The link between high factor VIII to protein C ratio values and poor liver function after major hepatectomy.

Our goal was to assess the coagulation profile in the immediate postoperative time after major liver surgery and its association with the liver function. Our hypothesis is that a decreased synthesis of the coagulation factor levels reflects an impaired liver synthesis following hepatic resection and will be associated with poor outcomes. This is a prospective, observational study recruiting consecutive patients scheduled for major liver resection in a tertiary hospital. Coagulation profile was assessed by conventional assays, viscoelastic assays and coagulation factor levels preoperatively and, on postoperative days 1, 2 and 6. Factor VIII to protein C (FVIII/PC) ratio has been used as a surrogate marker of hemostatic imbalance. Liver function was measured with conventional and indocyanine green (ICG) clearance tests, which were obtained preoperatively and on postoperative days 1 and 2. Sixty patients were recruited and 51 were included in the study. There is a clear increase in FVIII/PC ratio after surgery, which was significantly associated with low liver function, being more pronounced beyond postoperative day 2 and in patients with poorer liver function ( P  < 0.001). High FVIII/PC ratio values were significantly associated with higher postoperative morbidity, prolonged ICU and hospital stay and less survival ( P  < 0.05). High FVIII/PC ratio on postoperative day 2 was found to be predictor of posthepatectomy liver failure (PHLF; area under the ROC curve = 0.8129). Early postoperative high FVIII/PC ratio values are associated with low liver function, PHLF and poorer outcomes in patients undergoing major hepatic resection.

Updated Review and Clinical Recommendations for the Diagnosis and Treatment of Patients with Retroperitoneal Sarcoma by the Spanish Sarcoma Research Group (GEIS).

Soft tissue sarcomas (STS) are an uncommon and biologically heterogeneous group of tumors arising from mesenchymal cells. The incidence is estimated at five cases per 100,000 people per year. Retroperitoneal sarcomas (RPS) account for 10-15% of all STS, and their management depends on their anatomical characteristics and histotype. Due to their very low incidence, it is recommended that RPS be treated in reference centers and evaluated by an experienced multidisciplinary team (MDT). In Spain, the Spanish Group for Research in Sarcomas (GEIS) brings together experts from various specialties to promote research on sarcomas and improve treatment results. This paper summarizes the GEIS recommendations for the diagnosis, treatment, and follow-up of patients with RPS.

Clinical feasibility of combining intraoperative electron radiation therapy with minimally invasive surgery: a potential for electron-FLASH clinical development

Background Local cancer therapy by combining real-time surgical exploration and resection with delivery of a single dose of high-energy electron irradiation entails a very precise and effective local therapeutic approach. Integrating the benefits from minimally invasive surgical techniques with the very precise delivery of intraoperative electron irradiation results in an efficient combined modality therapy. Methods Patients with locally advanced disease, who are candidates for laparoscopic and/or thoracoscopic surgery, received an integrated multimodal management. Preoperative treatment included induction chemotherapy and/or chemoradiation, followed by laparoscopic surgery and intraoperative electron radiation therapy. Results In a period of 5 consecutive years, 125 rectal cancer patients were treated, of which 35% underwent a laparoscopic approach. We found no differences in cancer outcomes and tolerance between the open and laparoscopic groups. Two esophageal cancer patients were treated with IOeRT during thoracoscopic resection, with the resection specimens showing intense downstaging effects. Two oligo-recurrent prostatic cancer patients (isolated nodal progression) had a robotic-assisted surgical resection and post-lymphadenectomy electron boost on the vascular and lateral pelvic wall. Conclusions Minimally invasive and robotic-assisted surgery is feasible to combine with intraoperative electron radiation therapy and offers a new model explored with electron-FLASH beams (AU)

Clinical feasibility of combining intraoperative electron radiation therapy with minimally invasive surgery: a potential for electron-FLASH clinical development.

BACKGROUND: Local cancer therapy by combining real-time surgical exploration and resection with delivery of a single dose of high-energy electron irradiation entails a very precise and effective local therapeutic approach. Integrating the benefits from minimally invasive surgical techniques with the very precise delivery of intraoperative electron irradiation results in an efficient combined modality therapy. METHODS: Patients with locally advanced disease, who are candidates for laparoscopic and/or thoracoscopic surgery, received an integrated multimodal management. Preoperative treatment included induction chemotherapy and/or chemoradiation, followed by laparoscopic surgery and intraoperative electron radiation therapy. RESULTS: In a period of 5 consecutive years, 125 rectal cancer patients were treated, of which 35% underwent a laparoscopic approach. We found no differences in cancer outcomes and tolerance between the open and laparoscopic groups. Two esophageal cancer patients were treated with IOeRT during thoracoscopic resection, with the resection specimens showing intense downstaging effects. Two oligo-recurrent prostatic cancer patients (isolated nodal progression) had a robotic-assisted surgical resection and post-lymphadenectomy electron boost on the vascular and lateral pelvic wall. CONCLUSIONS: Minimally invasive and robotic-assisted surgery is feasible to combine with intraoperative electron radiation therapy and offers a new model explored with electron-FLASH beams.

Neoadjuvant therapy impact in early pancreatic cancer: "bioborderline" vs. "non-bioborderline".

Backgrounds/Aims: To analyze the results of the neoadjuvant treatment of patients in our center with early pancreatic cancer. Methods: Eighty-four patients with early pancreatic cancer (I-II) were included, of which 59 were considered "bioborderline" (carbohydrate antigen [CA] 19-9 > 37 U/L), and 25 were considered "non-bioborderline" (CA19-9 < 37 U/L). The R0 resection rate, presence of negative nodes, survival, and recurrence rates were analyzed in two groups, the NEO group (neoadjuvant + surgery) and the non-NEO group (upfront surgery). Results: A 28.6% pathologic complete response was observed in the NEO group of the whole sample. The residual R0 was 85.7%, and nodes were negative in 78.6% of the patients in the NEO group of bioborderline patients. All non-bioborderline patients treated with neoadjuvant were R0, and no affected nodes were observed in any of them. The median overall survival (OS) in patients with elevated CA19-9 levels in the NEO group was 31.4 months vs. 13.1 months in the non-NEO (log-rank test p = 0.006), with a 62% relative reduction in the mortality rate (hazard ratio = 0.38, 95% confidence interval: 0.20-0.79; p = 0.008). The median OS in patients with normal CA19-9 levels in the NEO group was 65.9 months vs. 16.2 months in the non-NEO group, without statistically significant differences between the two but with a trend toward significance (log-rank test p = 0.08). Conclusions: A neoadjuvant strategy seemed to improve local control and the survival of patients with early pancreatic cancer, both those with elevated CA19-9 and normal marker levels.

Usefulness of Indocyanine Green Plasma Disappearance Rate in Liver Donors and Recipients: A Prospective Observational Study.

BACKGROUND: Determination of indocyanine green (ICG) plasma disappearance rate (PDR) is a simple, inexpensive, and noninvasive tool to assess liver perfusion, absorption, and elimination. Its application in the liver transplant process has not been widely incorporated in clinical practice. This study aims to assess the usefulness of ICG PDR in the donor selection setting and in the early post-transplant phase and to analyze its variation between these 2 time points. METHODS: We performed a single-center prospective observational study. ICG clearance test was performed in 50 brain-dead donors (T0-PDR) to assess concordance with graft suitability. Rejected grafts biopsy specimens were analyzed to correlate histology with T0-PDR. In the recipients, ICG PDR was performed before wound closure (T1-PDR). The association of T0, T1, and T0-T1 variation with the development of early allograft dysfunction (EAD) was investigated. RESULTS: A total of 23 of 50 grafts were discarded because of poor macroscopic quality. A T0-PDR below 15.5%/min could predict graft rejection with 100% specificity and 69.6% sensitivity. All the biopsy specimens from donors with PDR < 10 %/min showed liver fibrosis. A total of 25 of the remaining 27 grafts were implanted; 5 patients (20%) developed EAD. T1-PDR performed better than T0-T1 variation to predict dysfunction. CONCLUSIONS: ICG PDR could be used in the donors as a filter to discard poor-quality grafts before procurement and, in the early post-transplant phase, to predict EAD.

Surgical Principles of Primary Retroperitoneal Sarcoma in the Era of Personalized Treatment: A Review of the Frontline Extended Surgery.

Surgery is the key treatment in retroperitoneal sarcoma (RPS), as completeness of resection is the most important prognostic factor related to treatment. Compartmental surgery/frontline extended approach is based on soft-tissue sarcoma surgical principles, and involves resecting adjacent viscera to achieve a wide negative margin. This extended approach is associated with improved local control and survival. This surgery must be tailored to tumor histology, tumor localization, and patient performance status. We herein present a review of compartmental surgery principles, covering the oncological and technical basis, and describing the tailored approach to each tumor subtype and localization in the retroperitoneum.

Intra-Operative Electron Radiation Therapy: An Update of the Evidence Collected in 40 Years to Search for Models for Electron-FLASH Studies.

INTRODUCTION: The clinical practice and outcome results of intraoperative electron radiation therapy (IOeRT) in cancer patients have been extensively reported over 4 decades. Electron beams can be delivered in the promising FLASH dose rate. METHODS AND MATERIALS: Several cancer models were approached by two alternative radiobiological strategies to optimize local cancer control: boost versus exclusive IOeRT. Clinical outcomes are revisited via a bibliometric search performed for the elaboration of ESTRO/ACROP IORT guidelines. RESULTS: In the period 1982 to 2020, a total of 19,148 patients were registered in 116 publications concerning soft tissue sarcomas (9% of patients), unresected and borderline-resected pancreatic cancer (22%), locally recurrent and locally advanced rectal cancer (22%), and breast cancer (45%). Clinical outcomes following IOeRT doses in the range of 10 to 25 Gy (with or without external beam fractionated radiation therapy) show a wide range of local control from 40 to 100% depending upon cancer site, histology, stage, and treatment intensity. Constraints for normal tissue tolerance are important to maintain tumor control combined with acceptable levels of side effects. CONCLUSIONS: IOeRT represents an evidence-based approach for several tumor types. A specific risk analysis for local recurrences supports the identification of cancer models that are candidates for FLASH studies.

National survey on the treatment of sarcomas in Spain.

Surgical units attending sarcomas in Spain are poor studied. The aim is to know the management of this pathology to identify areas of improvement through multicenter study based on a voluntary survey. The survey was completed by 74 surgeons of different hospitals, which 32,4% is exclusively dedicated to sarcomas. Only 24.3% declared to receive specific training in sarcomas. The most frequent type of hospital was the third level (56.8%), where 38,1% of the surgeons belong to societies or working-groups in sarcoma fields vs. 9,4% in first-second levels. The number of surgeons with specific theoretical training and papers published in this field are higher in third level hospitals. 55,4% belonged to a multidisciplinary unit. A multidisciplinary team was available in 57% of third level hospital vs 28% in others. Most services in charge of this patients are characterized by deficient specialization, low workload and the absence of a multidisciplinary team.

Uncommon and peculiar soft tissue sarcomas: Multidisciplinary review and practical recommendations. Spanish Group for Sarcoma research (GEIS -GROUP). Part II.

Among all Soft Tissue sarcomas there are some subtypes with low incidence and/or peculiar clinical behaviour, that need to be consider separately. Most of them are orphan diseases, whose biological characteristics imply a clearly different diagnostic and therapeutic approach from other more common sarcoma tumors. We present a brief and updated multidiciplinary review, focused on practical issues, aimed at helping clinicians in decision making. In this second part we review these subtypes: Alveolar Soft Part Sarcoma, Epithelioid Sarcoma, Clear Cell Sarcoma, Desmoplastic Small Round Cell Tumor, Rhabdoid Tumor, Phyllodes Tumor, Tenosynovial Giant Cell Tumors, Myoepithelial Tumor, Perivascular Epithelioid Cell Neoplasms (PEComas), Extraskeletal Myxoid Chondrosarcoma, NTRK-fusions Sarcomas. Most of them present their own radiological and histopathological feautures, that are essential to know in order to achieve early diagnosis. In some of them, molecular diagnosis is mandatory, not only in the diagnosis, but also to plan the treatment. On the other hand, and despite the low incidence, a great scientific research effort has been made to achieve new treatment opportunities for these patients even with approved indications. These include new treatments with targeted therapies and immunotherapy, which today represent possible therapeutic options. It is especially important to be attentive to new and potential avenues of research, and to promote the conduct of specific clinical trials for rare sarcomas.

National survey on the treatment of sarcomas in Spain. / Encuesta nacional sobre el tratamiento de los sarcomas en España.

Surgical units attending sarcomas in Spain are poor studied. The aim is to know the management of this pathology to identify areas of improvement through multicenter study based on a voluntary survey. The survey was completed by 74 surgeons of different hospitals, which 32.4% is exclusively dedicated to sarcomas. Only 24.3% declared to receive specific training in sarcomas. The most frequent type of hospital was the third level (56.8%), where 38.1% of the surgeons belong to societies or working-groups in sarcoma fields vs. 9.4% in first-second levels. The number of surgeons with specific theoretical training and papers published in this field are higher in third level hospitals. 55.4% belonged to a multidisciplinary unit. A multidisciplinary team was available in 57% of third level hospital vs. 28% in others. Most services in charge of these patients are characterized by deficient specialization, low workload and the absence of a multidisciplinary team.

Hepatic flow is an intraoperative predictor of early allograft dysfunction in whole-graft deceased donor liver transplantation: An observational cohort study.

BACKGROUND: Early allograft dysfunction (EAD) after liver transplantation (LT) is an important cause of morbidity and mortality. To ensure adequate graft function, a critical hepatocellular mass is required in addition to an appropriate blood supply. We hypothesized that intraoperative measurement of portal venous and hepatic arterial flow may serve as a predictor in the diagnosis of EAD. AIM: To study whether hepatic flow is an independent predictor of EAD following LT. METHODS: This is an observational cohort study in a single institution. Hepatic arterial blood flow and portal venous blood flow were measured intraoperatively by transit flow. EAD was defined using the Olthoff criteria. Univariate and multivariate analyses were used to determine the intraoperative predictors of EAD. Survival analysis and prognostic factor analysis were performed using the Kaplan-Meier and Cox regression models. RESULTS: A total of 195 liver transplant procedures were performed between January 2008 and December 2014 in 188 patients. A total of 54 (27.7%) patients developed EAD. The median follow-up was 39 mo. Portal venous flow, hepatic arterial flow (HAF) and total hepatic arterial flow were associated with EAD in both the univariate and multivariate analyses. HAF is an independent prognostic factor for 30-d patient mortality. CONCLUSION: Intraoperative measurement of blood flow after reperfusion appears to be a predictor of EAD; Moreover, HAF should be considered a predictor of 30-d patient mortality.

How to expand the safe limits in hepatic resections?

The size of the remnant liver after an extended hepatectomy is currently the main limiting factor for performing curative hepatic surgery in patients with tumors and liver metastasis. The current guidelines for extended hepatectomies require that the future remnant liver volume needs to be higher than 20% of the original liver in healthy organs, of 30% in livers with steatosis or exposed to chemotherapy, and of 40% in patients with cirrhosis in order to prevent the "small-for-size" syndrome, characterized by the development of liver dysfunction with ascites, coagulopathy and cholestasis. Observations from the use of small liver grafts in liver transplantation and an increased surgical experience has improved our understanding of the mechanisms responsible for the development of liver dysfunction after extended hepatectomies. Increasing the size of the future liver remnant, the introduction of the "small-for-flow" concept with the perioperative monitoring and modulation of portal blood flow and pressure, and the exploration of the potential effects of regeneration preconditioning, are all promising strategies that could expand the indications and increase the safety of liver surgery.

Hybrid notes cholecystectomy in an experimental model of laparoscopic acute cholecystitis.

The purpose of this study was to evaluate the feasibility of hybrid natural orifice translumenal endoscopic surgery (NOTES) transvaginal cholecystectomy in a porcine model of acute cholecystitis. We have developed an experimental model of acute cholecystitis in 8 female pigs (33.37±3.11 kg) through the surgical occlusion of the common bile duct. After 4 days, hybrid NOTES cholecystectomy was performed in all animals with the assistance of only one 5 mm trocar. The transvaginal approach and the abdomen exploration were performed without any complication. The hybrid NOTES cholecystectomy was successfully completed in all animals. The mean operative time was 76.50±10 minutes. Gallbladder rupture appeared in 2 cases, and there was no bleeding or laceration of adjacent organs. Our experiments showed the feasibility of hybrid NOTES cholecystectomy in an experimental model of acute cholecystitis. Additional research and training on experimental models of pathology will be necessary to validate NOTES surgery.

Technical feasibility of totally natural orifice cholecystectomy in a swine model.

The goal of this study was to evaluate the feasibility of totally NOTES performing a cholecystectomy without laparoscopic assistance. A gastroscope was used through a transvaginal access in five acute female pigs. An incision of 2 cm was created in the vagina and pneumoperitoneum was obtained with a Veress needle. The gallbladder was located in the abdominal cavity using endoscopic transillumination for spatial orientation. After the abdominal suspension of the gallbladder the cholecystectomy was completed with the NOTES technique in four animals without complications. In one animal we had technical problems and the procedure was stopped. The mean operative time was 110 minutes. The transvaginal approach provides complete abdominal exploration and both the cystic duct and artery were identified, clipped, and transected. After dissection the gallbladder was removed through the vagina. Our results showed that completely transvaginal NOTES cholecystectomy is a feasible technique performed only with a flexible endoscope.