Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy

BACKGROUND: Neoadjuvant chemotherapy has shown some success in the treatment of gastric carcinoma, but objective parameters for measuring its effects are lacking. The authors performed the current study to determine which histomorphologic features are correlated with patient prognosis after chemotherapy. METHODS: Thirty-six patients with gastric carcinoma were treated with a combination of etoposide, doxorubicin, and cisplatin. The entire tumor beds of the specimens were evaluated histologically and compared with specimens treated with surgery alone. Thirty-four patients were available for survival analysis (follow-up period, 60-130 months). RESULTS: None of the 36 patients had complete tumor regression, 4 patients had marked regression (less than 10% viable tumor), 9 patients had regression to 10-50% remaining viable tumor, and 23 patients had more than 50% viable tumor remaining. Currently, 9 patients are still alive (5-year survival rate, 27%). Tumor regression was found to be correlated significantly with survival (P = 0.01), but tumor size (P = 0.002) and lymphatic vessel invasion (P = 0.003) were better predictors of prognosis. CONCLUSIONS: Histologic tumor regression grade is an objective measure of the effects of neoadjuvant chemotherapy in patients with gastric carcinoma, but its accuracy may be improved by adding additional staging variables such as tumor size and lymphatic vessel involvement. Cancer 2003;98:1521-30.     

Individualizing therapy in gastric cancer

Although its incidence in developed countries has declined, gastric cancer remains one of the most common human malignancies. In western countries a shift from distal to proximal tumors has been noted during the past 15 years. Today, surgery is no longer the only treatment modality of gastric cancer, with the help of modern and sophisticated staging procedures it becomes increasingly possible to individually tailor therapy. Operative morbidity and mortality has markedly decreased. The importance of surgical expertise for short- as well as long-term outcome is emphasized. The knowledge of adequate surgery together with the use of combined modalities opens the door to the amelioration of the still dismal prognosis for patients with gastric cancer. This paper reviews the modern approach to gastric cancer using an individualized treatment concept.     

Barrett’s esophagus and Barrett’s carcinoma

The alarming rise in the incidence of esophageal adenocarcinomas in the Western world has focused interest on so-called Barrett’s esophagus. Barrett’s esophagus is characterized by specialized intestinal epithelium replacing the normal squamous epithelium in the distal esophagus and is considered a consequence of long-lasting and severe gastroesophageal reflux disease. A metaplasia-dysplasia-carcinoma sequence links Barrett’s esophagus with adenocarcinoma of the distal esophagus (Barrett’s cancer). Despite intensive research, many questions concerning the pathogenesis, diagnosis, and treatment of Barrett’s esophagus and associated adenocarcinoma are still unanswered. Based on current data, the malignant progression of Barrett’s esophagus cannot be substantially prevented by medical or surgical therapy for reflux. Although no firm data are available to show that surveillance strategies can reduce overall mortality from Barrett’s cancer, early detection and cure are possible. Management of Barrett’s esophagus and carcinoma is reviewed with reference to the sequence of disease from metaplasia to carcinoma.     

Lymphatic vessel invasion is an independent prognostic factor in patients with a primary resected tumor with esophageal squamous cell carcinoma

BACKGROUND: Little data exist about the prognostic role of a lymphatic vessel invasion (LVI) in patients with esophageal carcinoma. The objective of this study was to clarify the presence and prognostic impact of LVI in a large group of patients resected for esophageal squamous cell carcinoma (SCC) at one surgical center. METHODS: Three hundred sixty-six patients, who had a primary resection for SCC, were analyzed by univariate and multivariate analysis. Follow-up was complete for 93.7% patients with a median follow-up of 8.3 years. RESULTS: The total rate of LVI was 39.1% (n = 143). Univariate analysis revealed a significant relation between LVI and different T classifications (P = 0.001), N classifications (P < 0.0001), M classifications (P < 0.0001), International Union Against Cancer (UICC) stages (P < 0.0001), and residual tumor (P < 0.0001). Multivariate analysis of the patients with R0-resected tumors proved LVI as an independent prognostic factor. The 2-, 5- and 10-year survival rates in patients with LVI were 28.5%, 11.1%, and 9.2% compared with 63.4%, 46.6%, and 27%, respectively, without LVI (P < 0.0001). Patients with LVI had a median survival time of 11.4 months compared with 28.6 months without LVI (P < 0.0001). Patients with R0-resected tumors without LVI had a median survival time of 54.1 months compared with 12.1 months in patients with LVI (P < 0.0001) and compared with 11.3 months in patients with R1-resected tumors P < 0.0001). CONCLUSIONS: These data clearly show that LVI is an independent prognostic factor in patients with SCC and confirm the importance of a systematic pathohistologic workup. The prognosis of patients with R0-resected tumors with LVI is equal to patients with an incomplete tumor resection. This supports the inclusion of LVI in the UICC classification system for esophageal carcinoma.     

Distal esophageal resection and jejunum interposition for early Barrett carcinoma

Distal esophageal resection and jejunum interposition for early Barrett carcinoma. Limited resection with regional lymphadenectomy and jejunal interposition is safe, prevents gastroesophageal reflux and is associated with good quality of life. The procedure represents an oncologically adequate and thus attractive limited surgical alternative to radical esophagectomy or endoscopic resection and ablation techniques in patients with high grade dysplasia or T1 adenocarcinoma in Barrett's esophagus.     

Pre-operative staging of cervical cancer: comparison of magnetic resonance imaging (MRI) and computed tomography (CT) with histologic results

Thirty-two patients with histologically confirmed cervical carcinoma were preoperatively investigated using MRI; in addition, a CAT-scan was performed on 15 of these patients. The diagnostic results using both modalities were compared with the histological findings (after hysterectomy according to Wertheim-Meigs, including lymph node dissection in the pelvic and, in part, in para-aortal regions). Determination of tumour volume was possible with high accuracy using MRI. Accuracy in assessing the parametria was 86%, vagina 90%, bladder and rectum 97%. The shortcoming of MRI is still the detection of infiltrated lymph nodes. The accuracy of 69% achieved for lymph nodes is equal to results with computed tomography. The general accuracy for our patients in staging was 81% for MRI versus 47% for CT. MRI-based diagnosis enables us to determine a correct tumour staging preoperatively, and is therefore very helpful in planning an adequate therapy. If MRI were used more widely it would contribute to simplification and shortening of the preoperative diagnostic procedure in patients with cervical carcinoma.     

Influence of simultaneous neoadjuvant radiotherapy and chemotherapy on bronchoscopic findings and lung function in patients with locally advanced proximal esophageal cancer

To assess the bronchoscopic and lung function changes induced by preoperative radiochemotherapy (30 Gy radiation and 5-fluorouracil) in patients with proximal esophageal cancer, we prospectively compared the findings in 77 consecutive patients before and after the therapy. All patients completed the radiochemotherapy protocol; toxicity was minimal. Sixty-four patients underwent surgery, 48 had total gross removal of disease, and six had a complete histologic response. Of the 13 patients who developed apparent direct macroscopic signs of tumor invasion into the airways during therapy, histologic proof of cancer was obtained in only one of the abnormalities. Bronchoscopy was falsely negative in six patients in whom airway invasion of the cancer was found at surgery. Neoadjuvant therapy led to no systematic changes in the appearance of the uninvolved tracheal mucosa; microscopically, an increase in postinflammatory changes, hyperplasia, and metaplasia was found. There was no significant change in the values of lung function parameters after the therapy. No patient developed symptoms suggestive of radiation-induced lung changes, although in one of them, subtle radiologic features consistent with radiation pneumonitis were found. No patient died of postoperative pulmonary complications. The interpretation of bronchoscopy in the assessment of airway invasion of esophageal cancer after radiochemotherapy is more difficult than at baseline staging; the positive predictive value of macroscopic abnormalities without microscopic proof of cancer is low, and even with extensive sampling for histology and cytology, the procedure was falsely negative in 9.4%. Neoadjuvant therapy did not induce radiation pneumonitis or changes in lung function that could be of concern at the following operation.     

Surgical resection for cancer of the cardia.

From the pathogenic and therapeutic point of view, adenocarcinomas of the esophagogastric junction (AEG) should be classified into adenocarcinoma of the distal esophagus (Type I), true carcinoma of the cardia (Type II), and subcardial carcinoma (Type III). This classification can be easily performed by summarizing the information available from contrast radiography, endoscopy, and intra-operative findings; it allows comparison of data between various centers and facilitates the choice of surgical therapy. A complete removal of the primary tumor and its lymphatic drainage has to be the primary goal of any surgical approach to adenocarcinoma of the esophagogastric junction. In patients with potentially resectable, true carcinoma of the cardia (AEG Type II), this can be achieved by a total gastrectomy with transhiatal resection of the distal esophagus and en bloc removal of the lymphatic drainage in the lower posterior mediastinum and along the celiac axis and superior border of the pancreas. This approach is associated with lower morbidity and provides equal long-term survival as compared to the more radical transmediastinal or abdominothoracic esophagogastrectomy. Whether a routine splenectomy for lymphadenectomy in the splenic hilus offers a survival benefit in these patients is questionable. In patients with early tumors staged as uT1 on pre-operative endosonography, a limited resection of the proximal stomach, cardia, and distal esophagus with interposition of a pedicled isoperistaltic jejunal segment appears justified since this procedure allows a complete tumor removal with adequate lymphadenctomy and offers excellent functional results. Multimodal therapy with pre-operative polychemotherapy or combined radio-chemotherapy appears to offer a significant survival benefit in patients with locally advanced tumors. With this tailored approach, extensive pre-operative staging becomes mandatory for an adequate selection of the appropriate therapeutic concept.     

Pharmacodynamic profile of verapamil in relation to absolute bioavailability: investigations with a conventional and a controlled-release formulation.

The absolute bioavailability F and response (prolongation of the PR interval) of verapamil after single doses of the same oral formulation administered on two different days were investigated in 16 male subjects with an 80 mg fast dissolving and a 240 mg controlled-release preparation and compared with a bolus injection of 5 mg of verapamil. The absolute bioavailability was 23% in both investigations for the 80 mg preparation and 32% in both investigations for the 240 mg dosage form. The individual values obtained for tmax, cmax, F, and AUC0-alpha showed a wide intersubject variability; therefore, no significant differences could be observed between the two trials for each dosage, but significant differences existed between the investigations of the two preparations. After intravenous administration, concentration-effect curves were about twofold left shifted when compared with the 80 mg tablet and about threefold left shifted when compared with the 240 mg tablet. Estimation of the drug input rate showed significantly (p less than 0.05) smaller values when the controlled-release tablet was given (80 mg tablet: 95.1 and 107.7 mg/h; 240 mg tablet; 55.8 and 46.3 mg/h). Thus, the effect and bioavailability of verapamil show sufficient intersubject reproducibility if the same formulation is given. The differences between the responses and the bioavailability after administration of different preparations may be related as well to the drug absorption rate and the stereoselective first pass of verapamil as to saturation of first-pass metabolism.     

377. Histologische Beurteilung experimenteller mikrochirurgischer biliobiliärer Anastomosen

Zusammenfassung Auf der Basis unserer klinischen Erfahrung bei 71 Kranken mit cephaler Duodenopankreatektomie und Pancreatogastrostomie (47 x) und Pancreatojejunostomie (24 x ) und der tierexperimentellen Untersuchung bei 22 Hunden mit pancreatodigestiven Anastomosen konnten wir belegen, daß es nicht möglich ist, eine periductuläre Fibrose des Restpankreasganges aufzuhalten. Morphologische Untersuchungen der Anastomose zwischen Pankreasrest und Magen bzw. Jejunum bestätigen, daß ihr Drainageeffekt nur kurzzeitig ist.