Isolated Liver and Limb Perfusion in Preclinical and Clinical Studies: gene therapy and biochemotherapeutic strategies

__Abstract__ The liver is the major site of metastatic spread of primary colorectal cancer, whereas 3% of all patients with colorectal cancer will develop resectable liver metastases. If a resection with curative intent is done, a five year survival rate of 25-30% has been demonstrated in a large number of studies. The natural history of untreated patients with comparable liver involvement shows a five year survival rate of 0-3% (8). As noted above, the majority of patients with evidence of liver metastases are irresectable, because of extra-hepatic disease or excessive liver involvement. There is no standard treatment for unresectable hepatic metastases confined to the liver, so novel treatment modalities have to be developed. In order to achieve a better control of intrahepatic disease and to reduce systemic toxicity of the applied therapy, locoregional therapies have been developed. These therapies include hepatic arterial embolization (9), intratumoral injections of ethanol, acetic acid, biological agents, stereotactic or intra-arterial radiotherapy, intralesional laser therapy, cryotherapy, radiofrequency ablation and regional infusion or perfusion of chemotherapeutic drugs

Primary Leiomyosarcoma of the Adrenal Gland

We report a rare case of a primary leiomyosarcoma of the adrenal gland. A 73-year-old woman presented with an inferior vena cava syndrome. MR imaging was suggestive of a large tumour originating from the right adrenal gland. Angiography revealed a tumour vascularised by the right adrenal artery. At explorative laparotomy a tumour of 27 cm in diameter was found which was completely fixed to the liver; the tumour was therefore considered unresectable. As a consequence of the mechanical problems caused by this large tumour, the patient died 3 weeks after the operation. Autopsy revealed no distant metastases or other primary tumour site

Quality of Life, Sexual Functioning, and Physical Functioning Following Perineal Reconstruction with the Lotus Petal Flap

BACKGROUND: Lotus petal flaps (LPF) may be used for the reconstruction of extralevator abdominoperineal defects that cannot be closed primarily. Limited data are available on how perineal reconstruction with the LPF impacts on patients' quality of life (QoL), sexual functioning, and physical functioning. METHODS: A cross-sectional study was performed following perineal reconstruction with the LPF. The QoL of patients having undergone LPF reconstruction was compared with a control group in which perineal defects were closed without flaps. Sexual and physical functioning (presence of perineal herniation and range of motion [ROM] of the hip joints) could only be evaluated in the LPF group. Psychometrically sound questionnaires were used. Physical functioning was evaluated subjectively with binary questions and objectively by physical examination. RESULTS: Of the 23 patients asked to participate, 15 (65%) completed the questionnaires and 11 (47%) underwent physical examination. In the control group, 16 patients were included. There were no significant differences in QoL between the LPF and control groups. Within the LPF group, 33% of patients were sexually active postoperatively compared with 87% preoperatively. No perineal herniation was found. The ROM of the hip joints was bilaterally smaller compared with the generally accepted values. CONCLUSIONS: Conclusions should be made with care given the small sample size. Despite a supposedly larger resection area in the LPF group, QoL was comparable in both groups. Nonetheless, reconstruction seemed to affect sexual function and physical function, not hampering overall satisfaction

Re-Irradiation in Patients with Recurrent Rectal Cancer is Safe and Feasible

BACKGROUND: There is no consensus yet for the best treatment regimen in patients with recurrent rectal cancer (RRC). This study aims to evaluate toxicity and oncological outcomes after re-irradiation in patients with RRC in our center. Clinical (cCR) and pathological complete response (pCR) rates and radicality were also studied. METHODS: Between January 2010 and December 2018, 61 locally advanced RRC patients were treated and analyzed retrospectively. Patients received radiotherapy at a dose of 30.0-30.6 Gy (reCRT) or 50.0-50.4 Gy chemoradiotherapy (CRT) in cases of no prior irradiation because of low-risk primary rectal cancer. In both groups, patients received capecitabine concomitantly. RESULTS: In total, 60 patients received the prescribed neoadjuvant (chemo)radiotherapy followed by surgery, 35 patients (58.3%) in the reRCT group and 25 patients (41.7%) in the long-course CRT group. There were no significant differences in overall survival (p = 0.82), disease-free survival (p = 0.63), and local recurrence-free survival (p = 0.17) between the groups. Patients in the long-course CRT group reported more skin toxicity after radiotherapy (p = 0.040). No differences were observed in late toxicity. In the long-course CRT group, a significantly higher cCR rate was observed (p = 0.029); however, there was no difference in the pCR rate (p = 0.66). CONCLUSIONS: The treatment of RRC patients with re-irradiation is comparable to treatment with long-course CRT regarding toxicity and oncological outcomes. In the reCRT group, less cCR was observed, although there was no difference in pCR. The findings in this study suggest that it is safe and feasible to re-irradiate RRC patients

Torsion of the Gallbladder

A 77-year-old woman was seen with progressive abdominal pain. A CT scan was made and showed a large gallbladder extending into the right lower abdomen. Ultrasound was performed but demonstrated no gallstones. Laparoscopy showed a tordated, necrotic gallbladder that was attached to the liver only by the cystic artery and cystic duct. Cholecystectomy was performed. Torsion of the gallbladder is a rare but clinically important condition in which the diagnosis seldom is made preoperatively. In radiological and clinical signs of cholecystitis without gallstones, this condition should be considered

Effect of Extending the Original CROSS Criteria on Tumor Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer Patients:A National Multicenter Cohort Analysis

BACKGROUND: Extending the original criteria of the Chemoradiotherapy for Oesophageal Cancer followed by Surgery Study (CROSS) in daily practice may increase the treatment outcome of esophageal cancer (EC) patients. This retrospective national cohort study assessed the impact on the pathologic complete response (pCR) rate and surgical outcome. PATIENTS AND METHODS: Data from EC patients treated between 2009 and 2017 were collected from the national Dutch Upper Gastrointestinal Cancer Audit database. Patients had locally advanced EC (cT1/N+ or cT2-4a/N0-3/M0) and were treated according to the CROSS regimen. CROSS (n = 1942) and the extended CROSS (e-CROSS; n = 1359) represent patients fulfilling the original or extended CROSS criteria, respectively. The primary outcome was total pCR (ypT0N0), while secondary outcomes were local esophageal pCR (ypT0), surgical radicality, and postoperative morbidity and mortality. RESULTS: Overall, CROSS and e-CROSS did not differ in total or local pCR rate, although a trend was observed (23.2% vs. 20.4%, p = 0.052; and 26.7% vs. 23.8%, p = 0.061). When stratifying by histology, the pCR rate was higher in the CROSS group compared with e-CROSS in squamous cell carcinomas (48.2% vs. 33.3%, p = 0.000) but not in adenocarcinomas (16.8% vs. 16.9%, p = 0.908). Surgical radicality did not differ between groups. Postoperative mortality (3.2% vs. 4.6%, p = 0.037) and morbidity (58.3% vs. 61.8%, p = 0.048) were higher in e-CROSS. CONCLUSION: Extending the CROSS inclusion criteria for neoadjuvant chemoradiotherapy in routine clinical practice of EC patients had no impact on the pCR rate and on radicality, but was associated with increased postoperative mortality and morbidity. Importantly, effects differed between histological subtypes. Hence, in future studies, we should carefully reconsider who will benefit most in the real-world setting

Reorganizing the Multidisciplinary Team Meetings in a Tertiary Centre for Gastro-Intestinal Oncology Adds Value to the Internal and Regional Care Pathways. A Mixed Method Evaluation

Introduction: The reorganisation of the structure of a Gastro-Intestinal Oncology Multidisciplinary Team Meeting (GIO-MDTM) in a tertiary centre with three care pathways is evaluated on added value. Methods: In a mixed method investigation, process indicators such as throughput times were analysed and stakeholders were interviewed regarding benefits and drawbacks of the reorganisation and current MDTM functioning. Results: For the hepatobiliary care pathway, the time to treatment plan increased, but the time to start treatment reduced significantly. The percentage of patients treated within the Dutch standard of 63 days increased for the three care pathways. From the interviews, three themes emerged: added value of MDTMs, focus on planning integrated care and awareness of possible improvements. Discussion: The importance of evaluating interventions in oncology care pathways is shown, including detecting unexpected drawbacks. The evaluation provides insight into complex dynamics of the care pathways and contributes with recommendations on functioning of an MDTM. Conclusions: Throughput times are only partly determined by oncology care pathway management, but have influence on the functioning of MDTMs. Process indicator information can help to reflect on integration of care in the region, resulting in an increase of patients treated within the Dutch standard