Polyglactin 910 Meshes Coated with Sustained-Release Cannabigerol Varnish Inhibit Staphylococcus aureus Biofilm Formation and Macrophage Cytokine Secretion: An In Vitro Study.

Synthetic surgical meshes are commonly used in abdominal wall reconstruction surgeries to strengthen a weak abdominal wall. Common mesh-related complications include local infection and inflammatory processes. Because cannabigerol (CBG) has both antibacterial and anti-inflammatory properties, we proposed that coating VICRYL (polyglactin 910) mesh with a sustained-release varnish (SRV) containing CBG would prevent these complications. We used an in vitro infection model with Staphylococcus aureus and an in vitro inflammation model of lipopolysaccharide (LPS)-stimulated macrophages. Meshes coated with either SRV-placebo or SRV-CBG were exposed daily to S. aureus in tryptic soy medium (TSB) or macrophage Dulbecco's modified eagle medium (DMEM). Bacterial growth and biofilm formation in the environment and on the meshes were assessed by changes in optical density, bacterial ATP content, metabolic activity, crystal violet staining, spinning disk confocal microscopy (SDCM), and high-resolution scanning electron microscopy (HR-SEM). The anti-inflammatory effect of the culture medium that was exposed daily to the coated meshes was analyzed by measuring the release of the cytokines IL-6 and IL-10 from LPS-stimulated RAW 264.7 macrophages with appropriate ELISA kits. Additionally, a cytotoxicity assay was performed on Vero epithelial cell lines. We observed that compared with SRV-placebo, the segments coated with SRV-CBG inhibited the bacterial growth of S. aureus in the mesh environment for 9 days by 86 ± 4% and prevented biofilm formation and metabolic activity in the surroundings for 9 days, with respective 70 ± 2% and 95 ± 0.2% reductions. The culture medium that was incubated with the SRV-CBG-coated mesh inhibited LPS-induced secretion of IL-6 and IL-10 from the RAW 264.7 macrophages for up to 6 days without affecting macrophage viability. A partial anti-inflammatory effect was also observed with SRV-placebo. The conditioned culture medium was not toxic to Vero epithelial cells, which had an IC50 of 25 µg/mL for CBG. In conclusion, our data indicate a potential role of coating VICRYL mesh with SRV-CBG in preventing infection and inflammation in the initial period after surgery.

The Israeli Surgical Oral Board Examination: Improved Objectivity Increases Knowledge Authenticity.

The oral board examination in general surgery in Israel was recently revised aiming for improved objectivity and standardization. Herein, we describe the current exam model. Between 05/2018 and 11/2020, two exams per year were conducted with the current exam model. The examination consists of 12 stations, each focusing on a different field. Passing score is 80%. At the end of the examination, examiners and candidates complete a questionnaire regarding the examination's process and quality (scale 1-5). A total of 142 residents attended six oral board examinations. Mean pass rate was 76.6 ± 9.5%. Questions with overall highest pass rates were acute-care surgery (86.6 ± 4.8%), foregut surgery (84.6 ± 7.6%), and colorectal surgery (84 ± 8.1%). Questions with the highest fail rates were surgical oncology (31.7 ± 13.3%) and abdominal-wall surgery (28.8 ± 16.9%). Examiners' feedback scored highest the following: standardization of the exam (4.45 ± 0.63) and whether the presented cases reflect the daily work of an attending surgeon (4.35 ± 0.87). Candidates' feedback scored highest the following: did the examiners treat you in an appropriate manner (4.08 ± 1.17). In conclusion, oral exams are challenging and bear limitations, but properly constructed exams allow good evaluation of the trainees' thinking process and decision-making skills, without compromising exam's integrity and standardization.

[PRIMARY GASTRIC PLASMACYTOMA IN A BREAST CANCER MALE PATIENT].

INTRODUCTION: Plasmacytoma is a malignant tumor of the plasma cells. Extra-medullary plasmacytoma is rare and with an even lower incidence appears as a primary tumor of the stomach. Initial onset of the disease in the upper gastrointestinal tract is reported in the literature as just second to primary plasmacytomas of the head and neck system. The presenting symptoms are related to the organ involved and systemic symptoms can be weight loss, pain, bleeding and even fever. As this is a rare disease, there is no standard treatment and patients undergo endoscopic resection or chemotherapy with or without additional radiation. The prognosis of the disease depends on the possible future diagnosis of multiple myeloma which can be up to 50% within only a few years. We hereby report a case of a male patient with a past locally advanced breast cancer who was on prolonged adjuvant hormonal treatment. He developed a new symptom of melena and underwent a thorough evaluation including imaging and repeated biopsies from a large gastric lesion. The results were inconclusive mainly because of the differential diagnosis between breast cancer metastases and a new second primary malignancy. In view of a clinical deterioration and lack of diagnosis, an operation of radical gastrectomy was eventually performed only to surprisingly diagnose a rare hematologic disease of the stomach - gastric plasmacytoma. This diagnosis is rare in itself, especially having his previous male breast cancer and maternal multiple myeloma. The diagnostic procedure in this case had also provided the full treatment for his illness.

Adapting Surgical Clerkship Curricula in Response to the COVID-19 Pandemic.

BACKGROUND: Coronavirus disease-19 (COVID-19) impacted medical education and led to the significant modification or suspension of clinical clerkships and rotations. OBJECTIVES: To describe a revised surgery clerkship curriculum, in which we divided in-person clinical teaching into smaller groups of students and adopted online-based learning to foster student and patient safety while upholding program standards. METHODS: The third-year surgery core clerkship of a 4-year international English-language program at the Medical School for International Health at Ben Gurion University of the Negev, Beer Sheva, Israel, was adapted by dividing students into smaller capsules for in-person learning and incorporating online learning tools. Specifically, students were divided evenly throughout three surgical departments, each of which followed a different clinical schedule. RESULTS: National Board of Medical Examiners clerkship scores of third-year medical students who were returning to in-person clinical clerkships after transitioning from 8 weeks of online-based learning showed no significant difference from the previous 2 years. CONCLUSIONS: To manage with the restrictions caused by COVID-19 pandemic, we designed an alternative approach to a traditional surgical clerkship that minimized the risk of exposure and used online learning tools to navigate scheduling challenges. This curriculum enabled students to complete their clinical rotation objectives and outcomes while maintaining program standards. Furthermore, this approach provided a number of benefits, which medical schools should consider adopting the model into practice even in a post-pandemic setting.

A3 adenosine receptor agonist, CF102, protects against hepatic ischemia/reperfusion injury following partial hepatectomy.

Ischemia/reperfusion (IR) injury during clinical hepatic procedures is characterized by inflammatory conditions and the apoptosis of hepatocytes. Nuclear factor­κB (NF­κB), nitric oxide and the expression levels of inflammatory cytokines, tumor necrosis factor­α and interleukin­1 were observed to increase following IR and mediate the inflammatory response in the liver. CF102 is a highly selective A3 adenosine receptor (A3AR) agonist, and has been identified to induce an anti­inflammatory and protective effect on the liver via the downregulation of the NF­κB signaling pathway. The present study aimed to determine the effect of CF102 on protecting the liver against IR injury. The potential protective effect of CF102 (100 µg/kg) was assessed using an IR injury model on 70% of the liver of Wistar rats, which was induced by clamping the hepatic vasculature for 30 min. The regenerative effect of CF102 was assessed by the partial hepatectomy of 70% of the liver during 10 min of IR. CF102 reduced the levels of liver enzymes following IR injury. A higher regeneration rate in the CF102 treatment group was observed compared with the control group, suggesting that CF102 had a positive effect on the proliferation of hepatocytes following hepatectomy. CF102 had a protective effect on the liver of Wistar rats subsequent to IR injury during hepatectomy. This may be due to an anti­inflammatory and anti­apoptotic effect mediated by the A3AR.

Long-Term Outcome of Laparoscopic Totally Extraperitoneal Repair of Bilateral Inguinal Hernias with a Large Single Mesh.

BACKGROUND: A totally extraperitoneal (TEP) approach is currently the technique of choice for the laparoscopic repair of bilateral inguinal hernias in our institution. Most other surgeons use two meshes for the TEP repair, one for each side. We prefer a large single mesh when possible since it allows for easier correct placement of the mesh in one stage. We compared our long-term results of both techniques in terms of late complications and recurrence rates. METHODS: This study retrospectively evaluated the medical records of 108 patients who underwent bilateral laparoscopic TEP repair in our institution between January 2002 and December 2003. Excluded were patients who had a conversion to a transabdominal preperitoneal or open approach. A total of 73 (67 %) patients fulfilled study entrance criteria and were enrolled: 39 had undergone single mesh repair and 34 had undergone double mesh repair. RESULTS: There were no significant group differences in demographics, operating time, postoperative morbidity, or hospital stay. Likewise, after a median follow-up of 102 months (range 94­115 months), there were no significant group differences between the single and double mesh groups in persistent pain (5.8 vs 2.5 %, respectively; p = 0.476) and recurrence (7.6 vs 8.8 %, respectively; p = 0.55). CONCLUSION: The use of a large single mesh is an effective and safe alternative technique for TEP repair of bilateral inguinal hernias, and is technically easy to perform.

Changes in blood lipid levels following silastic ring vertical gastroplasty.

BACKGROUND: The purpose of this study was to evaluate the effect of the Silastic Ring Vertical Gastroplasty (SRVG) operation on blood lipid levels in obese men and women during the first year following surgery. METHODS: 25 patients (11 men and 14 women) age 17-50 (mean 33 years) who suffered from morbid obesity (BMI >40, range 45.9+/-4.7 kg/m2) underwent SRVG. Blood samples were collected before operation and 3, 6 and 12 months following surgery and tested for: triglycerides, total cholesterol, HDL-C, LDL-C, VLDL-C, and Lp(a). RESULTS: Both men and women lost weight significantly. Mean BMI decreased from 48.0 to 32.5 kg/m2 in men and from 44.3 to 29.0 kg/m2 in women (P<0.01). Blood lipid levels 1 year following surgery demonstrated the following changes: In women, triglycerides, total cholesterol, LDL, VLDL cholesterol and Lp(a) decreased from 160.7 mg/dL to 67.7 mg/dL (P<0.01), from 220 mg/dL to 189 mg/dL, from 138.3 mg/dL to 111 mg/dL, from 17 mg/dL to 12 mg/dL, and from 77.5 mg/dL to 18.5 mg/dL (P<0.01), respectively, and HDL increased from 45 mg/dL to 50.5 mg/dL. In men, triglycerides, total cholesterol, LDL, VLDL cholesterol and Lp(a) decreased from 246 mg/dL to 140 mg/dL (P<0.01), from 206 mg/dL to 170 mg/dL (P<0.01), from 134 mg/dL to 112 mg/dL (P<0.05), from 25 mg/dL to 15 mg/dL (P<0.01), and from 30.3 mg/dL to 11.6 mg/dL (P<0.01), respectively, and HDL increased from 31.3 mg/dL to 37.4 mg/dL (P<0.05). CONCLUSION: SRVG improved blood lipid profile in obese patients during the first year following surgery. Reduction in cholesterol and its fractions reaches statistical significance only in men.

Mid-term results of stapled hemorrhoidopexy for third- and fourth-degree hemorrhoids--correlation with the histological features of the resected tissue.

BACKGROUND: Stapled hemorrhoidopexy is used to remove a circumferential strip of mucosa and submucosa about 4 cm above the dentate line, in order to restore the correct anatomical relationships of the anal canal structures. We evaluated the histological features of the resected tissue obtained after stapled hemorrhoidopexy with correlation to the short-term and mid-term results. METHODS: This retrospective study evaluated 234 cases of stapled hemorrhoidopexy. Data concerning postoperative bleeding, anal pain, incontinence, stenosis, and recurrence of hemorrhoids were collected from hospital and outpatient clinic records. Histologic slides were examined for the type of epithelium, presence of muscle fibers, nerve endings, and degree of vascular ectasia. RESULTS: Some 52% of the biopsies revealed on the surface a combination of glandular with squamous epithelium, meaning a stapling line at the level of the transitional zone/dentate line. Smooth muscle fibers were more frequent as the stapling line approached the level of the dentate line/transitional zone (p = 0.0028). Internal sphincter fibers were present in 36% of the cases, yet there were no cases of anal incontinence. Inclusion of merely squamous epithelium in the resected tissue correlated with severe postoperative pain persisting one week after surgery (p < 0.0001), whereas the concurrent presence of squamous and glandular epithelium correlated only with severe pain on the first postoperative day (p = 0.018). Nerve endings were more frequent in patients with anal pain one week after surgery (p = 0.02). The rate of recurrence of symptoms was 3%, which did not correlate with any of the histological parameters tested. CONCLUSIONS: Though stapled hemorrhoidopexy is performed according to well-established technical guidelines, it is too difficult to be standardized.

Simultaneous repair of bilateral inguinal hernias: a prospective, randomized study of single versus double mesh laparoscopic totally extraperitoneal repair.

The aim of this study was to compare the double and the single mesh techniques, both used in the laparoscopic totally extra peritoneal (TEP) repair of bilateral inguinal hernia. Sixty-five patients with bilateral inguinal hernia were enrolled in a prospective, randomized trial comparing the single and the double mesh techniques. The single and the double mesh techniques compared favorably in terms of operating time, long-term morbidity, hospital stay, time for return to work, postoperative quality of life and recurrence rate. However, the cost of a single, large prosthesis was 38% to 40% lower than that of 2 small ones. The laparoscopic TEP repair of bilateral inguinal hernia with a large, single prosthetic mesh is a technically simple and safe procedure, which offers clear cost savings and a potentially shorter operating time over the double mesh repair. It is strongly recommended for the routine, laparoscopic TEP repair of bilateral inguinal hernias.

The A3 adenosine receptor is highly expressed in tumor versus normal cells: potential target for tumor growth inhibition.

PURPOSE: A(3) adenosine receptor (A(3)AR) activation was shown to inhibit the growth of various tumor cells via the down-regulation of nuclear factor kappaB and cyclin D1. To additionally elucidate whether A(3)AR is a specific target, a survey of its expression in tumor versus adjacent normal cells was conducted. EXPERIMENTAL DESIGN: A(3)AR mRNA expression in various tumor tissues was tested in paraffin-embedded slides using reverse transcription-PCR analysis. A comparison with A(3)AR expression in the relevant adjacent normal tissue or regional lymph node metastasis was performed. In addition, A(3)AR protein expression was studied in fresh tumors and was correlated with that of the adjacent normal tissue. RESULTS: Reverse transcription-PCR analysis of colon and breast carcinoma tissues showed higher A(3)AR expression in the tumor versus adjacent non-neoplastic tissue or normal tissue. Additional analysis revealed that the lymph node metastasis expressed even more A(3)AR mRNA than the primary tumor tissue. Protein analysis of A(3)AR expression in fresh tumors derived from colon (n = 40) or breast (n = 17) revealed that 61% and 78% had higher A(3)AR expression in the tumor versus normal adjacent tissue, respectively. The high A(3)AR expression level in the tumor tissues was associated with elevated nuclear factor kappaB and cyclin D1 levels. High A(3)AR mRNA expression was also demonstrated in other solid tumor types. CONCLUSIONS: Primary and metastatic tumor tissues highly express A(3)AR indicating that high receptor expression is a characteristic of solid tumors. These findings and our previous data suggest A(3)AR as a potential target for tumor growth inhibition.

Development of epidural abscess following surgical drainage of perianal abscess: report of a case.

PURPOSE: A case of epidural abscess originating from a perianal abscess is reported. METHODS: The history of the patient, erythrocyte sedimentation rate, magnetic resonance imaging, and bacteriological tests were used to reach a diagnosis and the possible mechanism. RESULTS: Epidural abscess was suspected because the patient had a fever and intense low back pain following drainage of a perianal abscess. Magnetic resonance imaging was used to correctly diagnose the epidural abscess and bacteriologic studies disclosed the pathophysiologic mechanism. CONCLUSIONS: Epidural abscess is an extremely rare complication of perianal abscess. It should always be suspected in a patient with acute onset of back pain, fever, history of recent infection, and an elevated erythrocyte sedimentation rate, because delay in diagnosis can cause neurologic compromise and even death.

An agonist to the A3 adenosine receptor inhibits colon carcinoma growth in mice via modulation of GSK-3 beta and NF-kappa B.

A(3) adenosine receptor (A(3)AR) activation with the specific agonist CF101 has been shown to inhibit the development of colon carcinoma growth in syngeneic and xenograft murine models. In the present study, we looked into the effect of CF101 on the molecular mechanisms involved in the inhibition of HCT-116 colon carcinoma in mice. In tumor lesions derived from CF101-treated mice, a decrease in the expression level of protein kinase A (PKA) and an increase in glycogen synthase kinase-3 beta (GSK-3 beta) was observed. This gave rise to downregulation of beta-catenin and its transcriptional gene products cyclin D1 and c-Myc. Further mechanistic studies in vitro revealed that these responses were counteracted by the selective A(3)AR antagonist MRS 1523 and by the GSK-3 beta inhibitors lithium and SB216763, confirming that the observed effects were A(3)AR and GSK-3 beta mediated. CF101 downregulated PKB/Akt expression level, resulting in a decrease in the level and DNA-binding capacity of NF-kappa B, both in vivo and in vitro. Furthermore, the PKA and PKB/Akt inhibitors H89 and Worthmannin mimicked the effect of CF101, supporting their involvement in mediating the response to the agonist. This is the first demonstration that A(3)AR activation induces colon carcinoma growth inhibition via the modulation of the key proteins GSK-3 beta and NF-kappa B.

Inguinal hernia: challenging the traditional indication for surgery in asymptomatic patients.

BACKGROUND: It is generally accepted that most inguinal hernias should be operated on electively in order to avoid the high morbidity and mortality associated with incarceration and small bowel obstruction. The present study reassesses the indication for surgery in asymptomatic inguinal hernia patients. METHODS: We analyzed profiles, separately, for elective and emergency inguinal herniorrhaphies and compared the morbidity and mortality rates. RESULTS: Two hundred randomly selected elective hernia repairs were compared with 67 incarcerated cases. Postoperative complications were more common following emergency (23.9%) than elective repair (10.5%); however, in both groups, minor complications predominated. The mortality rate in the incarcerated group (6%) was clearly linked with a high preoperative American Society of Anesthesiologists (ASA) score. A bowel resection rate of 4.5% was found in the incarcerated cases, which was not correlated with mortality. CONCLUSIONS: Patients with asymptomatic inguinal hernia and unfavorable medical conditions should be recommended an elective repair, preferably under local anesthesia, to avoid the high mortality associated with an emergency operation.

Small nonpolypoid colorectal carcinoma.

The objective of this study was to characterize and assess the presence and frequency of small nonpolypoid colorectal adenocarcinomas among patients with colorectal cancer referred for surgery. The medical, endoscopic, and surgical reports and the histopathologic slides of all patients operated on for colorectal cancer were retrospectively reviewed. Small nonpolypoid colorectal cancer (SNPCC) was defined as a malignant, nonpolypoid lesion smaller than 15 mm. SNPCC was classified according to the Japanese macroscopic classification of colorectal carcinoma. The frequency of SNPCC among patients referred for operation was 1.8%. Most of these patients were asymptomatic and were diagnosed by the same endoscopist using a high-resolution video-endoscope without the assistance of enhancement techniques. These lesions had a mean size of 10.8 mm, were mainly of the flat or flat elevated type, and were located in the distal colon. Among patients with colorectal cancer referred for surgery, 1.8% had SNPCC. These lesions can be detected using high-resolution video-endoscopy equipment without the need for enhancement techniques, as reported in Japanese series. Increased awareness of the existence of such SNPCC lesions may help the average endoscopist detect such lesions. As SNPCC represents colorectal cancer, all the cases in our series were treated by typical oncologic surgical resection.