Robotic vs laparoscopic total mesorectal excision for rectal cancers: has a paradigm change occurred? A systematic review by updated meta-analysis.

AIM: The debate about the oncological adequacy, safety and efficiency of robotic vs laparoscopic total mesorectal excision for rectal cancers continues. Therefore, an updated, traditional and cumulative meta-analysis was performed with the aim of assessing the new evidence on this topic. METHOD: A systematic search of the literature for data pertaining to the last 25 years was performed. Fixed- and random-effects models were used to cumulatively assess the accumulation of evidence over time. RESULTS: Patients with a significantly higher body mass index (BMI), tumours located approximately 1 cm further distally and more patients undergoing neoadjuvant therapy were included in the robotic total mesorectal excision (RTME) cohort compared with those in the laparoscopic total mesorectal excision (LTME) cohort [RTME, mean difference (MD) = 0.22 (0.07, 0.36), P = 0.005; LTME, MD = -0.97 (-1.57, 0.36), P < 0.002; OR = 1.47 (1.11, 1.93), P = 0.006]. Significantly lower conversion rates to open surgery were observed in the RTME cohort than in the LTME cohort [OR = 0.33 (0.24, 0.46), P < 0.001]. Operative time in the LTME cohort was significantly reduced (by 50 min) compared with the RTME cohort. Subgroup analysis of the three randomized controlled trials (RCTs) challenged all the significant results of the main analysis and demonstrated nonsignificant differences between the RTME cohort and LTME cohort. CONCLUSION: Although the RTME cohort included patients with a significantly higher BMI, more distal tumours and more patients undergoing neoadjuvant therapy, this cohort demonstrated lower conversion rates to open surgery when compared with the LTME cohort. However, subgroup analysis of the RCTs demonstrated nonsignificant differences between the two procedures.

What to consider when designing a laparoscopic colorectal training curriculum: a review of the literature.

Multiple studies have demonstrated the benefits of laparoscopic colorectal surgery (LCS), but in several countries it has still not been widely adopted. LCS training is associated with several challenges, such as patient safety concerns and a steep learning curve. Current evidence may facilitate designing of efficient training curricula to overcome these challenges. Basic training with virtual reality simulators has witnessed meteoric advances and may be essential during the early parts of the learning curve. Cadaveric and animal model training still constitutes an indispensable training tool, due to a higher degree of difficulty and greater resemblance to real operative conditions. In addition, recent evidence favors the use of novel training paradigms, such as proficiency-based training, case selection and modular training. This review summarizes the recent advances in LCS training and provides the evidence for designing an efficient training curriculum to overcome the challenges of LCS training.

B7H4, HSP27 and DJ-1 molecular markers as prognostic factors in pancreatic cancer.

OBJECTIVES: Pancreatic cancer (PC) is one of the most lethal tumors of the gastrointestinal tract. The ability to predict which patients would benefit most from surgical intervention and chemotherapy would be a great clinical tool. A large number of potential markers have been identified lately in pancreatic cancer and their clinical utilities as prognostic tools are under investigation. METHODS: We recruited 41 patients who had undergone radical surgical resection for PC between 2003 and 2010. To investigate the prognostic factors, we evaluated 3 possible markers: B7H4, HSP27 and DJ-1 protein expressions in the tissue specimens of these 41 patients by immunohistochemistry and analyzed the clinical and pathological features of these specimens. RESULTS: The expression of the three antigens was independently associated with a negative impact of chemotherapy with gemcitabine on patient's survival. Moreover, patients who overexpressed B7H4 had worse prognosis than the ones who did not. CONCLUSIONS: B7H4, DJ-1 and HSP27 may be used in the future as prognostic markers that express resistance of pancreatic cancer patients to chemotherapy with gemcitabine.

α-Defensins and hsCRP levels in inflammatory response of standard and laparoendoscopic single-site cholecystectomy.

BACKGROUND: Laparoendoscopic single-site (LESS) surgery is an evolution of laparoscopic surgery aiming at decreasing the patient's parietal trauma associated with abdominal operations. LESS has been found so far to be efficient and have the same good results as the standard four-port laparoscopic cholecystectomy. α-Defensins are antimicrobial peptides of the organism. They are the first cell components against pathogens. Cytokines are also mediators in the response to trauma. The aim of this study was to compare the inflammatory reaction in LESS and four-port laparoscopic cholecystectomy. METHODS: Forty patients with noncomplicated cholelithiasis were randomly assigned into one of two groups. Group A included the patients who would undergo four-port laparoscopic cholecystectomy and group B included the patients who would undergo LESS cholecystectomy. These patients had a BMI < 30, were ASA I or II, and had no previous upper-GI surgery. Blood was taken preoperatively and 6 and 24 h postoperatively. hsCRP (with automated analyzer) and α-defensins (using ELISA) were calculated for each sample. The same postoperative protocol was followed for both groups. Mann-Whitney U test was used to analyze the results. Pain was calculated with a visual analog scale (VAS) for shoulder and abdomen at 6 and 24 h. Hospital stay, nausea, and pain medication needed was noted. RESULTS: The α-defensins value was statistically significantly higher in the 24-h samples (P < 0.001) for LESS cholecystectomy. No statistically significant difference was shown for hsCRP, even though P = 0.05 for the 24-h samples with the values of LESS higher. No LESS was converted to a classical laparoscopic cholecystectomy, and none of the patients of either group needed conversion to open cholecystectomy. Pain was statistically significantly less for the LESS group at the 24-h interval (P < 0.0001). Less medication was needed for LESS patients after the 6th postoperative hour (P = 0.007). CONCLUSION: Higher inflammatory reaction in LESS cholecystectomy could be the result of greater tension on the tissues. More studies are needed to conclude if this has a significant clinical expression.

Laparoscopic cholecystectomy in acute cholecystitis: an analysis of the risk factors.

BACKGROUND AND AIM: Laparoscopic cholecystectomy (LC) is increasingly being used as the initial surgical approach in patients with acute cholecystitis (AC). We describe our experience with LC in the treatment of AC. MATERIALS AND METHODS: In this study 2 412 patients underwent LC, in 315 cases for AC. The diagnosis was based on clinical, laboratory and intra-operative findings. Rates of conversion, complications, length of hospital stay, operating times, and factors associated with conversion or morbidity were analysed. RESULTS: Conversion to open cholecystectomy was necessary in 60 patients (19.04%) with AC. Factors associated with conversion were age >65 years, male gender, presence of empyema, previous abdominal surgery, and fever (temperature >37.5oC). There were no deaths, and the complication rate was 6.4%. The only risk factor for morbidity was a bilirubin level of >20.52 µmol/l. The operating time and hospital stay were significantly longer in AC than in elective cases. CONCLUSIONS: LC for AC is technically demanding but safe and effective. With patience, experience, careful dissection and identification of vital structures, the laparoscopic approach is safe in the majority of cases.

Quality training in laparoscopic colorectal surgery: does it improve clinical outcome?

Laparoscopic colorectal surgery (LCRS) is a safe, effective and cost-efficient option for the treatment of various benign and malignant conditions. However, its implementation to surgical practice is still limited. That is mainly due to its association with a steep learning curve. We performed a review of the literature to determine whether quality training in LCRS can reduce that learning curve and lead to better clinical outcomes. We concluded that a structured training program with pre-clinical phase focused on basic skill acquisition and a clinical phase focused on mentoring from experts can shorten the learning curve and improve clinical outcomes.

Peri-operative management of a patient with hereditary angioedema undergoing laparoscopic cholecystectomy.

Hereditary angioedema is a rare genetic disorder resulting from an inherited deficiency or dysfunction of the C1-esterase inhibitor of the classic complement pathway. It is characterised by recurrent episodes of angioedema, without urticaria or pruritus, most often affecting the skin or the mucosal tissues of the upper respiratory and gastrointestinal tracts. We describe the peri-operative care of a woman with hereditary angioedema undergoing laparoscopic cholecystectomy with emphasis on the role of anaesthetists as peri-operative physicians.

Xenotransplantation of hepatocytes in rats with acute liver failure using sirolimus for immunosuppression.

This study aimed to evaluate the effect of sirolimus (SRL; rapamycin) as an immunosuppressant during xeno transplantation (XT) of rabbit hepatocytes into male Wistar rats with acute liver failure (ALF; n = 72). Isolated rabbit hepatocytes were transplanted intrasplenically into rats within 24 h of chemically induced ALF. Treatment groups received monotherapy with either cyclosporine (CsA) 20 mg/kg or SRL 0.20 mg/kg, or combination therapy with CsA 20 mg/kg + SRL 0.20 mg/kg for 14 days post-transplant. One control group with ALF received no treatment and a second group with ALF received only XT. Surviving rats were euthanized after 14 days, with concurrent blood sampling and organ retrieval for morphological evaluation. Survival rates at 14 days were: no XT/no treatment, 0%; XT alone, 29%; XT + CsA, 79%; XT + SRL, 33%; and XT + CsA + SRL, 33%. Liver morphology showed statistically superior liver regeneration for groups on SRL therapy. It is concluded that, in this hepatocyte XT model, SRL offered no survival advantage for ALF management so CsA still maintains a central role in attempts to develop alternative solutions for ALF.

The role of matrix metalloproteinases in the pathogenesis of abdominal wall hernias.

Surgical treatment of abdominal wall hernia has been based for many decades on observational evidence, as the disease physiopathology was ambiguous. The long-standing hypothesis of abnormal collagen metabolism as a causative factor of hernia disease seems to become substantiated by modern investigations, demonstrating a link between abnormal matrix metalloproteinase (MMP) expression and abdominal wall hernia. Current evidence suggests a strong correlation between MMP-2 and direct inguinal hernia, while the role of this MMP in indirect, incisional and recurrent hernias has not been completely elucidated yet. Furthermore, MMP-1 and MMP-13 seem to be implicated in the physiopathology of recurrent hernia, while limited data link MMP-1 also with incisional hernia formation. Despite the importance of MMP-9 in wound healing mechanisms, its role in hernia pathogenesis has not been adequately investigated. Future research is expected to decipher the complex physiopathological mechanisms of hernia development and provide a basis for potential therapeutic applications.

Intraoperative estimation of sentinel lymph nodes in breast cancer by imprint cytology.

BACKGROUND: Frozen section biopsy has been widely used for intraoperative diagnosis and evaluation of sentinel lymph nodes, so a decision can be made regarding whether to perform axillary clearance during primary surgery. This study aims to discuss the reliability of a simpler and faster method - touch imprint cytology - in the interpretation of metastasis from breast cancer. METHODS: A retrospective review of 41 sentinel lymph node biopsies from patients with breast cancer were examined by intraoperative imprint cytology using rapid Diff-Quick staining. Paraffin-embedded permanent sections were examined using hematoxylin and eosin stained sections from the sentinel lymph nodes in collaboration with the employment of an anti-cytokeratin antibody. RESULTS: Sixteen of all sentinel nodes harbored metastases in the paraffin sections, of which all 16 were identified by imprint cytology (sensitivity 93%). CONCLUSION: Touch imprint cytology is a fast and reliable alternative for intraoperative evaluation of sentinel lymph nodes in breast cancer patients.

Expression of autophagy-related proteins Beclin-1 and LC3A and proliferation marker Ki-67 in calculous and acalculous human gallbladder epithelium.

BACKGROUND: Autophagy is an inducible intracellular process that has been studied mostly in cancer and less in inflammatory diseases. To establish the relation between cholecystitis (calculous and acalculous) and autophagy, we studied the expressions of immunohistochemical markers Beclin-1, LC3A, and Ki-67 in gallbladder epithelium and their significance in the induction of autophagy. METHODS: Adult human gallbladder tissues were obtained from 100 patients (45 male, 55 female) who underwent cholecystectomy. According to the findings, the patients were divided into two groups: group A (calculous gallbladder: 24 male, 46 female; mean age 52.6 ± 16.0 years) and group B (acalculous gallbladder: 21 male, nine female; mean age 65.3 ± 12.4 years). The expressions of immunohistochemical markers Beclin-1, LC3A, and Ki-67 in gallbladder epithelium were studied using immunohistochemistry techniques. RESULTS: Beclin-1 expression was correlated with LC3A expression in group A with increased Beclin-1 expression promoting LC3A expression (p =0.0001). In group B, the LC3A expression did not follow Beclin-1 expression (p =0.09). The mean percentage of Beclin-1 expression in group A patients was 23.8 % compared to group B patients, where the corresponding percentage was only 17.3 %. Corresponding mean percent expressions of LC3A in groups A and B were 38.9 % and 50.7 %, respectively. The expression of Ki-67 was higher in group A patients compared to group B patients. The mean percentage of Ki-67 expression in group A patients was 3.75 %, whereas, in group B patients, it was only 0.5 % (statistically significantly different; p =0.0003). CONCLUSION: In the epithelium of calculous cholecystitis, overexpression of LC3A is related to Beclin-1 overexpression, which reinforces the view that Beclin-1 promotes autophagy in stone cholecystitis. HIPPOKRATIA 2019, 23(2): 64-69.

Recombinant leptin administration improves early angiogenesis in full-thickness skin flaps: an experimental study.

BACKGROUND: Leptin is a potent direct angiogenic factor that stimulates endothelial cell migration and activation in vitro, and angiogenesis in vivo. In addition, leptin seems to play an important role in angiogenesis as it promotes the formation of new blood vessels. OBJECTIVE: To determine the effect of local application of exogenous leptin on the survival of full thickness skin flaps in an experimental animal model. MATERIALS AND METHODS: Ninety Sprague-Dawley rats were used in this study. A full thickness dorsal flap (10 cm x 2 cm) with the pedicle located at the level of the iliac crest was designed. Animals were divided into ten groups of nine animals each. In the distal two thirds of the flap and by means of subdermal injection at 8 different locations, rats were injected with 100 ng/ml leptin, 250 ng/ml leptin, 500 ng/ml leptin, 1000 ng/ml leptin (groups A, B, C and D), 1 microg/ml VEGF (group E), or 1 ml saline (control group), respectively. For each of the four leptin doses used, another animal group was injected with a combination of leptin/antileptin: 100 ng/ml leptin with 150 ng/ml antileptin, 250 ng/ml leptin with 375 ng/ml antileptin, 500 ng/ml leptin with 750 ng/ml antileptin or 1000 ng/ml leptin with 1500 ng/ml antileptin (groups A1, B1, C1 and D1, respectively), in order to study the inhibition of the leptin factor. Nine rats served as controls and were injected with 1 ml saline solution. Rats were sacrificed 3, 7 and 9 days postoperatively. After sacrifice of the animals, the skin was grossly arranged on its appearance, colour and texture. Full thickness skin flaps were dissected for histological examination. A qualitative analysis of angiogenesis in the flap was conducted following a standard hematoxylin and eosin stain. The wound tissue samples from each experimental group underwent immunohistochemical evaluation of microvessel density by endothelial cell staining with mouse anti-rat CD 34 monoclonal antibody. RESULTS: Immunohistochemical staining revealed that more granulation tissue and improved angiogenesis were observed in group D (1000 ng/ml leptin) flaps compared to those in the VEGF, leptin/antileptin and saline groups. In addition, skin flap survival rate in group D (1000 ng/ml leptin) and group E (1 microg/ml VEGF) were significantly better than those of the other groups. The most impressive formation of new blood vessels was noted in the groups with the higher leptin doses. Surgical wounds in the control, as well as in the leptin/antileptin groups, did not demonstrate any new vessels. CONCLUSION: Exogenous administration of recombinant leptin increases early skin flap angiogenesis in an experimental animal model. Local application of leptin could efficiently improve survival of ischemic skin flaps.

Port-site metastasis of extrahepatic bile duct carcinoma after laparoscopic cholecystectomy without evidence of a primary tumour.

A 75-year-old man suffering from symptomatic cholelithiasis underwent laparoscopic cholecystectomy using the four-port technique. No malignancy was observed in the resected gall-bladder and the patient exhibited a good postoperative course. Eleven months postoperatively he presented with two subcutaneous tumours: one at the port-site on the right anterior axillary line (at the position of the vacuum drain) and the other at the subumbilical port-site. The patient underwent an incisional biopsy, which revealed metastatic adenocarcinomas of the primary extrahepatic duct, with no evidence of a primary tumour or other distant metastasis. The patient underwent wide excision of the subcutaneous tumours. Six months later he again presented with subcutaneous tumours at the same positions. Magnetic resonance imaging of the abdomen revealed only the subcutaneous tumours. The patient again underwent wide excision of the subcutaneous tumours, followed by radiotherapy. At a 21-month follow-up the patient was symptom-free. Magnetic resonance imaging of the abdomen and magnetic resonance cholangiopancreatography results were normal, and there was no evidence of other metastasis. Four months later the patient died from metastatic disease of the abdomen.

Double gall-bladder--two pathologies: a case report.

True gall-bladder duplication is a rare biliary anomaly, which is usually discovered as an incidental finding. There are reports of double gall-bladders missed during the first operation. We present the case of a double gall-bladder which, albeit suspected during the operation, was confirmed post-operatively. The patient underwent successful laparoscopic cholecystectomy and the examination of the resected gall-bladder revealed two chambers, only one containing stones. Predisposing factors for the development of gall-stones in one gall-bladder only, as well as surgical options, are briefly discussed.

Carcinoid tumor of the appendix during pregnancy. A rare case and a review of the literature.

We present a rare case of a carcinoid tumor of the appendix that was diagnosed during pregnancy in a 24-year-old female. The patient was admitted to our department for acute abdominal pain localized on the right half of the abdomen, mimicking acute appendicitis. Open appendectomy was carried out and at the histological examination carcinoid was found in the surgical specimen. Only few similar cases were found in the literature reporting appendiceal carcinoid tumor during pregnancy.

Hydroxyapatite Crystal Thickness and Buckling Phenomenon in Bone Nanostructure During Mechanical Tests.

An investigation of bone samples taken from the left ulna of New Zealand white rabbits, with and without stresses and hysteresis loop, was undertaken using Small Angle X-ray Scattering technique. The purpose of this study is to investigate the nanostructural changes in the mean size of hydroxyapatite crystals thickness (T) during different mechanical conditions. The experiments were performed using bone samples aged 2 and 4 weeks, with and without strontium ranelate treatment, after compressive load and hysteresis loop. We did not observe any clear effects of strontium ranelate on the bones since the MANOVA test for epiphysis and diaphysis were found. On the other hand, a significant difference appears in epiphysis between 2 and 4 weeks. Furthermore, a reduction in the mean size of hydroxyapatite crystal thickness was observed when the loading pressure force increased, due to the buckling phenomenon. A return of memory points in the elastic region of the bone was observed. The significance of these results lays on the development of nanoproducts, with properties that are closer to the actual bone structure.

Hyperthermia induces therapeutic effectiveness and potentiates adjuvant therapy with non-targeted and targeted drugs in an in vitro model of human malignant melanoma.

In the present study, we have aimed to characterize the intrinsic, extrinsic and ER-mediated apoptotic induction by hyperthermia in an in vitro model of human malignant melanoma and furthermore, to evaluate its therapeutic effectiveness in an adjuvant therapeutic setting characterized by combinational treatments with non-targeted (Dacarbazine & Temozolomide) and targeted (Dabrafenib & Vemurafenib) drugs. Overall, our data showed that both low (43 °C) and high (45 °C) hyperthermic exposures were capable of inducing cell death by activating all apoptotic pathways but in a rather distinct manner. More specifically, low hyperthermia induced extrinsic and intrinsic apoptotic pathways both of which activated caspase 6 only as opposed to high hyperthermia which was mediated by the combined effects of caspases 3, 7 and 6. Furthermore, significant involvement of the ER was evident (under both hyperthermic conditions) suggesting its role in regulating apoptosis via activation of CHOP. Our data revealed that while low hyperthermia activated IRE-1 and ATF6 only, high hyperthermia induced activation of PERK as well suggesting that ultimately these ER stress sensors can lead to the induction of CHOP via different pathways of transmitted signals. Finally, combinational treatment protocols revealed an effect of hyperthermia in potentiating the therapeutic effectiveness of non-targeted as well as targeted drugs utilized in the clinical setting. Overall, our findings support evidence into hyperthermia's therapeutic potential in treating human malignant melanoma by elucidating the underlying mechanisms of its complex apoptotic induction.

Exogenously-administered leptin increases early incisional wound angiogenesis in an experimental animal model.

BACKGROUND: Leptin is a potent direct angiogenic factor that stimulates endothelial cell migration and activation in vitro, as well as angiogenesis in vivo. In addition, leptin seems to play an important role in clinical angiogenesis by promoting the development of new blood vessels. OBJECTIVE: To determine the effect of exogenously administered leptin on incisional wound healing in an experimental animal model. MATERIALS AND METHODS: Sixty-three Sprague-Dawley male mice were used for the study. Full thickness incisional wound was considered as the wound model. The mice were divided into seven groups of nine animals each. Surgical wounds were injected with murine recombinant leptin. Three different leptin doses of 100 pg/ml, 200 pg/ml and 500 pg/ml were used in different animal groups (A, B and C). For each of the three leptin doses used, another animal group was evaluated with a combined injection of leptin and antileptin: 100 pg/ml leptin with 50 pg antileptin, 200 pg/ml leptin with 100 pg antileptin, 500 pg/ml leptin with 250 pg antileptin (A1, B1, and C1), in order to study the inhibitory effect on the leptin factor. Nine mice served as controls. These were injected with 0.3 ml water for injection solution. Mice were sacrificed 3, 7 and 9 days postoperatively. After sacrifice of the animals, the skin was grossly assessed for appearance, colour and texture. Full thickness incisional wounds were dissected for histological examination. A qualitative analysis of angiogenesis in the surgical wound was conducted following a standard hematoxylin and eosin stain. The wound tissue samples from each experimental group underwent immunohistochemical evaluation of microvessel density by endothelial cell staining with mouse anti-rat CD34 monoclonal antibody. RESULTS: The most impressive growth of new blood vessels appeared seven and nine days after treatment with the highest leptin doses. There were no significant differences in microvessel density at seven or nine postoperative days among different groups treated with leptin. None of the wounds from the control group, or those from animal groups treated with the combined injection of leptin and antileptin developed any new vessels. CONCLUSION: Exogenous administration of leptin may increase early tissue angiogenesis in the incisional wound of an experimental animal model.

Subcutaneous metastasis from a gastrointestinal stromal tumor of the stomach: a case report.

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms of the stomach, which account for approximately 3.6% of all gastric tumors. They may or may not be malignant. Malignant GIST rarely metastasizes to distant organs. We report a case of a gastric GIST diagnosed in a 69- year-old woman presented with a synchronous subcutaneous paraumbilical metastasis. Computed tomography (CT) scan demonstrated a space-occupying lesion arising from the gastric wall with a second well-circumscribed lesion in the subcutaneous tissue which infiltrated the aponeurosis of the right rectus abdominis. The patient underwent total gastrectomy and resection of the subcutaneous mass. Pathologic examination of the gastric tumor and subcutaneous mass showed histological and immunohistochemical characteristics of a GIST. The patient succumbed on the 4th postoperative day. Gastric stromal tumor metastasis must be taken into consideration in the differential diagnosis of a palpable paraumbilical mass in a patient diagnosed with malignant GIST.

Potentially probiotic Lactobacillus strains with anti-proliferative activity induce cytokine/chemokine production and neutrophil recruitment in mice.

Lactobacillus pentosus B281 and Lactobacillus plantarum B282 are two Lactobacillus strains previously isolated from fermented table olives. Both strains were found to possess probiotic properties and displayed desirable technological characteristics for application as starters in novel functional food production. In the present study the anti-proliferative and immunostimulatory activities of the two strains were investigated. Firstly, we demonstrated that live L. pentosus B281 and L. plantarum B282 significantly inhibited the growth of human colon cancer cells (Caco-2) in a time- and dose-dependent manner. By employing the air pouch system in mice, we showed that administration of both strains led to a rapid and statistically significant infiltration of leukocytes in the air pouch exudates. The phenotypical characterisation of the recruited immune cells was performed by flow cytometry analysis. We demonstrated that the majority of the infiltrated leukocytes were neutrophils. Finally by using the Mouse Cytokine Array Panel A Detection Antibody cocktail, we showed that both strains induced the expression of granulocyte-colony stimulating factor, interleukin (IL)-1α, IL-1ß, IL-6, chemokine (C-X-C motif) ligand (CXCL)-1, chemokine (C-C motif) ligand (CCL)-3, CCL-4, and CXCL-2 and diminished the expression levels of soluble intercellular adhesion molecule, macrophage colony-stimulating factor and metallopeptidase inhibitor 1. Our results showed that both strains display anti-proliferative and immunostimulatory properties equal or even better in some cases than those of established and commonly used probiotic strains. These findings further support the probiotic character of the two strains.