Risk Factor Analysis for Developing Major Complications Following Esophageal Surgery-A Two-Center Study.

BACKGROUND: Esophagectomy carries a high risk of morbidity and mortality compared to other major surgeries. With the aim of creating an easy-to-use clinical preoperative risk assessment tool and to validate previously described risk factors for major complications following surgery, esophagectomies at two tertiary medical centers were analyzed. METHODS: A total of 450 patients who underwent esophagectomy for esophageal carcinoma at the University Medical Centre, Hamburg, or at the Medical Center University Duisburg-Essen, Germany (January 2008 to January 2020) were retrospectively analyzed. Epidemiological and perioperative data were analyzed to identify the risk factors that impact major complication rates. The primary endpoint of this study was to determine the incidence of major complications. RESULTS: The mean age of the patients was 63 years with a bimodal distribution. There was a male predominance across the cohort (81% vs. 19%, respectively). Alcohol abuse (p = 0.0341), chronic obstructive pulmonary disease (p = 0.0264), and cardiac comorbidity (p = 0.0367) were associated with a significantly higher risk of major complications in the multivariate analysis. Neoadjuvant chemotherapy significantly reduced the risk of major postoperative complications (p < 0.0001). CONCLUSIONS: Various patient-related risk factors increased the rate of major complications following esophagectomy. Patient-tailored prehabilitation programs before esophagectomy that focus on minimizing these risk factors may lead to better surgical outcomes and should be analyzed in further studies.

A Phase II Study of Nab-Paclitaxel and Gemcitabine as First-Line Therapy in Patients with Cholangiocarcinoma Ineligible for Cisplatin-Based Chemotherapy (NACHO).

INTRODUCTION: Gemcitabine and cisplatin is the standard first-line systemic treatment in patients with advanced cholangiocarcinoma (CCA). However, a substantial number of patients do not qualify for cisplatin due to comorbidities or poor performance status. The phase II pilot study NACHO evaluated the efficacy of nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) given on days 1, 8, and 15 every 4 weeks as first-line therapy in patients with advanced CCA ineligible for cisplatin-based chemotherapy. METHODS: Patients with any comorbidity precluding cisplatin therapy, such as renal impairment, impaired hearing, increased risk or history for thromboembolic events, intolerance of extensive hydration, or significant cardiovascular disease were eligible. Primary endpoint was overall response rate (ORR) per RECIST 1.1. Secondary endpoints were progression-free survival (PFS), overall survival (OS), safety, and patient reported outcome. RESULTS: From December 2016 to July 2017, 10 patients were prospectively enrolled and treated. The ORR with nab-paclitaxel/gemcitabine was 50%, the disease control rate (DCR) was 90%. Median PFS was 5.7 months (95% CI: 5.3-6.1), and median OS was 7.8 months (95% CI: 5.4-10.2). In total, 13 SAEs were documented without any new safety signals. There were 14 grade 3-4 treatment-related adverse events (TRAEs) in 10 patients of the ITT population. Exploratory subgroup analyses including known prognostic markers were performed. CONCLUSIONS: The NACHO trial supports safety and efficacy of nab-paclitaxel and gemcitabine in patients with advanced CCA ineligible for cisplatin-based therapy and should be further evaluated in a larger prospective trial.

Clinical Outcome and Treatment Sequences of Patients with Advanced Pancreatic Cancer Treated with Contemporary Chemotherapy Protocols.

INTRODUCTION: Systemic therapy is firmly established in patients with advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). Clinical efficacy is still modest and options are limited. Combination therapy protocols such as FOLFIRINOX and gemcitabine/nab-paclitaxel (Gem/NP) define standard-of-care. Patients may receive a sequence of both regimens as first- and second-line palliative treatment. However, there is no guidance regarding a preferred order. METHODS: This is a retrospective analysis of clinical characteristics, treatment trajectories, and outcomes of patients with advanced PDAC treated at the West German Cancer Center Essen from 2014 to 2020 to inform treatment decisions with respect to predictive factors, impact of chemotherapy regimen sequence, and maintenance treatment. RESULTS: We identified 170 patients with available follow-up. Of those, 160 (94.1%) patients received palliative CTX for primary metastatic, locally advanced, or recurrent PDAC. Median progression-free survival (PFS) upon first palliative chemotherapy was 4.1 (3.1-5.9) months. First-line FOLFIRINOX was associated with superior PFS (median 6.3 months) and OS (9.7 months, HR 0.7, p = 0.03) as compared to Gem/NP or other regimens (PFS 3.0, OS 6.9 months). However, OS benefit of first-line FOLFIRINOX was lost in patients who received at least two treatment lines (median OS 12.1 vs. 13.1 months, p = 0.43). A landmark analysis of patients with clinical benefit (defined as CR/PR/SD for at least 20 weeks) upon first-line therapy revealed improved OS (HR 0.53, p = 0.02) for patients receiving continued deescalated maintenance therapy. Second-line regimens resulted in similar PFS (overall log-rank p = 0.92, median PFS upon second-line therapy 2.3 [1.8-2.9], per-regimen median between 1.8 and 3.9 months). A previously established systemic inflammation score proved to be strongly prognostic and allowed identification of a patient subgroup with dismal prognosis (OS 2.9 vs. 11.4 months, HR 5.23, p < 0.001), independent of other prognostic factors and with no relevant interaction with the choice of first-line regimen. CONCLUSION: In this real-world population of PDAC patients treated with contemporary combination chemotherapies, a positive impact of first-line FOLFIRINOX was only observed when no second or further line treatment was administered. Intensity-reduced maintenance therapy may lead to superior survival.

Localized Angiosarcoma, Not One Disease: A Retrospective Single-Center Study on Prognosis Depending on the Primary Site and Etiology.

BACKGROUND: Angiosarcomas are rare and heterogeneous tumors with poor prognosis. The clinical subtypes are classified depending on the primary site and etiology. METHODS: We conducted a retrospective, monocentric study of 136 patients with localized AS between May 1985 and November 2018. Overall survival (OS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS) were estimated using the Kaplan-Meier method. To identify prognostic factors, univariate and multivariate analyses were performed based on Cox regressions. RESULTS: The median age was 67 years (19-72.8 years). Primary sites were cutaneous (27.2%), breast (38.2%), and deep soft tissue (34.6%). The majority was primary angiosarcomas (55.9%) followed by postradiation (40.4%) and chronic lymphedema angiosarcomas (2.9%). Prognosis significantly differed depending on the primary site and etiology. Shortest median OS and MFS were observed in deep soft tissue angiosarcomas, whereas cutaneous angiosarcomas, angiosarcomas of the breast, and radiation-associated angiosarcomas displayed worse median LRFS. Univariate analyses showed better OS for tumor size <10 cm (p = 0.009), negative surgical margins (p = 0.021), and negative lymph node status (p = 0.007). LRFS and MFS were longer for tumor size <10 cm (p = 0.012 and p = 0.013). In multivariate analyses, age <70 years was the only independent positive prognostic factor for OS in all subgroups. For LRFS, secondary AS of the breast was a negative prognostic factor (HR: 2.35; p = 0.035). CONCLUSIONS: Different behaviors and prognoses depending on the primary site and etiology should be considered for the treatment of this heterogeneous disease. In cutaneous angiosarcomas of the head/neck and postradiation angiosarcomas of the breast, local recurrence seems to have a crucial impact on OS. Therefore, improved local therapies and local tumor staging may have to be implemented. However, in deep soft tissue angiosarcomas, distant recurrence seems to have a major influence on prognosis, which indicates a benefit of additional perioperative chemotherapy.

AST 17600 U/l after liver transplantation, what are you up to? - A case report.

BACKGROUND: Miscellaneous clinical classifications of liver function after liver transplantation are rested upon elevation of transaminases which represent damaging of hepatocytes and with it of the liver. CASE REPORT: We report the case of a 35-year-old man suffering from hepatocellular carcinoma in the setting of alcoholic liver cirrhosis. The patient underwent liver transplantation and developed an extreme peak of transaminases due to prolonged cold ischemia time and additional extended donor criteria. On the first postoperative day the laboratory results showed peak transaminases as follows: AST 17577 U/l and ALT 9884 U/l. Frequent ultrasound revealed no signs of vascular complications. In spite of the dramatically elevated transaminases the liver showed a good primary function and the patient was cardiopulmonary stable. The entire postoperative course was uneventful. We discharged the patient after three weeks in a very good general state of health, with normal laboratory values. CONCLUSIONS: Exclusive extreme elevation of transaminases after liver transplantation combined with adequate liver synthesis does not always require re-transplantation, if situation of the patient is stable. Nevertheless re-transplantation should be reconsidered in any case of clinical deterioration of the patient.