Publications by authors named "Oded Zmora"

78 Publications

Activity Tracking After Surgery: Does It Correlate With Postoperative Complications?

Am Surg 2022 Feb 30;88(2):226-232. Epub 2021 Jan 30.

Department of General Surgery (Surgery B), 26744Chaim Sheba Medical Center, Tel-Aviv University, Tel Hashomer, Israel.

Background: Postoperative ambulation is an important tenet in enhanced recovery programs. We quantitatively assessed the correlation of decreased postoperative ambulation with postoperative complications and delays in gastrointestinal function.

Methods: Patients undergoing major abdominal surgery were fitted with digital ankle pedometers yielding continuous measurements of their ambulation. Primary endpoints were the overall and system-specific complication rates, with secondary endpoints being the time to first passage of flatus and stool, the length of hospital stay, and the rate of readmission.

Results: 100 patients were enrolled. We found a significant, independent inverse correlation between the number of steps on the first and second postoperative days (POD1/2) and the incidence of complications as well as the recovery of GI function and the likelihood of readmission ( < .05). POD2 step count was an independent risk factor for severe complications ( = .026).

Discussion: Digitally quantified ambulation data may be a prognostic biomarker for the likelihood of severe postoperative complications.
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http://dx.doi.org/10.1177/0003134820988818DOI Listing
February 2022

Perioperative COX2 and β-adrenergic blockade improves biomarkers of tumor metastasis, immunity, and inflammation in colorectal cancer: A randomized controlled trial.

Cancer 2020 09 13;126(17):3991-4001. Epub 2020 Jun 13.

Sagol School of Neuroscience and School of Psychological Sciences, Tel-Aviv University, Tel-Aviv, Israel.

Background: Preclinical studies have implicated excess release of catecholamines and prostaglandins in the mediation of prometastatic processes during surgical treatment of cancer. In this study, we tested the combined perioperative blockade of these pathways in patients with colorectal cancer (CRC).

Methods: In a randomized, double-blind, placebo-controlled biomarker trial involving 34 patients, the β-blocker propranolol and the COX2-inhibitor etodolac were administered for 20 perioperative days, starting 5 days before surgery. Excised tumors were subjected to whole genome messenger RNA profiling and transcriptional control pathway analyses.

Results: Drugs were well-tolerated, with minor complications in both the treatment group and the placebo group. Treatment resulted in a significant improvement (P < .05) of tumor molecular markers of malignant and metastatic potential, including 1) reduced epithelial-to-mesenchymal transition, 2) reduced tumor infiltrating CD14 monocytes and CD19 B cells, and 3) increased tumor infiltrating CD56 natural killer cells. Transcriptional activity analyses indicated a favorable drug impact on 12 of 19 a priori hypothesized CRC-related transcription factors, including the GATA, STAT, and EGR families as well as the CREB family that mediates the gene regulatory impact of β-adrenergic- and prostaglandin-signaling. Alterations observed in these transcriptional activities were previously associated with improved long-term clinical outcomes. Three-year recurrence rates were assessed for long-term safety analyses. An intent-to-treat analysis revealed that recurrence rates were 12.5% (2/16) in the treatment group and 33.3% (6/18) in the placebo group (P = .239), and in protocol-compliant patients, recurrence rates were 0% (0/11) in the treatment group and 29.4% (5/17) in the placebo group (P = .054).

Conclusions: The favorable biomarker impacts and clinical outcomes provide a rationale for future randomized placebo-controlled trials in larger samples to assess the effects of perioperative propranolol/etodolac treatment on oncological clinical outcomes.
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http://dx.doi.org/10.1002/cncr.32950DOI Listing
September 2020

Harnessing cancer immunotherapy during the unexploited immediate perioperative period.

Nat Rev Clin Oncol 2020 05 17;17(5):313-326. Epub 2020 Feb 17.

Neuro-Immunology Research Unit, School of Psychological Sciences, Tel-Aviv University, Tel Aviv-Yafo, Israel.

The immediate perioperative period (days before and after surgery) is hypothesized to be crucial in determining long-term cancer outcomes: during this short period, numerous factors, including excess stress and inflammatory responses, tumour-cell shedding and pro-angiogenic and/or growth factors, might facilitate the progression of pre-existing micrometastases and the initiation of new metastases, while simultaneously jeopardizing immune control over residual malignant cells. Thus, application of anticancer immunotherapy during this critical time frame could potentially improve patient outcomes. Nevertheless, this strategy has rarely been implemented to date. In this Perspective, we discuss apparent contraindications for the perioperative use of cancer immunotherapy, suggest safe immunotherapeutic and other anti-metastatic approaches during this important time frame and specify desired characteristics of such interventions. These characteristics include a rapid onset of immune activation, avoidance of tumour-promoting effects, no or minimal increase in surgical risk, resilience to stress-related factors and minimal induction of stress responses. Pharmacological control of excess perioperative stress-inflammatory responses has been shown to be clinically feasible and could potentially be combined with immune stimulation to overcome the direct pro-metastatic effects of surgery, prevent immune suppression and enhance immunostimulatory responses. Accordingly, we believe that certain types of immunotherapy, together with interventions to abrogate stress-inflammatory responses, should be evaluated in conjunction with surgery and, for maximal effectiveness, could be initiated before administration of adjuvant therapies. Such strategies might improve the overall success of cancer treatment.
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http://dx.doi.org/10.1038/s41571-019-0319-9DOI Listing
May 2020

ECCO Guidelines on Therapeutics in Crohn's Disease: Surgical Treatment.

J Crohns Colitis 2020 Feb;14(2):155-168

Department of Gastroenterology, Hepatology and Nutrition, Pauls Stradins Clinical University Hospital, Department of Internal Medicine, Riga Stradiņš University, Riga, Latvia.

This article is the second in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of previous guidelines.
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http://dx.doi.org/10.1093/ecco-jcc/jjz187DOI Listing
February 2020

Perioperative Dietary Therapy in Inflammatory Bowel Disease.

J Crohns Colitis 2020 May;14(4):431-444

Department of Nutritional Sciences, King's College London, London, UK.

Background And Aims: The incidence of inflammatory bowel disease [IBD] is rising worldwide and no cure is available. Many patients require surgery and they often present with nutritional deficiencies. Although randomised controlled trials of dietary therapy are lacking, expert IBD centres have long-established interdisciplinary care, including tailored nutritional therapy, to optimise clinical outcomes and resource utilisation. This topical review aims to share expertise and offers current practice recommendations to optimise outcomes of IBD patients who undergo surgery.

Methods: A consensus expert panel consisting of dietitians, surgeons, and gastroenterologists, convened by the European Crohn's and Colitis Organisation, performed a systematic literature review. Nutritional evaluation and dietary needs, perioperative optimis ation, surgical complications, long-term needs, and special situations were critically appraised. Statements were developed using a Delphi methodology incorporating three successive rounds. Current practice positions were set when ≥80% of participants agreed on a recommendation.

Results: A total of 26 current practice positions were formulated which address the needs of IBD patients perioperatively and in the long term following surgery. Routine screening, perioperative optimisation by oral, enteral, or parenteral nutrition, dietary fibre, and supplements were reviewed. IBD-specific situations, including management of patients with a restorative proctocolectomy, an ostomy, strictures, or short-bowel syndrome, were addressed.

Conclusions: Perioperative dietary therapy improves the outcomes of IBD patients who undergo a surgical procedure. This topical review shares interdisciplinary expertise and provides guidance to optimise the outcomes of patients with Crohn's disease and ulcerative colitis. taking advantage of contemporary nutrition science.
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http://dx.doi.org/10.1093/ecco-jcc/jjz160DOI Listing
May 2020

Sexual Dysfunction in Patients With Inflammatory Bowel Disease.

Inflamm Bowel Dis 2018 10;24(11):2348-2349

Department of Gastroenterology, Medical School of Ioannina, Ioannina, Greece.

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http://dx.doi.org/10.1093/ibd/izy206DOI Listing
October 2018

Perioperative inhibition of β-adrenergic and COX2 signaling in a clinical trial in breast cancer patients improves tumor Ki-67 expression, serum cytokine levels, and PBMCs transcriptome.

Brain Behav Immun 2018 10 22;73:294-309. Epub 2018 May 22.

Sagol School of Neuroscience and School of Psychological Sciences, Tel Aviv University, Israel. Electronic address:

Catecholamines and prostaglandins are secreted abundantly during the perioperative period in response to stress and surgery, and were shown by translational studies to promote tumor metastasis. Here, in a phase-II biomarker clinical trial in breast cancer patients (n = 38), we tested the combined perioperative use of the β-blocker, propranolol, and the COX2-inhibitor, etodolac, scheduled for 11 consecutive perioperative days, starting 5 days before surgery. Blood samples were taken before treatment (T1), on the mornings before and after surgery (T2&T3), and after treatment cessation (T4). Drugs were well tolerated. Results based on a-priori hypotheses indicated that already before surgery (T2), serum levels of pro-inflammatory IL-6, CRP, and IFNγ, and anti-inflammatory, cortisol and IL-10, increased. At T2 and/or T3, drug treatment reduced serum levels of the above pro-inflammatory cytokines and of TRAIL, as well as activity of multiple inflammation-related transcription factors (including NFκB, STAT3, ISRE), but not serum levels of cortisol, IL-10, IL-18, IL-8, VEGF and TNFα. In the excised tumor, treatment reduced the expression of the proliferation marker Ki-67, and positively affected its transcription factors SP1 and AhR. Exploratory analyses of transcriptome modulation in PBMCs revealed treatment-induced improvement at T2/T3 in several transcription factors that in primary tumors indicate poor prognosis (CUX1, THRa, EVI1, RORa, PBX1, and T3R), angiogenesis (YY1), EMT (GATA1 and deltaEF1/ZEB1), proliferation (GATA2), and glucocorticoids response (GRE), while increasing the activity of the oncogenes c-MYB and N-MYC. Overall, the drug treatment may benefit breast cancer patients through reducing systemic inflammation and pro-metastatic/pro-growth biomarkers in the excised tumor and PBMCs.
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http://dx.doi.org/10.1016/j.bbi.2018.05.014DOI Listing
October 2018

Comparison between laparoscopic and open Hartmann's reversal: results of a decade-long multicenter retrospective study.

Surg Endosc 2018 12 15;32(12):4780-4787. Epub 2018 May 15.

Division of Surgery, Tel-Aviv Medical Center, Tel Aviv, Israel.

Background: Hartmann's reversal is a challenging surgical procedure with significant postoperative morbidity rates. Various surgical methods have been suggested to lower the risk of postoperative complications. In this study, we aimed to compare the postoperative results between open and laparoscopic techniques for Hartmann's reversal.

Methods: A retrospective study of all patients who underwent Hartmann's reversal in five centers in central Israel between January 2004 and June 2015 was conducted. Medical charts were reviewed, analyzing preoperative and operative parameters and short-term postoperative outcomes.

Results: 260 patients were included in the study. 76 patients were operated laparoscopically with a conversion rate of 26.3% (20 patients). No differences were found between patients operated laparoscopically and those operated in an open technique regarding gender (p = 0.785), age (61.34 vs. 62.64, p = 0.521), body mass index (26.6 vs. 26.2, p = 0.948), Charlson index score (1.79 vs. 1.95, p = 0.667), and cause for Hartmann's procedure (neoplastic vs. non-neoplastic, p = 0.644). No differences were seen in average time from the Hartmann's procedure to reversal (204.89 vs. 213.60 days, p = 0.688) and in overall complication rate (46.4 vs. 46.5%, p = 1). The Clavien-Dindo score for distinguishing between minor (0-2 score, p = 1) and major complications (3-5 score, p = 0.675) failed to demonstrate an advantage to laparoscopy, as well as to average length of stay (10.91 days in the laparoscopic group vs. 11.72 days in the open group, p = 0.529). An analysis based on the intention-to-treat with laparoscopy, including converted cases in the laparoscopic group, showed similar results, including overall complication rate (48.6 vs. 45.6%, p = 0.68) and Clavien-Dindo score in both minor (p = 0.24) and major complications (p = 0.44). Length of stay (10.92 vs. 11.81 days, p = 0.45) was also similar between the two groups.

Conclusion: In this series, a laparoscopic approach to Hartmann's reversal did not offer any short-term advantage when compared to an open surgical approach.
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http://dx.doi.org/10.1007/s00464-018-6227-8DOI Listing
December 2018

Planned Re-Laparotomy in a Non-Trauma Setting: A Single Center Experience.

Isr Med Assoc J 2018 05;20(5):300-303

Department of Surgery, Assaf Harofeh Medical Center, Zerifin, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: Damage control laparotomy (DCL) is the widely accepted procedure of choice in management of severely injured trauma patient. It has been implemented in non-trauma-related surgical pathology in the last decade.

Objectives: To evaluate our experience with planned re-laparotomy (PRL) in non-trauma patients and compare it to other reports.

Methods: Charts of all patients admitted to Assaf Harofeh Medical Center who underwent PRL for non-trauma-related abdominal pathology during a 6 year period were reviewed. Data regarding demographics, vital signs, laboratory tests, indications for surgery, length of hospital stay, and mortality were obtained from medical charts. Indications for surgery, risk factors, and mortality were analyzed.

Results: The study was comprised of 181 patients. Primary abdominal sepsis (50), postoperative sepsis (49), mesenteric event (32), and intestinal obstruction (28) were the most common indications for PRL. Mortality rate was 48.6%. Factors correlating with increased mortality were advanced age, hypotension, hypothermia, metabolic acidosis, and renal failure. Bowel resection was performed on 122 patients (67%) and primary intestinal anastomosis constructed in 46.7%. Mortality rate was lower in patients who underwent PRL with primary anastomosis compared to patients with postponed bowel anastomosis (33.3% vs. 55.4%, P = 0.018).

Conclusions: PRL in abdominal emergencies carries a high mortality rate. Primary anastomosis may be considered in non-trauma-related PRL.
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May 2018

Diagnostic Value of Serum Bilirubin and Liver Enzyme Levels in Acute Appendicitis.

Isr Med Assoc J 2018 Mar;20(3):176-181

Department of Surgery and Transplantation, Sheba Medical Center, Tel Hashomer, Israel.

Background: Acute appendicitis (AA) is one of the most common indications for emergency abdominal surgery.

Objectives: To assess the diagnostic and prognostic value of serum bilirubin and liver enzyme levels in the management of acute appendicitis.

Methods: Consecutive emergency department patients referred for a surgical consult for suspected AA were prospectively enrolled in the study. Data regarding demographic, clinical and laboratory results were recorded. Receiver operating characteristic (ROC) curve was performed for all evaluated parameters. Clinical and laboratory markers were evaluated for diagnostic accuracy and correlation to the clinical severity, histology reports, and length of hospital stay.

Results: The study was comprised of 100 consecutive patients. ROC curve analysis revealed white blood cell count, absolute neutrophils count (ANC), C-reactive protein, total-bilirubin and direct-bilirubin levels as significant factors for diagnosis of AA. The combination of serum bilirubin levels, alanine transaminase levels, and ANC yielded the highest area under the curve (0.898, 95% confidence interval 0.835-0.962, P<0.001) with a diagnostic accuracy of 86%. In addition, total and direct bilirubin levels significantly correlated with the severity of appendicitis as described in the operative and pathology reports (P < 0.01). Total and direct bilirubin also significantly correlated with the length of hospital stay (P < 0.01).

Conclusions: Serum bilirubin levels, alone or combined with other markers, may be considered as a clinical marker for AA correlating with disease existence, severity, and length of hospital stay. These findings support the routine use of serum bilirubin levels in the workup of patients with suspected AA.
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March 2018

Preoperative Nutritional Optimization for Crohn's Disease Patients Can Improve Surgical Outcome.

Dig Surg 2018 1;35(5):442-447. Epub 2017 Nov 1.

Background: Preoperative preparation of patients with Crohn's disease is challenging and there are no specific guidelines regarding nutritional support. The aim of this study was to assess whether preoperative nutritional support influenced the postoperative outcome.

Methods: A retrospective, cohort study including all Crohn's disease patients who underwent abdominal surgery between 2008 and 2014 was conducted. Patients' characteristics and clinical and surgical data were recorded and analyzed.

Results: Eighty-seven patients were included in the study. Thirty-seven patients (42.5%) received preoperative nutritional support (mean albumin level 3.14 vs. 3.5 mg/dL in the non-optimized group; p < 0.02) to optimize their nutritional status prior to surgery. Preoperative albumin level, after adequate nutritional preparation, was similar between the 2 groups. The 2 groups differ neither in demographic and surgical data, overall post-op complication (p = 0.85), Clavien-Dindo score (p = 0.42), and length of stay (p = 0.1). Readmission rate was higher in the non-optimized group (p = 0.047).

Conclusion: Nutritional support can minimize postoperative complications in patients with low albumin levels. Nutritional status should be optimized in order to avoid hazardous complications.
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http://dx.doi.org/10.1159/000481408DOI Listing
December 2018

Considerations for Hartmann's reversal and Hartmann's reversal outcomes-a multicenter study.

Int J Colorectal Dis 2017 Nov 6;32(11):1577-1582. Epub 2017 Sep 6.

Department of General Surgery and Transplantations B, Sheba Medical Center, Ramat Gan, Israel.

Purpose: Hartmann's procedure is commonly practiced in emergent cases with the restoration of bowel continuity planned at a second stage. This study assessed the rate of restorations following Hartmann's procedure and evaluated factors affecting decision-making.

Methods: Data on patient demographics, comorbidities, causes for Hartmann's procedure, reversal rate, and complications were collected in a multicenter retrospective cohort study of patients who underwent Hartmann's procedure in five medical centers.

Results: Six hundred forty patients underwent Hartmann's procedure for diverticular disease (36.1%), obstructing malignancy (31.8%), benign obstruction (5%), and other reasons (23.1%). Overall, 260 (40.6%) patients underwent subsequent restoration of bowel continuity. One hundred twenty-one (46.5%) patients had post-reversal complications, with an average Clavien-Dindo score of 1.4 and a mortality rate of 0.77%. Decision to avoid reversal was mostly related to comorbidities (49.7%) and metastatic disease (21.6%). Factors associated with the decision to restore bowel continuity included male gender (P = 0.02), patient age (62.3 years in Hartmann's reversal patients vs 73.5 years in non-reversal patients; P < 0.0001), number of comorbidities (1.1 vs 1.58; P < 0.001), average Charlson score (1.93 vs 3.44; P < 0.001), and a neoplastic etiology (P < 0.0001). A sub-analysis excluding all patients who died in the 30 days following Hartmann's procedure showed similar factors associated with ostomy closure.

Conclusion: Many patients do not have restoration of bowel continuity after undergoing Hartmann's procedure. Hartmann's reversal is associated with a significant postoperative morbidity. Surgeons and patients should be aware of the possibility that the colostomy might become permanent.
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http://dx.doi.org/10.1007/s00384-017-2897-2DOI Listing
November 2017

Perioperative COX-2 and β-Adrenergic Blockade Improves Metastatic Biomarkers in Breast Cancer Patients in a Phase-II Randomized Trial.

Clin Cancer Res 2017 Aug 10;23(16):4651-4661. Epub 2017 May 10.

Sagol School of Neuroscience and School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel.

Translational studies suggest that excess perioperative release of catecholamines and prostaglandins may facilitate metastasis and reduce disease-free survival. This trial tested the combined perioperative blockade of these pathways in breast cancer patients. In a randomized placebo-controlled biomarker trial, 38 early-stage breast cancer patients received 11 days of perioperative treatment with a β-adrenergic antagonist (propranolol) and a COX-2 inhibitor (etodolac), beginning 5 days before surgery. Excised tumors and sequential blood samples were assessed for prometastatic biomarkers. Drugs were well tolerated with adverse event rates comparable with placebo. Transcriptome profiling of the primary tumor tested hypotheses and indicated that drug treatment significantly (i) decreased epithelial-to-mesenchymal transition, (ii) reduced activity of prometastatic/proinflammatory transcription factors (GATA-1, GATA-2, early-growth-response-3/EGR3, signal transducer and activator of transcription-3/STAT-3), and (iii) decreased tumor-infiltrating monocytes while increasing tumor-infiltrating B cells. Drug treatment also significantly abrogated presurgical increases in serum IL6 and C-reactive protein levels, abrogated perioperative declines in stimulated IL12 and IFNγ production, abrogated postoperative mobilization of CD16 "classical" monocytes, and enhanced expression of CD11a on circulating natural killer cells. Perioperative inhibition of COX-2 and β-adrenergic signaling provides a safe and effective strategy for inhibiting multiple cellular and molecular pathways related to metastasis and disease recurrence in early-stage breast cancer. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-0152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559335PMC
August 2017

Laparoscopic Lymph Node Biopsy: Efficacy and Advantages.

Isr Med Assoc J 2017 Apr;19(4):231-233

Department of Surgery and Transplantation.

Background: Diagnosis of abdominal lymphadenopathy is challenging when not accompanied by peripheral lymphadenopathy. Computed tomography-guided core-needle biopsy has largely replaced open procedures in recent years, but this approach is limited by access to the anatomic region and the amount of tissue acquired.

Objectives: To demonstrate the feasibility of the laparoscopic approach in obtaining abdominal lymph node biopsies and to evaluate the diagnostic adequacy of the technique.

Methods: We reviewed the data of patients who underwent laparoscopic lymph node biopsy between 2014 and 2014 in our department. Demographics, intra-operative parameters and postoperative course were examined, as were histological reports. Postoperative complications were categorized according to the Clavien-Dindo(CD) classification.

Results: Between 2004 and 2014, 57 laparoscopic biopsies were performed for intra-abdominal lymphadenopathy. One case was a repeated attempt due to limited histologic material. The mean age was 49.5 ± 19.6 years. There were two conversions to open laparotomy, one due to small bowel injury and the other due to a sizable mass. Overall, 56 cases had full clinical data: 48 cases (85.7%) had CD=0, six (10.7%) had CD=1, one postoperative severe complication (CD=3) and one mortality (CD=5), which was related to preexisting hepatic insufficiency. Mean hospital stay was 1.6 days. Overall, adequate tissue samples were acquired in 96.7% and only 3 of these cases resulted in inconclusive diagnoses.

Conclusions: Laparoscopic lymph node biopsy is a viable alternative to the currently available methods of tissue retrieval. It provides an access for nodes which are inaccessible percutaneously, and may allow a superior diagnostic yield.
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April 2017

The effect of pre-operative optimization on post-operative outcome in Crohn's disease resections.

Int J Colorectal Dis 2017 Jan 26;32(1):49-56. Epub 2016 Oct 26.

Sheba Medical Center, Tel Hashomer, Israel.

Background: The timing of surgical intervention in Crohn's disease (CD) may depend on pre-operative optimization (PO) which includes different interventions to decrease the risk for unfavourable post-operative outcome. The objective of this study was to investigate the effect of multi-model PO on the post-operative outcome in CD.

Method: This is a multicentre retrospective cohort study. The primary outcome was 30-day post-operative complications. Secondary outcomes were intra-abdominal septic complications, surgical site infection (SSI), re-operation, length of post-operative stay in a hospital and re-admission. PO included nutritional support, discontinuation of medications, pre-operative antibiotic course and thrombosis prophylaxis.

Results: Two hundred and thirty-seven CD elective bowel resections were included. Mean age was 39.9 years SD 14.25, 144 (60.8 %) were female and 129 (54.4 %) had one or more types of medical treatment pre-operatively. Seventy-seven patients (32.5 %) optimized by at least nutritional support or change in pre-operative medications. PO patients were more likely to have penetrating disease phenotype (p = 0.034), lower albumin (p = 0.015) and haemoglobin (p = 0.021) compared to the non-optimized. Multivariate analyses showed that treatment with anti-TNF alpha agents OR 2.058 CI [1.043-4.4.064] and low haemoglobin OR 0.741 CI [0.572-0.0.961] increased the risk of overall post-operative complications. Co-morbidity increased the risk of SSI OR 2.567 CI [1.182-5.576] while low haemoglobin was a risk factor for re-admission OR 0.613 CI [0.405-0.926]. Low pre-operative albumin correlated with longer stay in hospital.

Conclusions: PO did not change post-operative outcome most likely due to selection bias. Anti-TNF alpha agents, low haemoglobin, low albumin and co-morbidity were associated with unfavourable outcome.
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http://dx.doi.org/10.1007/s00384-016-2655-xDOI Listing
January 2017

Emerging Trends in the Etiology, Prevention, and Treatment of Gastrointestinal Anastomotic Leakage.

J Gastrointest Surg 2016 12 16;20(12):2035-2051. Epub 2016 Sep 16.

Department of Colorectal Surgery, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd., Weston, FL, 33331, USA.

Anastomotic leaks represent one of the most alarming complications following any gastrointestinal anastomosis due to the substantial effects on post-operative morbidity and mortality of the patient with long-lasting effects on the functional and oncologic outcomes. There is a lack of consensus related to the definition of an anastomotic leak, with a variety of options for prevention and management. A number of patient-related and technical risk factors have been found to be associated with the development of an anastomotic leak and have inspired the development of various preventative measures and technologies. The International Multispecialty Anastomotic Leak Global Improvement Exchange group was convened to establish a consensus on the definition of an anastomotic leak as well as to discuss the various diagnostic, preventative, and management measures currently available.
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http://dx.doi.org/10.1007/s11605-016-3255-3DOI Listing
December 2016

Changing paradigms in the management of diverticulitis.

Int J Surg 2016 Sep 2;33 Pt A:146-50. Epub 2016 Aug 2.

Department of Surgery and Transplantation, Chaim Sheba Medical Center Ramat Gan Israel (affiliated to the Faculty of Medicine, Tel Aviv University), Israel.

The management of diverticular disease has evolved in the last few decades from a structured therapeutic approach including operative management in almost all cases to a variety of medical and surgical approaches leading to a more individualized strategy. There is an ongoing debate among surgeons about the surgical management of diverticular disease, questioning not only the surgical procedure of choice, but also about who should be operated and the timing of surgery, both in complicated and uncomplicated diverticular disease. This article reviews the current treatment of diverticulitis, with a focus on the indications and methods of surgery in both the emergency and elective settings. Further investigation with good clinical data is needed for the establishment of clear guidelines.
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http://dx.doi.org/10.1016/j.ijsu.2016.07.072DOI Listing
September 2016

Jejunal Diverticulitis.

J Laparoendosc Adv Surg Tech A 2016 Aug 16;26(8):596-9. Epub 2016 May 16.

1 Department of Surgery and Transplantation, Chaim Sheba Medical Center , Ramat Gan, Israel .

Background: Jejunal diverticulitis is a rare clinical entity often overlooked by physicians as a cause for abdominal pain. Although diagnostic capabilities improved in recent years, there is little data about diverticular disease in the proximal small bowel. The aim of this study is to present the clinical course and management in a series of eight cases of jejunal diverticulitis and possible therapeutic interventions.

Methods: A cohort retrospective analysis of all patients admitted for acute jejunal diverticulitis between January 2010 and June 2015 was conducted. Patient demographics, clinical, and surgical outcome were recorded and analyzed.

Results: Eight patients were admitted for acute jejunal diverticulitis with a mean age of 72.1 (range 55-87) years. Clinical presentation included six patients (75%) with a sealed perforation and only one patient demonstrated distant pneumoperitoneum. All patients were treated initially without surgery and only one patient required surgery because of diverticular complications. Recurrent episodes occurred in two patients (25%). Colonoscopy was performed in all patients after hospitalization that revealed large bowel diverticulosis in all patients (100%). Median follow-up was 8.2 months (3-15 months).

Conclusion: Jejunal diverticulitis can be initially treated conservatively but complicated disease should be considered for surgical management. Further study is required on the relationship between small and large bowel diverticulosis.
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http://dx.doi.org/10.1089/lap.2016.0066DOI Listing
August 2016

Diverticulitis: does age matter?

J Dig Dis 2016 May;17(5):313-8

Department of Surgery and Transplantation, Chaim Sheba Medical Center, Ramat Gan, Israel.

Objective: Acute diverticulitis has been traditionally associated with worse outcome in young patients, indicating a more aggressive surgical approach is required for them. The aim of this study was to assess whether acute diverticulitis was more virulent in young patients.

Methods: A retrospective, cross-sectional study included all patients who were admitted for a first episode of acute diverticulitis between January 2004 and December 2013. The patients were divided into two groups (≤50 years and >50 years) based on their age. Patients' characteristics, clinical and surgical data were recorded and analyzed.

Results: Overall, 636 patients were included in the database, including 177 (27.8%) in the younger group and 459 in the elder group. There were no significant differences between the groups in disease complexity, peritonitis, laboratory work-up, vital signs on presentation, bowel obstruction or the presence of fistula and abscess in need of drainage. Younger patients had more free extra-luminal air on computed tomography (CT) scan (P = 0.03). Surgical data, including the intra-operative modified Hinchey score and the need for emergency and additional surgery did not significantly differ between the two groups. Young patients had more readmissions (P = 0.01) due to acute diverticulitis, diverticular complications and elective surgery. Length of hospital stay (P = 0.0001) was longer and postoperative complications were more common in the elder patients.

Conclusions: The clinical presentation of acute diverticulitis does not seem to be worse in the young population. Younger patients tend to have a more severe presentation on CT scan and more readmissions, but this did not translate to a more severe disease course.
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http://dx.doi.org/10.1111/1751-2980.12350DOI Listing
May 2016

Stenting in malignant colonic obstruction--is it a real therapeutic option?

Int J Colorectal Dis 2016 Jan 28;31(1):131-5. Epub 2015 Aug 28.

Department of Surgery, Sheba Medical Center, Tel-Hashomer, and Faculty of Medicine, Tel-Aviv University, 52621, Tel-Aviv, Israel.

Background: Malignant colonic obstruction is commonly treated surgically. Colonic stents are a therapeutic option for palliation or used as a bridge to surgery or chemotherapy.

Objective: The aim of the study was to evaluate the clinical success rate of stenting as a bridge to one-step surgery, chemotherapy, or as a palliative measure.

Design: This was a retrospective observational study.

Settings: The study was conducted at a university-affiliated tertiary referral center.

Patients And Interventions: From 2007 to 2014, 45 patients with malignant colonic obstruction were referred for stent insertion.

Main Outcome Measures: Patients were grouped according to three pre-defined treatment goals: group 1: restorative one-step procedure without an ostomy, group 2: completion of scheduled chemotherapy before surgery, and group 3: palliation without surgical intervention.

Results: Group 1 included 11 patients. Three patients (27.3 %) met the treatment goal of one-step surgery. Eight patients (72.7 %) did not reach the primary goal due to stent insertion failure (four patients), stent-related complications (two patients), and failure to perform a one-step surgery after successful stent insertion (two patients). Group 2 included 12 patients. Chemotherapy was successfully completed prior to surgery in six patients (50 %). Six patients (50 %) did not achieve treatment goal due to stent insertion failure (two patients), stent migration (two patients), stent-related perforation (one patient), and mortality (one patient). Group 3 included 20 patients. Long-term palliation without surgical intervention was achieved in eight patients (40 %). Stent insertion failed in seven patients (35 %). Five patients (25 %) needed urgent surgery due to stent complications (three migrations and two perforations).

Limitations: The study was limited by its retrospective nature and small sample size.

Conclusions: This study demonstrates only a modest success rate of colonic stents in the treatment of malignant colonic obstruction. Although colonic stenting seems to be an effective method of relieving colonic obstruction, high failure rates limits its applicability.
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http://dx.doi.org/10.1007/s00384-015-2375-7DOI Listing
January 2016

Elevations of serum CA-125 predict severity of acute appendicitis in males.

ANZ J Surg 2016 Apr 12;86(4):260-3. Epub 2015 May 12.

Department of Surgery and Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, Israel.

Background: Acute appendicitis (AA) is a common indication for urgent abdominal surgery. CA-125 glycoprotein antigen is a non-specific marker for epithelial ovarian cancer; CA-125 serum levels also increased in the conditions of peritoneal inflammation. The aim of this study was to examine the correlation between serum CA-125 levels and AA.

Methods: All emergency department (ED) patients with suspected AA were prospectively enrolled in the study. The serum level of CA-125 was checked in every patient on arrival to the ED in addition to the routine clinical and laboratory evaluation. Data regarding demographic, clinical, radiological, operative and pathological features were analysed.

Results: One hundred consecutive patients (48 males) were enrolled in the study. We found a statistically significant correlation between CA-125 levels in males and the severity of appendicitis as described in the operative and pathology reports (P = 0.008 and P = 0.02, respectively). In addition, we observed a trend towards higher levels of CA-125 in males with AA compared with males without AA (9.9 ± 4.7 versus 7.8 ± 3.2 U/mL, respectively; P = 0.09).

Conclusions: CA-125 levels correlate with the severity of appendicitis in males and may serve as a surrogate marker for the severity of other intra-abdominal surgical diseases.
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http://dx.doi.org/10.1111/ans.13128DOI Listing
April 2016

Early experience with laparoscopic lavage in acute complicated diverticulitis.

Dig Surg 2015 5;32(2):108-11. Epub 2015 Mar 5.

Department of Surgery and Transplantation, Chaim Sheba Medical Center, Sackler Medical School and Tel Aviv University, Ramat Gan, Israel.

Background: Contemporary surgical management of complicated diverticulitis is controversial. Traditionally, the gold standard has been resection and colostomy, but recently peritoneal lavage and drainage without resection in cases of purulent peritonitis have been suggested. This study aims to review our initial experience with laparoscopic peritoneal lavage for complicated diverticulitis.

Methods: Retrospective review of all patients who underwent emergent peritoneal lavage and drainage for acute complicated diverticulitis.

Results: Five-hundred-thirty-eight patients admitted for acute diverticulitis between 2007 and 2012 were recorded in the database. Thirty seven underwent emergent surgery of which 10 had peritoneal lavage and drainage without colonic resection for complicated diverticulitis causing peritonitis. Peritoneal lavage and drainage resulted in the resolution of acute symptoms in all cases. In long-term follow-up, 3 (30%) patients required elective resection owing to symptomatic disease, two of these due to recurrent diverticulitis, and one owing to complicated fistula following the procedure.

Conclusion: Peritoneal lavage is a feasible option for complicated diverticulitis with purulent non-fecal peritonitis, but a significant portion of the patients may require elective resection. Comparative studies with emergent resection are needed to determine the role of peritoneal lavage in complicated diverticulitis.
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http://dx.doi.org/10.1159/000375539DOI Listing
February 2016

Hand-assisted laparoscopic colectomy for colovesical fistula associated with diverticular disease.

Surg Laparosc Endosc Percutan Tech 2014 Jun;24(3):251-3

Departments of *Surgery B, Rabin Medical Center, Beilinson Campus, Petach Tikva †Shiba Medical Center, Tel Hashomer ‡Meir Medical Center, Kfar Saba, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

To evaluate the feasibility and short-term outcome of hand-assisted laparoscopic colectomy (HALC) for the treatment of colovesical fistula complicating diverticulitis, we reviewed the files of all 34 patients who underwent surgery for diverticular colovesical fistula in 1999 to 2010 at a major tertiary medical center. Twenty-one were treated with HALC and 13 with open colectomy. There were no differences in demographic parameters among the groups. HALC and open colectomy had similar operating time. HALC was associated with a significantly shorter hospital stay compared with open colectomy (5 vs. 8 d, P=0.001). HALC proved to be technically feasible and safe in this setting. It provided benefits of tactile feedback and manual manipulation as in open colectomy while maintaining the advantages of a minimal invasive approach.
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http://dx.doi.org/10.1097/SLE.0b013e31828f6ce0DOI Listing
June 2014

Healing of ileocolic nitinol compression anastomosis: a novel porcine model of subtotal colectomy.

Surg Innov 2013 Dec 10;20(6):570-9. Epub 2013 Apr 10.

1Dept. of surgery B', HaEmek medical center, Faculty of medicine of the Technion, Israel institute of technology.

Background: There are limited large animal models for the research of novel anastomotic technologies. Subtotal colectomy requires the anastomosis of relatively remote segments of the alimentary tract that are different anatomically, histologically, and pose significant physiological challenge. The quest for a foreign material-free anastomotic line reintroduced nitinol compression anastomosis into clinical use in the last decade.

Objective: To evaluate the safety, histological, and physiological parameters of side-to-side ileocolic nitinol compression anastomosis in a newly developed large animal model, mimicking the human subtotal colectomy.

Intervention: Resection of the entire spiral colon with an ileocolic side-to-side compression anastomosis in 12 animals, compared to resection of a short ileal segment in 6 animals. All anastomoses were constructed by using a novel nitinol-based compression device. The animals were followed up to 30 days postoperatively and were reoperated and sacrificed.

Results: All 12 animals underwent successful subtotal colectomy with side-to-side nitinol compression anastomosis. No signs of abdominal infection were found. The increase in the colectomized animals' bodyweight over the postoperative course was significantly lower and the animals presented with longer periods of diarrhea. The histopathology revealed minimal inflammation and foreign body reaction with good alignment of the bowel wall layers in both groups. The anastomotic line width was shown to be reduced during the healing course of the compression anastomoses.

Conclusions: Side-to-side nitinol compression anastomosis is safe and demonstrates favorable functional and histopathological features. The porcine model of subtotal colectomy can be used for further research of novel anastomotic technologies.
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http://dx.doi.org/10.1177/1553350613484592DOI Listing
December 2013

Are there specific endosonographic features in Crohn's patients with perianal fistulae?

J Crohns Colitis 2013 Jul 21;7(6):490-6. Epub 2012 Aug 21.

Department of Surgery and Transplantation, Chaim Sheba Medical Center Ramat Gan Israel, Israel.

Both 2-dimensional and 3-dimensional endoanal ultrasounds have been shown to be accurate in the definition of the anatomy of complex fistulae-in-ano in patients with perianal Crohn's disease. Recently, a Crohn's Ultrasound Fistula Sign (CUFS) has been suggested as a discriminating feature of perianal Crohn's disease as has the presence of fistulous debris and fistular bifurcation. We blindly assessed 197 patients (39 Crohn's fistulae and 158 cryptogenic fistulae) to determine if these signs differentiated fistula types. The incidence of CUFS in Crohn's cases was 17/39 (43.6%) and in cryptogenic cases was 4/158 (2.5%) (P<0.0001). The sensitivity, specificity, positive and negative predictive values and accuracy for CUFS were 43.6%, 97.5%, 80.9%, 87.5% and 86.8%, respectively. The presence of debris and fistula bifurcation in evaluable cases had a high specificity (87.2% and 81.8%, respectively) but poor sensitivity. The kappa values for or against CUFS, debris and bifurcation in Crohn's cases between 2 observers blinded to the diagnosis were 0.85, 0.72 and 0.93, respectively and in cryptogenic fistulae were 0.89, 0.85 and 0.80, respectively. The kappa values of an agreed consensus for CUFS in Crohn's disease, cryptogenic fistulae and overall with a third observer with no ultrasound experience were 0.62, 0.85 and 0.77, respectively. The presence of CUFS differentiates Crohn's-related from cryptogenic fistulae-in-ano with a high level of agreement for this sign between experienced and inexperienced observers blinded to the underlying diagnosis.
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http://dx.doi.org/10.1016/j.crohns.2012.07.024DOI Listing
July 2013

A new approach to reducing postsurgical cancer recurrence: perioperative targeting of catecholamines and prostaglandins.

Clin Cancer Res 2012 Sep 2;18(18):4895-902. Epub 2012 Jul 2.

Neuroimmunology Research Unit, Department of Psychology, Tel Aviv University, Tel Aviv, Israel.

Surgery is a crucial intervention in most cancer patients, but the perioperative period is characterized by increased risks for future outbreak of preexisting micrometastases and the initiation of new metastases-the major cause of cancer-related death. Here we argue that the short perioperative period is disproportionately critical in determining long-term recurrence rates, discuss the various underlying risk factors that act synergistically during this period, and assert that this time frame presents an unexplored opportunity to reduce long-term cancer recurrence. We then address physiologic mechanisms that underlie these risk factors, focusing on excess perioperative release of catecholamines and prostaglandins, which were recently shown to be prominent in facilitating cancer recurrence through their direct impact on the malignant tissue and its microenvironment, and through suppressing antimetastatic immunity. The involvement of the immune system is further discussed in light of accumulating evidence in cancer patients, and given the recent identification of endogenously activated unique leukocyte populations which, if not suppressed, can destroy autologous "immune-resistant" tumor cells. We then review animal studies and human correlative findings, suggesting the efficacy of blocking catecholamines and/or prostaglandins perioperatively, limiting metastasis and increasing survival rates. Finally, we propose a specific perioperative pharmacologic intervention in cancer patients, based on simultaneous β-adrenergic blockade and COX-2 inhibition, and discuss specific considerations for its application in clinical trials, including our approved protocol. In sum, we herein present the rationale for a new approach to reduce long-term cancer recurrence by using a relatively safe, brief, and inexpensive intervention during the perioperative period.
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http://dx.doi.org/10.1158/1078-0432.CCR-12-1087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3445778PMC
September 2012

Anti-tumor necrosis factor and postoperative complications in Crohn's disease: systematic review and meta-analysis.

Inflamm Bowel Dis 2012 Dec 29;18(12):2404-13. Epub 2012 Mar 29.

Department of Gastroenterology, Chaim Sheba Medical Center, Tel Hashomer, Israel.

Background: Anti-tumor necrosis factor (TNF) antibodies are efficacious in patients with Crohn's disease (CD) but the influence of these medications on surgical outcomes in CD patients has been frequently debated. The aim was to evaluate the impact of preoperative treatment with anti-TNF antibodies on postoperative complications in CD patients undergoing abdominal surgery.

Methods: A systematic review and meta-analysis of comparative cohort studies was performed assessing postoperative complication rates in CD patients who were treated with anti-TNF antibodies within 3 months before surgery versus patients who were not. The primary outcome was overall complication rate within 1 month of surgery. Secondary outcomes included the rate of infectious and noninfectious complications. The quality of studies was assessed based on selection of patients and controls, comparability of the study groups, and assessment of outcomes. Odds ratios (OR) with 95% confidence intervals (CIs) were computed.

Results: A total of eight studies including 1641 patients were included in our meta-analysis. Preoperative infliximab therapy in CD patients undergoing abdominal surgery was associated with a trend toward an increased rate of total complications (OR 1.72, 95% CI, 0.93-3.19). Anti-TNF treatments were associated with a modestly increased risk of infectious complications (OR 1.50, 95% CI 1.08-2.08), mostly remote from the surgical site (OR 2.07 95% CI 1.30-3.30) and with a trend toward a higher rate of noninfectious complications (OR 2.00, 95% CI 0.89-4.46).

Conclusion: Preoperative infliximab treatment is associated with an increased risk of postoperative infectious complications, mostly nonlocal. A trend toward an increased risk of noninfectious and overall complications was also observed.
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http://dx.doi.org/10.1002/ibd.22954DOI Listing
December 2012
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