Stefan Paul Moenig

Prognostic impact of p21/waf1/cip1 in colorectal cancer

In addition to the tumor suppressor gene p53, Cyclin Dependent Kinases (CDK) are well known to influence the cell cycle in normal human tissues and various neoplasias as well. The purpose of our present study was to evaluate the expression of the CDK‐inhibitor p21/waf1/cip1 in colorectal cancer with special emphasis on the prognostic impact. Between 1985 and 1991, 294 patients (median age, 65 years) underwent surgical operative therapy for colorectal cancer. Formalin‐fixed and paraffin‐embedded tumor specimens were investigated. For immunohistochemistry the Catalysed Reporter Deposition (CARD) technique was performed. The survival propability was calculated and possible prognostic risk factors were tested using multivariate analysis. The p21/waf1/cip1 staining pattern was positive in 197 (67%) specimens and negative in 97 (33%) samples. No significant correlation could been calculated between p21/waf1/cip1 expression and other variables such as age, sex, WHO‐Classification, localisation, grading, TNM‐classification or UICC‐stage. Patients with a positive staining reaction had a significantly better survival (p < 0.0052). Moreover, p21/waf1/cip1 was shown to be an independent prognostic parameter by multivariate analysis (p < 0.022). In contrast with these findings, the p53 tumor status had no impact on survival. P21/waf1/cip1 appears to be an independent prognostic parameter in colorectal cancer and is associated with a favorable survival. This feature may be related to a cell cycle arrest in the G1 phase induced by p21/waf1/cip1, resulting in lower tumor cell proliferative activity. Int. J. Cancer (Pred. Oncol.) 89:14–18, 2000.

High Cyclooxygenase-2 Expression Following Neoadjuvant Radiochemotherapy Is Associated with Minor Histopathologic Response and Poor Prognosis in Esophageal Cancer

Purpose: High expression of cyclooxygenase-2 (COX-2) was shown to inhibit chemotherapy- and radiotherapy-induced apoptosis. We analyzed the association of COX-2 mRNA and protein expression with histomorphologic response to neoadjuvant radiochemotherapy in esophageal cancer. Experimental Design: Fifty-two patients with resectable esophageal cancers (cT2-4, Nx, and M0) received neoadjuvant radiochemotherapy (cisplatin, 5-5-fluorouracil, 36 Gy) followed by transthoracic en bloc esophagectomy. Histomorphologic regression was defined as major response when resected specimens contained less than 10% of residual vital tumor cells. RNA was isolated from endoscopic biopsies (paired tumor and normal tissue) before neoadjuvant treatment and quantitative real-time reverse transcriptase-PCR (Taqman) assays were done to determine COX-2 mRNA expression levels standardized for β-actin. COX-2 protein expression in pretreatment biopsies and post-therapeutic resection specimens was analyzed by immunostaining of tumor cells. Results: Median COX-2 mRNA expression levels were significantly (P < 0.0001) different between paired tumor (median, 2.2) and normal tissues (median, 0.159). Comparison of pre-therapeutic and posttherapeutic specimens showed a significant difference (P < 0.006) in COX-2 protein expression. Twelve of 52 tumors showed down-regulation and 3 of 52 showed up-regulation of COX-2 protein expression during neoadjuvant radiochemotherapy. High COX-2 protein expression in post-therapeutic resection specimens was significantly associated with minor histopathologic response (P < 0.04) and poor prognosis (5-year survival probabilities: 26.3 ± 8.2% for minor and 58.6% ± 12.9% for major histopathologic response; P < 0.01). Conclusion: High COX-2 protein expression following neoadjuvant radiochemotherapy in resection specimens is significantly associated with minor histopathologic response to neoadjuvant therapy and very poor prognosis.

Apoptosis and expression of bcl-2 protein are inverse factors influencing tumour cell turnover in primary carcinoid tumours of the lung.

This study evaluates potential regulating factors in primary pulmonary carcinoid tumours, 16 typical and four atypical samples, with special emphasis on apoptosis and the bcl‐2 gene family. Furthermore, p53‐related oncogenes were analysed in a search for associated biological parameters.

Pathohistological classification systems in gastric cancer: Diagnostic relevance and prognostic value

Several pathohistological classification systems exist for the diagnosis of gastric cancer. Many studies have investigated the correlation between the pathohistological characteristics in gastric cancer and patient characteristics, disease specific criteria and overall outcome. It is still controversial as to which classification system imparts the most reliable information, and therefore, the choice of system may vary in clinical routine. In addition to the most common classification systems, such as the Laurén and the World Health Organization (WHO) classifications, other authors have tried to characterize and classify gastric cancer based on the microscopic morphology and in reference to the clinical outcome of the patients. In more than 50 years of systematic classification of the pathohistological characteristics of gastric cancer, there is no sole classification system that is consistently used worldwide in diagnostics and research. However, several national guidelines for the treatment of gastric cancer refer to the Laurén or the WHO classifications regarding therapeutic decision-making, which underlines the importance of a reliable classification system for gastric cancer. The latest results from gastric cancer studies indicate that it might be useful to integrate DNA- and RNA-based features of gastric cancer into the classification systems to establish prognostic relevance. This article reviews the diagnostic relevance and the prognostic value of different pathohistological classification systems in gastric cancer.

Is the urokinase-type plasminogen activator system a reliable prognostic factor in gastric cancer?

AIM The aim of this prospective study was to evaluate the clinical and prognostic impact of immunohistochemically assessed uPA and PAI-1 in patients with gastric cancer. METHODS This prospective study analyzed specimens obtained from 105 gastric cancer patients who underwent gastrectomy with extended lymphadenectomy. The immunohistochemical expression of uPA and PAI-1 was studied semiquantitatively in the tumor epithelium and was correlated with the clinicopathological features of each patient. RESULTS Univariate analysis revealed no statistically significant association of uPA levels with pT and pN category (p=0.655 and 0.053, respectively), grading (p=0.374), depth of tumor invasion (p=0.665), UICC classification (p=0.21) and the Laurén classification (p=0.578). PAI-1 expression showed no statistically significant correlation with pT, pN and M category (p=0.589, 0.414, and 0.167, respectively), grading (p=0.273), and the Laurén classification (p=0.368). Only the UICC classification was significantly correlated with PAI-1 (p=0.016). Kaplan-Meier analysis revealed no significant association of uPA and PAI-1 with overall survival (p=0.0929 and 0.0870, respectively). CONCLUSIONS Our results could not verify any prognostic value of uPA and PAI-1 levels in patients with gastric carcinoma. Therefore, the uPA-system as a biologically defined prognostic marker to identify high-risk gastric cancers should be applied with caution. However, considering the number of patients involved and the borderline level of significance observed in this study, a larger number of events may have resulted in significant differences.

Third international conference of the European Union Network of Excellence on gastric and esophagogastric junction cancer, Cologne, Germany, June 2012.

Abstract In 2012 the European Union Network of Excellence on gastric and esophagogastric junction cancer (EUNE) held its third conference in Cologne, Germany. The main themes discussed included translational research, standard and audit, early diagnosis, development of surgical treatment, adequate surgery for EGJ cancer, adjuvant and neoadjuvant treatment, prevention of peritoneal carcinomatosis and finally education and training. The meeting was attended by 150 experts from 18 different countries.

Phytobezoar: Impact of Differential Diagnosis and Difficulties in Technical Diagnostics

For the diagnosis of phytobezoar, it is good to examine the stomach by endoscopy. In contrast, for the lower parts of the intestinal tract, the diagnosis can be challenging and the visible structure will frequently be impossible to distinguish from a tumor mass [2, 5] . Risk factors for the development of a phytobezoar are previous resections/reconstructions in the intestinal tract, stenosis (e.g. Crohn’s disease, tumor), disturbances of the GI motility, abnormal diet or vegetarianism [3, 4] . The localization can be in all parts of the intestinal tract. Severe complications can be an ileus or even a perforation of the intestinal wall [3] . Chemical dissolution and especially endoscopic treatment can be an appropriDear Sir, We read the article ‘Phytobezoar of the stomach’ by Park and Chae [1] with great interest. Despite the fact that the literature published on the matter is rare, with only a small number of case reports, the clinical incidence of phytobezoar seems not to be that rare in reality. I will cite here one case relevant from this point of view and which will be published shortly: we noticed a cherry pit ileus of the colon ascendens, which had been causing abdominal pain for a long period. Many previous clinical and technical examinations like endoscopy and even CT scan did not lead us to the correct diagnosis. When the patient was admitted to our hospital, we had a strong suspicion of an obstructing malignant tumor and performed a right hemicolectomy. Published online: August 3, 2010

Synchronous nonfunctioning neuroendocrine carcinoma of the pancreas and appendix.

To the Editor: We report the rare case of a female patient with a nonfunctioning neuroendocrine pancreatic carcinoma and a simultaneously and independently growing carcinoid tumor of the appendix. Although lymph node and liver metastases were present, extended multivisceral resection was performed. A 47-year-old female patient underwent laparotomy under the suspicion of pancreatic cancer. At operation, the tumor was found to grow within the pancreatic tail. Liver metastasis was detected and atypically completely resected. No tumor-suspicious lesions were seen in the pancreatic corpus or head. Further exploration revealed an additional tumor mass that developed out of the cecum, growing within the mesenterium of the small bowel and the right colon toward the lower margin of the pancreas. Multiple enlarged lymph nodes were found around the large blood vessels. Since intraoperative frozen-section diagnosis was not able to differentiate between a low-malignant pancreatic tumor and a pancreatic carcinoma, multivisceral resection including splenectomy, atypical liver resection, and resection of the pancreatic tail and the right hemicolon was performed (R0). The patient was discharged from the hospital symptom free on day 14 after surgery. Six months after discharge, the patient had gained weight and was free of any abdominal symptoms. Restaging, including somatostatin receptor scanning, showed no evidence of tumor recurrence or metastasis. Independently growing synchronous metastatic neuroendocrine carcinoma of the pancreas (pT3 N2 M1[hep]) and appendix (pT2 N2 Mx). The tumor cells were strongly positive for chromogranin A with a rare mitotic action. The expression for serotonin and synaptophysin was positive. Negative immunostaining was found for gastrin, 1antitrypsin, and insulin with positive internal control for insulin in normal pancreatic tissue. The patient had the extremely rare diagnosis of a welldifferentiated neuroendocrine carcinoma of the pancreas and a synchronously growing carcinoid tumor of the appendix. In contrast to acinous pancreatic carcinoma, the 5-year survival rate for patients with nonfunctioning neuroendocrine pancreatic carcinoma is between 40% and 50%. After curative resection, the 5-year survival even rises up to 75%, while noncurative resection is associated with a 5-year survival rate of 30%–40%. Because of the young age of the patient, the small amount of liver metastasis, and the resectable tumor masses, we believed that she would benefit in terms of survival from this extensive surgical procedure, which was performed. Pancreatic islet cell tumors with cytologic and immunohistochemical characteristics of functioning neuroendocrine tumors are classified as nonfunctioning neuroendocrine tumors if the patient lacks the clinical aspects of a specific neuroendocrine syndrome and does not, as our patient, have elevated serum gastrointestinal hormone levels. According to the literature, the annual incidence of neuroendocrine pancreatic carcinoma is 0.5 to 1 case per 100,000 population. Twenty percent to 30% of these carcinomas are nonfunctioning, present during the sixth decade of life, occur in the head of the pancreas, and are associated with a 5-year survival rate of ≈50% following resection. Carcinoid tumors of the appendix are almost always found accidentally during surgery for suspected appendicitis. The prevalence of carcinoid tumors after appendectomy is 0.69%. They comprise 18.9% of all carcinoid tumors and 25.7% of all gastrointestinal carcinoids. The frequency of metastasis from these tumors has been reported between 1.4% and 8.8% in different series and rises with the size of the tumor. Because most of the appendix carcinoids are <2 cm in size and have no metastasis, the 5-year survival rate is reported to be 90%–100%. To our knowledge, there is no report of two independently growing neuroendocrine carcinomas in the literature, although multifocal growth is well described. The central point of interest of this case is the site of the primary tumor, since two large tumor foci were detectable within the pancreas and the appendix. The suspicion of two similar and synchronous but independently growing tumors is the most probable, since lymphovascular invasion and metastasis of a primary pancreatic carcinoma into the appendiceal region are as unlikely as metastasis of a primary appendiceal carcinoid into the pancreas. In conclusion, patients with neuroendocrine pancreatic carcinoma seem to benefit from multivisceral resections since their prognosis is much better than of those with adenocarcinoma of the pancreas. As long as frozen-section diagnosis is not able to differentiate between neuroendocrine carcinoma and adenocarcinoma, extended resections should be performed.

Gastric cancer treatment in the world: Germany

Epidemiologically, around 15,500 persons per year contract gastric cancer with continuously decreasing incidence and a 5-year survival rate of only 30% to 35%. Contrary to the Asian countries, there are no prevention programs for gastric cancer in Germany, which leads to the disease frequently being diagnosed in locally advanced stages and predominantly being treated with multimodal therapy concepts. Complete (R0) resection is the therapy of choice for resectable gastric cancer. Special forms of gastric cancer that are limited to the mucosa can be endoscopically resected with a curative intent. Systematic D2 lymphadenectomy (LAD) plays a decisive role in the management of local advanced tumors because it significantly contributes to the reduction of tumor-related death and both local and regional relapse rates. Perioperative chemotherapy improves prognosis in the advanced stages, whereas palliative chemotherapy is normally indicated for metastatic diseases. Standardized resection procedures and the use of individualized multimodal therapy concepts have led to improvement in the 5-year survival rate.

Heterotopes Pankreasgewebe der Magenwand

ZusammenfassungEpigastrische Schmerzen, Übelkeit, Erbrechen und eine obere gastrointestinale Blutung werden gelegentlich durch heterotopes Pankreasgewebe der Magenwand verursacht. Trotz moderner diagnostischer Verfahren gestaltet sich die Diagnose heterotopen Pankreasgewebes oftmals schwierig. Daher wird von vielen Autoren die Magenwandresektion und Schnellschnittuntersuchung als diagnostische und therapeutische Maßnahme befürwortet. Zwei typische Kasuistiken werden im Folgenden mit einer Literaturübersicht vorgestellt. AbstractHeterotopic pancreas is an uncommon cause of gastrointestinal complaints such as epigastric pain, nausea, vomiting, and upper gastrointestinal bleeding. Despite the development of modern diagnostic procedures, it is still difficult to differentiate heterotopic pancreatic tissue from other benign or malignant gastric tumors. Local excision of the gastric wall is regarded as the diagnostic and therapeutic procedure of choice. We present two cases and an overview of the literature.