Postpancreatic Resection Nutrition Outcomes and Anastomotic Leak - Literature review Example

Literature Review Postpancreatic resection nutrition outcomes and anastomotic leak Table of Contents Literature Review 1 Postpancreatic resection nutrition outcomes and anastomotic leak 1 Table of Contents 1 Introduction 2 Outcomes for patients with pancreatic neuroendocrine tumor resections 3 Clinicopathological predictors of recurrence and survival  9 Pancreaticojejunostomy vs. pancreaticogastrostomy in nutritional outcomes and pancreatic anastomotic leak and perioperative complications 11 References 12 Introduction Group of malignancies which are genetically diverse, neuroendocrine tumours or NETs lead sometimes to hormonal syndromes by producing peptides. The malignant solid tumours arise from neuroendocrine system's secretory cells and can either be silent or nonfunctioning or clinically symptomatic or functioning. Recent surveys by SEER – Surveillance, Epidemiology, and End Results – program have revealed that the malignant NET incidence is increasing (Yao, Hassan, Phan, 2008). Improved diagnostic techniques and increased awareness of physicians on the disease is partly being attributed to the increased incidence data. In comparison to other malignancies which have, more or less, remained static since 1992, NETs have been increasing in incidence between 1973 and 2004 – where the incidence was 1.09 per 100,000 in the former and 5.25 per 100,000 in the latter. An alarming increase of 72 percent in incidence of NETS was reported by Norwegian Registry of Cancer. The Norwegian Registry of Cancer said that in comparison to incidence between 1993-1997 and 2000-2004 the incidence had increased by 72 percent. African-Americans show more incidence in its increase than Caucasian patients (Hauso, Gustafsson, Kidd et al, 2008). The graph below shows 1973 to 2003 incidence of malignant NETs by disease stage. It is important to note that the incidence is showing an upward statistical trend at every stage of the disease. Source: Expert Rev Endocrinol Metab. 2011; 6(1):49-62. Pancreatic neuroendocrine tumours or PNETs, on the other hand, are group of neoplasms which are heterogenous in nature, and their traditional incidence per 100,000 persons has been reported as 0.4 (Oberg & Eriksson, 2005). But of all the neoplasms, they constitute between 2-4 percent. Research done in this field has recently indicated that their incidence too is on the rise; one factor that is said to lead to such reporting is recent advances in radiographic imaging and thus incidental detection. Majority of PNETs have been reported as malignant even though their course has been considered as relatively indolent. To secure a chance for cure, surgery is the only option for intervention. Nearly 65 percent resectability rates have been reported in case of PNETs at present (Grant, 1993). Outcomes for patients with pancreatic neuroendocrine tumor resections The outcomes of pancreatic neuroendocrine tumours have been termed as favourable in comparison to the exocrine tumours. The WHO's classification, which it brought out in the year 2004, is being considered as guiding staff in predicting the outcomes of the endocrine tumours. However, since the PNETs are a rarity, any attempt at reaching a conclusive literature is fraught with the very scarcity of it. What is hailed as an important step toward predicting the outcomes is the new classification of these tumours by Capella et al (1995) and Kloppel et al (2004). Paulus et al (2007) from the Department of Pathology, University Medical Center of Hamburg-Eppendorf, University of Hamburg, Germany, and Department of General, Visceral and Thoracic Surgery University Medical Center of Hamburg-Eppendorf, University of Hamburg, Germany reported the outcomes of 62 consecutive patients admitted in their surgical units from 1987 till 2004 for sporadic pancreatic neuroendocrine tumours. All these patients were operated upon at their surgeries, but von Hippel-Lindau disease or multiple endocrine neoplasia type I (MEN I) were not included in the study. All patients fulfilled the criteria set by the surgical units which included surgeries done at these units, follow-ups done for more than 12 months, and 30.5 months as median follow-up for each patient. Data pertaining to all patients were computerised and analysed with respect to parameters like type of tumour, symptoms at the time of admission, and type and quality of resection done. International Union Against Cancer classification was used to determine the quality of resection undertaken, like R0, R1, and R2 – the first being ‘no residual tumour’; the second, ‘all identifiable tumour removed’; and the third, ‘tumour left macroscopically in situ’. Chemotherapy – definitive, adjuvant, and neoadjuvant – was administered to 49 percent patients. Disease-free survival (DFS) and overall survival (OS) were two primary end point selected in terms of outcomes, whereas distant and recurrence metastases were counted as separate outcomes. Disease-specific survival was taken as secondary endpoint. DF, DSS, and OS were assessed with regard to distant and local organ recurrence, and all assessments made were done with 95 percent confidence intervals using Kaplan-Meier method. Seventy-seven percent (48 of 62) patients were operated for resection of primary tumours, which included 45 patients on whom resection meeting R0/ R1 criteria were performed. Eight percent total pancreatectomies (5 patients), 10 percent Whipple resection (6 patient), 3 percent pylorus-preserving pancreaticoduodenectomies (2 patient), 13 percent duodenum-preserving pancreatectomies (8 patients), 7 percent duodenum-preserving segmental head and body resections (4 patients), 3 percent segmental body resections (2 patient), 5 percent spleen-preserving tail resections (3 patient), 21 percent distal splenopancreatectomies (13 patients), and 8 percent enucleations (5 patients) were performed. After postoperative analysis and follow-up the researchers concluded that in comparison to nonresected patients, those who were resected did better. The researchers also hypothesised that when comparison are made with large group of patients and in randomised settings, the outcome on both radical and egmental resection can be defined better (Dralle, Krohn & Karges, 2004). The study revealed that it was appropriate to resect PNET in case of primary tumour and metastases for better outcome, which keep in line with previous data a reported by Solorzano, Lee, Pisters, et al (2001). Data from National Cancer Institute's three consecutive registries have revealed a 5-year actuarial overall survival of 37.5 percent in case of 138 PNETs from a series of as many as 13,715 patients registered for carcinoid tumours. This overall survival was reported after a prolonged follow-up. Solorzano, Lee, Pisters, et al (2001) have reported from a surgical experience the median survival rate of 41 months in PNETs. Survival rates in PNET patients, reveals a recent study by Krampitz (2012) is decreased by lymph node metastases. This is because patients having developed lymph node metastases are left with shorter time towards the development of liver metastases. Higher the extent of metastases, lower is the survival. Haynes, et al (2011) from Department of Surgery, Massachusetts General Hospital, Wang Ambulatory Care Center, Boston, have remarked that if PNETs have been incidentally detected, their behaviour can be aggressive even if they are relatively small. Malignancies pose decreased survival and higher recurrence rates. And if the histological findings are benign, possibility of progression cannot be ruled out. Kazanjian, Reber, and Hines (2006), on the other hand, have argued that the malignancy of the neuroendocrine tumours can be classified with the assessment of presence of lymphovascular invasion which, in retrospect, can help predict survival. The researchers remarked as such on the basis of 70 single-institutional cases from Section of Gastrointestinal Surgery and the University of California. Of these cases, 71.4 percent patients had nonfunctional tumours, 52.9 percent neuroendocrine carnicomas, and 13 percent had benign islet cell neoplasms. Of the remaining 20 cases, all of whom had functional tumour, 2 were that of gastrinomas, 2 glucagonoma, and 16 insulinomas. Thirteen patients suffered postoperative complications. Zagar et al (2011) reported outcomes on 33 PNET patient who had undergone resection between 1994 and 2009 at the Duke University. They reported these cases on outcomes in conjunction with the use of radiotherapy. All of these patients presented with neuroendocrine tumour of the pancreatic head, on 16 of whom only resection was performed. On the remaining 17 neoadjuvant or adjuvant radiation therapy was employed, using concurrent CMT - fluoropyrimidine-based chemotherapy. While the median follow-up was of up to 28 months, 50.4 Gy was the median radiation dose used. In comparison to surgery alone patients, patients on whom radiation therapy was used had more involved margins, involved nodes, and more increased per high power field mitosis. Whole cohorts’ median survival was 52 months, and survival was exhibited more at 93 percent by surgery alone group in a two-year span than the CMT group, whose survival was 68 percent. The study found that surgery alone group demonstrated lesser adverse pathologic features in comparison to CMT group. A study by Gaia and Salacone (2007) has reported 39 percent morbidity associated with pancreatic head resection combined with Berger procedure or duodenum-preserving head resection and Frey procedure or longitudinal pancreaticojejunostomy. This is lesser than the 48 percent associated with other resections, and in both cases there is a 20 percent revision rate (Strate, 2005). Thirty-two percent long-term morbidity has been reported after both Berger and Frey procedures (Soha, et al, 2000: Frey, et al, 2003, Belina, et al, 2005). Sarmiento et al (2003) reported outcome on 23 patients who underwent pancreatic resections. There were not any perioperative deaths, but complications were reported in 18 percent patients. Seventy-one percent 5-year survival rates were reported, but the progression-free or recurrence-free survival rate was as low as 5 percent. It has been reported in numerous studies that resections are advantageous in PNETs, but it has not yet been conclusively proven which types of patients who present with malignancies could exhibit highly positive outcomes postoperatively. The reason for this lack of conclusively is that the populations of patients who have been reviewed are heterogeneous and most of the studies are interpreted from single-institutional backgrounds. The heterogeneous population does not present with a uniform disease burden. Most of the studies done so far are a combination of nonfunctional and functional and malignant and benign tumours. These studies are all-inclusive in nature and are not based on histologies that are well-differentiated. Furthermore since patients presenting with aggressive disease features do receive either additional therapies during or after resection or have already received other therapies, mostly nonsurgical, preoperatively. Such factors and more make correct interpretation of results very difficult. It, thus, becomes difficult to ascertain benefits and outcomes of 'resection only' procedures. Table I below shows some selected studies involving surgical resection and results got thereby with a 10-year span beginning 1998 till 2008. Table I: Authors No. of patients Type Grades Morbidity Mortality 5-yr survival rate for malignant tumours Median follow-up in months Bonney et al (2008) 12 Malignant only 9 WD 3 PD 43 percent 2.8 percent 49 percent 55 Fischer et al (2008) 118 Mixed 105WD 13 PD 36.4 percent 3.4 percent 44 percent 19 Schurr et al (2007) 52 Mixed 54 WD 8 PD Not reported Not reported 49 percent 30.5 Nguyen et al (2007) 73 Mixed Not reported 27 percent 0 percent 44 percent 48 Bahra et al (2007) 19 Mixed Not reported 10.5 percent 0 percent 26 percent 65 Teh et al (2007) 33 Mixed Not reported 36 percent 3 percent 36 percent 44 Kazanjian et al (2006) 70 Mixed Not reported 30 percent 0 percent 77 percent 50 Norton et al (2003) 20 Mixed Not reported 30 percent 0 percent 80 percent 19 Bartsch et al (2000) 18 Nonfunctional 16 WD 2 PD 44 percent 16.6 percent 65 percent 56 Phan et al (1998) 125 Mixed Not reported 43 percent 2.8 percent 49 percent 55 Clinicopathological predictors of recurrence and survival  Using univariate analysis Jarufe et al (2004) have reported that metastases and lymph node invasion is significant predictor of survival in postoperative resection of PNETs. They also noted that significance on multivariate analysis was retained by presence of metatases only. The two, as evidenced by univariate analysis were worse predictor of survival.Corelation between the two was significant in a study conducted on 44 patients enrolled for surgeries from 1998 to 2002 at Queen Elizabeth Hospital, UK. Of all the patients, 24 had functional tumours which included 1 each of vipoma, glucagonoma and carcinoid tumours; 2 somatostatinomas, 3 gastrinomas, and 16 insulinomas. Thirteen nonfunctional and 9 functional tumours belonged to a malignant phenotype. One exploratory laparotomy, five bypasses, two total pancreatectomies, seven distal pancreatectomies, and nine local excisions were performed. 31.8 percent patients (14 in all) presented with surgical complications, and 2.3 patients (1 in all) died perioperatively. At 5 and 10 years, the resected cases showed 74.4 and 42.5 percent survival rate respectively. Negative predictors of survival after PNET resection as seen on multivariate analysis included patients aged more than 55 years who presented with grades poorly differentiated, had distant metastases, and lack of clinical syndromes. Same was also true for patient who required pancreaticoduodenectomy. A number of other studies (Table II) that have been conducted have on variety of factors that affect prognosis after the PNET resections are done. A sizeable number of studies, in sheer contrast to the one mentioned previously in this paper, are equivocal in the conclusion that lymph node presence does neither affect survival significantly and nor do they preclude resection. However, some researchers argue that some of these studies might be biased Chung, Choi, & Jo (2007). Patients with low-grade and well-differentiated neoplasms fair better postoperatively than patient with high-grade and poorly-differentiated tumours. The latter stand chances of shorter disease-free intervals and higher recurrence levels (Bloomston, 2006). Bilimoria et al (2008) have opined that post-surgical resection positive margins to do not have any negative impact on survival. Table II: Authors No. of patients Analysis Lymph nodes positive Functional vs. nonfunctional tumour Tumour size Presence of distant or liver metastases Pateint’s age Grade Angiolymphatic invasion present Resection margins positive Bonney et al (2008) 12 Univariate NSSD NSSD NSSD No comment made NSSD WD> PD** Yes NSSD Fischer et al (2008) 118 Multivariate NSSD F>NF* No comment made No comment made No comment made No comment made No comment made NSSD Schurr et al (2007) 62 Univariate Yes No comment made No comment made Yes No comment made No comment made No comment made Yes Nguyen et al (2007) 73 Univariate No comment made NDDS No comment made No comment made No comment made No comment made No comment made No comment made Bahra et al (2007) 19 Multivariate NDDS No comment made Tumor >2cm No comment made No comment made No comment made No comment made No comment made Vagefi et al (2007) 168 Univariate No comment made NDDS No comment made No comment made No comment made No comment made No comment made No comment made Chung et al (2007) 22 Multivariate NDDS No comment made NDDS No comment made NDDS NDDS No comment made Yes Bloomston et al (2006) 120 Multivariate No comment made No comment made No comment made No comment made No comment made WD> PD** No comment made Yes Kazanjian et al (2006) 70 Univariate NDDS No comment made No comment made No comment made No comment made No comment made Yes NDDS Sarmiento et al (2002) 28 Univariate No comment made No comment made No comment made No comment made No comment made No comment made No comment made NDDS Phan et al (1998) 125 Univariate No comment made NDDS No comment made No comment made No comment made No comment made No comment made Yes Legend for Table II: NDDS: no statistically significant difference Yes: survival outcome affected adversely by the variable NF: nonfunctional F: functional PD: high grade or poorly differentiated *: nonfunctional tumours had worse urvival compared to functional tumours **: Low-grade or well-differentiated tumours demonstrated better survival than high-grade poorly-differentated tumours Pancreaticojejunostomy vs. pancreaticogastrostomy in nutritional outcomes and pancreatic anastomotic leak and perioperative complications Pancreaticogastrostomy (PG) and pancreaticojejunostomy (PJ) are two preferred methods of anastomosis post-pancreaticoduodenectomy (PD). Even though it is a continuing debate on which one is better than the other, nearly 13 OCSs - nonrandomised observational clinical studies have favoured PG in comparison to PJ. However 3 RCTs - randomised clinical trial done until March 2006 could not be conclusive in any specific technique (Wente et al, 2007). Pancreatic anastomotic leak after PD is a leading cause of mortality and morbidity. The rate of leak and morbidity is higher with PJ than PG. A study by Fang et al (2007) was conducted at Taipei Veterans General Hospital, Taipei, Taiwan, on 377 consecutive patients admitted there from March 1992 to March 2005 for undergoing PD. Out of total patients admitted; PG was performed on 189 and PJ on 188 patients. The overall pancreatic leakage, morbidity and mortality following PD were 10.6 percent, 45.1 percent and 5 percent respectively. In the PJ group the pancreatic leakage, morbidity and mortality were 17.6 percent, 56.4 percent and 8.9 percent respectively. Mean operative time for PG vs. PJ group was 6.7 vs. 9.3 hours. Mean blood loss was 891 mL vs. 1032 mL, and mean hospital stay was 26.1 day v. 34.8 days. Even though in the recent years post-pancreaticoduodenectomy mortality rate has been reported a decreased, the incidence of postoperative morbidity ometimes shots up to 50 percent. Most common complication include pancreatic fistula, would infection and delayed gastric emptying - all resulting from pancreatic anastomotic leak; the incidence of which is normally within the range of 5 percent to 25 percent. Yeo et al (1995) have argued that the incidence of pancreatic fistula cannot be attributed to PJ being less safe than PG. The underlying cause for the same can, instead, be associated with the underlying disease and the surgical volume. Since these complications, particularly the anastomotic leak and pancreatic fistula lengthen the hospital stay and expose the patient to other life-threatening complications like cholangitis, intra-abdominal abscess formation, pneumonia, sepsis and bleeding; Yeo et al have stressed the need for further research in finding the safest method for conducting a pancreatic enteric anastomosis. In the recent PG has gained acceptance in reducing post-PD formation of pancreatic fistula as a complication (Delcore et al, 1990) Comparisons have also been made between PG and PJ following pancreaticoduodenectomy on the nutritional status of patients. Ma et al (2012) conducted a retrospective analysis on 37 patients undergoing PD for pancreatic non-epithelial tumor and duodenal carcinoma. Of the total 37 patients PG was performed on 19 patients and PJ on 18 patients. These procedures were conducted from April 2006 to December 2010 at the First Hospital of Sun Yat-sen University, China. 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