Chirurgische Therapie von Magenkarzinomen und Adenokarzinomen des ösophagogastralen Übergangs

Context

The incidence of gastric cancer has been steadily declining during the last decade in the Western world. In contrast, the incidence of the adenocarcinoma of the esophagogastric junction (AEG) has been continually rising. Gastric cancer continues to be a leading cause of cancer death and has a poor prognosis despite subsequent 5-year survival improvement of 10?% during the last two decades.

Methods

Literature research and analysis of clinical trials.

Results

Adenocarcinoma of the esophagogastric junction have a different tumor biology and prognosis; hence, adenocarcinoma of the esophagogastric junction represents a separate tumor entity. Topographic-anatomical classification differentiates three subtypes (AEG I–III). Radical resection is the only option to cure the disease. In gastric cancer, the histological subtype (intestinal vs. diffuse) defines the extent of the resection (subtotal vs. total), whereas in AEG, topographical classification determines the resection dimensions (extended gastrectomy vs. esophagectomy). In gastric cancer, a D2 lymphadenctomy (compartments I and II) is the gold standard. In AEG type I, a 2-field lymphadenctomy and in AEG types II and III a D2 lymphadenctomy including dissection of the lower mediastinal lymph nodes is performed.

Conclusions

Surgical standards are available and should be followed for gastric cancer and AEG I and III tumors. The optimal surgical approach for AEG type II tumors remains at current open. Multimodal therapy concepts can increase R0-resection rates and improve prognosis in locally advanced disease. In the palliative situation, surgery in the context of multimodal therapy can contribute to improvement of quality of life and increased survival.     

Frühe Karzinome des Magens und ösophagogastralen Übergangs

Context

Due to the lack of screening programs in Western countries, most gastric cancers are diagnosed in advanced stages.

Method

Literature research and analysis of clinical trials.

Results and conclusion

For new therapeutic options, like mucosal resection and interdisciplinary protocols, sophisticated staging should include high-resolution computed tomography of the thorax, abdomen, and pelvis, video-documented endoscopy, and endoscopic ultrasound. This exact T- and N-staging allows for tailored therapy of the different tumors. In mucosal gastric cancer, endoscopic resection in specialized centers can replace surgical resection, if specific criteria are present.     

Adenokarzinome des Magens und gastroösophagealen Übergangs

Context

There is worldwide consensus that curative treatment of gastroesophageal adenocarcinoma can be optimized by a multidisciplinary approach.

Method

Literature research and analysis of clinical trials.

Results

In the USA adjuvant chemoradiotherapy is a standard of care for gastric cancer. Asian trials could show an improvement in survival by adjuvant chemotherapy. In Europe the recommendations are based on the British MAGIG trial and the French FNCLCC study. In these trials patients with adenocarcinoma of the stomach and gastroesophageal junction (GEJ) were treated with platinum 5-FU-based perioperative chemotherapy and overall survival could be significantly improved. For the treatment of adenocarcinoma of the GEJ preoperative radiochemotherapy is an equivalent standard. A significant improvement of survival could also be shown for this treatment.

Conclusion

The German S3 guidelines recommend perioperative chemotherapy for gastric tumors of at least stage uT3 and for GEJ adenocarcinoma either perioperative chemotherapy or preoperative radiochemotherapy.     

Pathologie des ösophagogastralen Adenokarzinoms

Context

Adenocarcinomas of the esophagogastric junction and the stomach share similar preneoplastic lesions and genetic alterations but are different according to their risk profiles and epidemiological characteristics.

Objective

The aim of the review was the comparison of pathohistological, molecular and therapeutic similarities and differences of these tumor entities.

Material and methods

The following review relied on a literature database search comprising the pathohistological, molecular and clinical characteristics of adenocarcinomas of the esophagogastric junction and the stomach.

Results

For both entities comparable alterations have been published even correlating with the pathohistological subtypes.

Conclusions

Despite many similarities concerning pathogenesis, the TNM classification for both tumor entities recommended by the WHO depends on the localization and is of particular importance for the clinical practice. Molecular targets for therapy optimization include Her2/neu and in the future, perhaps also c-Met.     

Definitive Radiotherapie und Radiochemotherapie des Ösophaguskarzinoms

The value of definitive radiotherapy for cancer of the esophagus has already been established in the early 1980s. In the following years studies to compare radiotherapy with radiochemotherapy were initiated. A phase III trial (RTOG 85–01) found better local control with radiochemotherapy and the long-term follow-up also revealed improved survival. An intergroup dose escalation study (INT 0123) showed no evidence of a higher rate of local control or better survival with 64 Gy instead of the standard dose of 50.4 Gy. Based on radiobiological considerations a moderate dose escalation to 60 Gy seems to be justified, especially with highly conformal radiation techniques (e.g. IMRT), whereby toxicity levels can be kept low. The only prospective study that compared radiochemotherapy with surgery found no difference between the two forms of treatment with respect to local control and overall survival. In the context of multimodality approaches definitive radiochemotherapy plays a role if patients have co-morbidities that hamper surgery or if they show good response to neoadjuvant treatment.     

Diagnostik und Therapie des hepatozellulären Karzinoms

Aims

Hepatocellular carcinoma (HCC) is a frequent complication of liver cirrhosis. Worldwide HCC is one of the most common cancers with a rising incidence.

Content

Rapid recognition of HCC and the earliest possible treatment are decisive for the further course. Both treatment of the tumor and the underlying chronic liver disease, including preservation of liver function, are important for the management of patients with HCC.

Conclusion/recommendations

Standard stage-adapted treatments include liver resection, transplantation, and interventional treatment such as thermal ablation and transarterial therapy. In the advanced stage, treatment with the tyrosinekinase inhibitor sorafenib is the standard of care.     

Diagnostik und Therapie des hepatozellulären Karzinoms

Die Onkologie - Die Inzidenz des hepatozellulären Karzinoms (HCC) steigt seit einigen Jahren weltweit. Die Grundlage für die HCC-Entwicklung ist meist eine Leberzirrhose verschiedener...     

Systemtherapie des Ösophaguskarzinoms und Stellenwert zielgerichteter Substanzen

Esophageal carcinomas are known to be moderately chemosensitive tumors. The value of chemotherapy with respect to improvement in prognosis of patients with metastasized disease is not clarified. The position on indications follows individual recommendations and takes palliative aspects into consideration. The two most common subtypes, adenocarcinoma and squamous epithelial carcinoma, respond to chemotherapy with an approximately equal probability. Combination therapies based on cisplatin and 5-fluorouracil are established regimes. In principle all regimes which can be used for gastric carcinoma can also be active for esophageal carcinoma. Approximately 25-30% of adenocarcinomas of the esophagogastric junction show an overexpression of HER2 protein. Tumors overexpressing HER2 profit from treatment with the Her-2 antibody trastuzumab in combination with cisplatin-fluoropyrimidine chemotherapy. Squamous epithelial carcinomas of the esophagus often show an overexpression of epidermal growth factor receptor (EGFR).Whether anti-EGFR antibodies and other targeted therapies contribute to improved effectiveness of conventional chemotherapy is the subject of currently planned studies.     

Klinische Aspekte und Pharmakoökonomie beim Ovarialkarzinom

Ovarialkarzinome haben die h?chste Mortalit?tsrate aller gyn?kologischen Karzinome. Trotz aggressiver operativer und intensiver Chemotherapie hat sich die Prognose von Patientinnen mit Ovarialkarzinom in den letzten 10 Jahren nur unwesentlich verbessert. Die Inte-gration von Taxanen in die Behandlung von suboptimal operierten Patientinnen wurde pharmako?konomisch evaluiert. Wenn auf Kosteneffektivit?t und Kosten-Nützlichkeit untersucht, ergab sich jeweils für das Taxan-haltige Protokoll ein klarer Vorteil gegenüber dem konventionellem Protokoll. Daher erscheint auch aus pharmako?konomi-schen überlegungen eine Integration von Taxanen in die Standardtherapie von Patientinnen mit fortgeschrittenem Ovarialkarzinom gerechtfertigt. Es bleibt zu beweisen, ob diese Feststel-lung auch für optimal tumorreduzierte Frauen mit Ovarialkarzinom gilt.     

Operative Therapie des Endometriumkarzinoms und seiner Präkanzerosen

Das Endometriumkarzinom des Korpus uteri ist mit einem Anteil von j?hrlich etwa 9.600 Neuerkrankungen und einem Anteil von 5–6% an allen b?sartigen Neubildungen, die z. Z. vierth?ufigste Krebserkrankung der Frau. Die Inzidenz der Erkrankung steigt mit dem Alter kontinuierlich an und erreicht ihren Gipfel zwischen dem 50. und 70. Lebensjahr [1]. Die operative Therapie des Endometriumkarzinoms ist die Standardtherapie. Neben der definitiven operativen Behandlung stellt die operative Therapie gleichzeitig auch die wichtigste Voraussetzung für das Staging der Erkrankung dar [11]. Die alte Klassifikation der FIGO ordnete das Endometriumkarzinom klinisch nur hinsichtlich seiner Ausbreitung innerhalb der Organgrenzen ein. Seit 1988 liegt eine neue Stadieneinteilung vor, welche die Tumorausbreitung innerhalb des Myometriums berücksichtigt, den Zervixbefall zwischen isoliertem Drüsenbefall und Stromainvasion unterscheidet und dem Stadium III alle F?lle mit Serosabefall, positiver Peritonealzytologie und Lymphknotenmetastasierung zuordnet [6, 7, 10, 18]. Diese Klassifizierung stellt das operative Staging in den Vordergrund und be- deutet für den Gro?teil der Patienten bereits die definitive Behandlung der Erkrankung.     

Operative Therapie des primären und metastasierten Melanoms

Ein allgemein gültiges Konzept zur operativen Prim?rversorgung des kutanen Melanoms existiert noch nicht, teils wegen unklarer Datenlage, teils wegen einer Vielzahl unbekannter Faktoren, so z. B. wie es zur Satelliten- oder Intransit-Metastasierung kommt. Gesichert ist jedoch erstens, dass ein Zuviel an lokoregion?rer cirurgischer Therapie keinen Nutzen bringt und zweitens, dass wegen unterschiedlicher lokaler Ausbreitungsmuster verschiedener Melanomtypen modifizierte lokale Therapiekonzepte m?glich sind. Bei dünnen Melanomen des superfiziellen und nodul?ren Typs bis zu 1,0 mm Tumordicke stellt heute die Exzision mit einem reduzierten Sicherheitsabstand von 10 mm die lokale Prim?rtherapie dar. Bei dickeren Tumoren scheint ebenfalls ein reduzierter Sicherheitabstand bis maximal 20 mm ausreichend zu sein. Bei den lentigin?sen Typen kann die Exzision mit prim?r 5 mm Sicherheitsabstand und topografisch orientierter lückenloser Schnittrandhistologie im Paraffinschnittverfahren eingesetzt werden. Die Eingriffe k?nnen in Lokalan?sthesie erfolgen. Die Art des Defektverschlusses richtet sich nach dem zu erreichenden optimalen kosmetischen Ergebnis. Ab einer Tumordicke von 1 mm wird eine Sentinel-Lymphknoten-Biopsie empfohlen, vorwiegend um ein individuelles Mikrostaging zu erm?glichen. Der therapeutische Nutzen ist dagegen noch nicht belegt. Region?re Lymphknotenmetastasen erfordern eine komplette Dissektion des Lymphabflussgebietes. Bei Intransit-Metastasen steht die Resektion im Vordergrund der therapeutischen Ma?nahmen. Durch eine isolierte Extremit?tenperfusion ist bei chirugisch nicht kontrollierbaren region?ren Metastasen in der Mehrzahl der F?lle eine lokale Tumorkontrolle m?glich. Die Extirpation von isolierten Organmetastasen kann das überleben verl?ngern. Voraussetzung ist dabei die komplette Resektion (R0-Resektion) der Metastasen. Bei chirurgischen Interventionen ist zu bedenken, dass in diesen Stadien fast ausschliesslich eine “Allgemeinerkrankung” am Melanom vorliegt, die mit chirugischen Ma?nahmen allein nicht heilbar ist.     

Möglichkeiten und Grenzen der Diagnostik beim Ovarialkarzinom

Background

Ovarian cancer is the gynecological malignancy with the highest mortality. This is mainly due to the absence of an efficient screening and diagnostic test; thus, most ovarian cancer patients are diagnosed in late stages when the survival rates are significantly worse.

Methods

A literature search of PubMed, Medline, and a manual internet search was performed. The most relevant studies regarding biomarkers, ultrasound and mini-invasive tests for early diagnosis are summarized. Due to the fact that CA-125 is considered the gold standard for ovarian cancer and that HE4 seems to be the most promising serum biomarker, these two proteins are the focus of this article.

Results

HE4 seems have more reliable results in premenopausal patients compared to CA-125, mainly due to not being increased in endometriosis cases. Standardized ultrasound examination seems to be suitable for discriminating patients with pelvic tumors. The opinion of IOTA (International Ovarian Tumor Analysis) experts seems to have the highest sensitivity and specificity; nevertheless, ultrasound is a very subjective examination and depends on the experience of the examiner.

Conclusion

Ultrasound and biomarkers failed to significantly increase sensitivity and specificity of early diagnostic tests for ovarian cancer. The combination of both ultrasound and biomarker improves early diagnosis. New techniques such as uterine lavage and detection of genetic changes might also lead to improvement in early diagnosis.     

Medikamentöse Therapie des metastasierten oder rezidivierten mutationsnegativen NSCLC

Background

The introduction of immune checkpoint inhibitors (ICI) has led to rapid changes in the treatment of metastatic non-small cell lung cancer (NSCLC) without treatable driver mutations over the last few years.

Objective

A brief historical outline of treatment before and a summary of changes after the arrival of ICI is given.

Material and methods

A selective Pubmed search was performed employing the keywords NSCLC stage IV, checkpoint inhibitors and chemotherapy.

Conclusion

The ICIs were initially introduced as second line treatment of metastatic NSCLC as several large phase III trials were able to show a clinically significant improvement compared to the standard docetaxel treatment. Meanwhile, pembrolizumab is the standard first-line treatment of NSCLC with high PD-L1 expression (TPS?>?50%). Recently, several phase III trials could show superior efficacy of the combination of an ICI with standard platinum-based doublet chemotherapy compared to chemotherapy alone. Some of the investigated combinations have already been approved for nonsquamous NSCLC and further approvals can be expected. Since the introduction of ICI long-term survival of 3 or more years has been achieved in some patients with metastatic NSCLC.

     

Nuklearmedizinische Therapie und Nachsorge des differenzierten Schilddrüsenkarzinoms: Status quo

Differentiated thyroid cancers (papillary and follicular cancers) have a good prognosis. The treatment of choice consists of total thyroidectomy and if necessary lymph node dissection followed by ablative radioiodine treatment. Only very small solitary papillary thyroid cancers with a diameter of ≤10 mm without lymph node and distant metastases may be treated sufficiently with lobectomy only. Nowadays, recombinant human thyrotropin (rhTSH) can be useful in the preparation for ablative radioiodine treatment. This protocol prevents the drawbacks of iatrogenic hypothyroidism and reduces the radiation exposure to the remainder of the body. Even in cases of distant metastases, which can be rarely cured but mostly treated effectively with a palliative approach, preparation with recombinant TSH is helpful. However, exogenous TSH stimulation is not yet approved for preparation of radioiodine treatment of metastases and can only be administered on a compassionate use basis. Current concepts for therapy of distant metastases often include dosimetric evaluations to avoid bone marrow toxicity while increasing the administered activity in an attempt to personalize the treatment. High rates of complete remission are reported in patients with pulmonary micrometastases and in this constellation endogenous TSH stimulation after thyroid hormone withdrawal is still the standard preparation for radioiodine treatment.     

Chirurgische Therapie im Stadium I und II des nichtkleinzelligen Lungenkarzinoms

Background

Despite modern diagnostics and multimodal treatment strategies, overall survival of lung cancer could not be significantly improved in recent decades. The majority of patients with non-small cell lung cancer (NSCLC) have distant metastases at the time of diagnosis (57%) and only approximately 40% of patients are in a potentially curable tumor stage.

Material and methods

A systematic literature search concerning original research and review articles on surgery of NSCLC in stages I and II was carried out in the PubMed database.

Results

For patients in an early tumor stage, stages I and II tumors according to the 8th edition of the Union for International Cancer Control (UICC) tumor stage classification, surgical removal of the tumor remains the therapeutic gold standard. By complete anatomical resection (lobectomy, bilobectomy or pneumonectomy) combined with a systematic mediastinal and hilar lymphadenectomy, 5?year survival rates of more than 80% in early stage IA and 48% in stage II can be achieved. In addition to open surgical resection, video-assisted, minimally invasive thoracoscopic (VATS) resection was successfully implemented worldwide for the treatment of NSCLC patients in stages I and II. For patients with stage II NSCLC, adjuvant chemotherapy was shown to improve the overall survival.

Discussion

Whether targeted therapies or immunotherapy in a neoadjuvant or adjuvant treatment modality further improve the survival of NSCLC patients in the multimodal treatment of early stage NSCLC, is currently under investigation in randomized studies.

     

Aktueller Stand der Diagnostik und Therapie des nichtkleinzelligen Lungenkarzinoms (NSCLC) im Stadium III

Based on the considerable heterogeneity of patient subgroups in stage III non-small-cell lung cancer (NSCLC)—despite the slightly more differentiated 8th edition of the Union Internationale Contre le Cancer (UICC)/International Association for the Study of Lung Cancer (IASLC) staging classification—increasingly individualized treatment of these patients has become necessary. Initial interdisciplinary assessment of potential operability is a key factor for treatment selection. Standard treatment for the majority of stage III NSCLC patients is still concurrent chemoradiotherapy. However, based on the equivocal and clinically relevant positive results of the phase III PACIFIC trial, this treatment should be followed by consolidation therapy with durvalumab for 12 months in patients with proven PD-L1 expression in the tumor. In patients who are evaluated as potentially operable in interdisciplinary consensus, multimodality treatment protocols including definitive surgical resection of the tumor are still standard. Based on the positive data on immunotherapy in inoperable patients, there are now multiple interesting scenarios for integration of this new modality into the treatment of patients with localized disease, which should be carefully analyzed in well-designed prospective clinical trials.     

Primärtherapie des Hodentumors und Prognosefaktoren nichtseminomatöser Keimzelltumoren im klinischen Stadium I

Die Primärdiagnostik bei Verdacht auf einen testikulären Keimzelltumor umfasst die Sonographie von Hoden und Retroperitoneum, die radiologische Stagingdiagnostik mittels CT von Abdomen und Thorax sowie die Bestimmung der Tumormarker AFP,-hCG und LDH. Die Primärtherapie des unilateralen Hodentumors besteht in der inguinalen Ablatio testis; metachrone Zweittumoren oder Tumoren in einem Solitärhoden können durch die Organ erhaltende Tumorenukleation behandelt werden. Die kontralaterale Hodenbiopsie zum Nachweis einer testikulären intraepithelialen Neoplasie (TIN) kann fakultativ erfolgen, die Standardtherapie der TIN besteht in der lokalen Radiatio mit 18 Gy. Im klinischen Stadium I nichtseminomatöser Keimzelltumoren existieren mit der Surveillance, der primären Nerv schonenden retroperitonealen Lymphadenektomie und der primären Chemotherapie 3 konkurrierende Therapiealternativen mit gleich hoher Heilungsrate bei unterschiedlichem Nebenwirkungsspektrum. Bei einer Heilungsrate von 98% muss im Vordergrund der therapeutischen Bemühungen die langfristige Aufrechterhaltung der Lebensqualität stehen, sodass klinisch und individuell nutzbare Prognosefaktoren wünschenswert wären, die eine Vorhersage okkulter retroperitonealer Metastasen erlauben. Auf dem Boden jüngster prospektiver Studien der German Testicular Cancer Study Group stellen der fehlende Nachweis einer vaskulären Invasion und ein niedriger Proliferationsindex (MIB- 1-Expression <70%) mit einem positiven Vorhersagewert von 86% reproduzierbare Risikofaktoren für die Definition einer Niedrigrisikogruppe und der Möglichkeit einer Surveillance-Strategie dar. Eine Hochrisikogruppe kann auf dem Boden histopathologischer oder molekularer Marker nicht definiert werden; es empfiehlt sich die Nerv schonende RPLA oder die primäre Chemotherapie.