In-vitro model for bacterial growth inhibition of compartmentalized infection treated by an ultra-high concentration of antibiotics.

BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli), and Staphylococcus aureus (S. aureus) are common pathogens encountered in infected cardiovascular-implantable electronic device (CIED). Continuous, in-situ targeted, ultra-high concentration antibiotic (CITA) treatment is a novel antibiotic treatment approach for localized infections. CITA provides sufficient local antibiotic concentrations to heavily infected cavities while avoiding systemic toxicity. AIM: In-vitro confirmation of the efficacy of the CITA treatment approach in simulated compartmentalized infections. MATERIALS AND METHODS: A rapid automated bacterial culture analyzing system) Uro4 HB&L™ (was applied to compare the efficacy of selected antibiotics at a standard minimal inhibitory concentration (1MIC), 4MIC, and CITA at 103MIC, for growth inhibition of high bacterial loads (106 colony-forming-units/ml) of ATCC strains of P. aeruginosa, E. coli, and S. aureus. RESULTS: The addition of gentamicin and amikacin at 1MIC concentrations only temporarily inhibited the exponential growth of E. coli and P. aeruginosa. 4MIC level extended the delay of exponential bacterial growth. Increasing concentrations of vancomycin similarly temporarily delayed S. aureus growth. All tested antibiotics at CITA of 103MIC totally inhibited the exponential growth of the tested bacteria through 72 hours of exposure. (P<0.001). CONCLUSION: In this in-vitro model, CITA at 103MIC effectively inhibited exponential bacterial growth of high loads of P. aeruginosa, E. coli, and S. aureus. This model offers preliminary laboratory support for the benefit of the in-situ antibiotic treatment, providing ultra-high concentrations directly at the compartmentalized infection site, not achievable by the conventional intravenous and oral routes.

Human Oral Mucosal Stem Cells Reduce Anastomotic Leak in an Animal Model of Colonic Surgery.

BACKGROUND: Anastomotic leak is regarded as one of the most feared complications of bowel surgery; avoiding leaks is a major priority. Attempts to reduce or eliminate leaks have included alternate anastomotic techniques. Human oral mucosa stem cells (hOMSC) are self-renewing and expandable cells derived from buccal mucosa. Studies have shown that hOMSC can accelerate tissue regeneration and wound healing. The objective of this study was to evaluate whether hOMSC can decrease anastomotic leak rates in a murine model of colon surgery. METHODS: Two experiments were performed. In the first study, mice underwent colonic anastomosis using five interrupted sutures. hOMSC (n = 7) or normal saline (NS; n = 17) was injected into the colon wall at the site of the anastomosis. To evaluate whether hOMSC can impact anastomotic healing, the model was stressed by repeating the first experiment, reducing the number of sutures used for the construction of the anastomosis from five to four. Either hOMSC (n = 8) or NS (n = 20) was injected at the anastomosis. All mice that survived were sacrificed on postoperative day 7. Anastomotic leak rate, mortality, daily weight, and daily wellness scores were compared. RESULTS: In the five-suture anastomosis, there were no differences in anastomotic leak rate, mortality, or daily weight. Mice that received hOMSC had significantly higher wellness scores on postoperative day 2 (p < 0.05). In the four-suture anastomosis, there was a significant decrease in leak rate (70% [NS] vs. 25% [hOMSC], p = 0.029) and higher wellness scores in mice that received hOMSC (p < 0.05). CONCLUSION: Our study suggests that injecting hOMSC at the colonic anastomosis can potentially reduce anastomotic leak and improve postoperative wellness in a murine model of colon surgery.

A T Drain Approach to Anastomotic Leaks: Another Important Tool in the General Surgeon's Armamentarium.

BACKGROUND: Following an intestinal anastomotic leak, stoma creation may be the safest approach. However, this method may be challenging and cause significant morbidity. In selected cases, a T drain approach can be beneficial and a stoma can be avoided. OBJECTIVES: To present one group's experience with a T drain approach for anastomotic leaks. METHODS: Data on patients who underwent emergent re-laparotomy following gastrointestinal anastomotic leaks were retrieved retrospectively and assessed with a new intra-operative leak severity score. RESULTS: Of 1684 gastrointestinal surgeries performed from 2014 to 2018, 41 (2.4%) cases of anastomotic leaks were taken for re-laparotomy. Cases included different sites and etiologies. Twelve patients were treated with a T-tube drain inserted through the leak site, 18 had a stoma taken out, 6 re-anastomosis, 4 were treated with an Endosponge, and one primary repair with a proximal ileostomy was conducted. T drain approach was successful in 11 of 12 patients (92%) with full recovery. One patient did not improve and underwent reoperation with resection and re-anastomosis. A severity score of anastomotic integrity is provided to help surgeons in decision making. CONCLUSIONS: A T drain approach can be an optimal solution in selected cases following an intestinal anastomotic leak. When the leak is limited, the remaining anastomosis is intact and the abdominal environment allows it, a T drain can be used and a stoma can be avoided.

Inhibition of TNFα in peritoneal fluids of patients following colorectal resection attenuates the postoperative stress-related increase in colon cancer cell migration: A prospective, in vitro study.

BACKGROUND AND OBJECTIVES: Surgical trauma in patients undergoing colorectal cancer resection generates local and systemic inflammatory responses that can affect oncological outcomes. Post-operative peritoneal fluids of patients undergoing colorectal surgery increase the pro-malignant effect of cancer cells in vitro with correlation to elevated TNFα in these fluids. This study evaluated whether inhibiting TNFα in patients' postoperative fluid biopsies would attenuate this effect. METHODS: Peritoneal fluids from 53 patients undergoing colorectal surgery were sampled before and daily after surgery via intra-abdominal drains. Fluid biopsies were evaluated for their impact on the migration capacity of colon cancer cells and for cytokine levels. TNFα was inhibited using infliximab and cell migration was reevaluated. RESULTS: Colon cancer migration capacity was increased in postoperative fluid biopsies from all patients (P < 0.005) and was elevated compared to pre-resection levels. Infliximab attenuated this effect in >90%, decreasing migration capacity by 30% (p < 0.001). CONCLUSIONS: Inhibition of TNFα in postoperative peritoneal fluids attenuates the increase in cancer cell migration capacity generated following colorectal resection. These findings correlate with other studies suggesting that attenuation of the post-operative inflammatory response may have oncological benefit. Clinical studies are needed to evaluate the effect of peri-operative TNFα inhibition in clinical settings.

A surgical solution to regain bowel continuity following an extended left colectomy-reviving and extending the indication for a "Flip-Flop" procedure.

BACKGROUND AND AIMS: Extended left hemicolectomy might be necessary for several indications. Once the resection is completed, it would be difficult or impossible to anastomose the transverse colon to the rectum due to the difficulty in mobilizing the transverse colon to reach for a tension-free rectal anastomosis. The aim of this report is to present the "Flip-Flop" technique to overcome this challenging situation. The procedure is based on a surgical technique published in the early 1960s to avoid permanent stoma after proctectomy and consists of changing the location of the right colon to reach the rectum. METHODS: Clinical parameters, surgical aspects, and postoperative outcome of patients that underwent the flip-flop procedure following an extended left colectomy in our medical service was reviewed. RESULTS: Three patients underwent a flip-flop procedure after an extended left colectomy performed for various reasons. The surgical technique is detailed in a step by step manner. Patients had uneventful postoperative recovery with an adequate functional outcome. CONCLUSIONS: We believe that this approach should be revived and be considered also in cases when the full length of the rectum is preserved to avoid ileo-rectal anastomosis or a high-tension colocolonic anastomosis. Popularization of this surgical solution among surgeons is highly important.

Postcolectomy Peritoneal Environment Increases Colon Cancer Cell Migration Capacity.

Background. Clinical data and animal models support an association between postoperative inflammatory response and the risk of colorectal cancer recurrence. Our aim was to evaluate postoperative peritoneal inflammation and its impact on cultured colon cancer cells' migration capacity. Methods. 23 patients undergoing elective colorectal resection with uneventful recovery were prospectively enrolled. Patients were operated on for both malignant and benign etiologies. Peritoneal fluids collected at surgery initiation and after surgery were evaluated for their effect on migration potential of human colon cancer cells using an in vitro scratch assay and on TNF-α, IL-1ß, IL-6, and IL-10 levels using bead-based fluorokine-linked multianalyte profiling. Results. Postoperative peritoneal fluid from all patients increased the migration capacity of colon cancer cells compared to preoperative levels. This effect was significant during the first two postoperative days and decreased thereafter. The increase in colon cancer cell migration capacity correlated with increased levels of peritoneal TNF-α and IL-10. Conclusion. In this pilot study, we have demonstrated that the intraperitoneal environment following colorectal resection significantly enhances colon cancer cells migration capacity. This effect is associated with postoperative intra-abdominal cytokines level. A larger scale study in colorectal cancer patients is needed in order to correlate these findings with perioperative parameters and clinical outcome.

[LAPAROSCOPIC APPROACH AND SURGICAL CONSIDERATIONS IN RESECTION OF A LARGE EPIPHRENIC ESOPHAGEAL DIVERTICULUM].

Epiphrenic diverticulum of the esophagus is an uncommon finding. Small diverticula are usually asymptomatic in nature. Large diverticula may present with dysphagia, chest or upper abdominal discomfort, vomiting, irritating cough or halitosis. There are a few different surgical approaches to epiphrenic diverticulum resection. It can be performed with an abdominal or a thoracic approach and in an open or a laparoscopic manner. In this case report we present a 70 years old male patient with a giant epiphrenic diverticulum and dysphagia. The patient was operated upon via a laparoscopic abdominal approach with intra-operative endoscopic assistance and underwent a diverticulum resection. We present a review of the different kinds of esophageal diverticula, the mechanism of their formation, and the surgical considerations associated with choosing the appropriate surgical approach.

Evaluation of peritoneal CEA levels following colorectal cancer surgery.

BACKGROUND: Peritoneal carcinoembryonic antigen (pCEA) levels in the early postoperative period following a curative resection of colorectal cancer (CRC) have not been previously studied. METHODS: Postoperative peritoneal fluids of 36 CRC patients followed by 24 benign colonic disease patients were evaluated for CEA levels and tumor cell presence. Serum CEA levels were also evaluated prior and after surgery. RESULTS: Although high postoperative pCEA levels were observed in some benign patients, more CRC patients exhibited significant elevation of postoperative pCEA (>5 ng/ml) compared to benign patients (50% vs. 23%, P = 0.039). Postoperative median pCEA levels of CRC patients were significantly higher compared to benign patients (5.4 vs. 2 ng/ml, P = 0.011). Specifically, pCEA levels in CRC patients were significantly elevated when measured during the first 24 hr after surgery. Postoperative pCEA levels were associated with colon tumor location compared to rectal location. However, no correlation was found with known risk factors for cancer recurrence or with serum CEA levels. CONCLUSIONS: Postoperative pCEA levels may be significantly elevated following a curative resection for CRC. Its significance within patient's prognostic evaluation remains to be studied. Inclusion of patient's follow-up data may reveal the significance of elevated pCEA levels following CRC resection.

[Laparoscopic management of peritoneal dialysis catheters].

INTRODUCTION: Peritoneal dialysis (PD) is one of the established methods for the management of patients with end-stage renal failure. Laparoscopy has been used to assist in the insertion of new catheters as well as for the salvage of malfunctioning peritoneal dialysis catheters (PDC). OBJECTIVES: The purpose of this retrospective study was to review our experience in the utilization of laparoscopy for the management of PDC. METHODS: We reviewed the charts of all consecutive patients who had undergone either a ap-assisted insertion of a PDC utilizing a modified peritoneoscopic Y-TEC [Medigroup, Inc, Oswego, Ill) technique (YT) under direct laparoscopic vision or laparoscopic-assisted procedures for the salvage of a malfunctioning PD catheter. RESULTS: Twenty nine patients had undergone 43 procedures that included the insertion of a new PD catheter using the modified YT technique, YT with simultaneous adhesiolysis and omentectomy; YT with repair of an epigastric hernia, omentectomy, adhesiolysis and repositioning of PDC; and ravage and repositioning of the obstructed PD catheter in all patients who needed repositioning of the catheter, the PDC was fixed with an intraperitoneal suture to the lower anterior abdominal wall. Postoperatively, malfunction of the catheter was found in one patient due to reclotting of PDC caused by oozing as a result of extensive adhesiolysis. One patient needed emergent laparotomy due to small bowel perforation that was missed during a difficult laparoscopic adhesiolysis. CONCLUSIONS: Laparoscopic surgery may be helpfuL for the diagnosis and the management of a malfunctioning PDC. A modified YT technique is safe and may be one of the alternative methods for the placement of a PDC.

Chemopreventive effects of Coltect, a novel dietary supplement, alone and in combination with 5-aminosalicylic acid in 1,2-dimethylhydrazine-induced colon cancer in rats.

OBJECTIVES: Coltect is a novel dietary supplement containing curcumin, green tea and selenomethionine. Previous reports have suggested that these agents can prevent colorectal cancer (CRC). The present study examined the chemopreventive effect of Coltect alone or combined with 5-aminosalicylic acid (5-ASA) using the 1,2-dimethylhydrazine (DMH) model in rats. METHODS: The effect of Coltect was examined on HT-29 CRC cells by growth inhibition assay. Apoptosis was determined by annexin V-FITC/PI staining. Male rats were injected with DMH in vivo and treated with Coltect 150 mg/kg, 5-ASA 50 mg/kg or their combination, by oral gavage. Aberrant crypt foci (ACF) were identified by methylene blue staining. RESULTS: HT-29 cells exhibited a dose-dependent response to Coltect. Part of the growth inhibition can be explained by the induction of mild-moderate apoptosis in cancer cells (28%) compared with the untreated cells (10%). In the in vivo model, the average number of ACF was divided into small (1-3 crypts) or large (≥4 crypts). The Coltect compound reduced the number of small and large ACF similarly to 5-ASA (40% reduction). This reduction was amplified by combining the two agents (70% reduction). CONCLUSION: Coltect inhibits the growth of colon cancer cells, induces apoptosis and inhibits ACF development. Furthermore, it augments the growth inhibitory effect of 5-ASA in vivo. This may be clinically important since this safe dietary supplement-drug combination can be administered as a chemopreventive regimen for the treatment of CRC.

Curcumin potentiates the pro-apoptotic effects of sulindac sulfone in colorectal cancer.

OBJECTIVE: The use of sulindac sulfone (SFN) for colorectal cancer (CRC) therapy is limited due to its toxicity. The present study was carried out to examine whether curcumin, a novel chemopreventive agent, can potentiate the effects of low dosages of SFN in CRC treatment. METHODS: HT-29 CRC cells were exposed to SFN (200 - 400 microM), curcumin (5 - 10 microM) or their combination. The cytotoxic effects of the drugs were evaluated using growth inhibition assays. Annexin V/PI and cell cycle analysis were employed to study the mechanism of action of the drugs. The therapeutic efficacy of the drugs in vivo was examined using the aberrant crypt foci (ACF) model. The treatment groups included eight rats/group. RESULTS: Treatment of cells with curcumin and SFN resulted in a synergistic inhibitory effect of 50 - 90% (p < 0.005) on cell growth. Growth inhibition was associated with inhibition of proliferation, G2/M arrest and induction of apoptosis. Administration of curcumin (0.6%) and SFN (0.06%) to 1, 2-dimethylhydrazine treated rats significantly reduced (by 75%, p < 0.01) the number of ACF. CONCLUSIONS: Curcumin augments the therapeutic effects of SFN. This may be clinically important since the addition of curcumin to low dosages of SFN may encourage a safer and potent combinatorial treatment regimen for CRC.

Laparoscopic colectomy for colonic polyps.

BACKGROUND: Benign colonic polyps not amenable to colonoscopic resection or those containing carcinoma require surgical excision. Traditionally, formal colectomy with clearance of the lymphatic basin has been performed. The aim of this study was to review our experience with the laparoscopic approach for retrieval of colonic polyps with specific emphasis on safety, feasibility, and tumor localization. METHODS: Retrospective chart review of all patients who underwent laparoscopic colectomy for colonic polyps was performed. Initial colonoscopic biopsies were compared with the postoperative pathology report of the resected specimen. RESULTS: Forty-nine patients (22 males, 27 males, mean age 66 years) underwent laparoscopic colectomy for colonic polyps. Indications for surgery were presumably benign polyps in 38 patients, and superficial carcinoma in a polyp, diagnosed by colonoscopy, in 11; twenty-three patients underwent preoperative localization procedures. In 19% of patients who did not have preoperative localization, difficulties locating the polyp were encountered during surgery, requiring intraoperative endoscopy or conversion to laparotomy. In 7 of the 38 patients with presumably benign lesion, colon cancer was diagnosed in the colectomy specimen. None of the 18 patients who had cancerous lesions had any positive lymph nodes. CONCLUSIONS: Laparoscopic surgery for the treatment of colonic polyps seems to be feasible and safe, with a low complication rate. Tumor localization is crucial for adequate resection. Although one-fifth of presumably benign polyps harbored cancer, none of these patients had positive lymph nodes. These preliminary results may question the need for radical lymph node clearance in these patients.

Specimen length as a perioperative surrogate marker for adequate lymphadenectomy in colon cancer: the surgeon's role.

The objective of this study was to determine whether there is a correlation between the length of the sigmoid colon removed and the number of harvested lymph nodes (LNs). Pathology charts of 137 sigmoid resections that were done over a 5-year period were reviewed. The length of removed sigmoid specimen reported in the pathology reports was correlated with the number of LNs retrieved from the specimen. The mean and median numbers of retrieved LNs were 9 and 10, respectively. There was an increase in the number of retrieved LNs with increasing length of resected sigmoid colon. For Dukes' B patients, the average length of the resected specimen was 15.1 cm for those with < 12 LNs and 20.3 cm for those with > 12 LNs (P = 0.01). Our data suggest that the surgeon may play an important role in determining the extent of LN harvesting during large bowel resection for cancer.

Predominance of younger age, advanced stage, poorly-differentiated and mucinous histology in Israeli Arab patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) incidence in the Israeli population is higher in the Jewish population than among Arabs. MATERIALS AND METHODS: To determine the differences in demographic, clinical, histopathological and molecular characteristics of CRC between these two ethnic groups, 125 Arab patients treated at 3 community hospitals over a 20-year period were compared to a group of 208 consecutive Jewish patients. The mutator (replication error-positive [RER]) phenotype was detected by immunohistochemical evaluation of hMLH1 and hMSH2 protein expression in tumor tissue. RESULTS: The Arab patients were younger than the Jewish patients with a higher percentage of poorly-differentiated and mucinous cancers and a higher percentage of advanced stage cancers (Dukes' C+D) at presentation. The mutator phenotype was detected at similar rates in both ethnic groups. CONCLUSION: Our study demonstrated that CRC patients from two major ethnic populations in Israel, Arabs and Jews, differed in terms of the prevalence of the disease, pathological features and age at presentation, but not in frequency of mismatch-repair-positive cancers.

Celecoxib and curcumin additively inhibit the growth of colorectal cancer in a rat model.

BACKGROUND: Multiple studies have indicated that specific COX-2 inhibitors may prevent CRC. However, the long-term use of COX-2 inhibitors is not toxicity-free and may be limited due to its cardiovascular side effects. The present study was carried out to examine the chemopreventive effects of celecoxib and curcumin alone and in combination using the 1,2-dimethylhydrazine (DMH) rat model. METHODS: Male rats were injected with DMH and randomly divided into four groups that consumed one of the following diets: (a) AIN-076 control diet; (b) AIN-076/curcumin (0.6%); (c) AIN-076/celecoxib (0.16%), or (d) AIN-076/celecoxib (0.16%) and curcumin (0.6%). Aberrant crypt foci (ACF) were identified by intensive staining with methylene blue in comparison to the surrounding normal crypts. RESULTS: The average number of ACF per rat colon was 64.2 +/- 3 in the control group, 39 +/- 5 and 47 +/- 10 for the curcumin- and celecoxib-treated group, respectively, and 24.5 +/- 6 in the group that had received both agents. CONCLUSIONS: In vivo, curcumin augments the growth inhibitory effect of celecoxib. This may be clinically important as this dose of celecoxib can be achieved in human serum following standard anti-inflammatory dosing of 100 mg.

Perioperative management of patients undergoing elective colorectal surgery in Israel: a national survey.

BACKGROUND: The approach to perioperative antibiotic prophylaxis, bowel preparation, and postoperative routines in elective colorectal resections has changed over the last two decades. The aim of this national survey was to document the current methods of perioperative management of those patients scheduled for elective colorectal resections in surgical departments in Israel. METHODS: A mail and telephone survey of surgical departments was conducted in 2001 in order to evaluate the routines of perioperative management of elective colorectal resections. Re-evaluation was performed in 2004. RESULTS: In 2001, all but one of the responders used low-residue diet preoperatively and combined oral and parenteral antibiotic prophylaxis. Polyethylene glycol or sodium phosphate bowel preparation was used by 69% of the responders. The most common oral regimens were a combination of neomycin plus metronidazole (43.5%) or neomycin plus erythromycin (47.8%). The most common parenteral regimens used were gentamicin plus metronidazole or gentamicin plus metronidazole plus ampicillin (56.5% and 17% of the responders, respectively). Cephalosporins alone or in combination were used in three departments. In 17 departments (74%), parenteral prophylactic antibiotics were continued for 24 h or longer (up to 72 h). All but one of the departments left a nasogastric tube for 1-5 days after surgery. There were substantial changes over the last three years-that is, less use of preoperative restriction diets, shorter duration of perioperative antibiotic coverage, more common use of cephalosporins, switch to sodium dihydrogen and sodium hydrogen phosphate bowel preparation, shorter use of postoperative nasogastric drainage, and faster resumption of peroral fluids. CONCLUSIONS: In 2001, the majority of surgical departments in Israel used a conservative approach to perioperative management of patients undergoing elective colorectal resections. Significant changes occurred during the last three years. The perioperative routines used today in most general surgery departments in Israel comply with current recommendations.

Early postoperative evaluation of groins after laparoscopic total extraperitoneal repair of inguinal hernias.

BACKGROUND: Minimally invasive laparoscopic total extraperitoneal (LTEP) repair of bilateral and/or recurrent groin hernias has been popularized as one of the procedures of choice in the past decade. The early postoperative course is uneventful in most cases. A few patients, however, will develop temporary postoperative groin swelling. The aim of our study was to evaluate clinical and sonographic findings in the groin during the early postoperative period following LTEP. METHOD: One hundred and five consecutive patients with primary bilateral (n = 90), recurrent unilateral (n = 12), and primary unilateral (n =3) groin hernias operated on during an 18-month period underwent clinical and sonographic examination two to three weeks after LTEP. RESULTS: On clinical examination, a localized groin swelling was found in 21 patients (20%). The most frequent sonographic findings were localized groin collections compatible with seroma or hematoma, found in 35 patients (33%). Hypoechoic diffuse tissue swelling around the mesh, lipomas, and residual hernias was found in four patients each (4%). None of the patients with hypoecoic mass had any clinical manifestations postoperatively. Extraperitoneal close suction drains were left for 8-12 hours in 46 patients. The average volume of fluid drained was 62 mL (range, 30-200 mL). There was no correlation between the use of suction drains and the frequency of fluid collections detected on sonography. Cord lipoma was detected postoperatively in four patients and was excised in one using an open anterior approach. Residual or recurrent hernia was detected postoperatively on sonography in four patients, but only one developed a symptomatic and clinically detectable hernia during eight months of follow-up. Overall, postoperative ultrasonographic findings following LTEP repair were found in 37% of patients. CONCLUSION: Clinical and sonographic findings such as localized fluid collections compatible with seroma or hematoma are common following LTEP. Postoperative suction drains did not reduce the frequency of sonographically detected collections. The clinical relevance of suspected postoperative hernia detected on sonography without clinical manifestations remains uncertain, and has to be determined on long-term follow-up.