Clinical Application of Liquid Biopsy in Pancreatic Cancer: A Narrative Review.

Pancreatic ductal adenocarcinoma contributes significantly to global cancer-related deaths, featuring only a 10% survival rate over five years. The quest for novel tumor markers is critical to facilitate early diagnosis and tailor treatment strategies for this disease, which is key to improving patient outcomes. In pancreatic ductal adenocarcinoma, these markers have been demonstrated to play a crucial role in early identification, continuous monitoring, and prediction of its prognosis and have led to better patient outcomes. Nowadays, biopsy specimens serve to ascertain diagnosis and determine tumor type. However, liquid biopsies present distinct advantages over conventional biopsy techniques. They offer a noninvasive, easily administered procedure, delivering insights into the tumor's status and facilitating real-time monitoring. Liquid biopsies encompass a variety of elements, such as circulating tumor cells, circulating tumor DNA, extracellular vesicles, microRNAs, circulating RNA, tumor platelets, and tumor endothelial cells. This review aims to provide an overview of the clinical applications of liquid biopsy as a technique in the management of pancreatic cancer.

Preliminary experience with a new robotic technique to facilitate distal pancreatectomy with spleen preservation: left lateral approach in right lateral decubitus position.

Spleen-preserving distal pancreatectomy (SP-DP), for patients with benign or small low-grade malignant tumors of the body or tail of the pancreas, is the ideal procedure although it is technically demanding. The robotic da Vinci system has been introduced to overcome these technical challenges and reduce operative risks. We report our experience of a new variation in surgical technique: the left lateral approach robotic spleen-preserving distal pancreatectomy (RSP-DP) in right lateral decubitus position. We performed this new variant of SP-DP, in five patients, using the da Vinci Xi system. Technical and clinical feasibility are described. The mean age and body mass index were 53.4 years and 31.4 kg/m2, respectively. The mean total operative time was 323 min. The estimated mean blood loss was 240 ml. In all patients, the spleen could be preserved. In four patients, the splenic vessels were also preserved. One patient required a Warshaw technique due to significant fibrosis attached to the splenic vein. The postoperative period of all patients was uneventful except the presence of biochemical leak (BL) in two patients that only required maintenance of the drainage at home. The mean length of hospital stay was 6 days after surgery. The left lateral approach robotic SP-DP in right lateral decubitus position is a feasible and safe procedure for distal benign or small low-grade malignant tumors of the left pancreas. The right lateral decubitus position associated to robotic surgery can facilitate this complex procedure, especially when splenic vessels preservation is indicated, with a lower risk of conversion and shortening of the learning curve.

Comparison between Comprehensive Complication Index (CCI®) and Clavien-Dindo Classification for laparoscopic single-stage treatment of choledocholithiasis with concomitant cholelithiasis.

PURPOSE: The Clavien-Dindo Classification (CDC) and the Comprehensive Complication Index (CCI®) are both widely used methods for reporting postoperative complications. Several studies have compared the CCI® with the CDC in evaluating postoperative complications of major abdominal surgery. However, there are no published reports comparing both indexes in single-stage laparoscopic common bile duct exploration with cholecystectomy (LCBDE) for the treatment of common bile duct stones. This study aimed to compare the accuracy of the CCI® and the CDC in evaluating the complications of LCBDE. METHODS: In total, 249 patients were included. Spearman's rank test was used to calculate the correlation coefficient between CCI® and CDC with length of postoperative stay (LOS), reoperation, readmission, and mortality rates. Student t-test and Fisher's exact test were used to study, if higher ASA, age, larger surgical time, history of previous abdominal surgery, preoperative ERCP, and intraoperative cholangitis finding were associated with higher CDC grade or higher CCI® score. RESULTS: Mean CCI® was 5.17 ± 12.8. CCI® ranges overlap among three CDC grades: II (20.90-36.20), IIIa (26.20-34.60), and IIIb (33.70-52.10). Age > 60 years, ASA ≥ III, and intraoperative cholangitis finding were associated with higher CCI® (p = 0.010, p = 0.044, and p = 0.031) but not with CDC ≥ IIIa (p = 0.158, p = 0.209, and p = 0.062). In patients with complications, LOS presented a significantly higher correlation with CCI® than with CDC (p = 0.044). CONCLUSION: In LCBDE, the CCI® assesses better the magnitude of postoperative complications in patients older than 60 years, with a high ASA as well as in those who present intraoperative cholangitis. In addition, the CCI® correlates better with LOS in patients with complications.

Impact of neoadjuvant chemotherapy on post-hepatectomy regeneration for patients with colorectal cancer liver metastasis - Systematic review and meta-analysis.

BACKGROUND: Today, there is still debate on the impact of neoadjuvant chemotherapy (NeoChem) on liver regeneration (LivReg). The objectives of this study were to assess the impact of NeoChem and its characteristics (addition of bevacizumab, number of cycles and time from end of NeoChem) on post-hepatectomy LivReg. MATERIAL & METHODS: Studies reporting LivReg in patients submitted to liver resection were included. Pubmed, Scopus, Web of Science, Embase, and Cochrane databases were searched. Only studies comparing NeoChem vs no chemotherapy or comparing chemotherapy characteristics from 1990 to present were included. Two researchers individually screened the identified records registered in a predesigned database. Primary outcome was future liver remnant regeneration rate (FLR3). Bias of the studies was evaluated with the ROBINS-I tool, and quality of evidence with the GRADE system. Data was presented as mean difference or standard mean difference. RESULTS: Eight studies with a total of 681 patients were selected. Seven were retrospective and one prospective comparative cohort studies. In patients submitted to major hepatectomy, NeoChem did not have an impact on LivReg (MD 3.12, 95% CI -2,12-8.36, p 0,24). Adding bevacizumab to standard NeoChem was associated with better FLR3 (SMD 0.45, 95% CI 0.19-0.71, p 0.0006). DISCUSSION: The main drawback of this review is the retrospective nature of the available studies. NeoChem does not have a negative impact on postoperative LivReg in patients submitted to liver resection. Regimens with bevacizumab seem to be associated with better postoperative LivReg rates when compared to standard NeoChem.

Prevention of Incisional Hernia after Open Hepato-Pancreato-Biliary Surgery: A Systematic Review.

INTRODUCTION: Most hepato-pancreato-biliary (HPB) procedures are still performed through open approach. Incisional hernia (IH) is one of the most common complications after open surgery. To date, published data on IH after HPB surgery are scarce; therefore, the aim of this study was to assess the current evidence regarding incidence, risk factors, and prevention. METHODS: Medline/PubMed (1946-2020), EMBASE (1947-2020), and the Cochrane library (1995-2020) were searched for studies on IH in open HPB surgery. Animal studies, editorials, letters, reviews, comments, short case series and liver transplant, laparoscopic, or robotic procedures were excluded. The protocol was registered with PROSPERO (CRD42020163296). RESULTS: A total of 5,079 articles were retrieved. Eight studies were finally included for the analysis. The incidence of IH after HPB surgery ranges from 7.7% to 38.8%. The identified risk factors were body mass index, surgical site infection, ascites, Mercedes or reversed T incisions, and previous IH. Prophylactic mesh might be safe and effective. CONCLUSIONS: IH after open HPB surgery is still an important matter. Some of the risk factors are specific for the HPB operations and the incision type should be carefully considered. Randomized controlled trials are required to confirm the role of prophylactic mesh after HPB operations.

The effect of preoperative chemotherapy on liver regeneration after portal vein embolization/ligation or liver resection in patients with colorectal liver metastasis: a systematic review protocol.

INTRODUCTION: Liver resection (LR) in patients with liver metastasis from colorectal cancer remains the only curative treatment. Perioperative chemotherapy improves prognosis of these patients. However, there are concerns regarding the effect of preoperative chemotherapy on liver regeneration, which is a key event in avoiding liver failure after LR. The primary objective of this systematic review is to assess the effect of neoadjuvant chemotherapy on liver regeneration after (LR) or portal vein embolization (PVE) in patients with liver metastasis from colorectal cancer. The secondary objectives are to evaluate the impact of the type of chemotherapy, number of cycles, and time between end of treatment and procedure (LR or PVE) and to investigate whether there is an association between degree of hypertrophy and postoperative liver failure. METHODS: This meta-analysis will include studies reporting liver regeneration rates in patients submitted to LR or PVE. Pubmed, Scopus, Web of Science, Embase, and Cochrane databases will be searched. Only studies comparing neoadjuvant vs no chemotherapy, or comparing chemotherapy characteristics (bevacizumab administration, number of cycles, and time from finishing chemotherapy until intervention), will be included. We will select studies from 1990 to present. Two researchers will individually screen the identified records, according to a list of inclusion and exclusion criteria. Primary outcome will be future liver remnant regeneration rate. Bias of the studies will be evaluated with the ROBINS-I tool, and quality of evidence for all outcomes will be determined with the GRADE system. The data will be registered in a predesigned database. If selected studies are sufficiently homogeneous, we will perform a meta-analysis of reported results. In the event of a substantial heterogeneity, a qualitative systematic review will be performed. DISCUSSION: The results of this systematic review may help to better identify the patients affected by liver metastasis that could present low regeneration rates after neoadjuvant chemotherapy. These patients are at risk to develop liver failure after extended hepatectomies and therefore are not good candidates for such aggressive procedures. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42020178481 (July 5, 2020).

Analysis of the long-term results of living donor liver transplantation in adults. / Análisis de los resultados a largo plazo del trasplante hepático de donante vivo en adulto.

INTRODUCTION: Living donor liver transplantation (LDLT) is an alternative to conventional transplantation given its excellent results. The aim of this study is to evaluate long-term outcomes in LDLT recipients. METHODS: 100 consecutive THDV recipients from the Hospital Clínic of Barcelona from March 2000 to October 2015 were included. The main indication for transplantation was end-stage liver disease (58%) followed by hepatocellular carcinoma (41%). 95% of grafts consisted of the right liver of the donor and the 5% of the left liver. RESULTS: After a median follow-up of 65.5 months, patient and graft survival at 1, 3, and 5 years was 93%, 80% and 74% and 90%, 76%, and 71%, respectively. The overall re-transplant rate was 9%. The most common long-term complication was biliary stenosis (40%) with an average time of onset of 13.5±12 months, with repeated admissions and an average of 1.9±2 endoscopic procedures and 3.5±3 Radiological procedures per patient. The definitive treatment was radiological dilation in 40% of cases, surgical intervention in 22.5% and re-transplantation in 7.5%. CONCLUSIONS: Given the long-term results, LDLT is confirmed as an alternative to conventional transplantation. However, the high rate of late biliary complications involves repeated admissions and invasive treatments that, while not compromising survival, can affect the patient's quality of life.

Correlation between intraoperative surgical diagnosis of complicated acute appendicitis and the pathology report: clinical implications.

BACKGROUND: The post-operative management of appendectomy for acute appendicitis is based primarily on the operative findings. The surgeon describes the severity of the disease, and antibiotic therapy is administered accordingly. The histologic findings are not always considered in the decision about the management and may not be correlated with the clinical outcome. The aim of this study was to investigate the agreement between the surgeon's intra-operative visual description of the appendix and the pathologist's report in a consecutive series of patients with acute appendicitis. Complications were analyzed in relation to the classification. METHODS: A comparative observational study was performed in 69 patients who underwent surgery for acute appendicitis at the same hospital during a one-year period (the entire year of 2011). The surgeon's classification of the severity of appendicitis was compared with the pathologist's report using the kappa coefficient. Patient demographics, surgical techniques, and post-operative complications also were analyzed. RESULTS: Complicated appendicitis (gangrenous or perforated) was considered to be present in 36.2% of patients in the surgeon's classification and 43% of the patients in the histopathologic reports (p=0.033). The kappa coefficient showed only a weak correlation between the surgeons' and pathologists' descriptions (κ=0.25). Significant differences in post-operative complications were found only in the surgeon's classification. CONCLUSION: We found a weak correlation between the surgeon's macroscopic diagnosis and the pathologic findings. However, the differences did not have meaningful clinical implications. Further studies are required to evaluate the clinical meaning of these results.

Risk factors for umbilical trocar site incisional hernia in laparoscopic cholecystectomy: a prospective 3-year follow-up study.

BACKGROUND: Trocar site incisional hernia (TSIH) is a common complication after laparoscopic cholecystectomy. The aim of this study was to evaluate the prevalence of TSIH and analyze the influence of several risk factors for this complication in a prospective series. METHODS: From 2007 to 2008, a prospective observational study with 3 years of follow-up was performed including all consecutive patients with cholelithiasis who underwent elective laparoscopic cholecystectomy. A multivariate analysis was performed to identify risk factors for TSIH. RESULTS: Overall, 241 patients were included. During a median follow-up period of 46.8 months, 57 patients (25.9%) were diagnosed with umbilical TSIH by physical exam or ultrasound. The multivariate analysis revealed that incision enlargement (odds ratio [OR], 14.17; 95% confidence interval [CI], 3.61 to 55.51; P < .001), wound infection (OR, 5.62; 95% CI, 2.35 to 13.42; P < .001), diabetes mellitus (OR, 2.79; 95% CI, 1.05 to 7.37; P = .0038), and obesity (OR, 2.71; 95% CI, 1.28 to 5.75; P = .009) contributed to the risk for developing a TSIH. CONCLUSIONS: Umbilical TSIH is highly prevalent. This study identified several factors that could be useful to introduce preventive measures in high-risk patients.

Single-port access: a feasible alternative to conventional laparoscopic splenectomy.

HYPOTHESIS: The laparoscopic approach has become the gold standard for splenectomy despite the fact that the spleen is a solid organ located deep in the splenic fossa. There is currently a trend to reduce the invasiveness of minimally invasive procedures. Transabdominal or transumbilical single-incision laparoscopic (SILS) approaches are an alternative to natural orifice transluminal endoscopic surgery techniques, but no reports of their use have yet been published in relation to the spleen. AIM: To describe the SILS technique for splenectomy in 2 patients. MATERIAL AND METHODS: Two patients were approached by SILS, a 26-year-old male diagnosed of autoimmune thrombocytopenia and a 45-year-old male with recurrent Hodgkin disease. In both cases 3 trocars (1 of 12 mm and 2 of 5 mm) were inserted through the umbilicus in one and in a left subcostal in the other, and a curved transanal endoscopic microsurgery instrument, a flexible-tip 10-mm scope, and the UltraCision were introduced. Visualization of the spleen and standard dissection of attachments were feasible, and splenectomy was completed using transumbilicus stapling of the splenic hilum. The spleen was extracted through the umbilical incision, intact in one case and after morcellation in the other. RESULTS: The postoperative course was uneventful. Both patients had minimal postoperative pain and scarring and were discharged on the second postoperative day. CONCLUSIONS: SILS access can be safely used for operative visualization, hilum transection, and spleen removal with conventional instrumentation, reducing parietal wall trauma to a minimum. The clinical, esthetic, and functional advantages require further analysis.