Dragon 1 Protocol Manuscript: Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization (PVE/HVE) to Accelerate Future Liver Remnant (FLR) Hypertrophy.

STUDY PURPOSE: The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. METHODS: The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. RESULTS: Not applicable. CONCLUSION: DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04272931 (February 17, 2020). Toestingonline.nl: NL71535.068.19 (September 20, 2019).

Detection of pancreatic neuroendocrine tumors: 23 years of experience. / Detección de tumores neuroendocrinos pancreáticos: 23 años de experiencia.

INTRODUCTION AND AIMS: Neuroendocrine tumors are of great scientific interest, given that they are difficult to diagnose and treat. Despite being relatively rare (< 1/100,000 individuals, 1-2% of the gastrointestinal neoplasias) and indolent, their potential malignancy must not be forgotten. An increase in the number of diagnosed tumors has been observed in recent years. The aim of the present study was to update a published case series of 19 patients suspected of presenting with pancreatic neuroendocrine tumor with 51 current cases, to study and compare the new results with those of the previous case series, as well as with other recent publications from Spain, the United States, China, and India. MATERIALS AND METHODS: A retrospective, multicenter case series was conducted on 70 patients (19 cases published in 2011), whose data has been collected over a period of 23 years. The variables analyzed were: age, sex, symptomatology, tumor size, location, metastasis, final diagnosis, and surgery, among others. RESULTS: Mean patient age was 55 years and 60% of the patients were men. Disease location was the pancreatic head in 28.5% of the patients and the tail in 27.1%, mean tumor size was 3.9cm (0.2-10cm), 71.4% of the patients had non-functioning tumors, 32.8% had metastases (100% to the liver), 74.2% of the patients were operated on, and actuarial survival was 75%. CONCLUSIONS: Differences were observed between the previously published case series and the current results. There was an increase in incidentalomas and non-functioning tumors, but no variation in the overall survival rate. The differences with other case series (age, sex, and tumor location) were dependent on the country where the cases were compiled. The increase in tumors could be related to a higher number of diagnoses made through imaging studies and to the greater sensitivity of the devices employed.

Prostacyclin, thromboxane, and oxygen free radicals and postoperative liver function in human liver transplantation.

The aim of this prospective study is to evaluate prostanoid (prostacyclin and thromboxane) and lipid peroxide levels at the portal and hepatic veins, and their relation to immediate postoperative liver function. Nineteen patients with liver cirrhosis undergoing orthotopic liver transplantation were prospectively studied. Blood samples were obtained within 5 min and 1 and 2 hr after reperfusion of the new liver, through a catheter placed at the portal vein in the recipient and another at the left hepatic vein in the donor liver. Plasma prostacyclin and thromboxane were analyzed by HPLC and RIA. The formation of lipid peroxides was determined and expressed in terms of thiobarbituric acid-reacting substances. Immediate postoperative liver function was evaluated using the transaminase levels within the first 48 hr and the early postoperative graft function score, as described previously. After reperfusion, only determinations at 5 min were related with liver function. Either prostacyclin (R = -0.61, P = 0.004) levels at the hepatic vein or prostacyclin production (subtraction between hepatic and portal vein levels) (R = -0.47, P = 0.04) correlated significantly with the early postoperative graft function score. Besides, there was a significant relationship between lipid peroxide production as measured by thiobarbituric acid-reacting substances and a worse early postoperative graft function score (R = 0.61, P = .005). These results suggest that prostacyclin released after liver grafting attenuates preservation and reperfusion damage of the liver, supporting the hypothesis that there is an imbalance of prostanoids within the microvasculature in patients with a compromised postoperative liver function. Our results agree with the involvement of some degree of lipid peroxidation products in the damage of hepatocytes during anoxia and reperfusion.

Hepaticothoracic transdiaphragmatic echinococcosis.

Between 1970 and 1985, seven patients were referred to us for surgical treatment of simultaneous hydatid cysts in the liver and the chest. Their mean age was 45.4 years (age range, 23-73 years), and they represented 46% of patients with hydatid cysts in the liver and thorax. Three patients had hepaticopleural involvement, and 3 patients had symptoms of pulmonary origin. In a single patient, only the diaphragm was involved along with the liver. Liver scintigraphy and ultrasonography were equally helpful in delineating the extent of the disease, but computed tomographic scanning is now the method of choice. The operations were through a thoracolaparotomy in 3 patients and a thoracotomy alone in 3 patients. A single patient had a thoracotomy with a transdiaphragmatic laparotomy. Complete drainage or excision of hydatid cavities was accomplished in all patients. Hydrogen peroxide instilled into the cysts was satisfactory for control of spread potentially secondary to possible intraoperative spillage. There have been no postoperative deaths. Follow-up has ranged from 6 months to 8 years, and 2 patients had relapsing hydatid disease 3 years postoperatively. These results suggest that, when hydatid disease of the liver is complicated by transdiaphragmatic extension and simultaneous pleural or pulmonary cysts, early surgical repair is indicated. Complete drainage and cyst excision are recommended.

Peripheral blood lymphocyte changes after benign gastrointestinal surgery. Role of thymostimulin in reversing the postoperative immunodepression seen in humans.

A generalized state of immunosuppression during surgery has been implicated in the development of septic complications postoperatively. We studied 18 patients operated upon for benign diseases, to examine the influence of surgical trauma on circulating lymphocyte subpopulations in man. Additionally, we evaluated the effect of thymostimulin on these changes, in another group of 10 patients. Our results suggest that the total number of lymphocytes, as well as lymphocyte subpopulations CD3+ and CD4+, fell significantly following surgery. This reduction in cell number is more pronounced on the helper/inducer lymphocytes. The CD4+/CD8+ ratio decreases significantly after operation. For patients with no complications, the immunosuppression in terms of peripheral lymphocyte population, seen in the postoperative period is usually reversible around the seventh day. On the other hand, peripheral blood lymphocyte changes in the postoperative period were less pronounced in patients treated with thymostimulin. Thymostimulin's action is predominantly on T lymphocytes, and within these, on the T helper/-inducer subpopulation. And finally, thymostimulin is capable of maintaining a normal relationship between helper/inducer and suppressor/cytotoxic cells (CD4+/CD8+ ratio) during the postoperative period, suggesting a better immune state.

Laparoscopic ultrasound guidance for laparoscopic resection of benign gastric tumors.

Laparoscopic excision of gastric leiomyoma is technically feasible and safe, but it may fail to localize the exact placement of the lesion because of the lack of tactile sensitivity. The authors present two cases of small gastric leiomyomas that were resected by a totally laparoscopic approach, assisted with intraoperative laparoscopic ultrasonography because the lesions could not be palpated. A gastric wedge resection with tumor-free margins was performed with an endostapler device. Use of a harmonic scalpel to divide the gastroepiploic vessels facilitated the laparoscopic procedure.

[Survival after resection of lung metastasis from colorectal cancer]. / Supervivencia tras resección de metástasis pulmonares de cáncer colorrectal.

OBJECTIVE: To analyze the results of resection of lung metastases from colorectal adenocarcinoma in selected patients, evaluating type of resection, morbidity and mortality associated with the procedure, and overall actuarial survival rates after surgery. PATIENTS AND METHODS: Between 1988 and 1996, 811 patients were treated surgically for colorectal adenocarcinoma. Recurrent chronic lung metastases were resected, presumably with the intention to cure, in 15 patients in the series. One patient underwent surgery for pelvic recurrence and another seven for liver metastases, before resection of the lung metastases. RESULTS: Twenty-seven wedge resections were performed, two being non-malignant and one patient requiring re-resection of new lung metastases. Unsuspected locations of lung metastasis were found in three patients during surgery. Perioperative mortality was zero. Mean follow-up was 50 months (range 28 to 99). Seven patients presented new occurrences of metastasis or tumor recurrence and died as a result. The actuarial survival rate was 48% at 5 years. CONCLUSIONS: In selected patients, surgical resection of lung metastasis from colorectal cancer, with the assumed intention of cure, has yielded a good survival rate and zero perioperative mortality. It appears advisable to use an approach that permits exhaustive palpation of the pulmonary parenchyma, due to the risk of finding unsuspected metastases.

[Laparoscopic resection of hepatic hydatid cyst under general anesthesia with remifentanil infusion]. / Resección de quiste hidatídico hepático por laparoscopia bajo anestesia general con perfusión de remifentanilo.

We report the case of a 52-year-old woman who underwent scheduled laparoscopic resection of a hydatid liver cyst under general anesthesia by infusion of remifentanil and sevoflurane. Surgery was uneventful, although invasive monitoring was required, just as it would have been in major open abdominal surgery, given the risk of bleeding secondary to organ manipulation, the risk of anaphylactic shock related to the etiology of the cyst and the possibility of gas embolism related to laparoscopy. The concept of "minimally invasive" surgery has developed thanks to continued progress in laparoscopy. The considerable advantages of such procedures in comparison with "open" or "conventional" surgery has led to their use with organs such as the liver, which in principle require caution. In such cases, the anesthesiologist must take an approach that is not as simple or minimalist as the term "minimally invasive" might lead us to expect.

[Initial results of the National Registry of Laparoscopic Liver Surgery]. / Resultados iniciales del Registro Nacional de Cirugía Hepática por Laparoscopia.

INTRODUCTION: Experience in laparoscopic liver surgery is limited, and multicenter studies with large series are required for a critical evaluation of this type of surgery. OBJECTIVE: To analyze the results of the National Registry of Laparoscopic Liver Surgery. Indications, technical features, conversion rates, morbidity, and mortality were analyzed. PATIENTS AND METHOD: Seventy-four patients from 10 centers who underwent surgery between February 2000 and April 2005 were included. There were 58 women and 16 men, with a mean age of 55 years. More than one lesion was present in 16 patients. Consequently, 74 patients with 156 lesions were treated. RESULTS: Forty-six patients had cystic lesions (26 simple cysts, 13 polycystic disease, five hydatid cysts and two cystic adenomas). Surgical treatment consisted of 37 fenestrations, five cystopericystectomies, two atypical resections, one segmentectomy and one bisegmentectomy of segments II-III. In 28 patients the lesions were solid (four adenomas, six focal nodular hyperplasias, three hemangiomas, four hepatocarcinomas, five colorectal metastases, two lung metastases, one breast metastasis, one malignant melanoma metastasis, one pancreatic vipoma metastasis, and one lymphoma). Ten bisegmentectomies of segments II-III, 17 atypical resections and one segmentectomy of segment III were performed. Other surgery was associated in 23 patients. The mean operating time was 160.5 minutes and the conversion rate was 8%. The mean length of hospital stay was 5.6 days and was less than 5 days in 78% of the patients. Analgesia was administered for less than 48 hours in 55%. Morbidity was observed in eight patients (10.8%). Reoperations were performed in three patients. There was no mortality in this series. CONCLUSIONS: Laparoscopic hepatic resection is safe and feasible in selected patients. Large, controlled series are required to determine long-term outcomes. The national registry provides a good basis for evaluating laparoscopic liver surgery in Spain.

Treatment options for villous adenoma of the ampulla of Vater.

INTRODUCTION: Duodenal villous adenoma arising from the ampulla of Vater has a high risk of malignant development. Excluding associated malignant disease prior to resection of an adenoma of the ampulla is not always possible. Therefore, the surgical procedure of choice to treat this rare tumour is still controversial. OBJECTIVE: To evaluate retrospectively results of treatment of villous adenoma arising from ampulla of Vater with dysplasia or associated carcinoma limited to the ampulla. PATIENTS AND METHODS: From 1985 to 1996, eight patients have been diagnosed with ampullary villous adenoma suitable for resection. We have reviewed treatment, morbidity, mortality, follow-up and final outcome. RESULTS: Pancreatoduodenectomy (PD) was performed in 4 patients. Transduodenal ampullectomy and endoscopic resection was performed in 2 patients each. There was no perioperative mortality. None of the patients had biliary, pancreatic or intestinal leakage but two patients who underwent PD had minor postoperative complications. The mean follow-up was 44 (range: 6-132) months. Villous adenoma was associated with adenocarcinoma in 50% of the cases (4/8 patients). During the follow-up both patients who underwent transduodenal ampullectomy developed recurrent disease. All patients initially treated by PD are alive without evidence of recurrent disease. CONCLUSIONS: Treatment of villous adenoma of the ampulla must be individualized within certain limits. In our series, PD achieve good results and it appears to be the procedure of choice in order to treat villous adenomas with proved presence of carcinoma, carcinoma in situ or severe dysplasia. Endoscopic or local resection may be appropriate for small benign tumours in high risk patients.