging laparoscopy changed the treatment strategy in 45% of the patients. Conversion to open surgery was necessary in 5% of the cases, and complications related to laparoscopy occured in 4% of the patients. Conclusions: Laparoscopy with laparoscopic ultrasound improves the staging of gastrointestinal tumors and has a significant impact on a stage-adapted surgical therapy. Received: 3 April 1997/Accepted: 26 September 1997     

Value of staging laparoscopy for multimodal therapy planning in esophago-gastric cancer

The importance of multimodal treatment for advanced esophago-gastric cancer has contributed to the development of more accurate preoperative staging strategies. The impact of staging laparoscopy and cytology after conventional staging is evaluated in this study. Staging laparoscopy was performed in 125 patients with potentially resectable cancer of the distal esophagus or gastric cancer. Results were registered separately on a database according to the TNM classification of the International Union Against Cancer (UICC). Laparoscopy changed TNM classification in 46 cases. Explorative laparoscopy resulted in up-staging concerning the N-factor (n = 15) and M-factor (n = 28). Downstaging of the T-factor was recorded in three cases. Cytologic examination gave no additional information in our series. Our experience suggests a clear benefit of laparoscopy in staging of patients with distal esophagus or gastric malignancy. Laparoscopy is a safe and effective staging modality, avoiding unnecessary laparotomies and providing new means of directing appropriate treatment strategy.     

Video-laparoscopic staging of gastric cancer

Background: The high proportion of gastric carcinomas present in an unresectable stage, together with the emergence of multimodal treatments, increases the usefulness of objective staging methods that avoid unnecessary laparotomies. Methods: A prospective evaluation of the accuracy of laparoscopy in the staging of 71 patients with gastric adenocarcinoma is presented. Serosal infiltration, retroperitoneal fixation, metastasis to lymph nodes, peritoneal and liver metastasis, and ascites were determined in the staging workup. Sensitivity, specificity, and predictive values were calculated and compared with those obtained with ultrasonography (US) and computed tomography (CT). Results: The diagnostic accuracy of laparoscopy in the determination of resectability was 98.6%. Consequently, over 40% of patients were spared unnecessary laparotomies. Laparoscopy yielded diagnostic indices superior to US and CT for all the tumoral attributes studied. Our technique permits accurate assessment and pathologic verification of liver and the peritoneal and retroperitoneal extent of tumor invasion in the majority of patients. Conclusions: Laparoscopy in gastric adenocarcinoma is a reliable technique that provides accurate assessment of resectability and stage, thus avoiding unnecessary laparotomies in patients in whom surgical palliation is not indicated. A stepwise diagnostic workup combining imaging and minimally invasive techniques is proposed. Received: 5 May 1996/Accepted: 10 March 1997     

Immediately preoperative laparoscopic staging for gastric cancer

Background: This ongoing study is a prospective evaluation of immediately preoperative video-laparoscopy compared to ultrasound/computed tomography (US/CT) staging for gastric cancer. An analysis of the first 70 cases is reported. Methods: TNM staging is used to compare the US/CT findings and the laparoscopic findings with the gold standard for pathologic findings in resected specimens. Results: In our series 47 out of 70 cases are locally advanced cancers (stages III and IV): In this subset the predictive value of laparoscopic staging is 86.4%. Laparoscopy shows an overall staging accuracy of 68.6%, compared to 32.8% for US/CT. The difference is statistically significant as regards the T factor (T3: 69.7% vs 12.1%, p < 0.002; T4: 84.2% vs 42.1%, p < 0.05); as regards the M factor, laparoscopy appears the most specific method for detecting peritoneal seeding. Conclusions: This procedure plays a crucial role in determining the resectability of the tumor, thus avoiding unnecessary laparotomies. A meticulous staging becomes mandatory when applying modem treatment options (e.g., neo-adjuvant chemotherapy) to locally advanced cancers; in this context the use of staging laparoscopy will have a relevant impact on future treatment.     

Usefulness of staging laparoscopy for advanced gastric cancer

Purpose  

The aim of this study was to clarify the usefulness of staging laparoscopy for planning the treatment strategy in patients with advanced gastric cancer.     

Laparoscopic staging of gastric cancer is safe and affects treatment strategy

The accuracy of laparoscopic staging has been documented, but its safety and impact on clinical decision making are less clear. In a prospective series of 64 patients referred to a single consultant, laparoscopy was performed in 49, after exclusion of patients unlikely to derive benefit from laparoscopic staging. The prelaparoscopy treatment plan was altered in 17 (34%). Laparoscopy detected 11 cases of peritoneal and four cases of liver metastasis, of which nine and two, respectively, were not detected by CT scan. Laparoscopy was useful in assessing fitness for major surgery, the planned extent of which was reduced in five cases as a result. Port site metastasis occurred in one case of stage IVB cancer, in conjunction with widespread progressive disease. Laparoscopic staging is recommended in gastric cancer, since it causes important changes to the management plan in one-third of cases, and the risks of port site metastasis appear low.     

Twenty-year experience with multimodal treatment of gastric cancer patients in Poland]

BACKGROUND: Poland is among the countries with high morbidity and mortality rates for gastric carcinoma (GC). Differences of GC biology depending on the geographical regions were assumed. In the literature, there are no reports from detailed clinicopathologic studies carried out in large series of GC patients in Poland. METHODS: Based on the prospectively collected data of 3 696 GC patients treated surgically between 1977-1999, potentially significant prognostic factors were analyzed to assess their prognostic value, and their time related distribution during the over 20-year period of the study. RESULTS: The mean age of the patients was 59.0 (SD 11.6) years and ranged from 20 to 93 years. The male-to-female ratio was 2.3. Overall cumulative 5-year survival was 0.28 (for early GC 0.85) and significantly increased over the period of study. Among factors analyzed the depth of invasion, lymph nodes status, tumor size, age, UICC-R classification and ratio of involved to removed lymph nodes are of statistically significant and most important prognostic value. In the over 20-year period of study the rate of diffuse type carcinoma according to Laurén increased, but the tumor locations did not change significantly. The rate of early GC did not change throughout the period of study but number of most advanced cases decreased. Chemo- and chemoimmunotherapy improved outcomes in some groups of patients. CONCLUSIONS: The basic clinicopathologic profile of Polish patients is similar to that reported in Western Europe and Japan, except for significantly higher early GC occurrence in Japan. According to the obtained results the prognosis of GC depends clearly upon the stage of the disease at the time of surgery. The improvement of outcomes during over 20 years of GC study in Poland was due to introducing better diagnosis and routine multimodal treatment.     

一种新的胃癌淋巴结分期方案

目的比较AJCC/UICC 1997年第五版胃癌TNM分期中的N分期与以淋巴结转移度为标准的新N分期. 方法行D2或D3术式的胃癌(皆无远处转移)标本用透光法摘取淋巴结,分别按2种方法分期,新法中N1为淋巴结转移度0.01%～10.00%, N2为10.01%～25.00%,N3为＞25.00%.全组随访,资料经统计学处理. 结果本组78例患者共取得淋巴结5388 枚,平均每例69枚(范围30～157枚).全组淋巴结转移率75.64%(59/78).新分期N0、N 1、N2、N3期患者3年生存率分别为100%、68.42%、7.58%、6.78%(χ2=35.85 0,P<0.01, r=0.95). 结论淋巴结转移度是一相对数,在预后的判断上,优于淋巴结转移数目.     

Preoperative staging and assessment of resectability of pancreatic cancer

To study the accuracy of preoperative staging techniques for assessing resectability of pancreatic and ampullary adenocarcinoma, we entered 88 consecutive candidates into a prospective study of contrast-enhanced computed tomography, magnetic resonance imaging, angiography, and laparoscopy. Resectability was proved in 16 (29%) of 55 patients for the head of the pancreas, 1 (6%) of 17 for the body and tail of the pancreas, and 14 (88%) of 16 for the ampulla. The combined findings of computed tomography and angiography showed that more than 87% of pancreatic head tumors were unresectable because of vascular encasement, but neither modality sufficed alone. Small liver and peritoneal metastases were found in 15 (27%) of 55 cancers of the head of the pancreas, 11 (65%) of 17 cancers of the body and tail of the pancreas, and 1 (6%) of 16 cancers of the ampulla; computed tomography missed all but 2 of these instances of metastasis, but laparoscopy with biopsy identified 22 (96%) of 23 instances. Magnetic resonance imaging findings did not differ significantly from computed tomography and conferred no added benefit. Ninety percent of unresectable tumors were identified. Seventy-eight percent of pancreatic head cancers were resectable when all test results were negative vs 5% (2/37) when any test result was positive. This study demonstrates that accurate and efficient triage is possible for patients with cancer of the pancreas and ampulla.     

胃癌腹腔灌注化疗的应用

术后腹腔转移是胃癌治疗失败的主要原因之一,而且一旦发生转移就很难进行有效治疗.腹腔灌注是有望最大程度的减少术后胃癌腹腔转移的有效手段之一.因此本文就针对灌注化疗的应用背景、临床疗效和药物选择等问题进行文献回顾.     

胃癌术前内镜超声检查与肿瘤血管内皮生长因子表达的检测分析

目的探讨内镜超声检查(EUS)对胃癌术前诊断和分期的应用价值及其影像学改变与肿瘤转移相关基因表达的分子生物学基础。方法联合应用电子胃镜和超声内镜诊断胃癌63例,对比胃镜检查加活检与超声内镜对胃癌诊断的准确率,同时应用超声内镜对胃癌进行术前分期,并与病理分期及血管内皮生长因子(VEGF)表达进行比较。结果63例胃癌中胃镜加病理活检诊断的准确率是94%,超声内镜诊断的准确率是92%,胃镜联合超声内镜诊断的准确率是100%。超声内镜对胃癌侵犯深度判断的准确率为81%,其中T1期为78%、T2期为79%、T3期为82%、T4期为83%,对淋巴结转移的准确率为73%。VEGF蛋白在胃癌组织中的阳性表达率为56%,其表达与EUS分期、淋巴结转移关系密切(P<0.05)。结论胃镜联合超声内镜诊断胃癌具有较高的准确率;胃癌术前内镜超声分期与术后病理有较高的一致性;VEGF蛋白表达与胃癌术前EUS分期呈正相关;EUS对胃癌的分期与分子生物学改变有关。