Friedrich Laengle

Resection of Hilar Cholangiocarcinomas: Pivotal Prognostic Factors and Impact of Tumor Sclerosis

The well-known poor prognosis of proximal bile duct cancer is due to its unfortunate anatomical location and its late diagnosis. Successful tumor resection, which is considered to be optimal treatment, depends on many factors. Eighty-eight patients suffering from proximal bile duct cancer underwent surgical exploration at our institution between 1977 and 1998. In 37 patients the tumor was resectable; in the remaining 51 patients exploratory laparotomy or a palliative operation was performed. The median survival after tumor resection was 18.6 months, but median survival after a palliative procedure or an exploratory laparotomy was only 3.4 months (p < 0.001). A curative R0 resection was possible in 11 patients, an R1 resection was performed in 22 patients, and 4 patients had an R2 resection. The median survival rate after R0 resection was 83.6 months, 12.3 months after R1 resection, and 2.7 months after R2 resection (p < 0.001). Survival after resection in patients with negative lymph nodes (n = 30) was significantly longer than in those with positive lymph nodes (n = 7) (p = 0.022). Grade of tumor sclerosis tended to have an influence on resectability rate (p = 0.076). The pattern of tumor growth was without statistical influence. Multivariate analysis revealed resection (p < 0.001) as the only significant prognostic marker for patient survival. Radical resection is the only therapy that provides a chance for long-term survival, with sclerosis of the cancer tending to have an influence on univariate analysis.

Limited value of CA 19-9 in predicting early treatment failure in patients with advanced pancreatic cancer.

Objective: The role of CA 19-9 in monitoring treatment response in advanced pancreatic cancer remains uncertain. We assessed its value in predicting early failure of first-line chemotherapy. Methods: Data of 84 patients with advanced pancreatic cancer who had received first-line chemotherapy were analyzed with regard to changes in CA 19-9 during the first 2 months of treatment. Results: Median time to progression and overall survival in patients with a transient increase in CA 19-9 during month 1 (n = 15; 5.5 and 13 months) and in those with no increase during the 2 months (n = 52; 6.5 and 12 months) were comparable and slightly above the median values of the entire study population. The hazard ratios for disease progression for a 20% increase in CA 19-9 during the first and second month of therapy were 1.065 and 1.339 in the univariate- and 1.092 and 1.298 in the multiple Cox regression model, respectively. CA 19-9 did not influence survival. Conclusion: Our results suggest that early CA 19-9 measurements are weakly associated with disease progression rather than survival in patients with advanced pancreatic cancer receiving palliative chemotherapy. In view of a possible tumor marker flare, values after the first month of therapy must be interpreted with caution.

Phase II trial of capecitabine plus nab-paclitaxel in patients with metastatic pancreatic adenocarcinoma

BACKGROUND Combination chemotherapy regimens including fluoropyrimidines as well as albumin-bound paclitaxel have shown promising results in patients with metastatic pancreatic adenocarcinoma (mPC). Based on the recently described excellent therapeutic index of capecitabine plus nab-paclitaxel in metastatic breast cancer, the present phase II trial was initiated. METHODS Patients with previously untreated mPC were treated with capecitabine (825 mg/m(2) orally bid on days 1-15) and nab-paclitaxel (125 mg/m(2) intravenously on days 1 and 8) every 3 weeks. In patients without clinically relevant adverse reactions after the 1st treatment course (≤ grade 2 toxicities according to NCI-CTC vs. 4.0, exuding alopecia and fatigue of any degree) and adequate bone marrow function, the nab-paclitaxel dose was escalated to 100 mg/m(2) on days 1, 8 and 15 of each cycle; this intra-individual dose escalation was maintained during subsequent treatment courses if tolerated. The primary endpoint was objective response rate (ORR) according to RECIST criteria, assessed by an independent radiological review committee with evaluation performed every 2 months. RESULTS Between 12/2013 and 01/2015, 30 patients were entered in this monocentric academic phase II trial. All patients had an ECOG performance status of 0-1, 80% had liver metastases and 23% had biliary stents in place at time of study initiation. Median CA19-9 was 1,004 U/mL (0.9-100.000 U/mL). In all patients except 2, a dose escalation of nab-paclitaxel after the 1st treatment course could be accomplished. The most common grade 3 adverse events (AEs) included transient sensory neuropathy (23%), (afebrile) neutropenia (17%), hand-foot-syndrome (13%) and phototoxic skin reaction (10%). Among 29 RECIST-response assessable patients, the ORR was 41.4% and stable disease (SD) was noted in 34.5%, resulting in a disease control rate (DCR) of 76%. After a median follow-up duration of 10.3 months (range, 1.9-19.0 months), 13/30 patients (43.3%) are presently being alive. CONCLUSIONS The combination of capecitabine + nab-paclitaxel at these doses and scheduling was well tolerated and showed substantial antitumor efficacy.

Influence of UW solution on in vitro platelet aggregability

Abstract  Bleeding problems in or‐thotopic liver transplantation (OLT), starting immediately after reperfusion of the graft, are complicating the outcome of transplantation. Platelets may be involved in this situation, but there is still a lack of information about the influence of UW solution on platelet function. We evaluated the effect of UW solution on in vitro platelet aggreg ability in healthy volunteers using whole blood electrical aggregometry and concluded, that UW solution causes impaired platelet aggregabil ity and may contribute to bleeding problems during OLT. The mechanism of impairment remains un clear, since central pathways as well as membrane receptors seem to be involved. Furthermore. our data support the necessity of extended flushing of the liver graft after re perfusion.