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1.
J Vasc Surg ; 76(2): 595-604.e1, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35358668

RESUMO

BACKGROUND: Clostridium septicum bacteremia is often associated with occult malignancies (approximately 80%), especially of the right colon. Furthermore, inflammation of the aortic wall can rapidly lead to aneurysm induction through bacterial seeding into atheromatous lesions with consecutive life-threatening rupture. We summarize all published data on this rare and lethal disease to evaluate therapeutic approaches and give valid treatment recommendations because there are no guidelines. METHODS: A systematic review of the literature was conducted screening EMBASE and MEDLINE databases following the PRISMA guidelines with search period from first description to August 25, 2021. RESULTS: There were 72 cases of C septicum aortitis reported in 64 publications. Endovascular aortic repair (EVAR) was performed in a minority of patients (n = 6) unfit for surgery but lacked long-term survivors. Antibiotic treatment was beneficial in a bridge to surgery concept, but up to now harbored a 6-month mortality rate of 100% (median overall survival, 0.5 months) when no additional aortic repair was performed. Open aortic repair was the only potential curative approach but was accompanied with a 90-day-mortality of 26.7% (4/15). CONCLUSIONS: Open aortic repair combined with perioperative antibiotic treatment should be offered to all patients as the only potentially curative approach. If applicable, resection of a coexisting colonic tumor should be performed after successful aortic repair. Alternatively, long-term antibiotic treatment can be offered to patients unfit for surgery in a palliative setting. Endovascular aortic repair has been performed on a minority of patients with a high risk for stent graft infection and should remain a salvage strategy when therapeutic pressure demands acute intervention in patients unfit for surgery.


Assuntos
Aneurisma da Aorta Abdominal , Aortite , Implante de Prótese Vascular , Clostridium septicum , Procedimentos Endovasculares , Antibacterianos/uso terapêutico , Aorta/cirurgia , Aneurisma da Aorta Abdominal/cirurgia , Aortite/diagnóstico por imagem , Aortite/cirurgia , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Humanos , Stents , Resultado do Tratamento
2.
Surg Endosc ; 35(7): 3670-3678, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32767145

RESUMO

BACKGROUND: AirSeal® is a valve-free insufflation system that enables a stable pneumoperitoneum with continuous smoke evacuation and CO2 recirculation during laparoscopic surgery. Comparative evidence on the use of AirSeal® and standard CO2 insufflator in laparoscopic general surgery procedures is scarce. The aim of this study was to compare surgical outcomes between AirSeal® and standard CO2 insufflators in patients undergoing the most frequently performed laparoscopic procedures. METHODS: One hundred and ninety-eight patients undergoing elective laparoscopic cholecystectomy, colorectal surgery and hernia repair were randomized to either AirSeal® (group A) or standard pressure CO2 insufflator (group S). The primary endpoints were operative time and level of postoperative shoulder tip pain (Visual Analog Scale). Secondary outcomes included Clavien-Dindo grade complications, surgical side effect and length of hospital stay. RESULTS: Patients were randomized to either group A (n = 101) or group S (n = 97) and were analyzed by intention-to-treat. There was no significant difference in mean operative time between the groups (median [IQR]; 71 min [56-94] in group A vs. 69 min [52-93] in group S; p = 0.434). Shoulder tip pain levels were significantly lower in group S (VAS 0 [0-3] in group S vs. 2 [0-4] in group A; p = 0.001). There was no significant difference in complications, surgical side effects (subcutaneous emphysema was not observed in any group) and length of hospital stay. CONCLUSION: This randomized controlled trial showed that using the AirSeal® system did not reduce operative time and was associated with a higher postoperative shoulder tip pain compared to standard CO2 insufflator for short elective surgeries. ClinicalTrials.gov (NCT01740011).


Assuntos
Colecistectomia Laparoscópica , Insuflação , Laparoscopia , Pneumoperitônio , Dióxido de Carbono , Colecistectomia Laparoscópica/efeitos adversos , Humanos , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Pneumoperitônio Artificial/efeitos adversos , Estudos Prospectivos
3.
Eur Surg Res ; 62(2): 80-87, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33827087

RESUMO

INTRODUCTION: Intraductal papillary mucinous neoplasms (IPMNs) represent the most common precancerous cystic lesions of the pancreas. The aim of our study was to investigate if resection for non-invasive IPMNs alters quality of life (QoL) in a long-term follow-up. METHODS: Patients (n = 50) included in the analysis were diagnosed and resected from 2010 to 2016. QoL was assessed at a median of 5.5 years after resection. At that point in time, the current QoL as well as the QoL before resection was evaluated retrospectively. The standardised European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Pancreatic Cancer (EORTC QLQ - PAN26) was applied for the QoL assessment. RESULTS: After a median of 66 months postoperatively, the total QoL score significantly worsened (92.13 vs. 88.04, p = 0.020, maximum achievable score = 100) for patients (median age at surgery 68.0 years), mostly due to digestive symptoms. During the same follow-up period, median Eastern Cooperative Oncology Group (ECOG) performance status did not worsen (p = 0.003). CONCLUSIONS: Long-term QoL statistically significantly worsened after pancreatic resection for IPMN. The extent of worsening, however, was small, and QoL still remained excellent. Therefore, resection in cases of IPMN is appropriate, if indicated carefully.


Assuntos
Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Carcinoma Papilar , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Adenocarcinoma Mucinoso/cirurgia , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Papilar/cirurgia , Humanos , Pancreatectomia , Neoplasias Intraductais Pancreáticas/cirurgia , Neoplasias Pancreáticas/cirurgia , Qualidade de Vida , Estudos Retrospectivos
4.
Oncology ; 98(10): 706-713, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32516775

RESUMO

BACKGROUND: Adenocarcinoma of the esophagogastric junction (AEG) is a rare but rising tumor entity in the Western world. Treatment is complex, as multimodality is key to optimal results. However, trials solely including AEG are rare, and the question if neoadjuvant radiochemotherapy (NRCT) or neoadjuvant/perioperative chemotherapy (NACT) is superior remains unanswered. PATIENTS AND METHODS: Patients with AEG I-III treated between October 2010 and August 2019 at the Ordensklinikum Linz or the Kepler University Hospital were identified either from a monitored tumor registry or by chart review. Time-to-event data were analyzed by Kaplan-Meier product limit estimation. The Kruskal-Wallis test and Fisher's exact test were used for comparing continuous and categorical data, respectively. RESULTS: A total of 85 patients (median age 63 years; median Charlson Comorbidity Index 3; 98.8% ECOG PS 0-1) were analyzed. Of these, 52 patients received NRCT (81% CROSS protocol) and 33 NACT (65% EOX and 35% FLOT protocol). There was a significantly higher pathological complete response rate in the NRCT group (30 vs. 12%; p = 0.010); distant relapse rates were higher in the NRCT group and local relapse rates were higher in the NACT group (both not significant). These differences, however, did not translate into a different disease-free survival (20 months; 95% CI: 13-34) or overall survival (44 months; 95% CI: 33-NA). Patients >65 years old had the same advantage from treatment as patients <65 years of age. CONCLUSIONS: Although treatment of AEG is complex, the progress documented over the last centuries can be reproduced in our real-life setting. Data regarding the superiority of either type of neoadjuvant/perioperative treatment are sparse. We assume no difference between EOX-based NACT and NRCT.


Assuntos
Neoplasias Esofágicas/terapia , Junção Esofagogástrica/patologia , Neoplasias Gástricas/terapia , Idoso , Quimiorradioterapia Adjuvante , Estudos de Coortes , Intervalo Livre de Doença , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Junção Esofagogástrica/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Assistência Perioperatória , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida , Resultado do Tratamento
5.
BMC Cancer ; 20(1): 1149, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33238958

RESUMO

BACKGROUND: Metastatic colorectal cancer (mCRC) remains a lethal disease. Survival, however, is increasing due to a growing number of treatment options. Yet due to the number of prognostic factors and their interactions, prediction of mortality is difficult. The aim of this study is to provide a clinical model supporting prognostication of mCRC mortality in daily practice. METHODS: Data from 1104 patients with mCRC in three prospective cancer datasets were used to construct and validate Cox models. Input factors for stepwise backward method variable selection were sex, RAS/BRAF-status, microsatellite status, treatment type (no treatment, systemic treatment with or without resection of metastasis), tumor load, location of primary tumor, metastatic patterns and synchronous or metachronous disease. The final prognostic model for prediction of survival at two and 3 years was validated via bootstrapping to obtain calibration and discrimination C-indices and dynamic time dependent AUC. RESULTS: Age, sidedness, number of organs with metastases, lung as only site of metastasis, BRAF mutation status and treatment type were selected for the model. Treatment type had the most prominent influence on survival (resection of metastasis HR 0.26, CI 0.21-0.32; any treatment vs no treatment HR 0.31, CI 0.21-0.32), followed by BRAF mutational status (HR 2.58, CI 1.19-1.59). Validation showed high accuracy with C-indices of 72.2 and 71.4%, and dynamic time dependent AUC's of 76.7 ± 1.53% (both at 2 or 3 years), respectively. CONCLUSION: The mCRC mortality prediction model is well calibrated and internally valid. It has the potential to support both, clinical prognostication for treatment decisions and patient communication.


Assuntos
Neoplasias Colorretais/mortalidade , Nomogramas , Idoso , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
6.
World J Surg Oncol ; 18(1): 248, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948207

RESUMO

BACKGROUND: Ganglioneuromas (GNs) are extremely rare, slowly growing, benign tumors that can arise from Schwann cells, ganglion cells, and neuronal or fibrous tissues. Due to their origin from the sympathetic neural crest, they show neuroendocrine potential; however, most are reported to be hormonally inactive. Nevertheless, complete surgical removal is recommended for symptom control or for the prevention of potential malignant degeneration. CASE REPORT: A 30-year-old female was referred to our oncologic center due to a giant retroperitoneal and mediastinal mass detected in computed tomography (CT) scans. The initial symptoms were transient nausea, diarrhea, and crampy abdominal pain. There was a positive family history including 5 first- and second-degree relatives. Presurgical biopsy revealed a benign ganglioneuroma. Total resection (TR) of a 35 × 25 × 25 cm, 2550-g tumor was obtained successfully via laparotomy combined with thoracotomy and partial incision of the diaphragm. Histopathological analysis confirmed the diagnosis. Surgically challenging aspects were the bilateral tumor invasion from the retroperitoneum into the mediastinum through the aortic hiatus with the need of a bilateral 2-cavity procedure, as well as the tumor-related displacement of the abdominal aorta, the mesenteric vessels, and the inferior vena cava. Due to their anatomic course through the tumor mass, the lumbar aortic vessels needed to be partially resected. Postoperative functioning was excellent without any sign of neurologic deficit. CONCLUSION: Here, we present the largest case of a TR of a GN with retroperitoneal and mediastinal expansion. On review of the literature, this is the largest reported GN resected and was performed safely. Additionally, we present the first systematic literature review for large GN (> 10 cm) as well as for resected tumors growing from the abdominal cavity into the thoracic cavity.


Assuntos
Ganglioneuroma , Neoplasias do Mediastino , Neoplasias Retroperitoneais , Adulto , Feminino , Ganglioneuroma/diagnóstico por imagem , Ganglioneuroma/cirurgia , Humanos , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/cirurgia , Prognóstico , Neoplasias Retroperitoneais/diagnóstico por imagem , Neoplasias Retroperitoneais/cirurgia , Espaço Retroperitoneal , Tomografia Computadorizada por Raios X
7.
World J Surg ; 41(12): 3212-3217, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28741192

RESUMO

BACKGROUND: Parastomal hernias (PSHs) are a common and challenging issue. In previous studies, three-dimensional (3D) funnel mesh devices have been used successfully for the repair of PSHs. METHODS: We performed an analysis of prospectively collected data of patients who underwent a same-sided stoma reposition with 3D funnel-shaped mesh augmentation in intraperitoneal (IPOM) position at our department between the years of 2012 and 2015. Primary outcome parameters were intra- and postoperative surgical complications and recurrence rate during the follow-up period. RESULTS: Fifty-six patients could be included in this analysis. PSH repair was performed in 89.3% as elective surgery and in 73% in laparoscopic technique. A concomitant incisional hernia (EHS type 2 and 4) was found in 50% and repaired in a single-step procedure with PSH. Major postoperative complications requiring redo surgery (Clavien-Dindo ≥3b) were identified in 8.9% (5/56). Overall recurrence rate was 12.5% (7/56). Median follow-up time was 38 months, and a 1-year follow-up rate of 96.4% was reached. CONCLUSION: PSH repair with 3D funnel mesh in IPOM technique is safe, efficient and easy to perform in laparoscopic and open surgical approaches providing advantageous results compared to other techniques. Furthermore, simultaneous detection and treatment of concomitant incisional hernias has shown favorable. However, the mesh funnel distends and becomes shortened encasing a bulky bowel mesentery and further shrinkage happens eccentric. Changing mesh construction according to lengthening the funnel could possibly lead to reduction in recurrence.


Assuntos
Hérnia Abdominal/cirurgia , Herniorrafia/métodos , Hérnia Incisional/cirurgia , Estomas Cirúrgicos/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hérnia Abdominal/etiologia , Herniorrafia/efeitos adversos , Herniorrafia/instrumentação , Humanos , Hérnia Incisional/etiologia , Laparoscopia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Próteses e Implantes/efeitos adversos , Recidiva , Reoperação , Telas Cirúrgicas/efeitos adversos
9.
World J Surg ; 39(11): 2795-804, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26264458

RESUMO

BACKGROUND: Over the years, various open and laparoscopic approaches toward the repair of parastomal hernias (PSH) have been described. The variety of published techniques itself can be seen as an indicator for the often low level of satisfaction reached with the surgical procedures. METHODS: From January 1999 to January 2014, we assessed all cases of PSH repair performed at the three participating surgical departments in a retrospective analysis. The results were evaluated with regard to different surgical techniques focusing on complications and recurrences. RESULTS: One hundred and thirty-five individuals could be included in the analysis. They were operated on with eight different surgical techniques. Laparoscopic procedures were carried out in 46.7 % (63/135) of the cases. Median follow-up was 54 months (12-146 months). We found 44 cases of recurrence (32.6 %) and 24 (17.8 %) of the patients experienced perioperative complications and 12 of them needed to return to theater. Fourteen of the 135 patients (10.4 %) were operated as emergency cases which were associated with a mortality of 28.6 % (4/14). In case of elective PSH repair, no mortality occured. CONCLUSION: The results achieved by direct suture or the use of incised flat meshes for the repair of PSH were poor with these procedures having unacceptably high recurrence rates. With regard to the latter ostomy revision through three-dimensional funnel-shaped meshes and the laparoscopic sandwich technique showed the best results. Emergency procedures were linked to a dramatic increase in morbidity and mortality (p < 0.001).


Assuntos
Hérnia Abdominal/cirurgia , Herniorrafia/métodos , Estomas Cirúrgicos/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Emergências , Feminino , Seguimentos , Hérnia Abdominal/etiologia , Herniorrafia/efeitos adversos , Herniorrafia/mortalidade , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Recidiva , Reoperação , Estudos Retrospectivos , Telas Cirúrgicas
10.
J Clin Med ; 12(13)2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37445564

RESUMO

Pancreatic fistulas belong to the most feared complications after surgery on or near the pancreas, abdominal trauma, or severe pancreatitis. The majority occur in the setting of operative interventions and are called postoperative pancreatic fistulas (POPF). They can lead to various complications, including abscesses, delayed gastric emptying or hemorrhages with a significant impact on morbidity and mortality. Several risk factors have been identified, including smoking, high BMI, male gender, and age. Prophylactic measures and treatment options have been explored but with limited success. This study aimed to analyze the incidence and management of pancreatic fistulas treated in a tertiary referral center, particularly focusing on an endoscopic approach. The data of 60 patients with clinically relevant pancreatic fistulas were analyzed between 2018 and 2021. Different treatment approaches, including conservative management, percutaneous drainage, transpapillary stenting, and endoscopic transmural drainage, were evaluated. An endoscopic transmural approach using lumen-apposing metal stents (LAMS) was used in almost half of this cohort showing promising results, with a high rate of fistula closure in refractory cases and a mean time until closure of 2.7 months. The findings suggest that an endoscopic approach, particularly using LAMS, can be effective in the management of pancreatic fistulas.

11.
J Clin Med ; 12(4)2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36836160

RESUMO

BACKGROUND: The incidence of benign diseases among pancreatic resections for suspected malignancy still represents a relevant issue in the surgical practice. This study aims to identify the preoperative pitfalls that led to unnecessary surgeries at a single Austrian center over a twenty-year period. METHODS: Patients undergoing surgery for suspected pancreatic/periampullary malignancy between 2000 and 2019 at the Linz Elisabethinen Hospital were included. The rate of "mismatches" between clinical suspicion and histology was considered as primary outcome. All cases that, despite that, fulfilled the indication criteria for surgery were defined as minor mismatches (MIN-M). Conversely, the true avoidable surgeries were identified as major mismatches (MAJ-M). RESULTS: Among the 320 included patients, 13 (4%) presented with benign lesions at definitive pathology. The rate of MAJ-M was 2.8% (n = 9), and the most frequent causes of misdiagnoses were autoimmune pancreatitis (n = 4) and intrapancreatic accessory spleen (n = 2). In all MAJ-M cases, various mistakes within the preoperative workup were detected: lack of multidisciplinary discussion (n = 7, 77.8%); inappropriate imaging (n = 4, 44.4%); lack of specific blood markers (n = 7, 77.8%). The morbidity and mortality rates for mismatches were 46.7% and 0. CONCLUSION: All avoidable surgeries were the result of an incomplete pre-operative workup. The adequate identification of the underlying pitfalls could lead to minimize and, potentially, overcome this phenomenon with a concrete optimization of the surgical-care process.

12.
Ther Adv Med Oncol ; 15: 17588359231200462, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37786537

RESUMO

Background: Serial analysis of circulating tumor DNA (ctDNA) levels is a promising tool for both relapse prediction in the curative setting, as well as predicting clinical benefit from systemic treatment in metastasic colorectal cancer (mCRC). Most data in this context are derived from treatment naive patients. Objective: To predict progressive disease (PD) as early as possible through monitoring of changes in ctDNA levels during systemic treatment in pretreated patients with mCRC. Design: A prospective, single-center, observational study. Methods: Patients treated beyond first-line were prospectively included between February 2020 and September 2021. Blood for ctDNA detection was taken before every treatment cycle from start of treatment until first restaging by CT-scan. ctDNA was detected by mutation- (mut-ctDNA) and methylation-specific ddPCR. Receiver Operating Characteristic (ROC)-analysis was used to describe sensitivity and specificity for prediction of PD at restaging for all time points. Results: A total of 42 patients were included who all carried a mutation in tumor tissue. Detection rate of mut-ctDNA was 88.1% and 74.4% for meth-ctDNA. Absolute ctDNA levels before treatment were prognostic in terms of overall survival. Levels of ctDNA were significantly higher in patients with PD at restaging. Median time from start of treatment to restaging was 93 days (95% CI 88.8-96). After a median of 19 days of treatment (95% CI 16.1-20.2), a decline of either mutation- or methylation-specific ctDNA levels of ⩽58% predicted PD at restaging with a sensitivity/specificity of 92.9/85.7% and 85.7/100%, respectively. Median time to restaging was 66 days (95% CI 56.8-75.2). There was no significant increase of sensitivity/specificity at later time points of ctDNA measurements. Conclusion: Monitoring early changes of ctDNA levels either by mut- or meth-ctDNA allows for early prediction of PD in pretreated patients with mCRC. This has the potential to complement RECIST-based treatment assessment with the aim to switch potentially insufficient treatments as early as possible, which is of particular interest in higher treatment lines.

13.
World J Clin Oncol ; 13(6): 473-484, 2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35949436

RESUMO

Minimally invasive detection of circulating tumor DNA (ctDNA) in peripheral blood or other body fluids of patients with gastrointestinal malignancies via liquid biopsy has emerged as a promising biomarker. This is urgently needed, as conventional imaging and plasma protein-derived biomarkers lack sensitivity and specificity in prognosis, early detection of relapse or treatment monitoring. This review summarizes the potential role of liquid biopsy in diagnosis, prognosis and treatment monitoring of gastrointestinal malignancies, including upper gastrointestinal, liver, bile duct, pancreatic and colorectal cancer. CtDNA can now be part of the clinical routine as a promising, highly sensitive and specific biomarker with a broad range of applicability. Liquid-biopsy based postoperative relapse prediction could lead to improved survival by intensification of adjuvant treatment in patients identified to be at risk of early recurrence. Moreover, ctDNA allows monitoring of antineoplastic treatment success, with identification of potentially developed resistance or therapeutic targets during the course of treatment. It may also assist in early change of chemotherapy in metastatic gastrointestinal malignancies prior to imaging findings of relapse. Nevertheless, clinical utility is dependent on the tumor's entity and burden.

14.
J Vasc Surg Cases Innov Tech ; 8(2): 227-231, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35493338

RESUMO

Clostridium septicum bacteremia is a rare (72 cases reported) aneurysm-inducing disease that has resulted in a 6-month mortality of 100% when treated conservatively. We report the case of a patient who was completely symptom free at 6 months of follow-up but who ultimately died at 8.9 months after aortic rupture. In compliance with the patient's choice, a long-time antibiotic regimen was applied, instead of the surgical approach recommended by our surgical department. The use of an antibiotic regimen represents an option for patients unfit for surgery or as a bridge to surgery for damage control; however, aortic repair represents the only curative approach. Definitive antibiotic treatment is limited to a palliative approach for patients with C. septicum aortitis and has been accompanied by 100% 1-year mortality (90-day mortality, 84.2%).

15.
Data Brief ; 41: 107944, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35242926

RESUMO

This data article subsumes the data acquiration process, analysis and results of 'Circulating tumor DNA correlates with tumor burden and predicts outcome in pancreatic cancer irrespective of tumor stage' published in European Journal of Surgical Oncology (Eur J Surg Oncol. 2021 Dec 1:S0748-7983(21)00947-1. doi:10.1016/j.ejso.2021.11.138. PMID: 34876329) (Kirchweger et al., 2021). 28.5 mL of blood was obtained from 60 patients with localized pancreatic cancer directly prior to curative intended surgery as well as from 47 patients with metastasized pancreatic cancer (PDAC) directly prior to palliative intended systemic treatment initiation. Cell-free DNA preparation was done on the Chemagic 360 (Perkin Elmer, Waltham, Massachusetts, USA) using the kits CMG-1304 and CMG-844 from the same provider and quantified using the Quantus fluorometer (Promega, Madison, Wisconsin, USA). Screening for most common KRAS alterations (KRAS G12/G13 screening kit and additionally for KRAS Q61 if screening was negative) was performed utilizing the QX200™ Droplet Digital™ PCR System from Bio-Rad (Bio-Rad Laboratories, Hercules, CA, USA). Volumetric analysis was performed on contrast enhanced dual-energy CT scans in the arterial and portal venous phase prior to treatment initiation using Syngo.via (Siemens Healthcare, Forchheim, Germany) on MM Oncology Workflow adhering to RECIST 1.1 criteria (Eisenhauer et al., 2009). CtDNA predicts outcome in localized and disseminated disease. Moreover, it correlates with distant metastasis volume and positive lymph nodes but not primary tumor volume and therefore could indicate subclinical synchronous distant metastases in localized PDAC undetectable by current gold standard (computed tomography).

16.
Eur J Surg Oncol ; 48(5): 1046-1053, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34876329

RESUMO

INTRODUCTION: Circulating tumor DNA (ctDNA) represents a promising tool for diagnosis, prognosis and treatment monitoring of several malignancies. Its association with tumor burden in pancreatic ductal cancer (PDAC), especially in localized disease, is not fully explored yet. We aimed to investigate the association of pretherapeutic ctDNA levels in localized and metastatic PDAC with tumor volume and clinical outcomes. MATERIAL AND METHODS: Liquid biopsy for ctDNA detection was prospectively obtained from patients with localized or disseminated PDAC prior to either resection or systemic treatment. Detection rates and levels of ctDNA (digital droplet PCR) were correlated to tumor volume, relapse rate and survival. RESULTS: 60 patients with localized and 47 patients with metastatic PDAC were included. ctDNA was detected in 10% of localized and 57.4% of metastasized PDAC samples. In localized disease, ctDNA detection significantly correlated with the numbers of involved locoregional lymph nodes (p = 0.030). Primary tumor volume did not correlate with ctDNA levels in neither localized (p = 0.573) nor metastasized disease (p = 0.878). In disseminated disease, ctDNA levels correlated with total tumor volume (p = 0.026) and especially with liver metastases volume (p = 0.004), but not with other metastases. Detection of pretherapeutic ctDNA was associated with shorter DFS in localized (3.3 vs. 18.1 months, p = 0.000), whereas ctDNA levels were associated with worse survival in metastatic PDAC (5.7 vs. 7.8 months, p = 0.036). CONCLUSION: ctDNA positivity indicates major nodal involvement or even presence of undetected distant metastases associated with early recurrence in localized PDAC. Moreover, it predicts worse clinical outcome in both localized and metastatic disease.


Assuntos
Carcinoma Ductal Pancreático , DNA Tumoral Circulante , Neoplasias Pancreáticas , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/patologia , DNA Tumoral Circulante/genética , Humanos , Mutação , Recidiva Local de Neoplasia/genética , Neoplasias Pancreáticas/patologia , Prognóstico , Carga Tumoral , Neoplasias Pancreáticas
17.
Front Oncol ; 12: 902177, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110940

RESUMO

Introduction: Pretherapeutic detectable circulating tumor DNA (ctDNA) represents a promising prognostic biomarker for predicting relapse and overall survival in patients with metastatic pancreatic cancer. However, the prognostic value of ctDNA dynamics during treatment has not been studied thus far. We aimed to investigate the correlation between the change of ctDNA levels and response to treatment in patients treated by systemic therapy. Material and methods: CtDNA detection using liquid biopsy (droplet digital PCR (ddPCR) utilizing KRAS G12/13 and, if negative, Q61 commercial test kits) was prospectively performed on patients with stage IV pancreatic cancer i) prior to initiation of systemic chemotherapy and ii) serially every 2 weeks until restaging. Detection rates, levels of ctDNA, and the course of the relative ctDNA change (ctDNA kinetics) were correlated to treatment response and clinical outcome. Results: The detection rate at baseline was 64.3% (45/70), and complete serial measurement records were available for 32 ctDNA-positive patients. Reduction of ctDNA levels below 57.9% of its baseline value at week 2 after treatment initiation was significantly predictive of response to treatment (area under the curve (AUC) = 0.918, sensitivity 91.67%, and specificity 100%) and was associated with prolonged overall survival (OS) (5.7 vs. 11.4 months, p = 0.006) and progression-free survival (PFS) (2.5 vs. 7.7 months, p < 0.000) regardless of treatment line. Pretherapeutic ctDNA detection was independently associated with worse OS in patients receiving a first-line regimen (7 vs. 11.3 months, p = 0.046) and regardless of treatment line (11.4 vs. 15.9 months, p = 0.045) as well as worse PFS (3.4 vs. 10.8 months, p = 0.018). Conclusion: The change in magnitude of ctDNA during systemic treatment allows the prediction of treatment response and is associated with both OS and PFS. This finding adds significant clinical potential to the already established prognostic value of ctDNA positivity in metastatic pancreatic cancer.

18.
Anticancer Res ; 40(4): 2151-2156, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234908

RESUMO

BACKGROUND/AIM: We compared patients with advanced gastric cancer [Union for International Cancer Control (UICC) III] versus patients with stage UICC IV and peritoneal carcinomatosis treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) versus patients with stage UICC IV treated without HIPEC to ascertain if CRS and HIPEC improve overall survival (OS). PATIENTS AND METHODS: We retrospectively analysed thirty-seven advanced gastric cancer patients who had been treated at our department from 2012 to 2017. The endpoint was median OS. RESULTS: Eighteen (49%) patients with UICC stage III showed a median OS of 37.4 months. Eight (21%) patients in the HIPEC group reached a median OS of 33.8 months. Median OS in the UICC IV group (11 patients, 30%) treated with a palliative concept was 6.2 months and therefore significantly worse (p=0.004). CONCLUSION: A systemic approach combined with CRS and HIPEC in selected stage IV gastric cancer patients improves the OS comparable to patients in UICC stage III.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida/métodos , Neoplasias Peritoneais/terapia , Neoplasias Gástricas/terapia , Idoso , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/complicações , Estudos Retrospectivos , Neoplasias Gástricas/complicações , Resultado do Tratamento
19.
J Clin Med ; 9(9)2020 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-32842617

RESUMO

Accurate staging and treatment planning are imperative for precise management in Anal Cancer (ACa) patients. We aimed to evaluate the additive and prognostic value of pre-treatment 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) in the staging and management of ACa compared to magnetic resonance imaging (MRI). This retrospective study was conducted on 54 patients. Pre-treatment 2-[18F]FDG PET/CT studies and MRI reports were compared considering the primary tumor, pelvic lymph nodes, and metastatic lesions. The impact of 2-[18F]FDG PET/CT in the management and its prognostic value, using maximum standardized uptake value (SUVmax), were assessed. Discordant findings were found in 46.3% of patients (5 in T; 1 in T and N; 18 in N; and 1 in M stage). 2-[18F]FDG PET/CT resulted in up-staging in 9.26% and down-staging in 3.7% of patients. Perirectal lymph nodes were metabolically inactive in 12.9% of patients. Moreover, 2-[18F]FDG PET/CT resulted in management change in 24.1% of patients. Finally, SUVmax provided no prognostic value. 2-[18F]FDG PET/CT altered staging and management in a sizable number of patients in this study, and supports a need for a change in guidelines for it to be used as a routine complementary test in the initial management of ACa.

20.
Cancers (Basel) ; 12(5)2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32423000

RESUMO

Background: Oncological survival after resection of pancreatic neuroendocrine neoplasms (panNEN) is highly variable depending on various factors. Risk stratification with preoperatively available parameters could guide decision-making in multidisciplinary treatment concepts. C-reactive Protein (CRP) is linked to inferior survival in several malignancies. This study assesses CRP within a novel risk score predicting histology and outcome after surgery for sporadic non-functional panNENs. Methods: A retrospective multicenter study with national exploration and international validation. CRP and other factors associated with overall survival (OS) were evaluated by multivariable cox-regression to create a clinical risk score (CRS). Predictive values regarding OS, disease-specific survival (DSS), and recurrence-free survival (RFS) were assessed by time-dependent receiver-operating characteristics. Results: Overall, 364 patients were included. Median CRP was significantly higher in patients >60 years, G3, and large tumors. In multivariable analysis, CRP was the strongest preoperative factor for OS in both cohorts. In the combined cohort, CRP (cut-off ≥0.2mg/dL; hazard-ratio (HR):3.87), metastases (HR:2.80), and primary tumor size ≥3.0cm (HR:1.83) showed a significant association with OS. A CRS incorporating these variables was associated with postoperative histological grading, T category, nodal positivity, and 90-day morbidity/mortality. Time-dependent area-under-the-curve at 60 months for OS, DSS, and RFS was 69%, 77%, and 67%, respectively (all p < 0.001), and the inclusion of grading further improved the predictive potential (75%, 84%, and 78%, respectively). Conclusions: CRP is a significant marker of unfavorable oncological characteristics in panNENs. The proposed internationally validated CRS predicts histological features and patient survival.

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