HER2 Overexpression in Periampullary Tumors According to Anatomical and Histological Classification-A Systematic Review.

Pancreatic cancer is one of the most aggressive, heterogeneous, and fatal types of human cancer; therefore, more effective therapeutic drugs are urgently needed. Human epidermal growth factor receptor 2 (HER2) overexpression and amplification have been identified as a cornerstone in this pathology. The aim of this review is to identify HER2 membrane overexpression in relation to pancreatic cancer pathways that can be used in order to develop a targeted therapy. After searching the keywords, 174 articles were found during a time span of 10 years, between 2013 and 2023, but only twelve scientific papers were qualified for this investigation. The new era of biomolecular research found a significant relationship between HER2 overexpression and pancreatic cancer cells in 25-30% of cases. The variables are dependent on tumor-derived cells, with differences in receptor overexpression between PDAC (pancreatic ductal adenocarcinoma), BTC (biliary tract cancer), ampullary carcinoma, and PNETs (pancreatic neuroendocrine tumors). HER2 overexpression is frequently encountered in human pancreatic carcinoma cell lines, and the ERBB family is one of the targets in the near future of therapy, with good results in phase I, II, and III studies evaluating downregulation and tumor downstaging, respectively.

Prognostic Indicators of Overall Survival in Hepatocellular Carcinoma Patients Undergoing Liver Resection.

Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer and the third contributor to malignancy-related deaths worldwide. The hepatic venous pressure gradient (HVPG), transient elastography-liver stiffness measurement (TE-LSM), and the association between TBS (tumor burden score), alpha-fetoprotein levels, and the Child-Pugh classification (TAC score) can serve as valuable prognostic indicators for these patients. Therefore, the main objective of our research was to analyze the prognostic value of the HVPG, TE-LSM, TBS, and TAC scores. An observational and survival study was conducted on 144 subjects. Our findings indicated that HVPG greater than 10 mmHg, AFP surpassing 400 ng/mL, an advanced C-P class, and low TAC score are independent predictors of overall survival. During the multivariate analysis, AFP serum levels and C-P class proved statistically significant. The present study revealed significant differences in overall survival between the two groups divided upon HVPG values and settled by the cutoff of 10 mmHg (p = 0.02). Moreover, by dividing the cohort into three groups based on the TAC score (very low, low, and moderate), statistically significant differences in overall survival were observed across the groups (p = 0.004).

Metabolic Signatures: Pioneering the Frontier of Rectal Cancer Diagnosis and Response to Neoadjuvant Treatment with Biomarkers-A Systematic Review.

Colorectal cancer (CRC) is one of the most aggressive, heterogenous, and fatal types of human cancer for which screening, and more effective therapeutic drugs are urgently needed. Early-stage detection and treatment greatly improve the 5-year survival rate. In the era of targeted therapies for all types of cancer, a complete metabolomic profile is mandatory before neoadjuvant therapy to assign the correct drugs and check the response to the treatment given. The aim of this study is to discover specific metabolic biomarkers or a sequence of metabolomic indicators that possess precise diagnostic capabilities in predicting the efficacy of neoadjuvant therapy. After searching the keywords, a total of 108 articles were identified during a timeframe of 10 years (2013-2023). Within this set, one article was excluded due to the use of non-English language. Six scientific papers were qualified for this investigation after eliminating all duplicates, publications not referring to the subject matter, open access restriction papers, and those not applicable to humans. Biomolecular analysis found a correlation between metabolomic analysis of colorectal cancer samples and poor progression-free survival rates. Biomarkers are instrumental in predicting a patient's response to specific treatments, guiding the selection of targeted therapies, and indicating resistance to certain drugs.

Emergency liver resection for non-traumatic lesions. A systematic review.

AIM: Primary liver tumors have an incidence of 20% regarding benign tumors respectively 5.7% of the overall incident cases of cancer. In any major hepatic injury, the surgical treatment has two main goals: hemostasis and excision of the affected liver segments. We aimed to systematic review the non-traumatic emergency liver resections, in order to raise concern about a rather rare, but difficult to treat hepatic pathology, which implies divergent therapeutical approach, and emergency liver surgery remains the first or backup option. METHODS: A literature survey was performed guided by the words "liver resections", "major liver resections", "emergency liver resection". "hepatocellular carcinoma" using four databases: Pubmed, Scopus, Web of Science and Embase. All titles referred in English, published from 2000 until 2021, were checked for eligibility. RESULTS: Six publications were considered relevant for major liver resections in emergency, from a total of 331 articles that were reviewed. Large hepatocellular carcinomas and adenomas were the most common types of tumors found at risk for spontaneous rupture. The patients with hemodynamic instability, reduced liver function and large tumors had lower long-term survival and disease-free survival. Major hepatectomy was indicated as a viable solution for prolonging survival rate, whenever the patient's general status permits it per primam. CONCLUSIONS: Emergency major liver resection for tumoral causes prolongs survival even if the cause is usually malignant. The tumor can be resected with negative resection margins, respecting the correct oncological requirements, both per primam or staged approach according to each case specifically. KEY WORDS: Adenoma, Emergency, Hemorrhage, Hepatocellular Carcinoma, Liver Resection, Liver Tumors.

Role of Metabolomics in Pathogenesis and Prompt Diagnosis of Gastric Cancer Metastasis-A Systematic Review.

INTRODUCTION: Gastric cancer is the fourth most frequently diagnosed form of cancer and the third leading cause of cancer-related mortality worldwide. The aim of this review is to identify individual metabolic biomarkers and their association with accurate diagnostic values, which can predict gastric cancer metastasis. MATERIALS AND METHODS: After searching the keywords, 83 articles were found over a period of 13 years. One was eliminated because it was not written in English, and two were published outside the selected period. Seven scientific papers were qualified for this investigation after eliminating duplicates, non-related articles, systematic reviews, and restricted access studies. RESULTS: New metabolic biomarkers with predictive value for gastric cancer metastasis and for elucidating metabolic pathways of the metastatic process have been found. The pathogenic processes can be outlined as follows: pro-oxidant capacity, T-cell inactivation, cell cycle arrest, energy production and mitochondrial enzyme impairment, cell viability and pro-apoptotic effect, enhanced degradation of collagen extracellular matrix, migration, invasion, structural protein synthesis, and tumoral angiogenesis. CONCLUSION: Metabolic biomarkers have been recognized as independent risk factors in the molecular process of gastric cancer metastasis, with good diagnostic and prognostic value.

Robot-Guided Ultrasonography in Surgical Interventions.

INTRODUCTION: The introduction of robotic-guided procedures in surgical techniques has brought an increase in the accuracy and control of resections. Surgery has evolved as a technique since the development of laparoscopy, which has added to the visualisation of the peritoneal cavity from a different perspective. Multi-armed robot associated with real-time intraoperative imaging devices brings important manoeuvrability and dexterity improvements in certain surgical fields. MATERIALS AND METHODS: The present study is designed to synthesise the development of imaging techniques with a focus on ultrasonography in robotic surgery in the last ten years regarding abdominal surgical interventions. RESULTS: All studies involved abdominal surgery. Out of the seven studies, two were performed in clinical trials. The other five studies were performed on organs or simulators and attempted to develop a hybrid surgical technique using ultrasonography and robotic surgery. Most studies aim to surgically identify both blood vessels and nerve structures through this combined technique (surgery and imaging). CONCLUSIONS: Ultrasonography is often used in minimally invasive surgical techniques. This adds to the visualisation of blood vessels, the correct identification of tumour margins, and the location of surgical instruments in the tissue. The development of ultrasound technology from 2D to 3D and 4D has brought improvements in minimally invasive and robotic surgical techniques, and it should be further studied to bring surgery to a higher level.

The Influence of Intravenous Lidocaine Infusion on Postoperative Outcome and Neutrophil-to-Lymphocyte Ratio in Colorectal Cancer Patients. A Pilot Study.

BACKGROUND AND AIMS: In the last years increasing scientific evidence drew attention on the potential effects of anesthetic drugs on postoperative outcome in cancer patients. Local anesthetics, especially lidocaine, have been intensively studied in relation with postoperative outcome in colorectal cancer patients. Our study objectives were to investigate the effects of perioperative intravenous lidocaine infusion on neutrophil-to-lymphocyte ratio and short-term postoperative outcome. Additionally, we also looked at 1 year outcome after intended radical colorectal cancer surgery. METHODS: 150 patients scheduled for colorectal cancer surgery were randomized to receive sevoflurane anaesthesia with or without 48 hours lidocaine infusion. RESULTS: 73 patients were included in the group A (sevoflurane) and 77 in the group B (sevoflurane with lidocaine). Lidocaine infusion did not modify neutrophil-to-lymphocyte ratio at 24 hours after surgery (p=0.58). Patients receiving intravenous lidocaine had significantly lower morphine consumption (p=0.04), faster mobilization time (p=0.001) and fewer days spent in the hospital (p=0.04). Moreover, at 1 year follow- up, patients in group B had a significant decreased rate of recurrences (p=0.03). There was no significant difference in 1 year survival (p=0.22). CONCLUSIONS: In our study, intravenous lidocaine infusion hastened the postoperative recovery of patients in terms of mobilization, hospital discharge and opioid consumption and reduced 1 year recurrence rate. Further studies on larger groups of patients are needed.

Surgical management of hydatid cyst disease of the liver: An improvement from our previous experience?

BACKGROUND: Hydatid liver disease remains an important issue in endemic areas, which may require immediate surgery. Although laparoscopic surgery is on the rise, the presence of certain complications may require conversion to the open approach. AIM: To compare the results of laparoscopic treatment and the open approach in the context of a 12-year single institution experience, and to perform a further comparison between results from the current study and those from a previous study. METHODS: Between January 2009 and December 2020, 247 patients underwent surgery for hydatic disease of the liver in our department. Of the 247 patients, 70 underwent laparoscopic treatment. A retrospective analysis between the two groups was performed, as well as a comparison between current and previous laparoscopic experience (1999-2008). RESULTS: There were statistically significant differences between the laparoscopic and open approaches regarding the cyst dimension, location, and presence of cystobiliary fistula. There were no intraoperative complications in the laparoscopic group. The cutoff value for the cyst size regarding the presence of cystobiliary fistula was 6.85 cm (P = 0.001). CONCLUSION: Laparoscopic surgery still plays an important role in the treatment of hydatid disease of the liver, with an increase in its usage over the course of years that has shown benefits regarding the postoperative recovery with a decreased rate of intraoperative complications. Although experienced surgeons can perform laparoscopic surgery in the most difficult conditions, there are some selection criteria that need to be maintained for higher quality results.

Exploratory Evaluation of Neopterin and Chitotriosidase as Potential Circulating Biomarkers for Colorectal Cancer.

Chronic inflammation is demonstrated to play a direct role in carcinogenesis. Our exploratory study aimed to assess the potential added value of two inflammation biomarkers, chitotriosidase and neopterin, in follow-up evaluation of patients with colorectal cancer (CRC). An observational exploratory study was conducted. Patients with CRC and matched controls (1:1, age, sex, and living environment) were evaluated. The patients with CRC (CRC group) and controls were assessed at baseline (before surgical intervention for patients with CRC). Patients with CRC were also evaluated at 1-year follow-up. Significantly more patients with blood group A (54.5% vs. 25.0%) and smokers (50.0% vs. 22.7%) were in the CRC group. The serum values of chitotriosidase and neopterin were higher in CRC patients than in controls, but only neopterin reached the conventional level of statistical significance (p-value = 0.015). The circulating chitotriosidase and neopterin values decreased significantly at 1-year follow-up (p-value < 0.0001). Patients with higher N- and M-stage showed statistically significant higher levels of chitotriosidase and neopterin at baseline and 1-year follow-up (p-values < 0.03). Circulating chitotriosidase levels also showed statistically significant differences regarding baseline and 1-year follow-up on patients with CRC and different differentiation grades (p-values < 0.02). The circulating levels of neopterin significantly decreased at 1-year follow-up, indicating its potential as a prognostic marker. The circulating values of chitotriosidase and neopterin exhibit significant differences in patients with than without recurrences. Our results support further evaluation of chitotriosidase and neopterin as prognostic markers in patients with CRC.

Trends in Minimally Invasive Approaches for Liver Resections-A Systematic Review.

BACKGROUND: SILS (single incision laparoscopic surgery) and NOTES (natural orifice transluminal endoscopic surgery) are considered breakthroughs in minimally invasive surgery, the first consisting in the surgeon working via a single entrance site and the second via a natural orifice (e.g., oral cavity). METHODS: Since 2000 until 2022, the original articles published in the online databases were analyzed. Eligible studies included information about the current therapy of patients with liver surgical pathology and how the two new techniques improve the surgical approach. RESULTS: A total of 798 studies were identified. By applying the exclusion criteria, nine studies remained to be included in the review. Two out of nine studies examined the NOTES approach in liver surgery, whereas the other seven focused on the SILS technique. The age of the patients ranged between 24 and 83 years. Liver resections for hepatocellular carcinoma or colorectal metastases were undertaken and biliary or hydatid cysts were removed. The mean procedure time was 95 to 205 min and the average diameter of the lesions was 5 cm. CONCLUSIONS: When practiced by multidisciplinary teams, transvaginal liver resection is feasible and safe. The goals of SILS and NOTES are to be less intrusive, more easily tolerated and aesthetic.

Perioperative Management of Patients with Pancreatic Cancer - the ERAS Protocols.

Background: Pancreatic cancer represents the fifth leading cause of death in industrialized countries. The prognosis is reserved, surgical resection being the only curative treatment, but the complications associated bear important impact on the patients survival, prognosis, and quality of life. The ERAS protocols come to meet these shortcomings for enhanced recovery after major pancreatic resections. Material and method: A systematic review was performed following the guidelines outlined by The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Original articles published in the online databases Pubmed (Medline), Embase and Cochrane since 2017 until 2022 were screened after using specific keywords. Results: A total of 252 studies was obtained by searching through online databases. Following the exclusion criteria, we included 7 studies in the systematic review. Conclusions: The ERAS protocols are safe to be applied in the common practice. They are efficient in the perioperative management of patients undergoing pancreatic resections. They can further decrease hospitalization stay, promote better recovery of gastrointestinal function, and speed up postoperative recovery.

Emergency Pancreatoduodenectomy: A Non-Trauma Center Case Series.

(1) Background: Emergency pancreatoduodenectomy (EPD) is a rare procedure, especially in non-trauma centers. Pancreatoduodenectomy is a challenging intervention, that has even higher risks in emergency settings. However, EPD can be a life-saving procedure in selected cases. (2) Methods: Our study is a single-center prospective consecutive case series, on patients that underwent emergency pancreatoduodenectomies in our surgical department between January 2014 to May 2021. (3) Results: In the 7-year period, 4 cases were operated in emergency settings, out of the 615 patients who underwent PD (0.65%). All patients were male, with ages between 44 and 65. Uncontrollable bleeding was the indication for surgery in 3 cases, while a complex postoperative complication was the reason for surgery in one other case. In three cases, a classical Whipple procedure was performed, and only one case had a pylorus-preserving pancreatoduodenectomy. The in-hospital mortality rate was 25% and the morbidity rate was 50%; the two patients that registered complications also needed reinterventions. The patients who were discharged had a good long-term survival. (4) Conclusion: EPD is a challenging procedure, rare encountered in non-traumatic cases, that can be a life-saving intervention in well-selected cases, offering good long-term survival.

Abilities of Pre-Treatment Inflammation Ratios as Classification or Prediction Models for Patients with Colorectal Cancer.

BACKGROUND: Systemic inflammatory status is known as an important factor of colorectal cancer prognosis. Our study aimed to evaluate the performances of inflammation biomarker ratios as classification models of seven outcomes in patients with colorectal cancer. METHODS: A retrospective cohort study was conducted on subjects with colorectal cancer over five years at a single center in Transylvania, Romania. Seven derived ratios were calculated based on laboratory data: neutrophil-to-lymphocyte (NLR), derived neutrophil-to-lymphocyte (dNLR), platelet-to-lymphocyte (PLR), lymphocyte-to-monocyte (LMR) and albumin-to-globulin (AGR) ratios, Systemic Immune Inflammation Index (SII) and Prognostic Nutritional Index (PNI). The utility of these ratios as predictors for seven outcomes was further evaluated in multivariable regression models. RESULTS: Our study shows that the evaluated ratios exhibit specific performances for individual outcomes, proving a fair ability as screening tools (NLR and dNLR for survival, T stage and M stage; NLR and SII for T stage; and PLR for M stage). A dNLR over 3.1 (OR = 2.48, 95% CI (1.421 to 4.331)) shows predictive value for survival. A value of NLR over 3.10 (OR = 1.389, 95% CI (1.061 to 1.817)) is positively associated with an advanced T stage, while LMR is negatively related to the T stage (OR = 0.919, 95% CI (0.867 to 0.975)). NLR over 4.25 (OR = 2.647, 95% CI (2.128 to 3.360)) is positively associated with, while PNI is negatively related (OR = 0.970, 95% CI (0.947 to 0.993)) to, the M stage. CONCLUSION: Each of the evaluated ratios possesses prognostic value for certain outcomes considered, but the reported models need external validation to recommend their clinical practice utilization.

The Pattern of Calculated Inflammation Ratios as Prognostic Values in Patients with Colorectal Cancer.

AIM: In this study, we evaluated the prognostic value of four calculated inflammatory ratios in patients with colorectal cancer. MATERIALS AND METHODS: A six-year retrospective study was conducted on subjects admitted for colorectal cancer at "Prof. Dr. Octavian Fodor" Regional Institute of Gastroenterology and Hepatology Cluj-Napoca, Romania, from January 2014 until September 2019. The medical charts of patients diagnosed with colorectal cancer were used as the source of raw data and for the calculation of four ratios (neutrophil-to-lymphocyte ratio-NLR, derived neutrophil-to-lymphocyte ratio-dNLR, platelet-to-lymphocyte ratio-PLR, and systemic immune-inflammation index-SII), considered as prognostic markers related to mortality in colorectal cancer. RESULTS: One thousand six hundred and eighty-eight patients, with ages ranging from 17 to 98 years, were evaluated. NLR and dNLR displayed significantly higher values among patients who died (NLR: 4.2 for deceased vs. 3.4 for alive, P-value=0.0224; dNLR: 2.7 for deceased vs. 2.3 for alive, P-value=0.0566). Ischemic cardiomyopathy (odds ratio (OR)=2.70), liver cirrhosis (OR=7.84), post-operative complications (OR=2.39), and neutrophil-to-lymphocyte ratio (OR=1.08) proved to be significant prognostic factors for the primary outcome, independent of age and gender. CONCLUSION: Patients with high NLR, post-operative complications, ischemic cardiomyopathy, and/or liver cirrhosis are the candidates to a less favorable outcome among subjects with colorectal cancer regardless the age and gender.

Relation between serum cotinine levels and trophic lesions in patients with critical limb ischemia: a pilot study.

Aim: To evaluate if smoking, quantified by the serum cotinine levels, is related to the evolution of patients with critical limb ischemia (CLI).Method: A pilot study was conducted on CLI patients who addressed at the Second Surgery Clinic of the Emergency County Hospital, Cluj-Napoca, Romania between November 2015 and December 2016. The sample of patients was split into two groups using the threshold of 15 ng/mL for the serum level of cotinine (low cotinine level - LCL vs. high cotinine level - HCL). Furthermore, the ROC analysis was conducted to identify the threshold of cotinine level able to discriminate between CLI patients with and without trophic lesions.Results: The mean age of patients was 60.7 ± 10.5 years with a significantly higher percentage of male patients (84%). A significant association was identified between urban origin and serum cotinine level, which is related to the increased number of cigarettes smoked per day among urban participants. Excepting necrectomy and toe disarticulation, no differences were found between LCL and HCL group regarding symptoms, signs or comorbidities. In smokers with CLI (38/43), a serum cotinine cut-off of 9.765 ng/mL was observed on eight out of 10 CLI patients with necrectomy and five out of 28 patients without necrectomy.Conclusion: Our study showed higher serum cotinine levels associated with a higher number of smoked cigarettes and necrectomy in patients with CLI. The serum cotinine could be a fair screening test for necrectomy in smokers CLI patients.

Histopathological changes in major amputations due to diabetic foot - a review.

Diabetes mellitus is the leading cause of non-traumatic amputations worldwide. Ulcer of the diabetic foot is one of the most prevalent lesions of diabetic patients and it occurs in the natural evolution of the disease as a tardive complication. Neuropathy is the main determinant of foot ulcer. A key role is played by the loss of sensitive nerves, which prove to be a protective barrier against high pressure applied otherwise on the foot. The morphopathological characteristics of neuropathic lesions in patients with diabetes show important improvement associated with the pressure relieving treatment strategies. Therefore, pressure seems to impose a continuous mechanical stress on the wounded foot and it also sustains a chronic inflammatory condition, which slows down the healing process. Atherosclerosis is an imminent process to every person, nonetheless patients with diabetes mellitus have this process highly accelerated and more diffuse. One of the main characteristics of macrovascular lesions in diabetes is Mönckeberg's medial calcific sclerosis, calcification of the muscular layer, which clinically translates into an ankle-brachial index of 1 or above. Diabetes affects not only the large vessels, but it also produces microvascular lesions, which in time leads to diseases like retinopathy or nephropathy. Osteomyelitis is very common in the diabetic foot infections and the medical treatments are not satisfying. It is also believed to be a consequence of peripheral neuropathy that diabetes comes with. Osteomyelitis plays an important role in the prevalence of amputations in patients with diabetes. Obtaining clean, infection free margins is the most important goal, because residual osteomyelitis is a strong predictor of clinical failure and comes with many postoperative complications, even the necessity to operate again or have a major amputation later in evolution.

Evaluation of Chitotriosidase as a Marker of Inflammatory Status in Critical Limb Ischemia.

BACKGROUND: Chitotriosidase is an enzyme secreted by activated macrophages. This study aims to investigate the usefulness of circulating chitotriosidase activity as a marker of inflammatory status in patients with critical limb ischemia (CLI). MATERIALS AND METHODS: An observational gender-matched case-control study was conducted on patients hospitalized with the primary diagnosis of CLI, as well as a control group. The control group consisted of healthy volunteers. RESULTS: Forty-three patients were included in each group. Similar demographic characteristics (median age of 60-62 years and overweight) were observed in both groups. Chitotriosidase activity ranged from 110 nmol/ml/hr to 1530 nmol/ml/hr in the CLI group and from 30 nmol/ml/hr to 440 nmol/ml/hr in the control group; demonstrating significantly elevated values in the CLI group (p<0.001). Median plasma chitotriosidase activity was significantly elevated in smokers compared with non-smokers in both groups (p<0.05). However, this activity had higher values in CLI than in control subjects. Receiver operating characteristic (ROC) analysis was then performed in order to verify the diagnostic accuracy of chitotriosidase as an inflammatory biomarker in CLI. CONCLUSION: Circulating chitotriosidase is a test which can potentially be used for the monitoring of CLI patients without other inflammatory conditions. However, the interpretation of elevated values must take into account the inflammatory response induced by tobacco exposure.

Demographic and Comorbidity Pattern of Patients with Critical Limb Ischemia.

AIM: The present study aimed at identifying the pattern of patients with critical limb ischemia (CLI) compared with those with peripheral arterial occlusive disease (PAOD). MATERIALS AND METHODS: A four-year retrospective study was conducted with patients hospitalized in the Second Surgical Clinic at the Emergency County Hospital Cluj-Napoca. The medical charts of patients with PAOD (n=466) and CLI (n=223) were reviewed and data were collected. RESULTS: The study included 689 patients; mean age 67 years for PAOD patients and 65 years for CLI patients. A significantly higher percentage of patients were male in both groups (79.25%, P < 0.0001). Most of the patients in both groups had received at least a secondary education (P < 0.0001). Most of the subjects in both groups were smokers (>71.30%) with no difference between groups (P = 0.566). No significant differences were found between the groups in comorbidities (diabetes, arterial blood hypertension, cardiac ischemia, rhythm disorders, P > 0.05). There were more CLI patients that were overweight than overweight patients with PAOD (P = 0.0004). High serum cholesterol (>200 mg/dL) and triglycerides (>150 mg/dL) levels were found in the CLI group (P < 0.05). Age was identified as a risk factors for amputation (OR = 1.03, 95%Cl [1.01-1.05], P = 0.0012). CONCLUSIONS: The profile of a patient with critical limb ischemia and peripheral arterial occlusive disease is a 65-67-year-old male smoker with at least a secondary education. The CLI patient is overweight with pathological serum levels of cholesterol and triglycerides.