[Complications and Management of Complications After Resection and Reconstruction of the Esophagus]. / Komplikationen und Komplikationsmanagement nach Resektion und Rekonstruktion der Speiseröhre.

Complications and Management of Complications After Resection and Reconstruction of the Esophagus Abstract. A curative therapy of advanced esophagus carcinoma is primarily made possible by radical esophagectomy with lymphadenectomy. Impressive advances in the surgical techniques of esophageal surgery through minimally invasive and robotic oesophagectomy have been made in the last two decades. The perioperative management with prehabilitation, PDK application, early mobilization and early food intake also contributed significantly to a reduction in complications. However, esophageal surgery is fraught with complications. Anastomotic leakage is the most common technical-surgical complication. The rate is approximately 10-16%, independent of the technique and procedure. In addition to an experienced, subtle, atraumatic and rapid surgical technique, early detection (clinical, endoscopic, radiological) and adequate, interdisciplinary management of perioperative complications in resecting esophageal surgery are the key to increasing the safety of these complex interventions. The treatment of the complications includes conservative, interventional and surgical measures. In the last few decades, there has been a radical change from once exclusively surgical revisions with a high degree of invasiveness and a poor outcome to today's mostly conservative-interventional management with little patient burden and - in centers with the appropriate expertise - good results.

[Curative Treatment of Esophageal Carcinoma - Disease, Diagnostics, Therapy in 2022]. / Kurative Therapie des Ösophaguskarzinomes.

Curative Treatment of Esophageal Carcinoma - Disease, Diagnostics, Therapy in 2022 Abstract. Surgical resection remains the gold standard for non-metastatic carcinoma of the lower and middle third of the esophagus. Locally advanced tumors (T3) are pretreated neoadjuvantly (radiochemotherapy) or perioperatively (chemotherapy). A differentiated primary staging and an interdisciplinary case presentation are of essential importance today. The individual risk assessment, the pre-habilitation and the individualized treatment play a major role. Clinically, the further advancement of access minimization - through laparoscopic/thoracoscopic and robot-assisted procedures and the associated reduction of access trauma - as well as the treatment of this entity in high volume centers are clearly in the foreground. For cervical carcinomas definitive radiotherapy is often the better alternative, both for tumor biological reasons and for reasons of the increase in complications during surgery.

Clinical significance of different types of p53 gene alteration in surgically treated prostate cancer.

Despite a multitude of p53 immunohistochemistry (IHC) studies, data on the combined effect of nuclear p53 protein accumulation and TP53 genomic inactivation are lacking for prostate cancer. A tissue microarray including 11,152 prostate cancer samples was analyzed by p53 IHC and fluorescence in situ hybridization. Nuclear p53 accumulation was found in 10.1% of patients including 1.4% with high-level and 8.7% with low-level immunostaining. TP53 sequencing revealed that 17 of 22 (77%) cases with high-level p53 immunostaining, but only 3% (1 of 31) low-level p53 cases carried putative dominant-negative mutations. TP53 deletions occurred in 14.8% of cancers. Both deletions and protein accumulation were linked to unfavorable tumor phenotype and prostate specific antigen (PSA) recurrence (p<0.0001 each). The combination of both methods revealed subgroups with remarkable differences in their clinical course. Tumors with either TP53 deletion (14%) or low-level p53 positivity (8.7%) had identical risks of PSA recurrence, which were markedly higher than in cancers without p53 alterations (p<0.0001). Tumors with both p53 deletion and low-level p53 positivity (1.5%) had a worse prognosis than patients with only one of these alterations (p<0.0001). Tumors with strong p53 immunostaining or homozygous inactivation through deletion of one allele and disrupting translocation involving the second allele had the worst outcome, independent from clinical and pathological parameters. These data demonstrate a differential clinical impact of various TP53 alterations in prostate cancer. Strong p53 immunostaining-most likely accompanying dominant negative or oncogenic p53 mutation-has independent prognostic relevance and may thus represent a clinical useful molecular feature of prostate cancer.

Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer.

Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with "classical" (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in 11 tumors diagnosed at young age, and pursued comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of > 10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity of a characteristic "androgen-type" pathomechanism in EO-PCA.