Identification of Circulating lncRNAs Associated with Gallbladder Cancer Risk by Tissue-Based Preselection, Cis-eQTL Validation, and Analysis of Association with Genotype-Based Expression.

Long noncoding RNAs (lncRNAs) play key roles in cell processes and are good candidates for cancer risk prediction. Few studies have investigated the association between individual genotypes and lncRNA expression. Here we integrate three separate datasets with information on lncRNA expression only, both lncRNA expression and genotype, and genotype information only to identify circulating lncRNAs associated with the risk of gallbladder cancer (GBC) using robust linear and logistic regression techniques. In the first dataset, we preselect lncRNAs based on expression changes along the sequence "gallstones → dysplasia → GBC". In the second dataset, we validate associations between genetic variants and serum expression levels of the preselected lncRNAs (cis-lncRNA-eQTLs) and build lncRNA expression prediction models. In the third dataset, we predict serum lncRNA expression based on individual genotypes and assess the association between genotype-based expression and GBC risk. AC084082.3 and LINC00662 showed increasing expression levels (p-value = 0.009), while C22orf34 expression decreased in the sequence from gallstones to GBC (p-value = 0.04). We identified and validated two cis-LINC00662-eQTLs (r2 = 0.26) and three cis-C22orf34-eQTLs (r2 = 0.24). Only LINC00662 showed a genotyped-based serum expression associated with GBC risk (OR = 1.25 per log2 expression unit, 95% CI 1.04-1.52, p-value = 0.02). Our results suggest that preselection of lncRNAs based on tissue samples and exploitation of cis-lncRNA-eQTLs may facilitate the identification of circulating noncoding RNAs linked to cancer risk.

Total Laparoscopic Pancreaticoduodenectomy with Venous Reconstruction for Pancreatic Head Cancer with Involvement of the Superior Mesenteric Vein-Portal Vein Confluence.

BACKGROUND: Laparoscopic pancreaticoduodenectomy with venous reconstruction is not commonly performed due to its technical challenges. In this video, we focus on the technical aspects for how to perform this procedure safely. METHODS: In a 69-year-old female with jaundice and diarrhea, a computed tomography scan showed a mass in the head of the pancreas, with a 180-degree involvement of the superior mesenteric vein. Endoscopic retrograde cholangiopancreatography with stenting was performed together with endoscopic ultrasound and fine-needle aspiration. Biopsy showed well-differentiated adenocarcinoma. The patient underwent six cycles of neoadjuvant chemotherapy, with reduction of the vein involvement to 90 degrees. The mass invaded the right lateral aspect of the superior mesenteric vein-portal vein confluence. As a result, this portion of the vein was removed en bloc with the specimen. The vascular defect was repaired using two running sutures. Once the choledocojejunostomy and intussuscepted pancreatico-gastric anastomosis were completed, the specimen was removed via a small subxiphoid incision. RESULTS: Operative time was 6 h and 30 min, blood loss was 50 mL, and hospital stay was 12 days. Histopathological examination was ypT3 N1 (1 of 18 lymph nodes was positive). All margins were negative. CONCLUSION: Laparoscopic pancreaticoduodenectomy with vascular reconstruction can be performed safely in selected cases of pancreatic head cancer with vein involvement. Advanced laparoscopic skills are necessary to complete such procedures safely.

Segment 7 Laparoscopic Liver Resection: Is It Possible to Resect When Metastatic Lesions Border Suprahepatic Veins?

INTRODUCTION: After nearly 25 years of experience, laparoscopic liver resection (LLR) is now recognized as being feasible and safe.1 However, laparoscopic resections of the posterosuperior segments are more technically demanding. They are associated with higher conversions rates, more intraoperative bleeding, and increased operating time.2 Appropriate training is required to approach these resections safely.3 This video demonstrates the technical maneuvers to laparoscopically approach a segment 7 tumor in contact with the right supra hepatic vein. METHOD: The pertinent aspect to perform a segment 7 metastasis resection using minimally invasive techniques is shown. The main steps of this operation include (1) complete release of the right liver from the coronary and triangular ligament, (2) dissection of the retrohepatic vena cava and transection of the hepatocaval ligament, (3) the use of intercostal trocars for direct vision of the inferior vena cava and the right suprahepatic vein,4,5 (4) the use of intraoperative ultrasound to evaluate the position and limits of vascular structures compared to the lesion, (5) careful transection of the hepatic parenchyma, and (6) dissection of the right hepatic vein to separate it from the lesion. RESULTS: The surgery was performed in a 68-year-old male patient. The patient developed synchronous metastases to the liver from a sigmoid colon tumor. Two lesions were identified; a 15 mm subcapsular lesion located in segment 5 and a 45 mm lesion located in segment 7 in contact with the right hepatic vein and inferior vena cava confluence. Previously, laparoscopic sigmoidectomy was performed without complications (TNM classification of the specimen: T3N0, with 31 resected lymph nodes, KRAS gene mutated). Following chemotherapy with FOLFOX + bevacizumab, a good response to the liver lesion was noted on imaging. Subsequently, a laparoscopic resection of the metastases in segment 7 and 5 was performed. The surgery lasted 210 min, intraoperative blood loss was 200 cm3, no Pringle maneuver was required, and the postoperative period was uneventful with the patient being discharged on postoperative day number four. Pathology of the liver specimens confirmed metastases from colon adenocarcinoma with free surgical margins. DISCUSSION: Some important points achieving easier and safer approach of the posterior segments of the liver by laparoscopic route should be discussed. First, the patient's semi-lateral position showed in the video allows placing the ports and the optic in a more comfortable position since the lateral portion of the abdominal and thoracic wall becomes anterior. Another important point is the complete liberation of the hepatorenal, falciform, triangular, and right coronary ligaments in order to fully mobilize the liver and convert a segment that is posterior in the anatomical position to an anterior segment for the surgeon. And finally, the use of intercostal trocars that allows a direct and perpendicular view of the right hepatic vein and vena cava represents the most important point. Interestingly, these specific trocars should be inserted through the pleural cavity, during a forced expiration or apnea to avoid lung injury. In this context, the trocar balloon helps the surgeon to avoid displacement or that pneumoperitoneum enters the pleural cavity. At the end of the procedure, we strongly recommend to stitch laparoscopically these diaphragmatic openings after removing the trocars in order to avoid migration of abdominal fluid or bowel incarceration into the pleural cavity during the postoperative period and also to avoid future diaphragmatic hernia. In the present case, the parenchymal transection was performed with Thunderbeat (Olympus®, Japan), a device integrating both ultrasound dissection and advanced bipolar energy. We use this device because it saves time by sealing vessels up to 7 mm in diameter avoiding the need to use clips in the majority of intrahepatic veins and portal branches. However, currently, several techniques and devices are equivalent for parenchymal transection in laparoscopic liver resection and should be left to the surgeon's preference, as in open liver procedures. CONCLUSION: Using laparoscopy to remove lesions in the posterior segments of the liver is safe and feasible. Vision from transthoracic port has the added benefit of making the dissection of right hepatic vein and inferior vena cava safer. Mastery of the anatomy is paramount before attempting this approach with minimally invasive techniques. Surgeons who attempt this operation should have expertise with both laparoscopy and liver surgery.

¿Influye el medio de preservación del injerto en los resultados y costos del trasplante hepático de donante fallecido?: Comparación de dos soluciones de preservación / Outcomes using two preservation solutions (UW/HTK) in liver transplantation from brain death donors

Background: Preservation solutions are critical for organ transplantation. In liver transplant (LT), the solution developed by the University Of Wisconsin (UW) is the gold-standard to perfuse deceased brain death donor (DBD) grafts. Histidine-Tryptophan-Ketoglutarate (HTK), formerly a cardioplegic infusion, has been also used in solid organ transplantation. Aim: To compare the outcomes of LT in our center using either HTK or UW solution. Patients and Methods: Retrospective study including 93 LT DBD liver grafts in 89 patients transplanted between March 1994 and July 2010. Forty-eight grafts were preserved with UW and 45 with HTK. Donor and recipient demographics, total infused volume, cold ischemia time, post-reperfusion biopsy, liver function tests, incidence of biliary complications, acute rejection and 12-month graft and patient survival were assessed. Preservation solution costs per liver graft were also recorded. Results: Donor and recipient demographics were similar. When comparing UW and HTK, no differences were observed in cold ischemia time (9.6 ± 3 and 8.7 ± 2 h respectively, p = 0.23), biliary complications, the incidence of acute rejection, primary or delayed graft dysfunction. Histology on post-reperfusion biopsies revealed no differences between groups. The infused volume was significantly higher with HTK than with UW (9 (5-16) and 6 (3-11) l, p < 0.001). The cost per procurement was remarkably lower using HTK. Conclusions: Perfusion of DBD liver grafts with HTK is clinically equivalent to UW, with a significant cost reduction.

[Outcomes using two preservation solutions (UW/HTK) in liver transplantation from brain death donors]. / ¿Influye el medio de preservación del injerto en los resultados y costos del trasplante hepático de donante fallecido?: Comparación de dos soluciones de preservación.

BACKGROUND: Preservation solutions are critical for organ transplantation. In liver transplant (LT), the solution developed by the University Of Wisconsin (UW) is the gold-standard to perfuse deceased brain death donor (DBD) grafts. Histidine-Tryptophan-Ketoglutarate (HTK), formerly a cardioplegic infusion, has been also used in solid organ transplantation. AIM: To compare the outcomes of LT in our center using either HTK or UW solution. PATIENTS AND METHODS: Retrospective study including 93 LT DBD liver grafts in 89 patients transplanted between March 1994 and July 2010. Forty-eight grafts were preserved with UW and 45 with HTK. Donor and recipient demographics, total infused volume, cold ischemia time, post-reperfusion biopsy, liver function tests, incidence of biliary complications, acute rejection and 12-month graft and patient survival were assessed. Preservation solution costs per liver graft were also recorded. RESULTS: Donor and recipient demographics were similar. When comparing UW and HTK, no differences were observed in cold ischemia time (9.6 ± 3 and 8.7 ± 2 h respectively, p = 0.23), biliary complications, the incidence of acute rejection, primary or delayed graft dysfunction. Histology on post-reperfusion biopsies revealed no differences between groups. The infused volume was significantly higher with HTK than with UW (9 (5-16) and 6 (3-11) l, p < 0.001). The cost per procurement was remarkably lower using HTK. CONCLUSIONS: Perfusion of DBD liver grafts with HTK is clinically equivalent to UW, with a significant cost reduction.

Steatotic livers. Can we use them in OLTX? Outcome data from a prospective baseline liver biopsy study.

INTRODUCTION: Steatotic livers have been associated with greater risk of allograft dysfunction in liver transplantation. Our aim was to determinate the prevalence of steatosis in grafts from deceased donors in Chile and to assess the utility of a protocol-bench biopsy as an outcome predictor of steatotic grafts in our transplant program. MATERIAL AND METHODS: We prospectively performed protocol-bench graft biopsies from March 2004 to January 2009. Biopsies were analyzed and classified by two independent pathologists. Steatosis severity was graded as normal from absent to < 6%; grade 1: 6-33%; grade 2: > 33-66% and grade 3: > 66%. RESULTS: We analyzed 58 liver grafts from deceased donors. Twenty-nine grafts (50%) were steatotic; 9 of them (16%) with grade 3. Donor age (p < 0.001) and BMI over 25 kg/m 2 (p = 0.012) were significantly associated with the presence of steatosis. There were two primary non-functions (PNF); both in a grade 3 steatotic graft. The 3-year overall survival was lower among recipients with macrovesicular steatotic graft (57%) than recipients with microvesicular (85%) or non-steatotic grafts (95%) (p = 0.026). CONCLUSION: Macrovesicular steatosis was associated with a poor outcome in this series. A protocol bench-biopsy would be useful to identify these grafts.

Anatomic hepatectomy as a definitive treatment for hepatolithiasis: a cohort study.

BACKGROUND: Treatment requirements in hepatolithiasis may vary and may involve a multidisciplinary approach. Surgical resection has been proposed as a definitive treatment. OBJECTIVES: This study aimed to evaluate the clinical results of anatomic liver resection among Chilean patients with hepatolithiasis. METHODS: An historical cohort study was conducted. Patients who underwent hepatectomy as a definitive treatment for hepatolithiasis from January 1990 to December 2010 were included. Patients with a preoperative diagnosis of cholangiocarcinoma were excluded. Preoperative, operative and postoperative variables were evaluated. RESULTS: A total of 52 patients underwent hepatectomy for hepatolithiasis. The mean ± standard deviation patient age was 49.8 ± 11.8 years (range: 24-78 years); 65.4% of study subjects were female. A total of 75.0% of subjects had a history of previous cholecystectomy. The main presenting symptom was abdominal pain (82.7%). Hepatic involvement was noted in the left lobe in 57.7%, the right lobe in 34.6% and bilaterally in 7.7% of subjects. The rate of postoperative clearance of the biliary tree was 90.4%. Postoperative morbidity was 30.8% and there were no postoperative deaths. Three patients had recurrence of hepatolithiasis, which was associated with Caroli's disease in two of them. Overall 5-year survival was 94.5%. CONCLUSIONS: Anatomic liver resection is an effective treatment in selected patients with hepatolithiasis and is associated with low morbidity and no mortality. At longterm follow-up, anatomic hepatectomy in these patients was associated with a lower rate of recurrence.

Completely laparoscopic versus open gastrectomy for early and advanced gastric cancer: a matched cohort study.

INTRODUCTION: The application of laparoscopic gastric surgery has rapidly increased for the treatment of early gastric cancer. However, laparoscopic gastrectomy for advanced tumor remains controversial, particularly in terms of oncologic outcomes. This study was designed to compare 3-year survival of laparoscopic versus open curative gastrectomy in early and advanced gastric cancer. METHODS: This was a retrospective matched cohort study. We included patients between 2003 and 2010 with an R0 resection. A totally laparoscopic technique was used and D2 lymph node dissection was practiced routinely. We performed an intracorporeal hand-sewn esophagojejunostomy in all laparoscopic total gastrectomy cases. We matched all laparoscopic cases 1:1 with open cases according to TNM AJCC seventh edition. We used Mann-Whitney or t test and Chi-square test to compare both groups. Kaplan-Meier analysis with log-rank test was performed to compare survival. RESULTS: We included 31 open and 31 laparoscopic cases (mean age 63 ± 14 years; 66% males). Both groups were identical in type of gastrectomy (71% total and 29% subtotal). There were no statistical difference between laparoscopic and open groups in age, sex, N category, tumor location and size, histological differentiation, and T category (48% T1, 13% T2, 16% T3, and 23% T4 in both groups), with 48% early and 52% advanced tumors. The median number of resected lymph nodes was similar: 35 (23-53) for laparoscopic and 39 (23-45) for open cases (P = 0.81). The median follow-up was 50 months. The overall 3-year survival was 82% for laparoscopic surgery and 87% for the open surgery group (P = 0.56). There were no difference in 3-year survival for the laparoscopic versus the open surgery groups for advanced tumors (74 vs. 75%, P = 0.88), N+ tumors (73 vs. 73%, P = 0.99) and for the different AJCC stages (stage 1: 94 vs. 100%, stage 2: 89 vs. 82%, and stage 3: 50 vs. 50%, P = 0.32, 0.83, and 0.98 respectively). CONCLUSIONS: In this preliminary report, with 52% of advanced tumor, the 3-year overall and stage-by-stage survival was comparable for laparoscopic and open curative gastrectomy.