BACKGROUND/AIM:Hepatic bile duct obstruction is a common cause of cholestasis. In cases of persistent obstruction, fibrosis and cirrhosis occur. A detailed analysis of fibrogenesis will allow the treatment for this condition to be refined and outcomes to be improved. We assessed the induction of fibrosis in selective obstructive cholestasis by determining the expression of alpha-smooth muscle actin (α-SMA) and transforming growth factor beta 1 (TGF-β1). MATERIALS AND METHODS:Selective bile duct ligation of two of four hepatic lobes was performed in rats. α-SMA and TGF-β1 expression was assessed at 30 days by immunohistochemistry, and hepatic fibrosis was quantified. The expression levels of the two markers were graded and compared, while the correlation with fibrosis was tested. Descriptive and inferential statistical tests were performed. RESULTS:At 30 days, a pre-fibrotic stage was reached. Marker expression was identified in both obstructed and unobstructed parenchyma, with higher expression in the obstructed tissue. TGF-β1 had a more intense expression, and α-SMA expression was significantly correlated with fibrosis. Ito cells showed the highest level of expression. CONCLUSION:Fibrogenesis appears to be initiated in all liver parenchyma early after the induction of cholestasis. α-SMA expression is highly correlated with the degree of fibrosis. A long-term evaluation of the model should be performed for better characterization.

Background and Objectives: Surgical wound analgesia has been analyzed in many studies, but few have focused on its relationship with inflammatory markers. As such, we aimed to determine the influence of analgesic surgical wound infiltration in open colorectal surgery on the seric levels of pro- and anti-inflammatory markers and the associated efficacy in postoperative pain control. Materials and Methods: Forty patients who underwent open colorectal surgery were prospectively randomized: group 0, epidural analgesia; group 1, intravenous analgesia (control), group 2, preincision and prelaparoraphy infiltration; and, group 3, prelaparoraphy infiltration. Wound infiltration was performed with ropivacaine. We analyzed the levels of IL-6 and IL-10 cytokines before and 6 h after surgery and their correlation with pain scores. Results: The postoperative Il-6 levels were significantly lower in group 0 than in the control (p = 0.041). The postoperative Il-10 levels were significantly higher in group 3 (p = 0.029) than in the control. Six hours after the operation, the pain scores were significantly lower in all groups than in the control (p = 0.005, p = 0.022, and p = 0.017 for groups 0, 2, and 3, respectively). Pain scores were significantly correlated with Il-10 levels in group 2 (p = 0.047); in group 3, IL-10 levels directly correlated with those of Il-6 (p = 0.026). Conclusions: The analgetic effect of preincisional and prelaparoraphy analgetic infiltration was efficient. The analgetic infiltration of the surgical wound prior to closure stimulates both the inflammatory activator and regulator interleukins.

Background: Anastomotic leak rates after colorectal surgery remain high. In most left-sided colon and rectal resection surgeries, a circular stapler is utilized to create the primary bowel anastomosis. However, it remains unclear whether a relationship between circular stapler technology and anastomotic leak in left-sided colorectal surgery exists. Methods: A post-hoc analysis was conducted using a prospectively collected data set of patients from the 2017 European Society of Coloproctology snapshot audit who underwent elective left-sided resection (left hemicolectomy, sigmoid colectomy, or rectal resection) with a manual circular stapled anastomosis. Rates of anastomotic leak and unplanned intensive care unit stay in association with manual circular stapling were assessed. Patient-, disease-, geographical-, and surgeon-related factors as well as stapler brand were explored using multivariable regression models to identify predictors of adverse outcomes. Results: Across 3305 procedures, 8.0% of patients had an anastomotic leak and 2.1% had an unplanned intensive care unit stay. Independent predictors of anastomotic leak were male sex, minimal-access surgery converted to open surgery, and anastomosis height C11 (lower third rectum) (all P < 0.050). Independent predictors of unplanned intensive care unit stay were minimal-access surgery converted to open surgery and American Society of Anesthesiologists grade IV (all P < 0.050). Stapler device brand was not a predictor of anastomotic leak or unplanned intensive care unit stay in multivariable regression analysis. There were no differences in rates of anastomotic leak and unplanned intensive care unit stay according to stapler head diameter, geographical region, or surgeon experience. Conclusion: In patients undergoing left-sided bowel anastomosis, choice of manual circular stapler, in terms of manufacturer or head diameter, is not associated with rates of anastomotic leak and unplanned intensive care unit stay.

BACKGROUND Superior mesenteric artery syndrome is a disease with a complex diagnosis, and it is associated with complications that make it even harder to identify. Currently, a frequent association with psychiatric disorders has been noted. Despite numerous case reports and case series, the variability of the disease has not allowed the development of protocols regarding diagnosis and management. CASE SUMMARY A 33-year-old woman presented with abdominal pain, nausea, and bile vomiting over the last 15 mo, associated with a 15-kg weight loss over the last three months. After the onset of the symptoms, the patient was diagnosed with anxiety-depressive disorder and treated appropriately. Standard examinations excluded an organic cause, and the cause of the symptoms was considered psychogenic. The persistence of symptoms, even under treatment, prompted a computer tomography angiography examination of the abdomen and pelvis. The examination identified emergence at a sharp angle of 13.7° of the superior mesenteric artery, with a reduced distance between the artery and the anterior wall of the aorta up to a maximum of 8 mm. A diagnosis of aortomesenteric clamp was established. Surgical treatment by laparoscopic duodenojejunostomy was performed. Postoperative evolution was marked by a patent anastomosis at 1 mo, with a 10-kg weight gain and improvement of the associated anxiety. CONCLUSION This case report underlines two major aspects. One aspect refers to the predisposition of patients with superior mesenteric artery syndrome to develop psychiatric disorders, with an excellent outcome when proper treatment is administered. The second aspect underlines the key role of a multidisciplinary approach and follow-up.

Aim The Enhanced Recovery After Surgery (ERAS (R)) Society guidelines aim to standardize perioperative care in colorectal surgery via 25 principles. We aimed to assess the variation in uptake of these principles across an international network of colorectal units. Method An online survey was circulated amongst European Society of Coloproctology members in 2019-2020. For each ERAS principle, respondents were asked to score how frequently the principle was implemented in their hospital, from 1 ('rarely') to 4 ('always'). Respondents were also asked to recall whether practice had changed since 2017. Subgroup analyses based on hospital characteristics were conducted. Results Of hospitals approached, 58% responded to the survey (195/335), with 296 individual responses (multiple responses were received from some hospitals). The majority were European (163/195, 83.6%). Overall, respondents indicated they 'most often' or 'always' adhered to most individual ERAS principles (18/25, 72%). Variability in the uptake of principles was reported, with universal uptake of some principles (e.g., prophylactic antibiotics; early mobilization) and inconsistency from 'rarely' to 'always' in others (e.g., no nasogastric intubation; no preoperative fasting and carbohydrate drinks). In alignment with 2018 ERAS guideline updates, adherence to principles for prehabilitation, managing anaemia and postoperative nutrition appears to have increased since 2017. Conclusions Uptake of ERAS principles varied across hospitals, and not all 25 principles were equally adhered to. Whilst some principles exhibited a high level of acceptance, others had a wide variability in uptake indicative of controversy or barriers to uptake. Further research into specific principles is required to improve ERAS implementation.

BACKGROUND:Anorectal melanoma is a tumour that is difficult to identify due to its rarity and variability of presentation. Insufficient data published in the literature do not allow for diagnostic and treatment guidelines to be established. Anorectal melanoma has the worst prognosis among mucosal melanomas and is frequently misdiagnosed by standard identification methods.CASE SUMMARY:A 66-year-old woman presented with intermittent anal bleeding, pain, and tenesmus in the past month, with no associated weight loss. Colonoscopy revealed a cauliflower-like tumour with a diameter of 1.5 cm, with exulcerated areas and an adherent clot but without obstruction. Biopsy results identified an inflammatory rectal polyp with nonspecific chronic rectitis. Tumour markers CA 19-9 and CEA were within the normal range. After 6 mo, due to the persistence of symptoms, a pelvic magnetic resonance imaging scan was performed. A lesion measuring 2.8 cm × 2.7 cm × 2.1 cm was identified at the anorectal junction, along with two adjacent lymphadenopathies. No distant metastases were detected. Immunohistochemistry was performed on the second set of biopsies, and a diagnosis of anorectal melanoma was established. Surgical treatment by abdominoperineal resection was performed. Evolution was marked by the appearance of lung metastases at 1 mo postoperatively, detected on a positron emission tomography-computer tomography scan, and perineal recurrence after 5 mo. After molecular testing, the patient was included in an immunotherapy trial.CONCLUSION:This case highlights the difficulty of establishing a definitive early diagnosis of anorectal melanoma, the importance of performing histological analysis on a well-represented biopsy specimen, and the poor prognosis, even with radical surgery.

Background and objectives: In patients with biliary atresia (BA), hepatoportoenterostomy (HPE) is still a valuable therapeutic tool for prolonged survival or a safer transition to liver transplantation. The main focus today is towards efficient screening programs, a faster diagnostic, and prompt treatment. However, the limited information on BA pathophysiology makes valuable any experience in disease management. This study aimed to analyze the evolution and survival of patients with BA referred for HPE (Kasai operation) in our department. Materials and Methods: A retrospective analysis was performed on fourteen patients with BA, diagnosed in the pediatric department and further referred for HPE in our surgical department between 2010 and 2016. After HPE, the need for transplantation was assessed according to patients cytomegalovirus (CMV) status, and histological and biochemical analysis. Follow-up results at 1–4 years and long term survival were assessed. Results: Mean age at surgery was 70 days. Surgery in patients younger than 60 days was correlated with survival. Jaundice’s clearance rate at three months was 36%. Total and direct bilirubin values had a significant variation between patients with liver transplants and native liver (p = 0.02). CMV was positive in eight patients, half with transplant need and half with native liver survival. Smooth muscle actin (SMA) positivity was proof of advanced fibrosis. The overall survival rate was 79%, with 75% for native liver patients and an 83% survival rate for those with liver transplantation. Transplantation was performed in six patients (43%), with a mean of 10 months between HPE and transplantation. Transplanted patients had better survival. Complications were diagnosed in 63% of patients. The mean follow-up period was six years. Conclusions: HPE, even performed in advanced cirrhosis, allows a significant survival, and ensures an essential time gain for patients requiring liver transplantation. A younger age at surgery is correlated with a better outcome, despite early CMV infection.

Objective. The access to surgical care has been limited throughout the world due to COVID-19 pandemics. This article aims to study the outcomes in locally advanced rectal cancer in our department, as a result of COVID-19 pandemics restrictions. Materials and methods. We included in the current study all patients who underwent surgery for locally-advanced rectal cancer in our department in 2019 (n=32, Group 1). We compared these patients with the patients operated after the resolution of the COVID-19 restrictions in 2020 (n=16, Group 2). All patients underwent long-course neo-adjuvant chemoradiotherapy. Results. The mean age of the patients was 64.5 years in Group 1 vs 65 years in Group 2 (p=0.99). In Group 1, the majority of the patients were clinically staged as cT3 (68.7%), similar to Group 2 (cT3 stage - 87.5%). The median time between neo-adjuvant treatment and the surgery was 8.4 weeks in Group 1 vs 11.1 weeks in Group 2 (p=0.009). During neoadjuvant treatment, none of the patients in Group 2 were diagnosed with SARS-COV2 infection and none of the surgeries were delayed due to the viral infection. There were no significant differences between the two groups in terms of pathologic staging (p=0.77), but complete pathologic response rate was higher in Group 2 as compared to Group 1 (25% vs. 12%). Conclusion. Neo-adjuvant long-course chemotherapy is a safe treatment option for patients with locally-advanced rectal cancer even during the COVID-19. Increased time to surgery leads to a higher rate of complete pathologic response, but further studies are needed to assess long-term impact of this outcome.

PURPOSEThe link between the pro-inflammatory status, tumor aggressiveness and treatment response has been well established in multiple cancers. Various hematologic and biochemical variables representing surrogates for inflammation have been used as predictive markers. Our primary aim was to assess the prognostic value of neutrophil-to-lymphocyte ratio (NLR) in evaluating neoadjuvant treatment response in locally advanced rectal cancer (LARC).METHODSWe included 60 consecutive patients with LARC, admitted for surgery, after completing a standard full-course neoadjuvant radio-chemotherapy regimen. NLR and other hematologic parameters were collected one day prior to surgery. Treatment response was assessed on the resection specimens.RESULTSOn univariate analysis, poor responders had a significantly higher NLR value when compared with good responders: 5.81 (5.40-7.28) vs. 3.51 (2.36-4.04), p<0.0001. NLR retained its significance on multivariate analysis, with an OR of 3.51 (1.54-6.57), p=0.001. A NLR cut-off value of 4.50 had the best predictive value for poor response, with an area under the curve (AUC) of 0.85, sensitivity of 83.3% and specificity of 83.3% (p<0.001). Other hematologic ratios, such as the derived NLR (dNLR) and platelet-to-lymphocyte ratio (PLR) were also significant predictors for poor response, although to a lesser extent when compared to NLR.CONCLUSIONNLR is a simple and cost-effective predictor for neoadjuvant treatment response in LARC. As more data is generated, clear cut-off values could provide valuable insight regarding the management of LARC.

Biliary atresia is the most frequent cause for neonatal obstructive cholestasis. Hepatoportoenterostomy (HPE) is the only method allowing survival until liver transplantation. For a maximum rate of success, the HPE procedure has to be performed within the 60 days of life. We aimed to create an experimental model for relieving obstructive cholestasis. In 20 Wistar rats selective bile duct obstruction was induced by the microsurgical ligature of the bile ducts corresponding to the median and left lateral liver lobes. After four weeks surgical re-intervention was carried out and HPE was performed microsurgically on the hilum of the median and left lateral liver lobes. One week after HPE, the integrity of the anastomosis and the hepatic changes were assessed. The survival rate throughout the study was 90%. The surgical re-intervention revealed hepatic-hilum adhesions, with fibrosis. Microscopically, an initial fibrogenic repair was identified, equivalent of moderate cholestasis. After the HPE, there was no bile leak from the anastomosis and no biliary peritonitis. The evolution was marked by a reduction in food intake. The experimental model we propose for the HPE is reliable by using microsurgical techniques. Based on it, one can study the changes induced by the bile duct obstruction.

BACKGROUND:Radiofrequency ablation (RF) is already a viable alternative to surgical resection for focal liver tumors treatment. The use of RF ablation in combination with surgery or chemotherapy and the large panel of RF tools need new experimental models to develop new opportunities for this kind of therapy.PURPOSE:The purpose of this study was to identify the optimal RF parameters that will allow in situ colic cancer liver metastases destruction with minimal secondary effects.MATERIALS AND METHODS:The CC531s colic cancer tumor cells were used to induce liver metastases in 30 synergic Wag/Rij rats. When metastases reached at least 1 cm in diameter, RF generator RITA 1500X, and expandable tip RF probe Starburst SDE (Angiodynamics, USA) was used for the RF ablation. The animal survival rate and the RF-induced lesions have been studied, while only the generator delivered power has been modified (90W, 20W, and 10W, respectively).RESULTS:Survival was significantly low in the group with 90W-delivered power RF. Moreover, statistically significant differences were revealed between groups with high and low RF power, regarding the morphological changes of the liver parenchyma and the adjacent organs, without significant difference on the RF therapeutically effect.CONCLUSIONS:In an experimental setting, an increased RF generator power induces important lesions of the abdominal organs with subsequently important mortality rate, without improving the RF therapeutic efficiency.

Introduction: Neoplastic invasion of the structures of the cervical region originating from a malignant tumour developed in one of the viscera of the throat may benefit from cervical exenteration. Defined as resection of the hypopharynx, cervical oesophagus, larynx and cervical trachea, exenteration has limited indications and is mandatorily accompanied by digestive tube reconstruction. The aim of this article is to highlight the indication, surgical strategy and important surgical stages illustrated by images from personal professional experience.MATERIALS AND METHODPharyngo-laryngo-oesophageal en bloc resection and radical cervical lymphadenectomy were followed by reconstruction via free jejunal transfer or colic pedicle grafting. Between 2000 and 2018 we have performed cervical exenteration in 25 patients with tumours originating in the pharynx, larynx or cervical oesophagus. In the cases of 5 patients in whom we did not obtain the oncological safety margin for oesophageal cancer we performed transhiatal pharyngo-laryngo-oesophagectomy. In these patients, we performed reconstruction of the oesophagus with colonic graft. In 20 cases we performed jejunal autotransplant. Results: We recorded 4 perioperative deaths, due to major arterial vessel haemorrhage (1 case), after jejunal necrosis (2 cases), and mediastinitis after oesophageal striping and colonic graft necrosis (1 case). One patient presented tumour recurrence at the level of the tracheal stump. Survival rate varied between 6 months and 4 years for the group of patients who presented for postoperative follow-ups. Conclusions: Cervical exenteration remains an option for tumour recurrence after radiochemotherapy or for obstructive airway or digestive tract tumours. It can be burdened by complications difficult to treat. The surgical team has to adapt its initial surgical strategy to the reality of the surgical field, both in terms of exeresis and in terms of types of pharyngo-oesophageal reconstruction.

Background: Major hepatectomies for hilar cholangiocarcinoma (HC) are associated with high rates of morbidity and mortality. We aimed to evaluate how and if surgical complications related to extended hepatectomies for HC type III and IV according to Bismuth-Corlette classification influence patients' long-term survival.Methods: The files of all patients with major hepatectomy for HC and postoperative complications were retrospectively reviewed. Only patients with a complete postoperative follow up have be taken into account for the study. Postoperative morbidity and mortality, length of hospital stay (LOS) as well as overall survival (OS) and disease free survival (DFS) were recorded.Results: Five patients have been found to respond to all inclusion criteria. Three of them required re-operation with one in hospital death. Two patients are still alive and two other died because of the tumor recurrence with a DFS of 36 and 49 months respectively. The actuarial mean OS for the group was 30 months and the actuarial DFS was 26 months.Conclusions: In patients with HC, extensive resections bring a clearly benefit in terms of survival, even though there is an increase in postoperative morbidity and mortality. However, postoperative complications, if managed susccesfully do not interfere with the long-term survival.

PURPOSEThe aim of this study was to evaluate whether there is a correlation between peripheral blood expression of angiogenic transcriptional factors/receptors and colorectal cancer (CRC).METHODSEighty six blood samples collected from patients with CRC (N=42), adenomas and/or hyperplastic polyps(AP, N=30) and individuals without colon pathology (control group/CTR, N=14) were used for this study. Twelve transcription factors and receptors were assessed by qRT-PCR in a case-control study. The molecules with a minimum of 30% differences in gene expression for CRC and AP compared to CTR were then analyzed separately for each sample. Gene expression was evaluated relatively to the CTR after normalization to the large ribosomal protein PO (RPLPO) housekeeping gene, and the differential expression between studied groups was assessed by ANOVA.RESULTSSeven out of 12 genes presented differences in expression between 10-29% in CRC and/or AP compared to CTR. Considering the selection criteria, we further individually evaluated the levels of expression of 5 genes that had a minimum of 30% expression in the case-control study. Our data showed a significant up-regulation of platelet derived growth factor (PDGF) C in the blood of the patients with CRC compared to CTR (p=0.007). Likewise, clusterin (CLU) was significantly up-regulated both in CRC and AP groups compared to healthy subjects (p=0.01). For VEGFR1, PDGFRA and TGFB1 we didn't find significantly differential expression between any of the studied groups, even if increased levels were observed in both CRC and AP vs CTR.CONCLUSIONSThe results of our study indicated that increased blood level of PDGFC mRNA was associated with the presence of CRC (p=0.007). Additionally, high levels of circulating CLU mRNA were observed in both malignant and benign colorectal pathologies.

UNLABELLED:The aim of this study was to establish the efficiency, safety and feasibility of laparoscopic surgery for rectal cancer by assessing the short-term outcomes.MATERIALS AND METHODS:In this prospective clinical study, from 2008 to 2011, 60 patients with laparoscopic resection for rectal cancer were included, treated in "Prof. Dr. Octavian Fodor" Gastroenterology and Hepatology Institute, Department of Surgery and Surgery Clinic I, Cluj-Napoca.RESULTS:Surgical procedures included 38 abdominal-perineal resections, 21 anterior resections and 1 Hartmann procedure. Average blood loss was 250 ml (100-800 ml) and median length of postoperative hospital stay was 9 days (4-91 days). Blood loss was significantly higher in patients with low rectal cancer than those with upper rectal cancer (300 ml vs 200 ml, p=0.031). Conversion to open surgery was required in 8 patients (13.3%). Overall postoperative complications were 28.8%. Positive circumferential margins occurred in 1 patient (1.7%), while distal margins were negative in all patients.CONCLUSIONS:Laparoscopic surgery is safe and feasible in selected patients with rectal cancer, with favorable shortterm results.

There are no data in the literature on the use of radio-frequency ablation (RFA) in emergency laparoscopy as a means of hemostasis after liver biopsy. In this case report we have described a case of a patient with Waldenstrom macroglobulinemia and hypervascularised hepatic tumor who developed severe hepatic bleeding after liver biopsy. Innovative, minimally invasive treatment consisted in a laparoscopic approach with introduction of RFA needle into the biopsy site, followed by immediate hemostasis with no complications. Laparoscopic surgery with RFA avoids unnecessary laparotomy in case of severe bleeding from a known source. It is therefore the optimal choice, even in patients for whom percutaneous biopsy would be a high-risk procedure.

This study describes an experimental model of accessory renal allotransplantation in the big laboratory animal (pig). A total of 24 common-breed pigs were used. All allografts were transplanted in an accessory manner and revascularized at the level of the infrarenal abdominal aorta and inferior vena cava. The urinary drainage was performed either through a nexternal uretheroneostomy at the ipsilateral lumbar region (Group A--n=8) or by internal uretheroneocystostomy (Group B--n=8). All transplants were monitored for 8 days postoperatively using translumbar ultrasound-guided biopsies at 1, 4, 7 days. A total of 16 transplants were performed. 1 ectopic donor kidney was found and transplanted in the same fashion. Mean operative time was 125 minutes, immediate postoperative survival was 100% and at 72 hours, 87.5%. The onset of acute rejection was at day 4, by massive lymphocyte infiltration and was directly correlated with the abrupt decrease of the allograft diuresis in Group A, at day 3. At day 7, the rejection was complete. Both methods of urinary drainage are functional and can be employed. This experimental model is a useful tool for training of the transplant surgeons or for transplantation research. The surgical technique for accessory renal allotransplantation in pig is easy to learn and offers the possibility for allograft monitoring until complete rejection without influencing the receptor health condition.