Routine Intra-Operative Bile Culture and Drainage Fluid Culture as a Guide for Antibiotic Therapy in Pancreatic Surgery

Context Despite improvement in mortality, surgical morbidity in pancreatic surgery remains high, and infectious complications have a main role. Objective To evaluate the role of intra-operative bile culture as a guide for post-operative antibiotic therapy in case of infectious complications. Methods From January 2010 to June 2012 we realized 136 pancreatico­duodenectomies for periampullary diseases. Intra-operative bile sampling and postoperative sampling from peri-pancreatic drainage fluid for culture were performed in 110 patients (81%) who were enrolled in this study. Forty-four patients (40%) experienced infectious complications (Group A) while 66 patients (60%) did not (Group B). Infectious surgical complications were: 31 POPFs (13 grade A, 18 grade B-C), 6 abdominal abscesses, 5 biliary fistulas, 1 gastro-duodenal fistula and 19 wound infections (some patients has more than one complication). Data were collected prospectively. Results Bile cultures resulted positive in 61/110 patients (56%), there were no differences in the rate of infected bile between the two Groups (57% vs. 55%); preoperative biliary stenting was strongly correlated with biliary infection (100% in stented patients vs. 18% in non-stented; P<0.001). Drainage fluid cultures resulted positive in 66/110 (61%) patients: in Group A they were positive in 40/44 patients (91%) while in Group B in 26/66 patients (40%) (P<0.05, chi-square test). In Group A negative drainage cultures belonged to patients who developed grade A POPF or wound infection. In Group B positive drainage cultures belonged to patients with infected bile in 62% of cases; in 19% of cases cultures were contaminated by skin germs (Staphylococcus). From drainage fluid culture, we isolated 102 germs (55 Gram +, 41 Gram -, 8 fungi) in Group A and 37 germs (26 Gram +, 11 Gram -) in Group B; 44/102 germs (43%) and 12/37 germs (32%) in Groups A and B, respectively were identical to that found in bile cultures. Conclusion In patients who develop abdominal infectious complications the high concordance between bile and drainage fluid cultures suggests that bile cultures can be useful as a guide for postoperative antibiotic therapy. The presence of infected bile can cause contamination of peritoneal fluid even in uncomplicated patients but it has no clinical relevance

History of Previous Cancer in Patients Undergoing Resection for Pancreatic Adenocarcinoma

Context The increase in mean expectancy of life observed in recent years in industrialized countries revealed how cellular aging processes lead to an higher risk of cancer development. This is the reason why surgeons are nowadays often facing with patients whose clinical history is positive for different tumors. Literature suggests a possible association between pancreatic and other cancers, with a genetic substrate probably but not exclusively implicated. Objective Evaluation of the prevalence of other tumors among patient with pancreatic ductal adenocarcinoma (PDAC) resected in a tertiary care center. Methods Between January 2010 and June 2013 we performed 161 pancreatic resection for PDAC. In the present study we retrospectively analyzed past medical history of these patients searching for previous occurred  neoplasms. Epidemiological data about cancer occurrence in our country were obtained from Tumors Registry Italian Association (AIRTUM) and ISS Epidemiology Service. Results Mean age of our 161 resected PDAC patients was 68±10 years. Among them, 35 (21.7%) had a previous history of cancer, diagnosed at a mean age of 60±11 years. The more frequent tumors observed were breast (n=15; 9.3%) and genitourinary tract neoplasms (n=11; 6.8%), of which 5 prostate cancer (3.1%). According to AIRTUM database, standardized breast cancer prevalence in Italy is 1,869/100,000 females (1.9%), while standardized prostate cancer prevalence is 896/100,000 (0.9%). Most of the patients with prostate or breast cancer (73%) received diagnosis of resectable pancreatic cancer during the follow-up of the previous neoplasm. However, the PDAC stage on surgical specimens of these patients (according to AJCC, TNM 7th Ed) was not significantly lower compared with the control group of patients without a previous cancer (P=0.181). Conclusions Even though breast and prostate cancer are notoriously high incidence and long survival related cancers, their prevalence among PDAC patients seems to be interestingly higher than in standard population. Further studies are necessary to investigate genetic and environmental bases of this relationship. A clinical implication of this correlation could be a different proportion of resectable and advanced PDAC at diagnosis among patient performing an oncological follow-up. For this reason, an accurate radiological assessment adequate for pancreas evaluation should be suggested during follow up of patient treated for breast and genitourinary cancer

Reactive C Protein and White Blood Cells Levels as Early Predictors of Postoperative Inflammatory Complications After Pancreatic Surgery

Context Pancreatic surgery is challenging and associated with high morbidity, even in high-volume surgical settings; this is probably the reason why, while in other surgical areas fast-track recovery programs are nowadays widely performed, pancreatic surgeons are still reluctant in applying them. The identification of clinical and diagnostic criteria to early predict postoperative inflammatory complications (PIC) development could be useful in tailoring postoperative management to patient personal risk. Objective Aim of the study is the assessment of diagnostic accuracy of reactive C protein (RCP) and white blood cells (WBC) levels as early predictors of PIC in pancreatic surgery. Methods Between January 2010 and June 2012 we performed 225 pancreatic resections for benign and malignant disease, of which: 136 pancreatico­duodenectomies (PD), 65 left pancreatectomies (LP), 11 total pancreatectomies (TP), 12 enucleations (EN). Postoperative levels of RCP (detected by our laboratory with a high-sensitivity method) and WBC from postoperative day 1 (POD 1) to POD 7, recorded in our perspective electronic database, were analyzed searching for association with PIC (anastomotic leakage, sepsis, airways, urinary tract and wound infection, abdominal collection); using the receiver operating characteristic method (ROC curve), diagnostic accuracy was evaluated by an area under the curve (AUC) analysis. Results PIC occurred in 39.6% of patients (43.4% after PD; 30.3% after LP; 45.5% after TP, 41.7% after EN). Cancer diagnosis, preoperative chemotherapy, age and ASA score did not influence PIC rates. Mean RCP levels were significantly higher in patients who developed PIC each day from POD 1 to POD 7 (P<0.001), while mean WBC levels were significantly higher in this group only from POD 4 to POD 7 (P<0.001). The highest diagnostic accuracy was observed for RCP levels on POD 4 (AUC=0.835), with a cut-off value of 14,62 mg/L, whose sensibility and specificity were 83% and 81%, respectively. In a similar way, RCP postoperative levels resulted significantly associated, from POD 1 to POD 7, with high grade PIC (grade II-V according to Clavien-Dindo classification) (P<0.001). We could not identify any valuable cut-off for WBC. Conclusion RCP postoperative level on POD 4 appears to be an useful early predictor for PIC in pancreatic surgery and could guide patient’s management (fast track recovery programs and/or further diagnostic research for septic processes); otherwise, WBC values, probably more influenced than RCP by physiological postoperative acute inflammatory response, fail in decisively distinguishing patients who are developing PIC

Frequent Ineffectiveness of Cefazolin as Perioperative Prophylaxis in Pancreatic Surgery

Context Cefazolin is widely accepted as routine antimicrobial prophylaxis in hepatobiliary and pancreatic surgery. Microbial resistance to this drug is rapidly increasing, nullifying the expected beneficial effects of its administration and exposing patients to potentially severe infective complications. Objective Analysis of bile culture results and comparison with postoperative outcomes in patients undergoing pancreatic surgery in a referral centre; definition of an alternative prophylaxis schedule. Methods Between Jan 2010 and Jan 2013 we performed 170 consecutive major resections requiring abdominal bile exposure, of which 156 pancreaticoduodenectomies and 14 total pancreatectomies. We routinely performed culture on bile samples obtained intraoperatively and on drain liquid samples taken on fifth postoperative day. We then prospectively recorded data about postoperative septic complications and analyzed them consulting our referral infectious disease specialist. Results Among the 170 patients, 95 (56%) had positive bile cultures, of which 73 (43%) with multiple microbes. The great majority of microbes obtained belonged to Enterococcus Spp. (E. Faecalis 29%, E. Facium 18%), while other well represented germs were E. Coli (18%), Enterobacter Spp. (18%), Klebsiella Spp. (12%). Eighty patients (47%) received preoperative biliary stenting, which resulted strongly associated with bile infection (100% vs. 17%, P<0.001). Bile infection was associated with higher morbidity both in patient with stent (72% vs. 56%, P=0.037), and without stent (87% vs. 56%, P=0.026). Forty-seven (49%) of infected bile samples harbored microbes resistant to cefazolin; in these patient postoperative infective complication rate was significantly higher (61% vs. 39%, P=0.016) than in patients that did not harbor. The rate of cefazolin resistant microbe identification was even higher on drain samples (58%), which shared microbes with previous bile sample in 80% of cases, even though it was not associated with higher morbidity. Analyzing antimicrobial susceptibility of these germs we identify the association ampicillin-sulbactam as a new possible drug for perioperative prophylaxis. Conclusions Infective complications in pancreatic surgery could lead to severe consequences. Adequate antimicrobial prophylaxis, selected using epidemiological evidence from patients samples, is mandatory. Ampicillin-sulbactam could be a viable alternative to cefazolin in surgical procedures involving abdomen bile exposure, although further studies are necessary to validate this drug benefits

Laparoscopic Versus Open Left Pancreatectomy: Short Term Outcome and Cost-Benefit Analysis

Context An increasing number of surgeons are today performing laparoscopic left pancreatectomy (LLP), since available nonrandomized studies demonstrated its feasibility, safety and oncologic adequacy. However, most existing data come from small single-institution reports or from heterogeneously composed multicenter comparisons. Moreover, there is very limited information about economic implications of minimally invasive pancreatic surgery. Objective This study reports our experience in laparoscopic left pancreatectomy compared with open technique (OLP), assessing perioperative outcomes and financial impact of this procedure in a high volume surgical setting. Methods Between February 2009 and June 2011 we performed 112 left pancreatectomies, 53 of which (47%) were LLP. Excluding the initial learning curve, the remaining 43 patients were matched with a control group selected from our perspective electronic database. Match criteria were gender, age, ASA score, BMI, lesion site, malignant or benign disease. Results Mean operative time was similar (LLP 216±61 min; OLP 214±7 min; P=0.885), blood loss was reduced in LLP (388±371 mL vs. 571±599 mL, P=0.092), especially in cancer patients (514±350 mL vs. 946±787 mL, P=0.072); intraoperative transfusion and unplanned splenectomy rates were similar. Larger lesions were associated with increased unplanned splenectomy rate. Conversion rate (CR) was 18%; higher BMI (>30 kg/m2) and pancreatic body site were associated with increased CR. There were no differences in positive margin rates, number of nodes examined and number of N1 patients. There was no mortality in both groups. Overall morbidity was equable (63% in LLP, 60% in OLP; P=0.958), as well as major complication rate (7% in LLP, 3% in OLP; P=0.604). Clinically significant pancreatic fistula rate was 14% in LLP and 9% in OLP (P=0.728). No grade C fistulas were observed. An equal proportion of patients in each group was discharged before removing surgical drain. Delayed gastric empting, wound and urinary tract infection were more frequent in OLP. Mean LOS was 8.37 days in LLP vs. 8.81 days in OLP (P=0.481); LOS in non complicated patients was 6.96 days in LLP vs. 7.50 days in OLP (P=0.220). Mean number of diagnostic test, transfusion rate, antibiotic administration and readmission rate were similar. Each patient of LLP group saved €168.47 because of shorter LOS and slightly fewer complication cost, generating however an extra cost of €767,01 due to more expensive surgical instruments. Conclusion This study confirms safety and oncologic adequacy of this technique, identifying probable risk factors for conversion and demonstrating economic sustainability of LLP. Final balance still have to be realized considering indirect costs as shorter home convalescence, quality of life and better cosmetic result

Morphological Features of Pancreatic Stump, Other than Wirsung Diameter and Pancreatic Texture, Influence Pancreatic Fistula Rate After Pancreaticoduodenectomy

Context Pancreaticoduodenectomy (PD) is still characterized by high morbidity rates even in high volume centers, mainly represented by postoperative pancreatic fistula (POPF) and its associated further consequences. Wirsung diameter and pancreatic texture are well known features related to increased POPF risk. However, limited information about the relationship between morphological features of pancreatic stump and POPF onset is available. Objective Aim of the study was to evaluate the relationship between pancreatic stump morphology, intra-operatively assessed, and the occurrence of POPF in patients undergoing PD in an high volume center. Methods Between January 2010 and June 2012 we performed 136 PDs for benign and malignant disease; in a subgroup composed by 72 cases we realized a prospective study recording intra-operative measurements of the remnant pancreatic stump, recording surgeon’s judgment about pancreatic texture, and highlighting the caliber of main pancreatic duct, its position and the whole area. Between March 2011 and June 2012, in a consecutive series of 72 PD, we prospectively recorded the following characteristics of the pancreatic stump: surgeon’s judgment about pancreatic texture, diameter of main pancreatic duct, the whole area of pancreatic section (approximately calculated as elliptic), the distance between Wirsung duct and cranio-caudal and antero-posterior margins. In all patients, post-operative complications were recorded. Results Pancreatic fistula occurred in 19 cases (23.8%), 10 of them clinically significant (grade B and C according to ISGPF classification). In univariate analysis, mean Wirsung diameter resulted significantly smaller in patients with POPF (3.18 vs. 4.48 mm; P=0.007) and in patients with clinically significant POPF (P=0.015); searching for a cut off value, Wirsung diameter smaller than 4 mm demonstrated an association with higher POPF incidence (37.5% vs. 4.35%; P=0.003). Similarly, soft pancreas texture resulted associated with an increasing POPF rate (75% vs. 7%; P<0.001). Analyzing pancreatic stump morphology, we observed a relationship between larger stump areas and POFP development (206 mm2 in POPF cases vs. 131 mm2 in patients without fistula; P=0.017); moreover, main pancreatic duct decentralization appeared significantly associated with a lower POPF risk (more evident on antero-posterior axis than on cranio-caudal; P=0.019 and P=0.144, respectively). In multivariate analysis, only pancreatic stump soft texture and Wirsung diameter smaller than 4 mm were associated with POPF. Conclusion This study confirms small Wirsung diameter and soft pancreatic texture as the main determinants for POPF development. Moreover, an higher risk of failure of pancreatic anastomosis is also observed in large pancreatic stumps and when main pancreatic duct is centrally located

Enucleation of Pancreatic Head Tumors Combined With Pre-Operative Wirsung Stenting, Intra-Operative Ultrasounds and Absorbable Fibrin Sealant Patch Application: Experience on 13 Cases

Context Benign/low malignant tumors or metastasis from renal cancer of the pancreatic head can be treated by enucleation; this procedure is technically demanding and it is often followed by high morbidity rates. Objective To analyze the peri-operative outcome of our series of enucleations for tumors of the pancreatic head. Methods From January 2010 to June 2012 29 out of 149 resected periampullary tumors were cystic neoplasms, 15 were neuroendocrine tumors (NET), 1 was metastasis from renal cancer and 1 was pseudopapillary solid tumor; in 13 of them (28% of 46 patients with pancreatic diseases eligible for atypical resection) an enucleation was performed. Enucleation was contraindicated when the lesion was deeply embedded in gland’s parenchyma involving Wirsung or originating from main pancreatic duct itself (main duct type IPMN), and in case of overt malignant appearance. We analyze the features of patients who underwent enucleation. Endoscopic ultrasound was performed preoperatively in 10 patients. ERCP with Wirsung stenting was realized when the distance between the main pancreatic duct and the lesion was less than 3 mm (4 cases). In patients submitted to stent positioning the mean distance between the lesion and the Wirsung duct was 1.9 mm while in the other group of patients it was 5 mm (P<0.05, t test). Intra-operative US was performed in all patients. At the end an absorbable fibrin sealant patch (Tachosil®) was placed on the area of enucleation. Results The mean diameter of the lesion was 1.9±1.1 cm (range: 1-4.5 cm); histology revealed 2 benign side branch IPMNs, 9 G1 NET, 1 metastasis from renal cancer and 1 pseudopapillary solid tumor. Mean operative time was 209.9±60.3 minutes and mean blood loss was 97.7±63.8 mL. No mortality was observed. Overall morbidity was 46% (including POPF rate of 31%): 4 POPF (2 grade B and 2 grade A). Mean length of hospital stay was 8.5±2.7 days. The reoperation rate was nihil. Readmission regarded only 1 patient. Conclusion Enucleation is a good alternative to pancreaticoduodenectomy in benign/low malignant tumors of the pancreatic head. Pre-operative Wirsung stenting, intra-operative ultrasounds and Tachosil® application appear related to a satisfactory postoperative outcome

Morphohistological Features of Pancreatic Stump Are the Main Determinant of Pancreatic Fistula after Pancreatoduodenectomy

Introduction. Pancreatic surgery is challenging and associated with high morbidity, mainly represented by postoperative pancreatic fistula (POPF) and its further consequences. Identification of risk factors for POPF is essential for proper postoperative management. Aim of the Study. Evaluation of the role of morphological and histological features of pancreatic stump, other than main pancreatic duct diameter and glandular texture, in POPF occurrence after pancreaticoduodenectomy. Patients and Methods. Between March 2011 and April 2013, we performed 145 consecutive pancreaticoduodenectomies. We intraoperatively recorded morphological features of pancreatic stump and collected data about postoperative morbidity. Our dedicated pathologist designed a score to quantify fibrosis and inflammation of pancreatic tissue. Results. Overall morbidity was 59,3%. Mortality was 4,1%. POPF rate was 28,3%, while clinically significant POPF were 15,8%. Male sex (P=0.009), BMI≥25 (P=0.002), prolonged surgery (P=0.001), soft pancreatic texture (P<0.001), small pancreatic duct (P<0.001), pancreatic duct decentralization on stump anteroposterior axis, especially if close to the posterior margin (P=0.031), large stump area (P=0.001), and extended stump mobilization (P=0.001) were related to higher POPF rate. Our fibrosis-and-inflammation score is strongly associated with POPF (P=0.001). Discussion and Conclusions. Pancreatic stump features evaluation, including histology, can help the surgeon in fitting postoperative management to patient individual risk after pancreaticoduodenectomy