Morbidity In Pancreatic Surgery Research Articles

Re-assessing the role of peri-operative nutritional therapy in patients with pancreatic cancer undergoing surgery: a narrative review.

Pancreatic cancer is the most common medical condition that requires pancreatic resection. Over the last three decades, significant improvements have been made in the conditions and procedures related to pancreatic surgery, resulting in mortality rates lower than 5%. However, it is important to note that the morbidity in pancreatic surgery remains r latively high, with a percentage range of 30-60%. Pre-operative malnutrition is considered to be an independent risk factor for post-operative complications in pancreatic surgery, such as impaired wound healing, higher infection rates, prolonged hospital stay, hospital readmission, poor prognosis, and increased morbidity and mortality. Regarding the post-operative period, it is crucial to provide the best possible management of gastrointestinal dysfunction and to handle the consequences of alterations in food digestion and nutrient absorption for those undergoing pancreatic surgery. The European Society for Clinical Nutrition and Metabolism (ESPEN) suggests that early oral feeding should be the preferred way to initiate nourishing surgical patients as it is associated with lower rates of complications. However, there is ongoing debate about the optimal post-operative feeding approach. Several studies have shown that enteral nutrition is associated with a shorter time to recovery, superior clinical outcomes and biomarkers. On the other hand, recent data suggest that nutritional goals are better achieved with parenteral feeding, either exclusively or as a supplement. The current review highlights recommendations from existing evidence, including nutritional screening and assessment and pre/post-operative nutrition support fundamentals to improve patient outcomes. Key areas for improvement and opportunities to enhance guideline implementation are also highlighted.

Surgical treatment of non-functioning pancreatic neuroendocrine tumors: current controversies and challenges

Abstract There has been a rising trend in the incidence and prevalence of non-functioning pancreatic neuroendocrine tumors (NFPanNETs). While a significant number of the newly diagnosed NFPanNETs are asymptomatic, a majority of patients will present with liver metastasis (LM) at the time of diagnosis. Surgical resection remains the only curative treatment, especially for localized NFPanNETs. While a majority of small NFPanNETs are indolent, some are not. This heterogeneity in tumor biology presents the surgeon with the unique challenge of determining which patient will benefit from surgery, given the morbidity of pancreatic surgery. There has been a recent push for a more aggressive approach to the care of these patients, given the emergence of data supporting such measures. However, the risk of over or under treatment has generated immense debate amongst experts in the field. The heterogeneity of current practice guidelines and institutional practices around the world is a reflection of the disparate opinion on the management of NFPanNET. In this review, we set out to examine the evidence regarding some of the most controversial and challenging aspects of the surgical treatment of NFPanNET. We evaluate the following questions; should patients with small NFPanNETs ≤ 2 cm in size be resected; should patients with metastatic NFPanNETs undergo surgical debulking, and should there be resection of the primary tumor in the setting of non-resectable metastatic disease? Although there are currently no Level 1 data to answer these questions conclusively, we believe that the current literature supports a more aggressive approach to the management of NFPanNET.

Neoadjuvant Chemotherapy Alters The Biliary Microbiome In Patients With Ductal Adenocarcinoma Undergoing Pancreaticoduodenectomy

Presenter: Syed Omair Nadeem MBBS | Emory University Background: Postoperative infectious complications constitute a major source of morbidity in pancreatic surgery. For patients with pancreatic ductal adenocarcinoma (PDAC), the use of neoadjuvant chemotherapy is becoming more commonly adopted. Yet data is limited regarding its impact on the biliary microbiome. It has been hypothesized that the currently recommended peri-operative antibiotic coverages may be inadequate prophylaxis for patients undergoing pancreatic resection. The aim of this study was to determine the effect of neoadjuvant therapy on the biliary microbiome in patients with and without preoperative stenting as a surrogate for overall patient microbiome status Methods: Demographic, operative, post-operative, and biliary pathogen morphology and antibiotic sensitivity data was reviewed from consecutive patients with pathologically confirmed PDAC from January 2014 to December 2017. Data was expressed as percentages. Chi square and ANOVA testing was performed for comparison between groups. Results: A total of 263 patients with PDAC were identified. 258 cases with complete stent data were included in the analysis. Of them 199 (77.1%) had received preoperative stenting, amongst whom 71 (35.7%) had received neoadjuvant chemotherapy. Ancef/Flagyl (n=167, 84%) was the most common antibiotic combination for perioperative prophylaxis followed by Clindamycin/Aztreonam (n=16, 8%). There were no significant differences in baseline characteristics between the people who did and did not receive neoadjuvant chemotherapy. The most common pathogens isolated from biliary cultures were Klebsiella Pneumoniae (n=31, 18.5%), Enterobacter Clocae (n=20, 11.9%) and E.Coli (n=16, 9.5%). Patients who did not receive neoadjuvant chemotherapy were more likely to grow, fungi (5.5% vs 0% p=0.039), E.Coli and Enterobacter (25% vs 12.7%, p=0.039). However, growth of Gram-negative anaerobes (32.4% vs 18.8%, p= 0.030) and unspecified bacterial species (31% compared to 14.8%, p=0.007) was higher in the patients who received neoadjuvant chemotherapy. Patients who did not receive neoadjuvant therapy were more likely to grow gram-negative pathogens resistant to Ampicillin-Sulbactam (47% vs 21%, p=0.007), Cefazolin (49% vs 28%, p=0.040), Cefoxitin (42% vs 11%, p=0.009) and Cefuroxime (26% vs 4%, p=0.019) than the patients who did receive neoadjuvant chemotherapy. No differences were seen in resistance to Ampicillin (p=0.376), Aztreonam (p=0.977), Cefepime (p=0.172), Ceftriaxone (p=0.183) and Piperacillin-Tazobactam (p=0.36) (figure 1). Stratified by stent status, there were no differences in resistance patterns among patients who did and did not receive neoadjuvant chemotherapy. Conclusion: Neoadjuvant chemotherapy significantly alters the biliary microbiome in patients with PDAC undergoing pancreaticoduodenectomy. Patients who did not receive neoadjuvant chemotherapy were more likely to grow pathogens resistant to cephalosporin antibiotics and have fungal colonization of their bile compared to patients who did receive neoadjuvant chemotherapy. Perioperative antibiotic coverage should be tailored to cover enterococci and gram negative organisms, especially for the subset of patients who had a biliary stent placed

Severe morbidity after pancreatectomy is accurately predicted by preoperative pancreatic resection score (PREPARE): A prospective validation analysis from a medium-volume center

BackgroundMajor morbidity in pancreatic surgery remains high. Different scores for predicting complications have been described. Preoperative pancreatic resection (PREPARE) score is based on objective preoperative variables and offers good predictive accuracy for Clavien ≥ III complications. This study aimed to validate this score and analyze other preoperative variables in a prospective study performed in a medium-volume center. MethodsA total of 50 pancreatic resections were included. Preoperative variables were registered and PREPARE was calculated. The main outcome was severe morbidity (Clavien ≥ III) up to 30 days after discharge. The secondary outcomes were length of stay (LOS) and readmission. Statistical validation was performed to compare severe morbidity rate among the scores categories. Association with other preoperative variables (not included in PREPARE) was also tested. ResultsOf the 50 pancreatic resections, the severe morbidity was 34.0%, with median LOS of 11 days. Readmission rate was 25.5%. Severe morbidity rates according to PREPARE categories were 18.5% in low-risk group, 41.7% in intermediate-risk group, and 63.6% in high-risk group, respectively (P = 0.023). The accuracy was 72% (Hosmer–Lemeshow, P = 0.86). ROC curve was obtained both for PREPARE score expressed as incremental values and categorized as the three risk groups, showing an area under curve (AUC) of 0.736 (95% CI: 0.586–0.887; P = 0.007) and 0.712 (95% CI: 0.555–0.869; P = 0.015), respectively. PREPARE was significant in multivariate analysis. Median LOS was statistically higher as PREPARE category increases (9, 11 and 15 days in low-, intermediate- and high-risk groups, respectively; P = 0.009). Readmission was not associated with any variables. ConclusionsPREPARE behaves as an independent risk factor for severe morbidity after pancreatic surgery. Score validation shows good accuracy prediction. Increasing PREPARE category is also associated with longer LOS.

Branch duct intraductal papillary mucinous neoplasm - contra resection

Due to improvements in imaging modalities the diagnosis of branch duct intraductal papillary mucinous neoplasms (BD-IPMN) has been significantly increased in recent years. A BD-IPMN is frequently diagnosed as an incidental finding in asymptomatic patients. The optimal management of BD-IPMN is the subject of controversial discussions. Numerous studies have shown that an individualized therapeutic strategy with afollow-up observation of most BD-IPMNs is feasible and safe, considering age, comorbidities and patient preference. An accurate evaluation of BD-IPMN with adetailed anamnesis, high-resolution imaging techniques and endoscopic ultrasound is necessary. Symptomatic patients as well as patients with so-called high-risk stigmata should undergo resection. Asymptomatic patients with so-called worrisome features can either undergo surveillance or surgical resection, taking age and comorbidities into account. For BD-IPMN patients without high-risk stigmata and worrisome features and showing no symptoms, surveillance of the pancreatic lesion is the preferred approach. The high prevalence of BD-IPMN, limitations in differential diagnostics, an overestimation of the risk of malignancy due to an overrepresentation of symptomatic and suspected BD-IPMN in resected cohorts, an overestimated role of BD-IPMN as precursor lesions for pancreatic carcinoma and evidence of the safety of follow-up surveillance, underline the enormous importance of surveillance. Based on this and considering the background of anotable mortality and morbidity of pancreatic surgery, aggressive management with prophylactic surgical resection is not justified for all BD-IPMN, in particular for low-risk lesions.

Effect of preoperative biliary drainage for obstructive jaundice on postoperative course after pancreaticoduodenectomy

s / Pancreatolog S108 Aims: Definition of an alternative prophylaxis targeted on bile cultures in pancreatic surgery and validation of SSIs incidence. Patients & methods: Between Jan-2010 and Oct-2013 we performed 222 consecutive pancreatic resections with bile contamination (203 pancreaticoduodenectomies, 19 total pancreatectomies). We routinely performed culture on intra-operative bile samples and prospectively recorded SSIs. Analyzing antimicrobial susceptibility of detected germs, we introduced from Mar-2013 ampicillin-sulbactam as alternative to cefazolin for perioperative prophylaxis; we therefore realized a comparison between patients receiving standard (n1⁄4170) and new (n1⁄452) schedule. Results: Analyzing the standard group, 56% of patients had positive bile cultures; 49% of microbes belonged to Enterococcus Spp. 47% of patients had a preoperative biliary stent: it was strongly associated with bile infection (100% vs 17%, p<0,001); bile infection was associated with higher morbidity in patients with (72% vs 56%, p1⁄40,037) or without stent (87% vs 56%, p1⁄40,026), as well as with higher SSIs (63% vs 37%, p1⁄40,113). 49,5% of infected bile samples harbored cefazolin-resistant microbes: in these patients postoperative global SSIs were higher (71% vs 30%, p1⁄40,023) as well as superficial, deep and organ/space-SSIs. Since we administered ampicillin-sulbactam perioperative prophylaxis, we observed a significant decrease of superficial (20,6% vs 3,8%, p1⁄40,005) and deep (8,8% vs 0, p1⁄40.025) SSIs; we noted no difference in organ/space-SSIs. Conclusion: Bile infection leads to a significant increase of postoperative morbidity in pancreatic surgery. Bile-culture targeted prophylaxis seems effective in reducing SSIs.

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.

Abstract PR-9: Results of surveillance for hereditary pancreatic cancer using MRI(CP)

Abstract PR-9 Introduction Surveillance for pancreatic cancer (PC) in high risk groups may lead to early detection and may improve overall survival. We screened for early pancreatic neoplasia in individuals with a p16- germline mutation or with a strong family history of PC (FPC). Methods Since 2000, high risk individuals were offered annual surveillance by Magnetic Resonance Imaging (MRI(CP)). In case of suspected lesions, surgery or additional follow up (FU) was provided. In case of doubt, the examination was repeated within 2-4 months. Results A total of 66 (28 M) individuals with an average age of 56 yrs (range: 40-72) were studied (60 from p16, six from FPC families). The median FU was 3.4 yrs (range: 0-7). In 20% of the patients, a (pre)malignant lesion was detected. Ductectasias or IPMN (intraductal papillary mucinous neoplasm) were identified in eight patients (12%). Three patients underwent a prophylactic partial resection of the pancreas; histology showed IPMN in one and PanIn-II lesions in two patients. Five patients (8%) were diagnosed with PC. Three asymptomatic patients underwent partial pancreatectomy. One patient had no evidence for residual disease after surgery. The second patient had positive resection margins and nodes but survived 21 months. The third patient had metastatic carcinoid at surgery (in addition to pancreatic cancer). The remaining two patients did not undergo surgery because of metastatic disease (pulmonary metastases of melanoma, metastatic pancreatic cancer). Conclusion (Pre)malignant lesions were identified in a high proportion of patients. Small lesions of a few mm can be detected by MRI(CP). In view of the substantial morbidity of pancreatic surgery, a major challenge is to decide at what stage and to what extent prophylactic surgery should be performed. Close observation of high risk groups provides valuable information on the natural history of neoplastic lesions in the pancreas. Citation Information: Cancer Prev Res 2008;1(7 Suppl):PR-9.

Sutureless Pancreatojejunal Anastomosis Using an Absorbable Sealant: Evaluation in a Pig Model

Leakage from pancreatojejunal anastomosis continues to be a major source of morbidity in pancreatic surgery. In the present study, we test the hypothesis that a safe, sutureless pancreatojejunal anastomosis can be constructed using a synthetic surgical sealant. Ten pigs weighing 20 to 25 kg underwent distal pancreatectomy and anastomosis of the pancreatic remnant with a jejunal limb with the use of an absorbable surgical sealant. Integrity of the anastomosis was checked on the 10th postoperative d by means of an autopsy study and histological examination. One animal died on the 3rd postoperative d of peritonitis. The remaining 9 animals had an uneventful postoperative course. Gross and microscopic pathological examination revealed intact pancreatojejunal anastomosis in all surviving animals. Following distal pancreatectomy in pigs, pancreatojejunal anastomoses with the use of sealant are technically feasible. During a 10-d observation period, the sealant appeared to prevent anastomotic dehiscence and allow normal anastomotic healing.

Beeinflussen Mindestmengen die Ergebnisse der Pankreaschirurgie?

Hospital volume is one of the most discussed but also disputed subjects of surgery during the recent years. In no other surgical entity as in pancreatic surgery the number of performed operations has as much influence on morbidity and mortality. Despite of decreasing mortality, morbidity in pancreatic surgery remains relatively high even in specialized centres. Numerous studies demonstrated a reduction of perioperative mortality in centres with more than 10 patients per year by over 50%. In our own collective we demonstrated a significant reduction of mortality by 4% to 1% in two successive periods and a significant reduction of morbidity from 47% to 35%. We review the factors that are held responsible for decreasing mortality and complication rate in specialized centres and review published studies on this subject up to date. Our results confirm studies form other countries that increasing centre experience as well as operations performed in high volume hospitals decrease the complication rate and mortality after pancreatic head resection.

Microscopically incomplete resection offers acceptable palliation in pancreatic cancer

Because mortality and morbidity of pancreatic surgery have decreased to acceptable levels, the complex question arises whether pancreatic resection should be performed in patients with preoperatively doubtful resectable pancreatic cancer. Perioperative parameters and outcome of 80 patients who underwent a microscopically incomplete (R1) resection were compared with those of 90 patients who underwent a bypass for locally advanced disease for pancreatic adenocarcinoma. All patients initially underwent exploratory laparotomy with the intention to perform a resection. Quality of life was assessed by analyzing readmissions and their indications. Groups were similar with respect to age, presenting symptoms, and preoperative health status. Tumors were significantly larger in the bypass group (3.5 cm vs 2.9 cm, P < .01). Hospital mortality was comparable: zero after R1 resection and 2% after bypass. Of all severe complications, only intra-abdominal hemorrhage occurred significantly more frequently after resection (10% vs 2%; P = .03). Hospital stay after resection was significantly longer than after bypass (16 vs 10 days; P < .01). Survival was significantly longer after R1 resection (15.8 vs 9.5 months, P < .01). Sixty-one percent of patients were readmitted for a total of 215 admissions, equally distributed between groups. After R1 resection, 0.58% of the total survival time after initial discharge was spent in the hospital, after bypass, 0.69%, which was not significantly different. R1 pancreatic resection and bypass for locally advanced disease can be performed with comparable low mortality and morbidity rates. Readmission rates are also comparable between groups and time spent in the hospital after initial discharge is low. Because resection offers adequate palliation in pancreatic cancer, a more aggressive surgical approach in patients who are found to have a doubtfully resectable tumor could be advocated, even if only an R1 resection can be achieved.

Does Size Matter Most? Reassessing Clinical Staging for Pancreatic Cancer

Cancer staging is an ever-evolving entity. Most would agree that staging systems are generally accurate and never perfect but, nonetheless, an integral tool in treatment planning, communication, research, and education. Although current American Joint Committee on Cancer (AJCC) staging systems fulfill these missions adequately for most solid tumors, in this issue of Annals of Surgical Oncology, Morganti et al. 1 question the utility of staging for pancreatic cancer. It is certainly true that AJCC staging is rarely referred to during treatment planning for pancreatic cancer patients. Clinically, patients are generally classified as potentially resectable, unresectable because of locally advanced disease, and incurable because of the presence of metastatic disease. These clinical strata and the AJCC stages they encompass successfully segregate patients by their median survival and have formed the basis for clinical trial design. As is all too familiar to the readership, with current available therapies nearly all patients with pancreatic cancer are incurable at diagnosis because of the presence of metastatic disease, whether it is immediately visible or occult. Although we strive to cure, even for resectable patients, prolongation of survival with acceptable quality of life is what we can realistically achieve for most patients. Because of the morbidity of pancreatic surgery, numerous studies have been performed to determine whether clinical factors can identify patients who, even in the face of radiographically resectable disease, are unquestionably incurable and therefore should not be considered for operation. Although various authors have reported that CA19-9 levels of >750 or 1000 U/ml are associated with an ultimately fatal outcome, the ability to prognosticate length of life after resection is more difficult. 2 This, coupled with the lack of alternative treatments, makes it difficult for the surgeon to counsel against operation on the basis of a single clinical factor. Apart from the question of operability, then, what information should we seek from the diagnostic imaging tests we obtain in newly diagnosed pancreatic cancer patients?