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.
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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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.
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.
Background
The traditional open approach to incarcerated inguinal hernia has several drawbacks including difficulty avoiding tension in the swollen and edematous tissues leading to a higher ...recurrence rate, possible contamination of the mesh if it is implanted in an area of bowel strangulation, and proper evaluation of whether ischemic bowel requires resection or not, which may mandate laparotomy. This study aimed to evaluate an approach that combines intraperitoneal laparoscopic exploration with hernia reduction and total extraperitoneal (TEP) repair of the hernia.
Methods
An exploratory laparoscopy is performed. The incarcerated content is gently retracted into the abdominal cavity and inspected. If no resection is needed, the gas is deflated, the umbilical trocar is removed, and the preperitoneal space is accessed with a Hasson trocar inserted behind the rectus muscle toward the pelvis. Two additional 5-mm trocars are inserted into the preperitoneal space in the lower midline. A standard TEP repair with mesh is performed.
Results
Between 2005 and 2008, 15 patients underwent laparoscopic exploration for incarcerated inguinal hernia followed by TEP repair. Of the 15 patients, 8 had acute incarceration and 7 had chronic irreducible hernia. Reduction of the incarcerated content was straightforward, and no bowel resection was needed. No major complications or wound or mesh infections occurred.
Conclusion
The combined laparoscopic approach offers a solution to incarceration of inguinal hernias while taking advantage of each separate approach. The first part of the procedure enables easy reduction of the incarcerated content and assessment of its viability. The second part enables a simple and standard repair, similar to that for an elective case. If bowel necrosis is suspected preoperatively, an open anterior approach should be taken to avoid possible intraabdominal contamination.
The surgical management of complex perineal fistulas, such as high transsphincteric and suprasphincteric fistulas, or those associated with Crohn's disease, radiotherapy, surgical trauma, or cavity ...or a secondary tract, is associated with the risk of sphincter injury and significant discomfort. Fibrin glue may close fistula tracts without muscle division. Therefore, the aim of this study was to evaluate the use of fibrin glue sealing in treatment of perineal fistulas.
A retrospective chart review of all patients in whom fibrin glue was used for the treatment of perineal fistula was performed. Patients were contacted by telephone to establish follow-up.
Thirty-seven patients underwent injection of fibrin glue for complex perineal fistulas. Twenty-four patients had fibrin glue injection as the principal treatment for the perineal fistula, and 13 had fibrin glue in conjunction with an endorectal advancement flap. The fistula was of cryptoglandular origin in 16 (42 percent) cases and associated with Crohn's disease and trauma in 7 (19 percent) and 14 (38 percent) patients, respectively. At a mean follow-up of 12.1 months, healing occurred in only 15 (41 percent) patients. The healing rate was 33 percent when fibrin glue was the principal treatment, and 54 percent when used with an endorectal advancement flap. Fistulas of noncryptoglandular origin had a higher success rate, although this difference did not reach statistical significance. There was no morbidity associated with the injection of fibrin glue.
In this study, fibrin glue had moderate success in the definitive treatment of perineal fistulas. However, 33 percent of the patients in whom fibrin glue was the only treatment used were able to avoid more extensive surgery. Fibrin glue is associated with minimal risk, therefore its application should be considered in patients with complex anal fistulas.
The utility of antibiotic and mechanical preparation for colorectal surgery is controversial, and numerous different regimens are used. The aim of this study was to detect trends in preparation for ...surgery among American colon and rectal surgeons. Members of the American Society of Colon and Rectal Surgeons practicing in the United States were surveyed with a postal questionnaire regarding their routine preparations for colon and rectal surgery. Five hundred fifteen (40%) of the 1295 questionnaires sent were returned. Eighty-one per cent of the respondents had completed an accredited colorectal training program, and the average experience in practice was 13.7 (±8.7) years. Half of the surgeons felt that prophylactic oral antibiotic is essential, 41 per cent felt it was doubtful, and 10 per cent considered oral prophylaxis unnecessary. Despite these statements 75 per cent of the surgeons routinely utilized oral antibiotics (96% of them used a combination of two drugs), 11 per cent used them selectively, and only 13 per cent omitted oral prophylaxis from their practice. Similarly although the usefulness of intravenous antibiotics was questioned by 11 per cent of the surgeons 98 per cent routinely used them. The average number of postoperative doses was two (±1.9). Although 10 per cent of the surgeons questioned the importance of mechanical preparation more than 99 per cent routinely used it. Forty-seven per cent of the surgeons used sodium phosphate, 32 per cent used polyethylene glycol, and 14 per cent alternated between these two options. We conclude that although the use of oral antibiotic prophylaxis for colorectal surgery is controversial among surgeons it is still routinely practiced by 75 per cent. Intravenous antibiotic prophylaxis and mechanical cleansing, however, are still a dogma and almost invariably used. There is a trend toward the use of a shorter course of postoperative intravenous antibiotics and the use of sodium phosphate for mechanical cleansing.
Purpose
Acute gastrointestinal bleeding is a common emergency. Tranexamic acid (TXA) reduces clot breakdown by inhibiting the action of plasmin and has been shown to reduce the need for blood ...transfusion in trauma, surgical procedures, and upper gastrointestinal bleeding. This study examined the efficiency of intravenous TXA in patients with acute lower gastrointestinal bleeding.
Methods
Eighty‐one patients aged >18 years with lower GI hemorrhage, presenting as active rectal bleeding and anemia (hemoglobin lower than 11 g/dL or a decrease of 2 gr/dl from the patient's base level), were enrolled in this single center, double blind prospective research. Patients were randomly assigned to receive intravenous TXA or placebo from admission until colonoscopy took place. The need for transfusion of packed red blood cells (PRBC) and number of units was recorded and compared between the two groups.
Results
Eighty‐one patients were randomized in this study, thirty‐nine in the TXA arm, and forty‐two in the placebo arm. Patient characteristics did not differ between the groups. Forty‐three out of the 81 patients received blood transfusion; twenty‐two were on the placebo arm and twenty‐one on the TXA arm (p = 0.89). Twenty‐nine patients required 2 or more units, 14 in the TXA arm and 15 in the placebo arm (p = 0.98).
Conclusions
Intravenous TXA has no significant effect on blood requirement in patients with lower GI bleeding. There was no difference in the consumption of PRBC units among the patients in the placebo and TXA groups. It seems that tranexamic acid has no significant effect on transfusion of PRBC units in lower GI bleeding.
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