Gene Expression in Solitary Fibrous Tumors (SFTs) Correlates with Anatomic Localization and NAB2-STAT6 Gene Fusion Variants.

Solitary fibrous tumors (SFTs) harbor recurrent NAB2-STAT6 gene fusions, promoting constitutional up-regulation of oncogenic early growth response 1 (EGR1)-dependent gene expression. SFTs with the most common canonical NAB2 exon 4-STAT6 exon 2 fusion variant are often located in the thorax (pleuropulmonary) and are less cellular with abundant collagen. In contrast, SFTs with NAB2 exon 6-STAT6 exon 16/17 fusion variants typically display a cellular round to ovoid cell morphology and are often located in the deep soft tissue of the retroperitoneum and intra-abdominal pelvic region or in the meninges. Here, we employed next-generation sequencing-based gene expression profiling to identify significant differences in gene expression associated with anatomic localization and NAB2-STAT6 gene fusion variants. SFTs with the NAB2 exon 4-STAT6 exon 2 fusion variant showed a transcriptional signature enriched for genes involved in DNA binding, gene transcription, and nuclear localization, whereas SFTs with the NAB2 exon 6-STAT6 exon 16/17 fusion variants were enriched for genes involved in tyrosine kinase signaling, cell proliferation, and cytoplasmic localization. Specific transcription factor binding motifs were enriched among differentially expressed genes in SFTs with different fusion variants, implicating co-transcription factors in the modification of chimeric NGFI-A binding protein 2 (NAB2)-STAT6-dependent deregulation of EGR1-dependent gene expression. In summary, this study establishes a potential molecular biologic basis for clinicopathologic differences in SFTs with distinct NAB2-STAT6 gene fusion variants.

Preventive HIPEC in combination with perioperative FLOT versus FLOT alone for resectable diffuse type gastric and gastroesophageal junction type II/III adenocarcinoma - the phase III "PREVENT"- (FLOT9) trial of the AIO /CAOGI /ACO.

BACKGROUND: 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. METHODS: 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/m2; Oxaliplatin 85 mg/m2; Leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2wk). Pts will be randomized 1:1 to receive surgery only and postoperative FLOT (control arm) or surgery + intraoperative HIPEC (cisplatin 75 mg/m2 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. DISCUSSION: 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. TRIAL REGISTRATION: The study is registered on June 25th, 2020 under ClinicalTrials.gov Identifier: NCT04447352 ; EudraCT: 2017-003832-35 .

Preoperative Pazopanib in High-Risk Soft Tissue Sarcoma: Phase II Window-of Opportunity Study of the German Interdisciplinary Sarcoma Group (NOPASS/GISG-04).

BACKGROUND: Preoperative devascularization might improve local control and thus the outcome of patients with soft tissue sarcoma (STS). The multikinase inhibitor pazopanib has antiangiogenic effects and is approved for treating metastatic STS. We conducted a trial of preoperative pazopanib therapy in high-risk STS. METHODS: This single-arm, phase II trial included patients with resectable, non-metastatic, treatment-naïve, high-risk STS. Patients received pazopanib 800 mg daily while waiting for surgery (21-day 'window of opportunity'). The primary endpoint was metabolic response rate (MRR; proportion of patients with ≥ 50% reduction of mean standardized uptake value [SUVmean] in post- vs. pretreatment fluorodeoxyglucose-positron emission tomography/computed tomography [FDG-PET-CT]). Planned sample size was 35 patients (type I error, 5%; type II error, 20%). A translational substudy explored associations between response and concentration of circulating angiogenic factors. RESULTS: Futility analysis was performed after 21 patients (11 female, mean age 67 years; liposarcoma n = 15); 17/21 patients were evaluable for the primary endpoint. The MRR was 1/17 (5.9%, 95% confidence interval < 0.01-0.29). Mean change in SUVmean of post- versus pretreatment PET was a 6% decrease (range 65% decrease to 34% increase); 7/21 (33.3%) patients had 12 grade 3/4 toxicities, and 19/21 (95.2%) patients were resected (all R0). One (4.8%) patient suffered a grade 4 postoperative complication (anastomotic leakage). Circulating endothelial progenitor cells, soluble vascular endothelial growth factor, and angiopoietin-2 concentrations showed no relevant changes during treatment. CONCLUSIONS: Although this study showed that preoperative pazopanib is not effective for unselected high-risk STS patients, relevant treatment effects were observed in a single patient. Future research needs to better define subgroups potentially benefiting from preoperative pazopanib treatment. CLINICALTRIALS. GOV IDENTIFIER: NCT01543802.

The RENAISSANCE (AIO-FLOT5) trial: effect of chemotherapy alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction - a phase III trial of the German AIO/CAO-V/CAOGI.

BACKGROUND: Historical data indicate that surgical resection may benefit select patients with metastatic gastric and gastroesophageal junction cancer. However, randomized clinical trials are lacking. The current RENAISSANCE trial addresses the potential benefits of surgical intervention in gastric and gastroesophageal junction cancer with limited metastases. METHODS: This is a prospective, multicenter, randomized, investigator-initiated phase III trial. Previously untreated patients with limited metastatic stage (retroperitoneal lymph node metastases only or a maximum of one incurable organ site that is potentially resectable or locally controllable with or without retroperitoneal lymph nodes) receive 4 cycles of FLOT chemotherapy alone or with trastuzumab if Her2+. Patients without disease progression after 4 cycles are randomized 1:1 to receive additional chemotherapy cycles or surgical resection of primary and metastases followed by subsequent chemotherapy. 271 patients are to be allocated to the trial, of which at least 176 patients will proceed to randomization. The primary endpoint is overall survival; main secondary endpoints are quality of life assessed by EORTC-QLQ-C30 questionnaire, progression free survival and surgical morbidity and mortality. Recruitment has already started; currently (Feb 2017) 22 patients have been enrolled. DISCUSSION: If the RENAISSANCE concept proves to be effective, this could potentially lead to a new standard of therapy. On the contrary, if the outcome is negative, patients with gastric or GEJ cancer and metastases will no longer be considered candidates for surgical intervention. TRIAL REGISTRATION: The article reports of a health care intervention on human participants and is registered on October 12, 2015 under ClinicalTrials.gov Identifier: NCT02578368 ; EudraCT: 2014-002665-30.

Fluorine-18-FDG PET/CT in a patient with angiomyolipoma: Response to mammalian target of rapamycin inhibitor therapy.

We report on a 27 years old female patient who was referred to our department for whole-body as well as dynamic positron emission tomography/computed tomography (dPET/CT) scan of the upper and middle abdomen with fluorine-18-fluorodeoxy glucose (18F-FDG), for further evaluation of a mass in the left adrenal gland region. Positron emission tomography showed a suspicious, enlarged, hypermetabolic mass with an average standardized uptake value (SUV) of 4.5 and a maximum SUV of 5.9. The patient was referred for biopsy, which revealed an angiomyolipoma, a perivascular epithelioid cell tumor (PEComa) of the adrenal gland. Perivascular epithelioid cell tumors are mesenchymal tumors consisting of blood vessels, smooth muscles and fat cells. The patient received anti-proliferative treatment with Afinitor, a mammalian target of rapamycin (mTOR) inhibitor, and was referred again one month after onset of therapy for early response assessment. The follow-up 18F-FDG PET/CT scan showed a nearly complete resolution of the previously detected adrenal mass, with very low tracer uptake and a decrease in its functional volume. Fluorine- 18-FDG PET/CT can be used for treatment response evaluation of angiomyolipoma treated with mTOR-inhibitors.

A mechanistic study on the metastasis inducing function of FUS-CHOP fusion protein in liposarcoma.

The FUS-CHOP fusion protein has been found to be instrumental for specific oncogenic processes in liposarcoma, but its ability to induce metastasis and the underlying mechanisms by which this can be achieved remain unknown. To dissect its functional role in this context, we stably overexpressed this protein in SW872 liposarcoma and HT1080 fibrosarcoma cell lines, and were able to demonstrate that forced expression of FUS-CHOP significantly increases migration and invasion, as well as enhances lung and liver metastasis in the in vivo chicken chorioallantoic membrane (CAM) model, that is proliferation independent. Additionally, FUS-CHOP enhances the expression of matrix-metalloproteinases -2 and -9, and transactivates their promoters in vitro. Mutational analysis showed that C/EBP-ß- (-769/-755), NF-κB (-525/-516) and CREB/AP-1 (-218/-207) sites were important for MMP-2 and NF-κB (-604/-598), AP-1 (-539/-532) and AP-1 (-81/-72) for MMP-9 transactivation. Moreover, a direct in vivo interaction of FUS-CHOP was observed in case of the MMP-2 promoter within region (-769/-207). siRNA data revealed that MMP-2 expression is essential in the FUS-CHOP induced metastatic phenotype. MMP-2-mRNA and protein expression correlated significantly with FUS-CHOP positivity in 46 resected patient liposarcoma tissues. We have for the first time provided substantial evidence for the FUS-CHOP oncoprotein as an inducer of metastasis that is due to the transcriptional induction of specific tumor-associated proteases. Insights gained from this study not only support a deeper understanding of the mechanistic properties of FUS-CHOP, but also open up new avenues for targeted therapy.

Technical considerations for isolated limb perfusion: A consensus paper.

BACKGROUND: Isolated limb perfusion (ILP) is a well-established surgical procedure for the administration of high dose chemotherapy to a limb for the treatment of advanced extremity malignancy. Although the technique of ILP was first described over 60 years ago, ILP is utilised in relatively few specialist centres, co-located with tertiary or quaternary cancer centres. The combination of high dose cytotoxic chemotherapy and the cytokine tumour necrosis factor alpha (TNFα), mandates leakage monitoring to prevent potentially serious systemic toxicity. Since the procedure is performed at relatively few specialist centres, an ILP working group was formed with the aim of producing technical consensus guidelines for the procedure to streamline practice and to provide guidance for new centres commencing the technique. METHODS: Between October 2021 and October 2023 a series of face to face online and hybrid meetings were held in which a modified Delphi process was used to develop a unified consensus document. After each meeting the document was modified and recirculated and then rediscussed at subsequent meeting until a greater than 90% consensus was achieved in all recommendations. RESULTS: The completed consensus document comprised 23 topics in which greater than 90% consensus was achieved, with 83% of recommendations having 100% consensus across all members of the working group. The consensus recommendations covered all areas of the surgical procedure including pre-operative assessment, drug dosing and administration, perfusion parameters, hyperthermia, leakage monitoring and theatre logistics, practical surgical strategies and also post-operative care, response evaluation and staff training. CONCLUSION: We present the first joint expert-based consensus statement with respect to the technical aspects of ILP that can serve as a reference point for both existing and new centres in providing ILP.

Perioperative chemo(radio)therapy versus primary surgery for resectable adenocarcinoma of the stomach, gastroesophageal junction, and lower esophagus.

BACKGROUND: The outcome of patients with locally advanced gastroesophageal adenocarcinoma (adenocarcinoma of the esophagus, gastroesophageal (GE) junction, and stomach) is poor. There is conflicting evidence regarding the effects of perioperative chemotherapy on survival and other outcomes. OBJECTIVES: To assess the effect of perioperative chemotherapy for gastroesophageal adenocarcinoma on survival and other clinically relevant outcomes in the overall population of participants in randomized controlled trials (RCTs) and in prespecified subgroups. SEARCH METHODS: We performed computerized searches in the Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Review of Effectiveness (DARE), the Cochrane Database of Systematic Reviews (CDSR) from The Cochrane Library, MEDLINE (1966 to May 2011), EMBASE (1980 to May 2011), and LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud), combining the Cochrane highly sensitive search strategy with specific search terms. Moreover, we handsearched several online databases, conference proceedings, and reference lists of retrieved papers. SELECTION CRITERIA: We included RCTs which randomized patients with gastroesophageal adenocarcinoma, in the absence of distant metastases, to receive either chemotherapy with or without radiotherapy followed by surgery, or surgery alone. DATA COLLECTION AND ANALYSIS: Two independent review authors identified eligible trials. We solicited individual patient data (IPD) from all selected trials. We performed meta-analyses based on intention-to-treat populations using the two-stage method to combine IPD with aggregate data from RCTs for which IPD were unavailable. We combined data from all trials providing IPD in a Cox proportional hazards model to assess the effect of several covariables on overall survival. MAIN RESULTS: We identified 14 RCTs with 2422 eligible patients. For eight RCTs with 1049 patients (43.3%), we were able to obtain IPD. Perioperative chemotherapy was associated with significantly longer overall survival (hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.73 to 0.89). This corresponds to a relative survival increase of 19% or an absolute survival increase of 9% at five years. This survival advantage was consistent across most subgroups. There was a trend towards a more pronounced treatment effect for tumors of the GE junction compared to other sites, and for combined chemoradiotherapy as compared to chemotherapy in tumors of the esophagus and GE junction. Resection with negative margins was a strong predictor of survival. Multivariable analysis showed that tumor site, performance status, and age have an independent significant effect on survival. Moreover, there was a significant interaction of the effect of perioperative chemotherapy with age (larger treatment effect in younger patients). Perioperative chemotherapy also showed a significant effect on several secondary outcomes. It was associated with longer disease-free survival, higher rates of R0 resection, and more favorable tumor stage upon resection, while there was no association with perioperative morbidity and mortality. AUTHORS' CONCLUSIONS: Perioperative chemotherapy for resectable gastroesophageal adenocarcinoma increases survival compared to surgery alone. It should thus be offered to all eligible patients. There is a trend to a larger survival advantage for tumors of the GE junction as compared to other sites and for chemoradiotherapy as compared to chemotherapy in esophageal and GE junction tumors. Likewise, there is an interaction between age and treatment effect, with younger patients having a larger survival advantage, and no survival advantage for elderly patients.

The Evaluation of the 1318 nm Diode Laser in Open Liver Surgery.

(1) Background: Numerous dissection instruments are available for liver resection. So far, there has been no evidence in favor of a specific dissection device effecting a reduction in postoperative mortality and morbidity or a reduction in intraoperative blood loss. The aim of the study was to evaluate the safety of liver resection with the 1318 nm surgical laser. (2) Methods: 151 consecutive patients who underwent liver resection using the 1318 nm surgical laser (n = 119) or conventional dissection methods (n = 32) were evaluated retrospectively. As primary outcome, postoperative complications were assessed using the Clavien-Dindo classification. Secondary outcomes were postoperative mortality, reoperations and reinterventions, intraoperative blood loss, the need for vascular control using the Pringle maneuver and oncological safety assessed through histopathological evaluation of resection margins. (3) Results: For liver resections using the 1318 nm surgical laser, the postoperative morbidity (41.2% vs. 59.4%, p = 0.066), mortality (1.7% vs. 3.1%, p = 0.513) and the reoperation rate (2.5% vs. 3.1%, p = 1.000) were not significantly different from conventional liver resections. In the laser group, a lower reintervention rate (9.2% vs. 21.9%, p = 0.050) was observed. The oncological safety demonstrated by a tumor-free resection margin was similar after laser and conventional resection (93.2% vs. 89.3%, p = 0.256). The median intraoperative blood loss was significantly lower in the laser group (300 mL vs. 500 mL, p = 0.005) and there was a significantly lower need for a Pringle maneuver (3.4% vs. 15.6%, p = 0.021). (4) Conclusions: Liver resections using the 1318 nm surgical laser can be routinely performed with a favorable risk profile. Compared to alternative resection methods, they are associated with low blood loss, appear adequate from an oncological point of view, and are not associated with increased mortality and morbidity.

Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy for Patients With Locally Advanced Rectal Cancer: Long-term Results of the CAO/ARO/AIO-12 Randomized Clinical Trial.

IMPORTANCE: Total neoadjuvant therapy has been increasingly adopted for multimodal rectal cancer treatment. The optimal sequence of chemoradiotherapy (CRT) and chemotherapy needs to be established. OBJECTIVE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: 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. MAIN OUTCOMES AND MEASURES: 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. RESULTS: 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. CONCLUSIONS AND RELEVANCE: 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. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02363374.

Perioperative quality of care is modulated by process management with clinical pathways for fast-track surgery of the colon.

PURPOSE: Clinical pathways (CPs) are increasingly used to improve quality of care. However, evidence if such improvements are also feasible in fast-track colorectal surgery is lacking. This study evaluates effects of a CP for fast-track colonic resections with respect to process and outcome quality. METHODS: We compared 78 consecutive patients undergoing colonic resections in 2008 and being treated with a CP (CP group) with 133 consecutive patients treated without CP between 2006 and 2007 (pre-CP group). Indicators for process quality were epidural catheter placement, postoperative mobilisation, resumption of solid diet, Foley catheter removal and length of stay. Outcome quality was measured through morbidity, mortality, re-operations and readmissions. RESULTS: In the CP group, patients received epidural analgesia significantly more often (87.2% vs. 75.2%; p =0.04), were mobilized (38.9% vs. 20.6% on the day of surgery; p = 0.03) and resumed a solid diet earlier (60.5% vs. 49.6% on day 1; p = 0.002). Foley catheter removal and length of stay did not differ between the groups. There were no significant differences regarding morbidity (28.2% vs. 32.3%), mortality (1.2% vs. 2.3%), re-operations (6.4% vs. 9.0%) and readmissions (2.6% vs. 3.8%). CONCLUSIONS: After CP implementation for fast-track surgery of the colon, several indicators of process quality improved while others such as length of stay remained unaltered. There were no significant changes in outcome parameters. CPs are a viable instrument to improve specific aspects of perioperative process management, but their selective benefits have to be critically weighed against the infrastructural and personal efforts required for design and implementation.

Effects of a clinical pathway of pulmonary lobectomy and bilobectomy on quality and cost of care.

PURPOSE: This study evaluates medical and economic effects of a clinical pathway (CP) for open lobectomy and bilobectomy with respect to process quality, outcome quality, and hospital cost. METHODS: We compared 38 consecutive patients who underwent open lobectomy or bilobectomy between April 2007 and June 2008 and were treated with a CP (CP group) with 43 consecutive patients treated without CP between 2005 and 2007 (pre-pathway group). Indicators for process quality were duration of catheter placement, pain intensity, respiratory exercising, and mobilization. Outcome quality was measured through morbidity, mortality, re-operations, and re-admissions. Cost of hospital stay was calculated using an imputed daily rate. RESULTS: Central venous catheters were used in 90% of patients in the CP group (pre-pathway group 40%; p < 0.0001). Epidural catheters were placed in 84% of patients in the CP group (pre-pathway group 56%; p = 0.01). Variation in duration of catheter placement was reduced in the CP group. The reduction of hospital stay was 3 days (-19%, p = 0.003). Perioperative outcome quality remained unchanged. There was a significant cost reduction of 1,614 euros per stay after CP introduction (-19%; p = 0.003). CONCLUSIONS: After CP implementation for open lobectomy the quality and standardization of care improved. Although length of hospital stay was significantly reduced, there was no significant increase of re-admissions or morbidity. Patients benefited from a shortened hospital stay while the hospital achieved cost reduction. This early analysis shows that the implementation of CP for open lobectomy has positive effects in terms of quality and cost of care.

Effects of a clinical pathway on quality of care in kidney transplantation: a non-randomized clinical trial.

PURPOSE: Standardization of care is essential for improving outcome of kidney transplantation (KT). Clinical pathways (CPs) are known to standardize and improve perioperative care for a number of interventions. In transplantation medicine, however, pertinent evidence is very limited. This study evaluates effects of a CP on quality of care in KT. MATERIALS AND METHODS: Consecutive patients (n=32) undergoing KT between July 2006 and August 2007 who were treated with a CP were compared to patients (n=44) treated without CP between January 2005 and June 2006. Several quality indicators regarding process and outcome were compared between groups. RESULTS: Quality of care was significantly higher in the CP group for the following indicators: timely removal of central venous catheters, wound drains, and Foley catheters and control of cyclosporine levels, respiratory exercising, and pain control. Median stay decreased non-significantly from 21.4 to 18.3 days. There was significantly less delayed graft function in the CP group. All other outcome indicators showed no significant differences. CONCLUSIONS: Implementation of a CP for KT improves the quality of perioperative treatment by standardizing care. Regarding effects on outcome, no clear conclusion can be drawn. We recommend that large randomized studies are conducted to evaluate the latter issue.

Effects of a clinical pathway for video-assisted thoracoscopic surgery (VATS) on quality and cost of care.

PURPOSE: The purpose of this study was to evaluate effects of a clinical pathway (CP) for video-assisted thoracoscopic surgery (VATS) on process quality, outcome quality, and hospital costs. MATERIALS AND METHODS: We implemented a CP for VATS and compared 34 patients treated with CP to 77 patients treated without CP. Indicators for process quality were duration of catheter placement, pain intensity, respiratory exercising, and mobilization. Outcome quality was measured through morbidity, mortality, reoperations, and readmissions. Cost of hospital stay was calculated using an imputed daily rate. RESULTS: Foley catheters were removed significantly earlier after CP implementation. All patients on CP were mobilized and received pulmonary exercising on the operation day. Pain levels were low after CP implementation. Median hospital stay significantly reduced by 5 days. Perioperative outcome quality remained unchanged. Costs significantly diminished by 1,510 Euro per stay. CONCLUSIONS: CP implementation had positive effects on process quality. Specifically, catheter management was improved and a good pain control achieved. Patients benefited from shortened stay and were treated at lower cost. A clear effect on outcome quality was not found. CPs are a promising tool for quality improvement and cost containment in thoracic surgery.

Bone marrow-sparing intensity-modulated radiotherapy (IMRT) for neo-adjuvant therapy of inoperable cervical cancer in a patient with severe thrombocytopenia.

BACKGROUND: Therapy possibilities are limited in patients with cervix carcinoma and thrombocytopenia. CASE REPORT: We describe a 50-year-old woman with inoperable cervical carcinoma and chronic lymphatic B cell leukemia (B-CLL). Due to thrombocytopenia, a combined radiochemotherapy could not be performed. Intensitymodulated radiotherapy (IMRT) aiming at maximal bone sparing was planned. After a total dose of 45 Gy, a laparoscopic omentum plastic was performed to enable radiotherapy (RT) to full dose. 3 days later, an external beam boost was restarted to a cumulative dose of 50.4 Gy. Regular blood analysis showed low but stable blood counts. 4 weeks after RT, magnetic resonance imaging (MRI) showed a 30% regression of the tumor volume and, after transfusion of fresh-frozen plasma, a hysterectomy could be performed. 6 months after therapy, no recurrence or late toxicities had occurred. CONCLUSION: The clinical implementation of IMRT may potentially improve the therapeutic outcome of patients with cervix cancer, allowing dose escalation without increasing normal-tissue toxicity.

Clinical Pathways for Oncological Gastrectomy: Are They a Suitable Instrument for Process Standardization to Improve Process and Outcome Quality for Patients Undergoing Gastrectomy? A Retrospective Cohort Study.

(1) Background: Oncological gastrectomy requires complex multidisciplinary management. Clinical pathways (CPs) can potentially facilitate this task, but evidence related to their use in managing oncological gastrectomy is limited. This study evaluated the effect of a CP for oncological gastrectomy on process and outcome quality. (2) Methods: Consecutive patients undergoing oncological gastrectomy before (n = 64) or after (n = 62) the introduction of a CP were evaluated. Assessed parameters included catheter and drain management, postoperative mobilization, resumption of diet and length of stay. Morbidity, mortality, reoperation and readmission rates were used as indicators of outcome quality. (3) Results: Enteral nutrition was initiated significantly earlier after CP implementation (5.0 vs. 7.0 days, p < 0.0001). Readmission was more frequent before CP implementation (7.8% vs. 0.0%, p = 0.05). Incentive spirometer usage increased following CP implementation (100% vs. 90.6%, p = 0.11). Mortality, morbidity and reoperation rates remained unchanged. (4) Conclusions: After implementation of an oncological gastrectomy CP, process quality improved, while indicators of outcome quality such as mortality and reoperation rates remained unchanged. CPs are a promising tool to standardize perioperative care for oncological gastrectomy.

Influence of Clinical pathways on treatment and outcome quality for patients undergoing pancreatoduodenectomy? A retrospective cohort study.

BACKGROUND: Pancreatic surgery demands complex multidisciplinary management. Clinical pathways (CPs) are a tool to facilitate this task, but evidence for their utility in pancreatic surgery is scarce. This study evaluated the effect of CPs on quality of care for pancreatoduodenectomy. METHODS: Data of all consecutive patients who underwent pancreatoduodenectomy before (n = 147) or after (n = 148) CP introduction were evaluated regarding catheter and drain management, postoperative mobilization, pancreatic enzyme substitution, resumption of diet and length of stay. Outcome quality was assessed using glycaemia management, morbidity, mortality, reoperation and readmission rates. RESULTS: Catheters and abdominal drainages were removed significantly earlier in patients treated with CP (p < 0.0001). First intake of liquids, nutritional supplement and solids was significantly earlier in the CP group (p < 0.0001). Exocrine insufficiency was significantly less common after CP implementation (47.3% vs. 69.7%, p < 0.0001). The number of patients receiving intraoperative transfusion dropped significantly after CP implementation (p = 0.0005) and transfusion rate was more frequent in the pre-CP group (p = 0.05). The median number of days with maximum pain level >3 was significantly higher in the CP group (p < 0.0001). There was no significant difference in mortality, morbidity, reoperation and readmission rates. CONCLUSIONS: Following implementation of a CP for pancreatoduodenectomy, several indicators of process and outcome quality improved, while others such as mortality and reoperation rates remained unchanged. CPs are a promising tool to improve quality of care in pancreatic surgery.

Management of locally recurrent soft tissue sarcoma after prior surgery and radiation therapy.

Surgery and radiation therapy are the standard for local tumour control in the treatment of soft tissue sarcoma. Sarcoma recurrence within a previously irradiated area is one of the most problematic therapeutic challenges in soft tissue tumours. Any information on previous therapy needs to be available in detail. In case of recurrent sarcoma not amenable to surgical resection with wide and clear margins, a multimodality therapy needs to be applied. The armamentarium usually looks for a neoadjuvant downstaging of the sarcoma by radiotherapy, chemo-radiotherapy or isolated limb perfusion with all of those strategies bearing benefits, but also specific risks. The potential of repeated radiotherapy and the modality that can be used (intraoperative radiotherapy, brachytherapy) needs to be carefully evaluated. The pathologist saves these major problems in intraoperative frozen section histology or resection margins and thus needs to be aware of the type of cancer cells potentially present within the resection specimen. Plastic and reconstructive surgery to cover the area of re-resection with viable and well-v tissue is absolutely crucial to prevent lymphatic fistula. Thus, adequate treatment of those specific situations usually involves postoperative physiotherapy and a specific rehabilitation, which is extremely important.

Current concepts in the management of retroperitoneal soft tissue sarcoma.

Soft tissue sarcomas (STS) in the retroperitoneum are usually diagnosed at the late stages. Surgery is the mainstay of treatment. The technique of resection is standardized. After dissection of the retroperitoneal blood vessel, a retroperitoneal plane of dissection adjacent to the spinal foramina is established in between the layers of the abdominal wall. Complete resection with tumor-free resection margins is the primary goal in retroperitoneal sarcoma surgery. Preoperative assessment of pathoanatomical growth patterns with respect to retroperitoneal vascular structures--as well as to visceral and retroperitoneal organs--influences surgical strategies and thus the surgical outcome. Blood vessel replacement and a multivisceral en bloc approach improve the quality of resection. Blood vessel involvement is stratified in type I (arterial and venous involvement), type II (arterial involvement), type III(venous involvement), and type IV (no vascular involvement). Adjuvant and neoadjuvant treatment options (chemotherapy, targeted therapy, and radiation therapy) are currently being investigated. A prospective randomized phase III trial has shown a positive effect of neoadjuvant chemotherapy combined with regional hyperthermia in disease-free survival, response rate, and local control. Subsets of liposarcomas (myxoid and round cell type) are selectively responsive to novel drugs, such as trabectedin, a DNA-binding agent. Radiotherapy is applied in higher-grade locally advanced retroperitoneal STS. The optimal technique of delivering radiotherapy remains to be determined. The restricted number of patients with retroperitoneal STS and unsatisfying results in local tumor control and long-term survival indicate the need for multi-institutional cooperative studies. An international effort is required to improve the evidence level on multimodal treatment algorithms.

Quantitative, dynamic 18F-FDG-PET for the evaluation of soft tissue sarcomas: relation to differential diagnosis, tumor grading and prediction of prognosis.

The purpose of this study was to evaluate soft tissue sarcomas by dynamic (18)F-FDG-PET studies, and to establish an index of kinetic parameters for evaluation of their malignancy, histological grade and prognosis, after surgical resection. One hundred and seventeen patients including 79 with histologically proven soft tissue malignancies, 14 with primary benign soft tissue tumors and 24 with postoperative scar tissues were examined. The (18)F-FDG studies were accomplished as a dynamic series for 60 min. The evaluation of the (18)F-FDG kinetics was performed using the following parameters: standardized uptake value (SUV), global influx (Ki), computation of transport constants (k1-k4) with consideration of the vascular fraction (VB) according to a two tissue compartment model, and fractal dimension (FD) based on the box-counting procedure (non-compartmental model). Discriminant analysis (DA) was used for data evaluation. Multivariate analysis was performed to assess the predictive value of each kinetic parameter on survival. Our results showed that in the primary cases (n=46), SUV, k1, Ki and FD were higher in sarcomas than benign tumors. The diagnostic sensitivity of 62.50%, a specificity of 92.86%, and an accuracy of 71.74% were achieved by using the combination of k1 and SUV as input variables for DA. In the postoperative cases (n=71), SUV, VB, k3, Ki, and FD were higher in recurrent lesions than in scar tissues. DA revealed a sensitivity of 80.85%, a specificity of 87.50%, and an accuracy of 83.10% by using the combination of SUV, Ki and FD. In liposarcoma patients (n=32), SUV and FD were higher in GII,III tumors as compared with GI. DA led to a sensitivity of 86.96%, a specificity of 55.56%, and an accuracy of 78.13% by using the combination of SUV and FD. By multivariate analysis of primary soft tissue sarcomas (n=26) after surgical resection, groups with k3>0.025 (P<0.0026) or FD>1.25 (P<0.0162) had significantly poor prognosis. In conclusion, the evaluation of full (18)F-FDG kinetics provides important information for the diagnosis of malignant lesions, histological grading and prognosis of soft tissue sarcomas.