Preoperative staging of gastric cancer plays a crucial role every multimodal treatment protocol. At present, staging intends to be far more than evaluation of the depth of tumor infiltration into the organ wall, that is, T stage, nodular status (N category), and the presence of distant metastases (M stage) according to UICC criteria. In modern surgical oncology it includes more often the evaluation of prognostic factors such as the RAS-protein, p53 tumor suppressor gene, growth factor receptors, cell adhesion molecules, proteolytic factors, and proliferation-associated antigens. Furthermore, evaluation of nodular status is possible by sophisticated computer programs. The conventional staging of gastric cancer using endoscopy and sonography, conventional ultrasonography, computed tomography, and magnetic resonance imaging is discussed. Possible improvements of staging in oncologic centers should include surgical laparoscopy, laparoscopic ultrasonography, and meticulous evaluation of an abdominal lavage including immunohistochemical detection of free tumor cells. The most promising tumor biology-related prognostic factors in gastric cancer are briefly discussed.

Combined Modality Therapy↗

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Neoadjuvant chemotherapy for gastric cancer: update.

Neoadjuvant chemotherapy has recently received increasing attention in an attempt to increase the rate of complete tumor resections, combat systemic metastases, and prolong survival in patients with gastric cancer. The available data indicate that neoadjuvant chemotherapy is feasible and does not increase postoperative morbidity and mortality. Compared to the results that can today be obtained with primary resection and lymphadenectomy, however, preoperative chemotherapy has so far failed to show a clear increase in the rate of complete tumor removal in patients with resectable gastric cancer. In patients with locally advanced or unresectable gastric cancer, preoperative chemotherapy may cause substantial reduction in locoregional tumor mass and thus increase the resection rate. This finding appears to translate into a survival benefit for those who respond to chemotherapy and have subsequent complete tumor resection. Because of severe shortcomings in the study design of the published reports, definite conclusions cannot be drawn from the available studies. Randomized controlled prospective trials are therefore clearly warranted. Exact pretherapeutic tumor staging, standardized resection and lymphadenectomy techniques, diligent evaluation of the resected specimen, and close follow-up are essential when designing these trials to identify subgroups of patients who may benefit from neoadjuvant chemotherapy for gastric carcinoma.

Chemotherapy, Adjuvant↗

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Multimodal treatment and prognostic factors in GI cancer--introduction.

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Antineoplastic Agents↗

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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.

Combined Modality Therapy↗

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Multimodal treatment for squamous cell esophageal cancer.

Preoperative chemotherapy (CTx) and combination radiochemotherapy (RTx/CTx) in patients with squamous cell esophageal carcinoma has recently received increasing attention. Although several prospective randomized trials could not show any benefit of neoadjuvant therapy in patients with potentially resectable tumors, preoperative CTx and combination RTx/CTx appear to increase the resection rate, the rate of complete tumor resection, and survival time in patients with locally advanced tumors. Most available studies show that a survival benefit from multimodal therapy can be expected primarily in patients who have a complete histopathologic response to preoperative treatment (i.e., no viable tumor in the resected specimen). Preoperative RTx/CTx increases the response rate and improves local tumor control compared to preoperative CTx alone, but it is associated with substantial perioperative mortality and morbidity. Distant tumor recurrences are insufficiently controlled with current combined modality protocols. These data indicate that neoadjuvant therapy must be considered investigational in patients with potentially resectable esophageal carcinoma but may soon become standard in patients with locally advanced tumors. Research must focus on modalities that allow pretherapeutic identification of those patients who will respond to neoadjuvant therapy. Furthermore, more effective and less toxic preoperative therapy regimens are required to increase the response rates and combat systemic recurrences. Finally, randomized prospective studies are essential to assess the role, extent, and timing of surgical resection for the combined modality approach to patients with squamous cell esophageal carcinoma.

Antineoplastic Agents↗

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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.

Antineoplastic Agents↗

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Peripheral DSA with automated stepping.

Peripheral digital angiography can be applied with automated stepping and in digital subtracted technique to evaluate the complete lower extremities angiographically with one single injection of contrast medium. Altogether 25 DSA-examinations were compared with non-substracted technique. By DSA-technique additional series could be reduced to only those, where significantly different flow in both extremities necessitated different timing as known from conventional angiography. DSA-technique with automated stepping may in the future totally replace conventional angiography of the peripheral arteries.

Angiography↗

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Preoperative evaluation of bronchogenic carcinoma: value of MR in T- and N-staging.

Seventy consecutive patients with a bronchogenic carcinoma, in whom chest radiographs did not allow a sufficient evaluation of primary tumor localization or extension were examined by MR (1T). All diagnoses were confirmed by operation and histopathologic examination (Stage T1: 6 patients, Stage T2: 36 patients, Stage T3: 19 patients, Stage T4: 9 patients). T-staging was correct in 79% of patients. Significant infiltration of major bronchi, of the pericardium, heart, mediastinal fat and chest wall can be visualized with a reasonable degree of accuracy. N-staging based on lymph-node size was correct in 56%. A correlation between lymph-node size and metastatic involvement was not found. MR is limited by the spatial resolution, by the lack of tissue specificity and by artifacts. MR is a useful diagnostic tool in the evaluation of the primary tumor extension, however, especially in borderline cases histopathologic examination is required. A reliable N-staging is not possible based on lymph-node size measurement.

Adult↗

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Clinical value of diagnostic laparoscopy with laparoscopic ultrasound in patients with cancer of the esophagus or cardia.

Accurate pretherapeutic tumor staging becomes increasingly important for the selection of therapy in patients with cancer of the upper gastrointestinal tract. We prospectively assessed the clinical value of diagnostic laparoscopy with laparoscopic ultrasound and peritoneal lavage in 127 consecutive patients with cancer of the esophagus or cardia but no evidence of hepatic metastases, peritoneal tumor dissemination, or other systemic tumor manifestations on standard staging techniques. There was no mortality or morbidity associated with diagnostic laparoscopy. Diagnostic laparoscopy with laparoscopic ultrasound showed relevant previously unknown findings, particularly in patients with locally advanced adenocarcinoma of the distal esophagus or cardia (hepatic metastases in 22% and peritoneal tumor spread or free tumor cells in the abdominal cavity in 25%), whereas the diagnostic gain was low in those with squamous cell esophageal cancer. The sensitivity and specificity of laparoscopic ultrasound in predicting positive celiac axis lymph nodes were 67% and 92%, respectively. These data indicate that diagnostic laparoscopy with laparoscopic ultrasound and peritoneal lavage is safe and frequently provides therapeutically relevant new information in patients with locally advanced adenocarcinoma of the distal esophagus or cardia, whereas the clinical value in patients with squamous cell esophageal cancer is limited.

Adenocarcinoma↗

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[Intensification of insulin substitution in adolescents and children with type I diabetes mellitus].

In order to approach the therapeutic goal of normoglycemia in diabetic children and adolescents, new forms of insulin substitution have been developed and subsequently tested as "intensified conventional insulin therapy" or "multiple daily insulin injections". Typical for this therapy are unmodified insulin injections before each main meal, administration of basal delayed insulin at night and if necessary also during the day, regular daily blood sugar analyses as an aid to decisions regarding therapy, and variation of the unmodified doses according to certain general or individual rules. The article reviews the principles of this therapy, indications for it and the method employed, as well as the authors' own results and those published in the literature. It concludes with a discussion of complications in therapy, of controversial aspects of practical management and of the long-term perspectives.

Adolescent↗

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The role of surgery in the treatment of liver metastases for colorectal cancer patients.

BACKGROUND/AIMS: Liver metastases deriving from colorectal cancer can be treated with curative intention in a select number of patients. Controversy does, however, persist pertaining to the impact of adjuvant treatment strategies. The aim of this study is to elucidate upon the various treatment modalities for patients suffering from liver metastases of colorectal primary tumor as well as to provide a rationale for surgical and adjuvant treatment. METHODOLOGY: From November 1987 to September 1998, a total of 449 consecutive patients suffering from liver metastases deriving from a colorectal cancer were documented at our institution in a prolective study. Prognostic factors providing the most beneficial outcome (whether with surgical and/or adjuvant treatment modalities) were analyzed by univariate and multivariate analysis. RESULTS: Whenever possible, curative (R0) surgical resection of colorectal liver metastases provides the most benefit to the patient. Multivariate analysis revealed tumor infiltration of the lymph nodes of the hepatoduodenal ligament and metachronous occurrence of liver metastases as most independent factors related to survival. CONCLUSIONS: Adjuvant post-operative chemotherapy fails to significantly improve survival following resection of liver metastases when compared to the liver resection only group. In patients with unresectable metastases, regional arterial chemotherapy did not improve survival significantly when compared with systemic chemotherapy.

Adult↗

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New aspects of prognostic factors in adenocarcinomas of the small bowel.

BACKGROUND/AIMS: Primary small bowel tumors are rare and the prognosis is generally considered to be poor. Histologically chiefly adenocarcinomas are reported. The surgeon is challenged in their treatment, because of the infrequency, unspecific symptoms and delay in diagnosis. Retrospectively we investigated the surgical therapy, combined morbidity, survival rates and prognostic factors in a large series of primary adenocarcinomas of the small bowel at a single surgical center. METHODOLOGY: Between 1985 and 1998, 94 patients with a primary tumors of the small bowel (malignant n = 62 [65.9%], benign n = 32 [34.1%]) were operated on. The subgroup of the adenocarcinomas (n = 22) were considered for this study. RESULTS: The median follow-up is 8.4 years (range: 0.9-14.2 years). Sixteen patients had a follow-up more than 5 years. The main surgical procedure was a small bowel segment resection. Morbidity was 13.6% (only in patients with a duodenal tumors) and the 30-day mortality 5.6%. The estimated 2-year-survival rate was 66%, the 5-year-survival rate 45%. Univariate analysis identified the presence of the residual tumor (R-status) (P = 0.004), tumor stage according to the UICC (P = 0.01), lymph node metastasis (P = 0.007), distant metastasis (P = 0.001), lymphangiosis carcinomatosa (P = 0.001) and vascular invasion (P = 0.0008) as prognostic factors. CONCLUSIONS: A complete macroscopic and microscopic tumor resection including a systemic lymph node dissection has to be the aim of any curative surgical approach in patients with adenocarcinoma of the small bowel.

Adenocarcinoma↗

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[Askin tumor. Rare neurogenic tumor with metastasis to mouth, jaw and face regions].

One case of a malignant peripheral neuroectodermal tumor of the thoracopulmonary region (Askin-Tumor) is reported. The tumor represents a distinct pathologic entity of neuroectodermal origin. The patient developed a metastasis in the upper jaw and in a lumbar vertebra. Morphologic and immunocytochemical findings of this extremely rare tumor were described and differential diagnosis from other soft-tissue round-cell sarcomas, such as Ewing's sarcoma and neuroblastoma are discussed. Problems associated with the clinical behavior and treatment are outlined. The prognosis in most cases of Askin-tumor is poor. The recommended therapy is radical resection, irradiation and combination chemotherapy containing anthracyclines and a high dose of alkylating agents.

Diagnosis, Differential↗