[Neuroendocrine tumors : Classification, clinical presentation and imaging]. / Neuroendokrine Tumoren : Klassifikation, Klinik und Bildgebung.

CONTEXT: Neuroendocrine tumors (NET) are a heterogeneous group of neoplasms found in all organs. They often present with characteristic clinical syndromes due to hormone hypersecretion. DIAGNOSTICS: In addition to hormone diagnostics molecular-genetic work-up can play an important role. IMAGING: Morphological imaging comprises ultrasound, endoscopy, computed tomography (CT) and magnetic resonance imaging (MRI) scans. Functional imaging of NET relies on radioligands that bind to specific receptors or transporters (Ga-68-DOTATATE-PET-CT, Tc-99-tektrotyd-SPECT/CT, F­18-DOPA-PET/CT). THERAPY: Somatostatin analogs either native or coupled to radionuclides are potent drugs for treating various neuroendocrine tumors. CONCLUSION: The requirements of imaging are determined by clinical presentation, laboratory findings, tumor stage, the presence of a tumor syndrome and the need of a personalized systemic treatment modality.

[Rectal neuroendocrine tumors: endoscopic therapy]. / Neuroendokrine Tumoren des Rektums: endoskopische Therapie.

Clinically detected neuroendocrine neoplasms of the rectum have increased 10- to 30-fold in frequency over the past 45 years in Germany. Endoscopic ultrasonography is the method of choice for exact determination of the size of the tumor, depth of infiltration and detection of local lymph node metastases. Well-differentiated neuroendocrine tumors ≤ 10.0 mm in size that do not infiltrate the muscularis propria can be endoscopically resected. In the case of lymphatic or blood vessel invasion or spread to lymph nodes, surgical lymph node dissection is indicated. The management of well-differentiated, neuroendocrine rectal tumors 10.1-20 mm in size is still a matter of debate. Old age and multimorbidity favor a conservative endoscopic approach; however, in the case of fit young patients, surgical management has to be considered. For neuroendocrine rectal neoplasms ≥ 20 mm in size, the risk of metastatic spread increases to 60-80 % indicating that an endoscopic resection is not adequate. Due to the introduction of screening colonoscopy, neuroendocrine rectal tumors are nowadays diagnosed mostly at a prognostically favorable early stage.

[Neuroendocrine neoplasms of the appendix and colorectum]. / Neuroendokrine Neoplasien der Appendix und des Kolorektums.

Appropriate diagnosis and treatment of neuroendocrine neoplasms (NENs) of the appendix and colorectum requires a detailed knowledge of their proper classification according to the updated WHO and TNM systems. The WHO classification distinguishes well differentiated NEN, the neuroendocrine tumors (G1 and G2 NETs), from the poorly differentiated carcinomas (G3 NECs). While NETs are common in the appendix and rectum, NECs occur predominantly in the colon. G1 appendiceal and rectal NETs of 1 cm in size or below that do not invade either the muscular wall or vessels bear almost no metastatic risk and can be treated by appendectomy or endoscopic resection. G2 appendiceal and rectal NETs larger than 1 cm in size in combination with other risk factors have an increased risk of metastasis and need to be treated more aggressively. NECs of the colon usually require chemotherapy in addition to resection. Today, most patients with NETs of the appendix and rectum have an excellent prognosis when these diagnostic and therapeutic guidelines are borne in mind.

Neuroendocrine tumors of the stomach (gastric carcinoids) are on the rise: small tumors, small problems?

Well differentiated neuroendocrine tumors (NETs) of the stomach (gastric carcinoid tumors) are observed more often, with a tenfold increase in the US in the last 30 - 35 years, and the prognosis has improved greatly in that time. Nowadays most carcinoids of the stomach are diagnosed at an early stage. Four types of gastric NETs have been proposed and recognition of the type is important for defining the diagnostic approach and treatment. Often gastric NETs (especially type 1) are found incidentally during a gastroscopy performed for other reasons; most of these NETs are smaller than 20 mm in size. Conservative management and endoscopic surveillance is adequate for well differentiated, multifocal gastric carcinoids (type 1 or type 2 gastric NETs) that are less than 10 - 20 mm in diameter, unless they show angioinvasion, infiltrate the muscular wall, or have a proliferation rate above 2 %. Endoscopic ultrasound is the method of choice to determine tumor size and depth of infiltration. It is essential to distinguish between multifocal (types 1 and 2) and unifocal type 3 or type 4 gastric NETs, since surgery is indicated for type 3 gastric NETs larger than 10 mm in diameter and for poorly differentiated (localized) neuroendocrine gastric carcinomas (type 4 gastric NET). For optimal management, the type, biology, and stage of the tumor as well as the individual situation of the patient must be considered. Most patients with well differentiated gastric NETs can be treated conservatively and be followed up with endoscopic surveillance.

[Neuroendocrine tumors of the stomach. Risk stratification and therapy]. / Neuroendokrine Tumoren des Magens. Risikostratifizierung und Therapie.

The diagnosis and therapy of neuroendocrine tumors (NETs) of the stomach are based on their exact classification and risk stratification. Since the incidence of gastric NETs has risen sharply over the last 35 years and most tumors are detected endoscopically at an early stage, they have come to represent a challenge for the pathologist. Gastric NETs are classified according to the WHO and TNM classifications and additionally separated into four biologically distinct types: Well differentiated type 1 and 2 gastric NETs (G1) smaller than 2 cm, and type 3 smaller than 1 cm that do not infiltrate the muscularis propria or show angioinvasion have a good prognosis and can be removed endoscopically. Well differentiated type 1 and 2 gastric NETs (G1-G2) larger than 2 cm or type 3 with a diameter above 1 cm or with infiltration of the muscular wall and/or angioinvasion and poorly differentiated (type 4) neuroendocrine carcinomas carry a poor prognosis and need to be treated aggressively. Endosonography is the method of choice for determining the size, depth of infiltration and presence of lymph node metastases. With exact diagnosis and adequate treatment, the majority of patients with gastric NETs have a favorable prognosis.

[Neuroendocrine tumors of the small bowels are on the rise: early tumors and their management]. / Neuroendokrine Tumoren des Dünndarms nehmen zu: frühe Tumoren und deren Management.

Neuroendocrine tumors (NETs) of the small bowels are on the rise: in the US they have increased by 300-500% in the last 35 years. At the same time their prognosis has been much improved. Most NETs of the duodenum are nowadays detected "incidentally" and therefore recognized at an early stage. Duodenal NETs that are well differentiated, not larger than 10 mm in greatest dimension and limited to the mucosa/submucosa can be endoscopically resected. In NETs with a size between 10 mm and 20 mm the therapeutic strategy has to be individually discussed. Endoscopic ultrasound is the method of choice to determine tumor size and depth of infiltration. Surgery is indicated for well differentiated duodenal NETs greater than 20 mm, for localized sporadic gastrinomas and for localized poorly differentiated NE cancers. Surgery is also indicated for localized/regional ileal NETs. Advanced ileal NETs with a carcinoid syndrome are treated with stable somatostatin analogs. This treatment also significantly improves the (progression-free) survival in patients with metastatic NETs of the ileum. For optimal NET management tumor biology, type, localization and stage of the neoplasm as well as the individual situation of the patient have to be taken into account.

[Neuroendocrine tumors of the stomach (gastric carcinoids) are on the rise: good prognosis with early detection]. / (Neuro-)Endokrine Tumoren des Magens sind auf dem Vormarsch: Gute Prognose bei frühem Nachweis.

Neuroendocrine tumors (NET) of the stomach are on the rise. In the United States they have increased about tenfold in the last 35 years. Prognosis has been much improved over the last three to four decades. Nowadays most of such NETs are diagnosed at an early stage. Quite often gastric NETs are found incidentally during a gastroscopy, performed for other reasons. Most of the asymptomatic, well differentiated gastric NETs are less than 2 cm in diameter. Conservative management and endoscopic surveillance is adequate for well differentiated, multifocal type 1 or type 2 gastric NETs (gastric carcinoids) of 10-20 mm , unless they are angio-invasive, have infiltrated into the muscularis propria or have metastasized. Endoscopic ultrasound is the method of choice to determine tumor size and depth of infiltration. Surgery is, however, indicated for all NETs larger than 20 mm. For optimal management tumor biology, type and stage of the neoplasm as well as the individual situation of the patient have to be taken into account. Most of the patients can be treated conservatively and be followed up with endoscopic surveillance.

[Rectal carcinoids on the rise - update]. / Neuroendokrine Neoplasien des Rektums auf dem Vormarsch - ein Update.

Rectal carcinoids are becoming more common: in the USA they have increased in frequency by 800 - 1000 % in the past 35 years. This dramatic increase is probably related to the introduction of colonoscopic screening which also results in the "incidentally" detected neuroendocrine rectal tumours/carcinomas being smaller than in the pre-screening era. Endosonography is the method of choice for determining the size and depth of penetration of the tumours and for detecting lymph node metastases. Tumours of < 10 mm in size that have not infiltrated the muscularis propria can usually be removed endoscopically. When invasion of lymph or blood vessels or lymph node metastases are found, surgical resection of the lymph nodes is indicated. Neuroendocrine rectal neoplasms (rectal carcinoids) of 10.1 - 20 mm in diameter have a metastasis risk of 17 - 42 (81) % for neuroendocrine rectal neoplasms > 20 mm in size this risk increases to 60 - 80 %. A carcinoid syndrome is rarely observed, even in cases of distant metastases of neuroendocrine rectal carcinomas. Stable somatostatin analogues and interferon-alpha constitute the drug therapies of choice for carcinoid syndrome. As a result of the increasing early detection of rectal carcinoids/carcinomas the prognosis for the patients has improved considerably in the last 30 years. In addition to the early detection of colorectal adenoma and adenocarcinoma, screening colonoscopy also makes possible the early detection and early therapy for neuroendocrine rectal tumours/carcinomas.

Rectal carcinoids are on the rise: early detection by screening endoscopy.

Rectal carcinoids are on the rise; in the United States the age-adjusted incidence has increased by 800% -1000% in the last 35 years. The incidence of carcinoids of the stomach, pancreas, or small bowels has also multiplied. The reasons for these epidemiological changes are not yet understood. Both screening sigmoidoscopy and screening colonoscopy lead to a shift to smaller-sized (< or =13 mm) rectal carcinoids and earlier tumor stages at diagnosis. During the last 35 years the overall 5-year survival of patients with rectal carcinoid disease has increased by almost 20% (in the US). Thus, endoscopic screening of the colorectum is effective in the early diagnosis not only of colorectal adenomas and adenocarcinomas but also of carcinoids. Rectal carcinoids that are 10.0 mm or less and do not infiltrate the muscularis propria can be removed endoscopically. If histological angioinvasion or lymph node metastases are found, surgical lymph node dissection has to be considered. Before deciding on definitive therapy, rectal carcinoids should be staged by means of endoscopic ultrasonography, CT, or MRI and somatostatin receptor scintigraphy.

[Coincidental squamous cell cancers of the esophagus, head, and neck: risk and screening]. / "Field cancerization" im oberen Aerodigestivtrakt: Uberwachungsempfehlungen für Risikopersonen.

The term "field cancerization" was coined by Slaughter in1953 when describing multifocal synchronous and metachronous carcinogenesis in the upper aerodigestive system. Patients suffering from head and neck cancer (HNC) have or develop a second esophageal squamous cell cancer (ESCC) or bronchial cancer (BC) in 5-14% of cases. When a second esophageal cancer occurs in a patient with HNC, the prognosis is generally determined by the ESCC, and, unfortunately, it is poor. Screening and surveillance by Lugol chromoesophagoscopy enable early detection and curative treatment of second esophageal neoplasias. Surveillance appears to result in a survival benefit for HNC patients. Vice versa, patients with ESCC or BC have a risk of about 10% for developing HNC. Periodic pharyngolaryngoscopy is recommended for curatively treated ESCC or BC patients. Patients with field cancerization should be surveilled by a multidisciplinary approach.

[Coincidental squamous cell cancers of the esophagus and head and neck: risk and surveillance]. / Koinzidenz von Plattenepithelkarzinomen der Speiseröhre und Kopf-Hals-Karzinomen: Risiko und Früherkennung.

Patients suffering from head and neck cancer (HNC) have or will develop a second esophageal squamous cell cancer (ESCC) in 5 - 14 %. When a second esophageal neoplasm occurs in a HNC patient, the prognosis is generally determined by the ESCC, and unfortunately it is poor. Prospective clinical studies in Japan, Brazil, Taiwan, France and Germany have shown that screening or surveillance using Lugol chromoesophagoscopy enables early detection of second esophageal neoplasias. Such a surveillance results in a survival benefit for HNC patients. Vice versa, ESCC patients also have a risk of 9.3 - 11.4 % for a head and neck cancer. Periodic otolaryngeal examination and pharyngoscopy is recommended for curatively treated ESCC patients. Patients with a so-called field cancerisation of the airways and upper digestive tract thus require an interdisciplinary management and monitoring.

[Increased incidence of hepatocellular and intrahepatic cholangiocellular carcinoma in northeast Germany]. / Zunahme des hepatozellulären und des intrahepatischen cholangiozellulären Karzinoms im Nordosten Deutschlands.

BACKGROUND AND OBJECTIVE: Hepatocellular cancer (HCC) is one of the five most common cancers worldwide. In Western countries the incidence of both HCC and intrahepatic cholangiocellular cancer (iCCC) has increased quite dramatically in the last 20 years. It was the aim of this study to assess the epidemiological changes of both cancers in the Northeast of Germany. METHODS: Using the data base of the Joint German Cancer Registry of the New Federal States and of Berlin, the age- and world-population-adjusted incidence of HCC and iCCC and their 5-year survival were calculated. The states of Brandenburg, Mecklenburg-Vorpommern and Saxony were chosen for this study because of the high quality of their registration base. RESULTS: In men the age-adjusted incidence of HCC increased from 3.6 in 1976 to 5.7 in 2002, the absolute number of newly diagnosed HCCs rising from 192 to 383 males within this period. In women the incidence was much lower. While only 30 males and 36 females were diagnosed with iCCC in 1976, in 2002 there were 64 men and 75 women with iCCC. In 1976, the corresponding age-adjusted incidence was 0.5 in men and 0.4 in women. Up to 2002 the incidence of iCCC rose to 0.8 and 0.6, respectively. The cumulative 5-year survival of HCC and iCCC was less than 10% for each. Comparison of the early period (1978-1979) with the later one (1998-1999) demonstrated a statistically significant improvement in survival for HCC. This was most likely due to earlier diagnosis and treatment of HCC. CONCLUSION: In the Northeast of Germany the incidence of both HCC and iCCC have increased markedly in the last 20 years. The recently improved survival of HCC patients most likely reflects earlier diagnosis and treatment.

[Current diagnosis and therapy of esophageal carcinoma]. / Aktuelle Diagnostik und Therapie des Osophaguskarzinoms.

In Germany the incidence of esophageal cancer is 6 - 10 per 100,000. At the time of diagnosis about 75 % of the patients suffer from UICC stage III or IV esophageal cancer. Less than 10 % of patients are diagnosed with early (T1) cancer. Diagnosis and staging relies on esophagoscopy including biopsies, endoscopic ultrasonography, and computerized tomography of the chest and abdomen. Intramucosal early cancer (T1a) and high-grade dysplasia can be treated either by surgery or by endoscopic mucosal resection. Chemoradiation is the definitive treatment of choice for localized squamous cell cancer of the proximal esophagus. As far as overall survival is concerned definitive chemoradiation is not inferior to esophagectomy even in patients with localized squamous cell cancer of the middle or lower esophagus. In case of high surgical risk chemoradiation should be offered to those patients as the therapy of choice. Esophagectomy should be performed in operable patients suffering from resectable adenocarcinoma of the esophagus. Preoperative chemoradiation is recommended in locally advanced (non-resectable) adenocarcinoma. If staging reveals distant metastases, palliative therapy is indicated. Palliative chemotherapy with 5-fluorouracil and cisplatin should be offered to patients with good performance status. Esophageal intubation (with expandable metal stents) is the palliative treatment of choice for firm stenosing, non-resectable tumors, where rapid relief of dysphagia is required.

Recent results in understanding molecular pathways in the medical treatment of esophageal and gastric cancer.

Cancers of the esophagus and stomach constitute a major cause of cancer deaths worldwide. Despite improvements in both surgical techniques and (radio) chemotherapy regimens, these tumors remain a great therapeutic challenge. Thus, there is a need for innovative medical treatment strategies effective even in advanced disease. An emerging understanding of the molecular events that characterize carcinogenesis, tumor growth and spread may provide novel targets in cancer therapy. In this review we discuss novel strategies to inhibit growth, angiogenesis, invasion, and spread of tumors and to induce apoptosis. Therapeutic strategies discussed include agents targeting the epidermal growth factor receptor (EGFR) family, the mitogen-activated protein kinase (MAPK) pathway, regulators of apoptosis (NF-kappaB, bcl-2, and the peripheral benzodiazepine receptor), cyclooxygenase-2, the vascular-endothelial growth factor receptor and matrix metalloproteinases.