1,721,141 research outputs found
Surgical Therapy in Patients with Colorectal Liver Metastases
No full textBackground: Liver metastases (LM) occur in about 50% of patients with colorectal cancer. Besides the multimodal treatment of the primary tumor, the only way to cure patients with colorectal LM (CRLM) is complete resection. Different surgical procedures for this purpose are available depending on location, size, and number of LM. Additional concepts for patients with primary unresectable LM exist, ranging from Chemotherapy to induction of liver hypertrophy and even liver transplantation. This review intends to provide an overview of the surgical approach. Summary: Surgical options in the treatment of CRLM are defined and limited by their intraparenchymal location and their proximity to major vessels and intrahepatic bile ducts. Lesions located in the periphery can be excised in a parenchymal sparing fashion with a small tumor-surrounding resection margin of healthy liver parenchyma. If this is not possible, anatomical resections based on segmental boundaries are performed. In these cases, a sufficient functional volume of liver parenchyma after resection (future liver remnant volume [FLRV]) has to be preserved. This FLRV depends on various factors such as bodyweight and possible preexisting liver damage, such as cirrhosis, fibrosis, or chemotherapy-induced liver impairment. Liver hypertrophy via partial occlusion of the portal venous system is a standard procedure for patients with primary unresectable LM to increase FLRV. Furthermore, discussion of liver transplantation in cases of unresectable LM is gaining importance again. A combination of surgery and adjuvant and/or neoadjuvant chemotherapy may be indicated in individual cases, but general evidence-based recommendations cannot be given without further studies. Key Messages: Surgical removal of all metastases represents the only option of a potentially curative treatment of UICC stage IV colorectal carcinoma with liver involvement. An interdisciplinary approach consisting of chemotherapeutical downsizing and hypertrophy of the FLRV offers potential curative treatment for patients with initially unresectable metastases. For all others, liver transplantation is seeing a revival showing promising results in overall survival compared to chemotherapy alone.Background: Liver metastases (LM) occur in about 50% of patients with colorectal cancer. Besides the multimodal treatment of the primary tumor, the only way to cure patients with colorectal LM (CRLM) is complete resection. Different surgical procedures for this purpose are available depending on location, size, and number of LM. Additional concepts for patients with primary unresectable LM exist, ranging from Chemotherapy to induction of liver hypertrophy and even liver transplantation. This review intends to provide an overview of the surgical approach. Summary: Surgical options in the treatment of CRLM are defined and limited by their intraparenchymal location and their proximity to major vessels and intrahepatic bile ducts. Lesions located in the periphery can be excised in a parenchymal sparing fashion with a small tumor-surrounding resection margin of healthy liver parenchyma. If this is not possible, anatomical resections based on segmental boundaries are performed. In these cases, a sufficient functional volume of liver parenchyma after resection (future liver remnant volume [FLRV]) has to be preserved. This FLRV depends on various factors such as bodyweight and possible preexisting liver damage, such as cirrhosis, fibrosis, or chemotherapy-induced liver impairment. Liver hypertrophy via partial occlusion of the portal venous system is a standard procedure for patients with primary unresectable LM to increase FLRV. Furthermore, discussion of liver transplantation in cases of unresectable LM is gaining importance again. A combination of surgery and adjuvant and/or neoadjuvant chemotherapy may be indicated in individual cases, but general evidence-based recommendations cannot be given without further studies. Key Messages: Surgical removal of all metastases represents the only option of a potentially curative treatment of UICC stage IV colorectal carcinoma with liver involvement. An interdisciplinary approach consisting of chemotherapeutical downsizing and hypertrophy of the FLRV offers potential curative treatment for patients with initially unresectable metastases. For all others, liver transplantation is seeing a revival showing promising results in overall survival compared to chemotherapy alone
Dual silencing of insulin-like growth factor-I receptor and epidermal growth factor receptor in colorectal cancer cells is associated with decreased proliferation and enhanced apoptosis
No full textOverexpression and activation of tyrosine kinase receptors are common features of colorectal cancer. Using the human colorectal cancer cell lines DLD-1 and Caco-2, we evaluated the role of the insulin-like growth factor-I (IGF-I) receptor (IGF-IR) and epidermal growth factor receptor (EGFR) in cellular functions of these cells. We used the small interfering RNA (siRNA) technology to specifically down-regulate IGF-IR and EGFR expression. Knockdown of IGF-IR and EGFR resulted in inhibition of cell proliferation of DLD-1 and Caco-2 cells. An increased rate of apoptosis was associated with siRNA-mediated silencing of IGF-IR and EGFR as assessed by activation of caspase-3/caspase-7. The combined knockdown of both EGFR and IGF-IR decreased cell proliferation and induced cell apoptosis more effectively than did silencing of either receptor alone. Comparable effects on cell proliferation and apoptosis were observed after single and combinational treatment of cells by the IGF-IR tyrosine kinase inhibitor NVP-AEW541 and/or the EGFR tyrosine kinase inhibitor erlotinib. Combined IGF-IR and EGFR silencing by either siRNAs or tyrosine kinase inhibitors diminished the phosphorylation of downstream signaling pathways AKT and extracellular signal-regulated kinase (ERK)-1/2 more effectively than did the single receptor knockdown. Single IGF-IR knockdown inhibited IGF-1-dependent phosphorylation of AKT but had no effect on IGF-1- or EGF-dependent phosphorylation of ERK1/2, indicating a role of EGFR in ligand-dependent ERK1/2 phosphorylation. The present data show that inhibition of the IGF-IR transduction cascade augments the antipoliferative and proapoptotic effects of EGFR inhibition in colorectal cancer cells. A clinical application of combination therapy targeting both EGFR and IGF-IR could be a promising therapeutic strategy. [Mol Cancer Ther 2009;8(4): 821-33
Rolle und Aufgaben der chirurgischen Onkologie im Rahmen molekular definierter Therapien [Role and function of surgical oncology in molecular defined therapy]
No full textContext: The progressive development of molecular analyses allows a comprehensive clinical establishment of biomarkers. Embedded in multimodal therapy concepts it is the surgeon’s duty to understand the underlying mechanisms of predictive, prognostic and therapeutic biomarkers. Besides an increasingly successful therapy of cancer the application of these markers presents the basis of personalized cancer therapy. Method: Selective review of the literature. Results and conclusions: However, implementation of these techniques in the daily clinical practice requires an extensive education of surgeons. The attending physician is forced to understand the molecular principles and the limitations of these markers. Furthermore, surgeons also need to understand the forthcoming difficulties arising from the side effects. To meet these demands tumor surgeons need to evolve into surgical oncologists
The molecular basis of chemoradiosensitivity in rectal cancer:implications for personalized therapies
Full text linkPreoperative chemoradiotherapy represents the standard treatment for patients with locally advanced rectal cancer. Unfortunately, the response of individual tumors to multimodal treatment is not uniform and ranges from complete response to complete resistance. This poses a particular problem for patients with a priori resistant tumors because they may be exposed to irradiation and chemotherapy, treatment regimens that are both expensive and at times toxic, without benefit. Accordingly, there is a strong need to establish molecular biomarkers that predict the response of an individual patient's tumor to multimodal treatment and that indicate treatment-associated toxicities prior to therapy. Such biomarkers may guide clinicians in choosing the best possible treatment for each individual patient. In addition, these biomarkers could be used to identify novel molecular targets and thereby assist in implementing novel strategies to sensitize a priori resistant tumors to multimodal treatment regimens. The aim of this review is to summarize recent findings about the molecular basis of treatment resistance and treatment toxicity in patients with rectal cancer. Whole-genome, as well as single-biomarker or multibiomarker, analyses and their potential implications will be highlighted. At the end, we will outline a future vision of rectal cancer treatment in the era of personalized medicine.Deutsche Forschungsgemeinschaft [KFO179
Volumetric intensity-modulated arc therapy vs. 3-dimensional conformal radiotherapy for primary chemoradiotherapy of anal carcinoma Effects on treatment-related side effects and survival
No full textBackground Primary chemoradiotherapy (CRT) is the standard treatment for locally advanced anal carcinoma. This study compared volumetric intensity-modulated arc therapy (VMAT) to 3-dimensional conformal radiotherapy (3DCRT) in terms of treatment-related side effects and survival. Patients and methods From 1992-2014, 103 consecutive patients with anal carcinoma UICC stage I-III were treated. Concomitant CRT consisted of whole pelvic irradiation, including the iliac and inguinal lymph nodes, with 50.4 Gy (1.8 Gy per fractions) by VMAT (n = 17) or 3DCRT (n = 86) as well as two cycles of 5-fluorouracil and mitomycin C. Acute organ and hematological toxicity were assessed according to the Common Terminology Criteria (CTC) for Adverse Events version 3.0. Side effects a parts per thousand yen grade 3 were scored as high-grade toxicity. Results High-grade acute organ toxicity CTC a parts per thousand yenaEuro parts per thousand 3 (P < 0.05), especially proctitis (P = 0.03), was significantly reduced in VMAT patients. The 2-year locoregional control (LRC) and disease-free survival (DFS) were both 100 % for VMAT patients compared with 80 and 73 % for 3DCRT patients. Conclusion VMAT was shown to be a feasible technique, achieving significantly lower rates of acute organ toxicity and promising results for LRC and DFS. Future investigations will aim at assessing the advantages of VMAT with respect to late toxicity and survival after a prolonged follow-up time
Inzidenz und prädiktive Faktoren des bilateralen papillären Schilddrüsenkarzinoms
No full textZusammenfassung Hintergrund Nach Diagnose eines papillären Schilddrüsenkarzinoms (PTC) mit einer Primärtumorgröße von ≥ 10 mm und < 10 mm wird, vor dem Hintergrund eines möglichen bilateralen Tumorbefalls, das Konzept der weiteren chirurgischen Therapie nach wie vor kontrovers diskutiert. Ziel dieser Studie war es, die Inzidenz sowie prädiktive Faktoren für das Vorhandensein eines bilateralen papillären Schilddrüsenkarzinoms hinsichtlich der Auswahl einer optimalen chirurgischen Therapie zu identifizieren. Material und Methoden Anhand einer retrospektiven Datenbank wurden bei 123 Patienten mit einem PTC, die entweder primär eine totale Thyreoidektomie oder eine Komplettierungsoperation nach Hemithyreoidektomie erhielten, die Parameter Tumorgröße, histopathologische Charakteristika, Multifokalität sowie Lymphknotenmetastasierung mit dem Vorhandensein eines bilateralen Tumorbefalls für die Primärtumorgrößen ≥ 10 mm und < 10 mm sowie ≥ 7 mm und < 7 mm korreliert. Ergebnisse Im gesamten Patientenkollektiv zeigte sich in 26 Fällen ein bilaterales PTC. Dieses war signifikant häufiger, wenn die Primärtumorgröße ≥ 10 mm betrug (77 %). Im Vergleich dazu boten Patienten mit einer Primärtumorgröße von < 10 mm nur in 23 % der Fälle ein bilaterales PTC (p = 0,004). Die Multifokalität des Primärtumors erwies sich hierbei als positiver prädiktiver Faktor für ein bilaterales PTC (p = 5,022e-18). Bei bilateralem Nachweis eines PTCs zeigte sich ein Trend für das Auftreten von metachronen Lymphknotenmetastasen (p = 0,0691). Darüber hinaus konnten in den Analysen bezogen auf eine Primärtumorgröße von ≥ 7 mm und < 7 mm die oben genannten Ergebnisse reproduziert werden. Schlussfolgerung Die vorliegende retrospektive Datenanalyse zeigt, dass eine Primärtumorgröße von ≥ 10 mm mit einem signifikant häufigeren bilateralen Tumorbefall korreliert. Multifokalität erwies sich als positiver prädiktiver Faktor für das Vorhandensein eines bilateralen PTCs. Bei Nachweis eines multifokalen PTCs, auch bei Primärtumorgrößen < 10 mm, sollte demnach eine primäre totale Thyreoidektomie bzw. eine Komplettierungsoperation als chirurgisches Therapieverfahren erwogen werden. Bei Multifokalität und nicht erfolgter Komplettierungsoperation ist eine engmaschige Nachsorge notwendig, um frühzeitig einen bilateralen Tumorbefall oder Lymphknotenmetastasen detektieren zu können
Emergency Repair of Giant Inguinoscrotal Hernia in a Septic Patient
No full textGiant inguinoscrotal hernias are rare but still exist even in developed countries. Although accompanied by a higher perioperative mortality, an elective surgical approach should be undertaken. In critically ill patients, however, the surgical intervention requires specific demands. We report a case of a 45-year-old man who was referred to the hospital after perforation of the hernia with concomitant peritonitis and sepsis. After initial stabilization of the patient, a subtotal colectomy and a partial small bowl resection was performed. In a second step after stabilization of organ functions, the hernia sac was resected, and the abdominal cavity was reconstructed. The patient was discharged and is doing well until today but still refuses any plastic surgery. Resection of giant inguinoscrotal hernia is feasible even in patients being administered in an emergency setting. Especially in case of an intra-abdominal infection, intestinal resection is the therapy of choice to allow the reconstruction of the abdominal cavity. A two-step approach should be considered to allow a successful recovery
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