CONTEXT The role of adjuvant therapy in resectable pancreatic cancer is still uncertain, and no recommended standard exists. OBJECTIVE To test the hypothesis that adjuvant chemotherapy with ...gemcitabine administered after complete resection of pancreatic cancer improves disease-free survival by 6 months or more. DESIGN, SETTING, AND PATIENTS Open, multicenter, randomized controlled phase 3 trial with stratification for resection, tumor, and node status. Conducted from July 1998 to December 2004 in the outpatient setting at 88 academic and community-based oncology centers in Germany and Austria. A total of 368 patients with gross complete (R0 or R1) resection of pancreatic cancer and no prior radiation or chemotherapy were enrolled into 2 groups. INTERVENTION Patients received adjuvant chemotherapy with 6 cycles of gemcitabine on days 1, 8, and 15 every 4 weeks (n = 179), or observation (control n = 175). MAIN OUTCOME MEASURES Primary end point was disease-free survival, and secondary end points were overall survival, toxicity, and quality of life. Survival analysis was based on all eligible patients (intention-to-treat). RESULTS More than 80% of patients had R0 resection. The median number of chemotherapy cycles in the gemcitabine group was 6 (range, 0-6). Grade 3 or 4 toxicities rarely occurred with no difference in quality of life (by Spitzer index) between groups. During median follow-up of 53 months, 133 patients (74%) in the gemcitabine group and 161 patients (92%) in the control group developed recurrent disease. Median disease-free survival was 13.4 months in the gemcitabine group (95% confidence interval, 11.4-15.3) and 6.9 months in the control group (95% confidence interval, 6.1-7.8; P<.001, log-rank). Estimated disease-free survival at 3 and 5 years was 23.5% and 16.5% in the gemcitabine group, and 7.5% and 5.5% in the control group, respectively. Subgroup analyses showed that the effect of gemcitabine on disease-free survival was significant in patients with either R0 or R1 resection. There was no difference in overall survival between the gemcitabine group (median, 22.1 months; 95% confidence interval, 18.4-25.8; estimated survival, 34% at 3 years and 22.5% at 5 years) and the control group (median, 20.2 months; 95% confidence interval, 17-23.4; estimated survival, 20.5% at 3 years and 11.5% at 5 years; P = .06, log-rank). CONCLUSIONS Postoperative gemcitabine significantly delayed the development of recurrent disease after complete resection of pancreatic cancer compared with observation alone. These results support the use of gemcitabine as adjuvant chemotherapy in resectable carcinoma of the pancreas. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN34802808
Purpose
The International Study Group of Liver Surgery (ISGLS) defined post-hepatectomy biliary leakage as drain/serum bilirubin ratio > 3 at day 3 or the interventional/surgical revision due to ...biliary peritonitis. We investigated the definition’s applicability.
Methods
A retrospective evaluation of all liver resections over a 6-year period was performed. ROC analyses were performed for drain/serum bilirubin ratios on days 1, 2, and 3 including grade A to C (analysis I) and grade B and C biliary leakages (analysis II) to test specific cutoff values.
Results
A total of 576 patients were included. One hundred nine (18.9%) postoperative bile leakages occurred (19.6% of the whole population grade A, 16.5% grade B/C). Areas under the curve (AUC) for analysis I were 0.841 (day 1), 0.846 (day 2), and 0.734 (day 3). The highest sensitivity (78% on day 1/77% on day 2) and specificity (78% on day 1/79% on day 2) in analysis I were obtained for a drain/serum bilirubin ratio of 2.0. AUCs for analysis II were similar: 0.788 (day 1), 0.791 (day 2), and 0.650 (day 3). The highest sensitivity (73% on day 1/71% on day 2) and specificity (74% on day 1/76% on day 2) in analysis II were detected for a drain/serum bilirubin ratio of 2.0 on postoperative day 2.
Conclusion
Biliary leakages should be defined if the drain/serum bilirubin ratio is > 2.0 on postoperative day 2.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
23.
Posthepatectomy liver failure Schreckenbach, Teresa; Liese, Juliane; Bechstein, Wolf O ...
Digestive surgery,
01/2012, Volume:
29, Issue:
1
Journal Article
Peer reviewed
Open access
Posthepatectomy liver failure (PHLF) is one of the most serious complications after liver resection and is still reported in up to 8% after liver resection.
To provide an overview about the current ...status of risk analysis and definition of PHLF. Prevention and treatment is also discussed.
A literature review was carried out on PubMed using the terms 'liver failure', 'posthepatectomy' and 'liver surgery' to search relevant papers.
PHLF remains a serious problem in patients undergoing major liver resection. Adequate preoperative risk assessment and an optimal postoperative treatment are essential for PHLF prevention.
The main reason for treatment failure after curative surgical resection of gastric cancer is intra-abdominal spread, with 40-50% peritoneal seeding as primary localization of recurrence. Peritoneal ...relapse is seen in 60-70% of tumors of diffuse type, compared to only 20-30% of intestinal type. Hyperthermic IntraPEritoneal Chemoperfusion (HIPEC) is an increasingly used therapy method for patients with peritoneal metastases. The preventive use of HIPEC could represent an elegant approach for patients (pts) before macroscopic peritoneal seeding, since pts. with operable disease are fit and may have potential risk of microscopic involvement, thus having a theoretical chance of cure with HIPEC even without the need for cytoreduction. No results from a PCRT from the Western hemisphere have yet been published.
This is a multicenter, randomized, controlled, open-label study including a total of 200 pts. with localized and locally advanced diffuse or mixed type (Laurens's classification) adenocarcinoma of the stomach and Type II/III GEJ. All enrolled pts. will have received 3-6 pre-operative cycles of biweekly FLOT (Docetaxel 50 mg/m
; Oxaliplatin 85 mg/m
; Leucovorin 200 mg/m
; 5-FU 2600 mg/m
, q2wk). Pts will be randomized 1:1 to receive surgery only and postoperative FLOT (control arm) or surgery + intraoperative HIPEC (cisplatin 75 mg/m
solution administered at a temperature of 42 °C for 90 min) and postoperative FLOT (experimental arm). Surgery is carried out as gastrectomy or transhiatal extended gastrectomy. Primary endpoint is PFS/DFS, major secondary endpoints are OS, rate of pts. with peritoneal relapse at 2 and 3 years, perioperative morbidity/mortality and quality of life. The trial starts with a safety run-in phase. After 20 pts. had curatively intended resection in Arm B, an interim safety analysis is performed. Recruitment has already started and first patient in was on January 18th, 2021.
If the PREVENT concept proves to be effective, this could potentially lead to a new standard of therapy. On the contrary, if the outcome is negative, pts. with gastric cancer and no peritoneal involvement will not be treated with HIPEC during surgery.
The study is registered on June 25th, 2020 under ClinicalTrials.gov Identifier: NCT04447352 ; EudraCT: 2017-003832-35 .
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Deep Vein Thrombosis of the Upper Extremity Heil, Jan; Miesbach, Wolfgang; Vogl, Thomas ...
Deutsches Ärzteblatt international,
2017-Apr-07, 20170407, Volume:
114, Issue:
14
Journal Article
Peer reviewed
Open access
Deep venous thrombosis (DVT) arises with an incidence of about 1 per 1000 persons per year; 4-10% of all DVTs are located in an upper extremity (DVT-UE). DVT-UE can lead to complications such as ...post-thrombotic syndrome and pulmonary embolism and carries a high mortality.
This review is based on pertinent literature, published from January 1980 to May 2016, that was retrieved by a systematic search, employing the PRISMA criteria, carried out in four databases: PubMed (n = 749), EMBASE (n = 789), SciSearch (n = 0), and the Cochrane Library (n = 12). Guidelines were included in the search.
DVT-UE arises mainly in patients with severe underlying diseases, especially cancer (odds ratio OR 18.1; 95% confidence interval 9.4; 35.1). The insertion of venous catheters-particularly central venous catheters-also elevates the risk of DVT-UE. Its clinical manifestations are nonspecific. Diagnostic algorithms are of little use, but ultrasonography is very helpful in diagnosis. DVT-UE is treated by anticoagulation, with heparin at first and then with oral anticoagulants. Direct oral anticoagulants are now being increasingly used. The thrombus is often not totally eradicated. Anticoagulation is generally continued as maintenance treatment for 3-6 months. Interventional techniques can be used for special indications. Patients with DVT-UE have a high mortality, though they often die of their underlying diseases rather than of the DVT-UE or its complications.
DVT of the upper extremity is becoming increasingly common, though still much less common than DVT of the lower extremity. The treatment of choice is anticoagulation, which is given analogously to that given for DVT of the lower extremity.
Objective:
The aim of this study was to pool data from randomized controlled trials (RCT) limited to
resectable
pancreatic ductal adenocarcinoma (PDAC) to determine whether a neoadjuvant therapy ...impacts on disease-free survival (DFS) and surgical outcome.
Summary Background Data:
Few underpowered studies have suggested benefits from neoadjuvant chemo (± radiation) for strictly resectable PDAC without offering conclusive recommendations.
Methods:
Three RCTs were identified comparing neoadjuvant chemo (± radio) therapy
vs.
upfront surgery followed by adjuvant therapy in all cases. Data were pooled targeting DFS as primary endpoint, whereas overall survival (OS), postoperative morbidity, and mortality were investigated as secondary endpoints. Survival endpoints DFS and OS were compared using Cox proportional hazards regression with study-specific baseline hazards.
Results:
A total of 130 patients were randomized (56 in the neoadjuvant and 74 in the control group). DFS was significantly longer in the neoadjuvant treatment group compared to surgery only
hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.4–0.9 (
P
= 0.01). Furthermore, DFS for the subgroup of R0 resections was similarly longer in the neoadjuvant treated group (HR 0.6, 95% CI 0.35–0.9,
P
= 0.045). Although postoperative complications (Comprehensive Complication Index, CCI
®
) occurred less frequently (
P
= 0.008), patients after neoadjuvant therapy experienced a higher toxicity, but without negative impact on oncological or surgical outcome parameters.
Conclusion:
Neoadjuvant therapy can be offered as an acceptable standard of care for patients with purely resectable PDAC. Future research with the advances of precision oncology should now focus on the definition of the optimal regimen.
Patients with locally advanced gastric cancer benefit from combined pre- and postoperative chemotherapy, although fewer than 50% could receive postoperative chemotherapy. We examined the value of ...purely preoperative chemotherapy in a phase III trial with strict preoperative staging and surgical resection guidelines.
Patients with locally advanced adenocarcinoma of the stomach or esophagogastric junction (AEG II and III) were randomly assigned to preoperative chemotherapy followed by surgery or to surgery alone. To detect with 80% power an improvement in median survival from 17 months with surgery alone to 24 months with neoadjuvant, 282 events were required.
This trial was stopped for poor accrual after 144 patients were randomly assigned (72:72); 52.8% patients had tumors located in the proximal third of the stomach, including AEG type II and III. The International Union Against Cancer R0 resection rate was 81.9% after neoadjuvant chemotherapy as compared with 66.7% with surgery alone (P = .036). The surgery-only group had more lymph node metastases than the neoadjuvant group (76.5% v 61.4%; P = .018). Postoperative complications were more frequent in the neoadjuvant arm (27.1% v 16.2%; P = .09). After a median follow-up of 4.4 years and 67 deaths, a survival benefit could not be shown (hazard ratio, 0.84; 95% CI, 0.52 to 1.35; P = .466).
This trial showed a significantly increased R0 resection rate but failed to demonstrate a survival benefit. Possible explanations are low statistical power, a high rate of proximal gastric cancer including AEG and/or a better outcome than expected after radical surgery alone due to the high quality of surgery with resections of regional lymph nodes outside the perigastic area (celiac trunc, hepatic ligament, lymph node at a. lienalis; D2).
Total neoadjuvant therapy has been increasingly adopted for multimodal rectal cancer treatment. The optimal sequence of chemoradiotherapy (CRT) and chemotherapy needs to be established.
To report the ...long-term results of the secondary end points prespecified in the Randomized Phase 2 Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy (CAO/ARO/AIO-12 trial) for Locally Advanced Rectal Cancer.
This secondary analysis of a randomized clinical trial included 311 patients who were recruited from the accrued CAO/ARO/AIO-12 trial population from June 15, 2015, to January 31, 2018, from 18 centers in Germany. Patients with cT3-4 and/or node-positive rectal adenocarcinoma were included in the analysis. Data were analyzed from June 15, 2015, to January 31, 2018. The follow-up analysis was conducted between January 31, 2018, and November 30, 2020.
Patients were randomly assigned to group A for 3 cycles of fluorouracil, leucovorin, and oxaliplatin before fluorouracil/oxaliplatin CRT (50.4 Gy), or to group B for CRT before chemotherapy. Total mesorectal excision was scheduled on day 123 after the start of total neoadjuvant therapy in both groups.
The end points assessed in this secondary analysis included long-term oncologic outcomes, chronic toxicity, patient-reported outcome measures for global health status (GHS) and quality of life (QoL), and the Wexner stool incontinence score.
Of the 311 patients enrolled, 306 were evaluable, including 156 in group A (mean SD age, 60 11 years; 106 men 68%) and 150 in group B (mean SD age, 62 10 years; 100 men 67%). After a median follow-up of 43 months (range, 35-60 months), the 3-year disease-free survival was 73% in both groups (hazard ratio, 0.95; 95% CI, 0.63-1.45, P = .82); the 3-year cumulative incidence of locoregional recurrence (6% vs 5%, P = .67) and distant metastases (18% vs 16%, P = .52) were not significantly different. Chronic toxicity grade 3 to 4 occurred in 10 of 85 patients (11.8%) in group A and 8 of 66 patients (9.9%) in group B at 3 years. The GHS/QoL score decreased after total mesorectal excision but returned to pretreatment levels 1 year after randomization with no difference between the groups. Stool incontinence deteriorated 1 year after randomization in both groups and only improved slightly at 3 years, but never reached baseline levels.
This secondary analysis of a randomized clinical trial showed that CRT followed by chemotherapy resulted in higher pathological complete response without compromising disease-free survival, toxicity, QoL, or stool incontinence and is thus proposed as the preferred total neoadjuvant therapy sequence if organ preservation is a priority.
ClinicalTrials.gov identifier: NCT02363374.
Patient Blood Management (PBM) is a systematic quality improving clinical model to reduce anemia and avoid transfusions in all kinds of clinical settings. Here, we investigated the potential of PBM ...in oncologic surgery and hypothesized that PBM improves 2-year overall survival (OS).
Retrospective analysis of patients 2 years before and after PBM implementation. The primary endpoint was OS at 2 years after surgery. We identified a sample size of 824 to detect a 10% improvement in survival in the PBM group.
The analysis comprised of 836 patients that underwent oncologic surgery, 389 before and 447 after PBM, was implemented. Patients in the PBM+ presented significantly more frequent with normal hemoglobin values before surgery than PBM- (56.6 vs. 35.7%; p < 0.001). The number of transfusions was significantly reduced from 5.5 ± 11.1 to 3.0 ± 6.9 units/patient (p < 0.001); moreover, the percentage of patients being transfused during the clinic stay was significantly reduced from 62.4 to 40.9% (p < 0.001). Two-year OS was significantly better in the PBM+ and increased from 67.0 to 80.1% (p = 0.001). A normal hemoglobin value (> 12 g/dl in female and > 13 g/dl in male) before surgery (HR 0.43, 95% CI 0.29-0.65, p < 0.001) was the only independent predictive factor positively affecting survival.
PBM is a quality improvement tool that is associated with better mid-term surgical oncologic outcome. The root cause for improvement is the increase of patients entering surgery with normal hemoglobin values.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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