Safety and Hemostatic Effectiveness of the Fibrin Pad for Severe Soft-Tissue Bleeding During Abdominal, Retroperitoneal, Pelvic, and Thoracic (Non-cardiac) Surgery: A Randomized, Controlled, Superiority Trial.

BACKGROUND: In surgery, rapid hemostasis can be required in various settings and bleeding intensities to minimize complications related to blood loss. While effective hemostats are available for mild-to-moderate surgical bleeding, few are effective against challenging severe hemorrhage. We report the effectiveness and safety of the fibrin pad (FP), a novel combination hemostat (device/human biologic), in controlling severe soft-tissue bleeding as compared to the standard of care (SoC). METHODS: This randomized, controlled, superiority study enrolled subjects ≥18 years, requiring elective abdominal, retroperitoneal, pelvic, or thoracic (non-cardiac) surgery. A severe target bleeding site (TBS) was identified intra-operatively following which, subjects were randomized to the FP or the SoC group. Hemostatic status was observed at 4 min (primary endpoint) and 10 min post-randomization. Safety variables included TBS-related bleeding and thrombotic events. RESULTS: At 4 min post-randomization, 50/59 (84.7 %) subjects in the FP group and 10/32 (31.3%) [Corrected] subjects in the SoC group achieved hemostasis without needing re-treatment (P < 0.0001). Compared to the SoC group, the FP group showed better hemostasis at 10 min post-randomization [58/59 (98.3 %) vs. 28/32 (87.5 %); P = 0.01], lower mean time to hemostasis (6.1 ± 13.5 vs. 17.8 ± 32.0 min), and a less frequent need for re-treatment (5.1 vs. 53.1 %). The triangular test for binary response demonstrated the FP to be superior to SoC (95 % CI 1.474-3.290; P < 0.0001). Safety profiles in both groups were similar to those typically observed after long-duration surgery. CONCLUSION: The FP is safe and superior to SoC for controlling challenging severe soft-tissue bleeding encountered during intra-abdominal and thoracic surgical procedures.

A prospective, randomized, controlled trial of the efficacy and safety of fibrin pad as an adjunct to control soft tissue bleeding during abdominal, retroperitoneal, pelvic, and thoracic surgery.

BACKGROUND: This study evaluated the hemostatic effectiveness and safety of Fibrin Pad (Omrix Biopharmaceuticals Ltd.) vs absorbable hemostat in patients undergoing nonemergent surgery. Fibrin Pad is a topical absorbable hemostat designed to be effective in a variety of soft tissues and across multiple bleeding intensities. STUDY DESIGN: Patients 18 years and older, requiring abdominal, retroperitoneal, pelvic, or thoracic (noncardiac) surgery and with an appropriate soft-tissue target bleeding site (TBS), were randomized to receive Fibrin Pad or absorbable hemostat (NCT00658723). Patients were stratified by bleeding severity at the TBS. Assessments included percentage of patients achieving hemostasis at 4 minutes after randomization with no rebleeding requiring treatment during the subsequent 6 minutes (primary endpoint), proportion of patients achieving hemostasis at 10 minutes, and incidence of treatment failure. RESULTS: On the primary endpoint, 98.3% of patients with Fibrin Pad and 53.3% with absorbable hemostat achieved hemostasis at 4 minutes (p < 0.0001). The treatment differential was magnified (efficacy was maintained with Fibrin Pad but decreased with absorbable hemostat) with increasing bleeding intensity: in patients with mild bleeding, 100.0% vs 80.0% achieved hemostasis with Fibrin Pad and absorbable hemostat (p = 0.03), respectively; rates were 96.6% vs 26.7%, respectively (p < 0.0001) with moderate bleeding. Percentages of patients who achieved hemostasis at 10 minutes were: Fibrin Pad, 98.3% and absorbable hemostat, 73.3% (p < 0.0001). Incidences of adverse events were comparable between groups. CONCLUSIONS: Fibrin Pad is superior to absorbable hemostat (SURGICEL Original Absorbable Hemostat [Ethicon]) in soft-tissue bleeding control and is safe and effective as an adjunct for rapidly and reliably achieving hemostasis for soft-tissue bleeding during surgery.

A phase III, randomized, controlled, superiority trial evaluating the fibrin pad versus standard of care in controlling parenchymal bleeding during elective hepatic surgery.

INTRODUCTION: Haemostasis after liver resection may be difficult to achieve as a result of the presence of challenging bleeding, the anatomic landscape of the liver and the quality of tissue making up the hepatic parenchyma. The fibrin pad (FP) is a topical absorbable haemostat designed to be effective in a variety of tissues and across multiple bleeding intensities. This is the first clinical trial to evaluate the hemostat's safety and effectiveness in controlling bleeding during elective hepatic resection. METHODS: This prospective, randomized, controlled superiority trial enrolled 104 subjects undergoing elective hepatectomy in 5 countries. After parenchymal transection, subjects with an appropriately defined target bleeding site (TBS) were stratified according to the type of hepatic parenchyma and immediately randomized 1:1: FP versus Standard of Care (SoC). SoC comprised manual compression with the use of an approved topical absorbable haemostat. The primary endpoint was haemostasis at 4 min from identification of the TBS, with no re-bleeding requiring re-treatment prior to abdominal closure. Results were stratified for both normal and abnormal (steatosis or cirrhosis) hepatic parenchyma. All subjects were followed for 60 days post-operatively. RESULTS: The intent-to-treat (ITT) analysis showed an overall treatment difference of 53.0% (P < 0.001), 82.5% (33/40 FP) versus 29.5% (13/44 SoC) in achieving haemostasis at 4 min with no re-bleeding requiring treatment up to wound closure. The per protocol analysis showed an overall treatment difference of 65.7% (P < 0.001), with 33/35 successes (94.3%) in the FP group and 12/42 in the SoC group (28.6%). The stratification results showed treatment differences between the normal parenchyma group, 63.6% (95.8% FP versus 32.3% SoC P < 0.001) and a larger difference of 72.7% in the abnormal parenchyma group (90.9% FP versus 18.2% SoC P = 0.0003). Post-operative intra-abdominal fluid collections were less frequent in the FP group (3.4% FP versus 13.3% SoC P = 0.059). There was no difference in the safety profile between the FP or SoC groups. CONCLUSIONS: The FP is safe and effective when used as an adjunct to achieve haemostasis during hepatic surgery. The success rate of achieving haemostasis with a FP remained high compared with the SOC group, especially in steatotic or cirrhotic liver tissue where the control success rates diminish. In addition, FP treatment of hepatic parenchymal surfaces may reduce the risk of post-operative biliary and fluid collections.

Synchronous resection of colorectal primary and hepatic metastasis.

Up to 50% of the over 140,000 new colorectal cancer patients will present with synchronous colorectal cancer and liver metastasis. Surgical management of patients with resectable synchronous colorectal hepatic metastasis is complex and must consider multiple factors, including the presence of symptoms, location of primary tumor and liver metastases, extent of tumor (both primary and metastatic), patient performance status, and underlying comorbidities. Possible approaches to this select group of patients have included a synchronous resection of the colorectal primary and the hepatic metastases or a staged resection approach. The available literature regarding the safety of synchronous versus staged approaches confirms that a simultaneous resection may be performed in selected patients with acceptable morbidity and mortality. Perioperative mortality when minor hepatectomies are combined with colorectal resection is consistently ≤5%. Perioperative morbidity varies considerably following both synchronous and staged resections. However, the bulk of the existing literature confirms that simultaneous resections are both feasible and safe when hepatic resections are limited to <3 segments. Data regarding the oncologic outcomes following synchronous versus staged resections for Stage IV colorectal cancer are more limited than those available regarding postoperative morbidity and mortality. The available data suggest equivalent overall and disease-free survival regardless of timing of resection. Experience with minimally invasive combined colorectal and hepatic resections is extremely limited to date and consists exclusively of small single center series. The potential benefits of a minimally invasive approach will await the results of larger studies.

A randomized trial of aprotinin-free fibrin sealant versus absorbable hemostat.

BACKGROUND: This study evaluated the safety and hemostatic effectiveness of a tranexamic acid- and aprotinin-free fibrin sealant versus an absorbable hemostat in soft tissue during elective retroperitoneal or intra-abdominal surgery. MATERIALS AND METHODS: This randomized, active-controlled, multicenter study enrolled patients who were undergoing elective retroperitoneal or intra-abdominal surgery and required adjunctive hemostatic measures at the target bleeding site (TBS). Patients were randomized (time = 0 minutes) to receive fibrin sealant or absorbable hemostat. The primary endpoint was the absence of bleeding at the TBS at 10 minutes. Secondary endpoints included the absence of bleeding at 4 and 7 minutes and the incidence of treatment failure (bleeding at 10 minutes or brisk bleeding requiring additional hemostatic measures), and the incidence of complications potentially related to bleeding. Adverse events were assessed. RESULTS: Patients (N = 124) were randomized to receive fibrin sealant (n = 62) or absorbable hemostat (n = 62). A higher percentage of patients who received fibrin sealant versus absorbable hemostat achieved hemostasis within 10 minutes (95.2% vs 82.3%; 95% CI, 1.02-1.35) and also at 4 (74.2% vs 54.8%; 95% CI, 1.04-1.80) and 7 (90.3% vs 77.4%; 95% CI, 1.00-1.39) minutes. A lower incidence of treatment failure was observed for patients receiving fibrin sealant. Similar incidences of adverse events and complications potentially related to bleeding were observed. CONCLUSIONS: This tranexamic acid- and aprotinin-free fibrin sealant is safe and effective for achieving hemostasis in soft tissue during elective retroperitoneal or intra-abdominal surgery.

Predicting poor outcome following hepatectomy: analysis of 2313 hepatectomies in the NSQIP database.

BACKGROUND: For the past two decades multiple series have documented that liver resection has become safer. The purpose of this study was to determine the current status of hepatic resection in the USA by analysing the multi-institutional experience within the National Surgical Quality Improvement Program (NSQIP) dataset. METHODS: Of the 363,897 cases in the 2005-2007 NSQIP Participant Use File, 2313 elective open hepatectomy cases were identified (1344 partial, 230 left, 510 right and 229 extended hepatectomies). A total of 57 perioperative risk factors and 28 postoperative complications were compared. To determine the applicability of NSQIP general risk models to hepatic surgery, the prognostic value of standard multivariate analysis was compared with the NSQIP general surgery aggregate risk indices (expected probability of morbidity [morbprob], expected probability of mortality [mortprob]). RESULTS: The median age of patients listed in the database was 60 years; sex distributions were equivalent; 78% were White; 65% of patients had an ASA score of 3 or 4, and the most prevalent co-morbidity was hypertension (46%). A total of 41% of patients had disseminated cancer, 19% of whom had received chemotherapy within 30 days of surgery. The overall 30-day mortality rate was 2.5% (57/2313) and the 30-day major morbidity rate was 19.6% (453/2313). Multivariate analysis identified nine risk factors associated with major morbidity and two risk factors associated with mortality. In contrast, the morbprob and mortprob statistics did not predict outcomes accurately. For those patients who developed major morbidity, the median length of stay was longer (10 vs. 6 days; P = 0.001) and the mortality rate was higher (11.3% vs. 0.3%; P = 0.001). CONCLUSIONS: Analysis of the NSQIP experience with hepatectomy indicates that the current mortality and major morbidity rate benchmarks are 2.5% and 19.6%, respectively. Poor outcomes were associated with nutritional status, liver function and the extent of hepatectomy. The NSQIP general surgery morbprob and mortprob values were relatively poor predictors of post-hepatectomy observed morbidity, indicating the need for specialty-specific NSQIP modelling.

Timing of referral impacts surgical outcomes in patients undergoing repair of bile duct injuries.

Bile duct injury (BDI) after laparoscopic cholecystectomy (LC) remains a significant surgical challenge. Despite claims to the contrary, the incidence of bile duct injury has remained elevated since the introduction of LC. Several issues regarding the surgical management of BDI are controversial, including: (i) identification of the surgeon and centre most capable of managing the injury, (ii) timing of surgical repair, (iii) incidence and significance of associated vascular injury and (iv) identification of patient factors which significantly impact outcome after repair. Variability in timing of referral of BDI to tertiary centres has been noted in the literature. The impact of timing of referral upon post-operative outcomes after definitive surgery has yet to be clearly investigated. We report our experience with 44 patients who required reconstructive surgery after BDI. In contrast to the many studies available in the literature, patients in the current study were classified according to a modern injury classification system. Additionally, we examined the impact of delayed referral to our centre on short- and long-term outcomes after surgical repair of BDI.

Chemotherapy within 30 days prior to liver resection does not increase postoperative morbidity or mortality.

BACKGROUND: Liver resections (LRs) are performed with increasing frequency for metastatic disease. To minimize the risk of postoperative complications, a period of 6 weeks between the last dose of chemotherapy and LR is typically recommended. The current study examines postoperative morbidity and mortality following LR in patients who received chemotherapy within 30 days prior to LR. METHODS: The merged 2005-2007 National Surgical Quality Improvement Program (NSQIP) Participant Use File was queried for perioperative risk factors, laboratory values and postoperative occurrences or complications in patients who underwent LR. Patients were grouped according to their receipt or non-receipt of chemotherapy within 30 days prior to LR and major postoperative complications. RESULTS: A total of 2331 patients underwent LR; 2147 did not receive chemotherapy within 30 days of resection (No Chemo group) and 184 received chemotherapy within 30 days prior to resection (Chemo group). The groups were similar with regard to preoperative co-morbidities and operative factors. The median NSQIP statistically computed morbidity probability was similar between the groups (No Chemo 0.32, Chemo 0.34; P= 0.07), whereas the median mortality probability was higher in the Chemo group (0.02) than the No Chemo group (0.014; P= 0.001). Thirty-day survival was similar between the two groups (No Chemo 97%, Chemo 98%; P= 0.44). Major complication rates did not differ between the groups (No Chemo 20%, Chemo 18%; P= 0.51). Factors associated with major complications in the Chemo group included: extent of resection; intraoperative transfusion; preoperative ascites, and preoperative haematocrit. DISCUSSION: Major morbidity was not increased in Chemo patients. The strongest predictors of major postoperative complications in the Chemo group were extent of resection and intraoperative red cell transfusion. Although the NSQIP dataset does not include data about tumour type or chemotherapy regimen, these data suggest that LR may be safely performed within 30 days of chemotherapy, thereby minimizing the length of time during which patients do not receive systemic treatment.

Transampullary pancreatic duct stenting decreases pancreatic fistula rate following left pancreatectomy.

BACKGROUND/AIMS: Significant improvements in mortality following pancreatic surgery have been noted by high-volume centers in recent years. Despite this, morbidity from pancreatic resection remains high, with postoperative pancreatic fistula remaining a common problem following distal pancreatectomy (DP). Rates of pancreatic fistula following distal pancreatectomy have ranged from 0 to 61% in a recent meta-analysis of surgical techniques and impact upon pancreatic fistula rates. We postulated that intraoperative placement of a transampullary pancreatic duct stent (TAPDS) at the time of distal pancreatectomy, would decrease ampullary complex-mediated elevation in pancreatic duct pressures, improve healing of the ligated pancreatic duct and result in a decrease in pancreatic fistula following distal pancreatectomy. METHODOLOGY: Sixteen consecutive patients underwent distal pancreatectomy plus TAPDS and were compared to 43 control patients who underwent distal pancreatectomy by the same surgeon, with identical management of the pancreatic remnant. Distal pancreatectomy was performed as the primary operation or as part of an en-bloc resection for a primary malignancy other than pancreatic adenocarcinoma. In patients who underwent transampullary pancreatic duct stenting (TAPDS), the pancreatic duct was identified after transection of the pancreatic parenchyma. A soft, pediatric feeding tube was inserted directly into the pancreatic duct and carefully fed into the duodenum (confirmed by palpation). The stent was placed distally, one centimeter from the cut-edge of the pancreatic duct, which was then ligated as described earlier. Closure of the pancreatic parenchyma was identical to those patients who did not undergo TAPDS placement. Common perioperative outcomes were assessed, including pancreatic fistula. RESULTS: No statistically significant differences where found between the rates of intraabdominal abscess, intraabdominal hemorrhage or need for reoperation. Pancreatic fistula rates and average length of stay were significantly decreased in patients undergoing distal pancreatectomy with TAPDS (p<0.05 and p<0.0001 respectively). CONCLUSIONS: Statistically significant reductions in pancreatic fistula and average length of stay were noted in patients who underwent stenting of the pancreatic duct with TAPDS.

Phase 3, randomized, double-blind study of plasma-derived human thrombin versus bovine thrombin in achieving hemostasis in patients undergoing surgery.

OBJECTIVE: To compare the effectiveness of plasma-derived human thrombin and bovine thrombin for achieving hemostasis during surgery. METHODS: Adults (N = 305) with > or = 1 mild or moderate bleeding site not manageable by conventional modalities during elective cardiovascular, neurologic, or general surgical procedures at multiple study centers were randomized to human (n = 153) or bovine (n = 152) thrombin, applied topically with an absorbable gelatin sponge. Bleeding was assessed 3, 6, and 10 min post-application. Other evaluations included laboratory assessments, vital signs, blood loss, blood transfusions, time in specialty-care units, procedure duration, and length of hospital stay. Blood samples for antibody assessment were collected at baseline and postoperative week 5. RESULTS: The proportion of patients achieving hemostasis within 10 min (primary outcome) was equivalent for human and bovine thrombin (97.4 vs. 97.4%, respectively; ratio, 1.00; 95% CI, 0.96-1.05). The proportions of patients achieving hemostasis at 6 min (94.8 vs. 92.8%) and 3 min (73.2 vs. 72.4%) were also equivalent. No clinically meaningful differences were noted for other variables. The products had similar adverse event profiles. More patients (12.7%) who received bovine thrombin demonstrated seroconversion for > or = 1 of the 4 antibodies assayed than patients who received human thrombin (3.3%). No patients in the human thrombin group developed seroconversion for anti-human thrombin or anti-human factor V/Va antibodies. Limitations of this study include the lack of a placebo-control group, the potential for inter-surgeon variability, and the fact that antibody assessment was not evaluable in all patients. CONCLUSIONS: Plasma-derived human thrombin and bovine thrombin were equivalent in achieving hemostasis within 10, 6, and 3 min and had comparable safety profiles. None of the patients receiving human thrombin developed seroconversion for antibodies to any of the human antigens.

The inflammatory cascade in acute pancreatitis: relevance to clinical disease.

Acute pancreatitis is an inflammatory condition that is initiated by the intra pancreatic activation of proteases. Pancreatic enzyme activation triggers a local and systemic inflammatory response that is associated with recruitment of inflammatory cells into the pancreas and a widespread up-regulation of inflammatory markers in distant tissues.

Gastroduodenal artery used for arterial reconstruction during the Whipple operation.

The right hepatic artery and the common hepatic artery originate from the superior mesenteric artery in approximately 10-15% of the population. Reconstruction of the hepatic artery using the gastroduodenal artery has previously been described to repair hepatic artery injury during the performance of biliary and pancreatic resections. We report the utilization of this technique in patients undergoing pancreaticoduodenectomy for a periampullary neoplasm involving a replaced right hepatic artery.

Early perioperative outcomes and pancreaticoduodenectomy in a general surgery residency training program.

Current trends in national health care are triggering a reassessment of training in general surgery. Currently, 75% of general surgery residents seek postgraduate fellowship training, and significant debate has occurred regarding the best manner for surgeons to acquire competency in performing complex operations. Pancreaticoduodenectomy (PD) is a complex procedure performed infrequently by most surgical graduates. From 1990 through 1997, the average number of PD operations performed per general surgery graduate ranged from 1.5 to 2.5. We examine the surgical outcomes following PD performed by surgical resident staff in a university-based general surgery training program. Between January 2001 and October 2004, 164 patients underwent PD for periampullary disease. Data were prospectively entered into a computerized database, including resident participation. We analyzed 30-day mortality and morbidity rates. Perioperative outcomes were 30-day mortality (2.2%), pancreatic fistula (6.1%), reoperation (2.2%), average length of hospital stay (13.5 days), mean operating time (489 minutes), and median estimated blood loss (1274 ml per case). PD can be performed with an acceptable morbidity and mortality within the teaching structure of a general surgery training program. These outcomes are likely related to the performance of PD at a high-volume, tertiary center by a single surgeon and compare favorably to best-practice benchmark outcomes.

Method of pyloric reconstruction and impact upon delayed gastric emptying and hospital stay after pylorus-preserving pancreaticoduodenectomy.

Preservation of the pylorus at the time of pancreaticoduodenectomy has been associated with equal oncological outcomes when compared to the classical Whipple operation. Multiple studies have demonstrated that pylorus-preserving pancreaticoduodenectomy (PPPD) has equal or superior outcomes regarding quality of life when compared with the traditional Whipple operation, but many studies have suggested a higher incidence of delayed gastric emptying (DGE). DGE prolongs hospital stay, and its association with PPPD has hampered its adoption by many pancreatic surgery centers. We describe a novel surgical technique for the prevention of delayed gastric emptying following pylorus-preserving pancreaticoduodenectomy. The technique of pyloric dilatation appears to decrease the incidence of delayed gastric emptying and facilitates earlier hospital discharge, when compared with standard pylorus preserving pancreaticoduodenectomy.

Brief intervention by surgeons can influence students toward a career in surgery.

BACKGROUND: General surgery training programs are experiencing an alarming decrease in applicants. The purpose of the current study was to determine whether exposing students to surgery through a brief intervention early in their medical education could influence perceptions toward surgery as a career choice. METHODS: First-year medical students were asked to rank 19 items coded on a Likert-type scale from 1 (not important) to 8 (very important) regarding their beliefs about surgery as a career both before and after a brief 1-h intervention with a panel of surgeons. Each panelist spoke about his or her professional and personal lives, followed by a question and answer period. Survey data were analyzed by Wilcoxon sign-rank and Spearman rank correlation. RESULTS: Of 210 first year students, 121 (58%) students voluntarily attended and completed the presurvey and 94 (45%) the post, of which 82 were matched responses. Preintervention responses revealed that career opportunities, intellectual challenge, and the ability to obtain a residency position were positively correlated with surgery (P < 0.007) whereas length of training, lifestyle during residency, lifestyle after training, and work hours during residency were negatively correlated (P < 0.01). The following factors were significantly influenced by the intervention: academic opportunities, patient relationships, prestige, and gender distribution became more important whereas concern about debt and length of training became less important. CONCLUSIONS: Positive encounters with surgeons can favorably influence the perceptions of first-year medical students toward a career in surgery. In addition to addressing lifestyle issues, surgeons can and must make a concerted effort to interact with medical students early in their education and foster their interest throughout their career.

Lessons learned from the evacuation of an urban teaching hospital.

HYPOTHESIS: Valuable lessons can be learned from the emergent evacuation of a large urban teaching hospital because of flooding. DESIGN: Case report. SETTING: Four hundred fifty-bed adult and 150-bed children's tertiary referral teaching hospital. CASE SUMMARY: Massive rainfall from tropical storm Allison caused extensive flooding. Emergency power came on at 1:40 AM. Complete power loss occurred at 3:30 AM. The decision to begin evacuation of patients was made at approximately 10:30 AM. All 575 patients were either discharged from the hospital (169 patients) or evacuated (406 patients) to 29 other facilities by both ambulance and helicopter by 3 PM the next day. Six deaths occurred, none of which could be attributed to the conditions created by the flooding. CONCLUSIONS: The lessons learned from this experience included the following: (1) flooding will occur in a flood plain; (2) electrical power outages are not necessarily temporary-begin evacuation; (3) appoint a triage officer from those available; (4) have a reliable in-house communication system not dependent on telephone lines or electricity; (5) have a reliable telephone system for contacting outside facilities; (6) have flashlights available on all units; (7) have battery-operated exit signs and stairway lights; (8) maximize use of volunteers when they are available and fresh; (9) maintain a paper record of all patient transfers; (10) coordinate loading of ambulances and helicopters for patient transfer; and (11) reassign staff as necessary to care for transferred patients. Emergent evacuation of a large, tertiary hospital requires extensive effort from both the hospital staff and the community.