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Comparison of Standard Distal Pancreatectomy and Splenectomy with Radical Antegrade Modular Pancreatosplenectomy [American Surgeon, The](American Surgeon, The Via Acquire Media NewsEdge) Radical antegrade modular pancreatosplenectomy (RAMPS) has been reported to provide improved margin resection and lymph node retrieval for tumors of the body and tail of the pancreas compared with standard resection. We examined our experience with RAMPS and standard re-section to determine differences in clinicopathologic outcomes. A comparison of RAMPS procedures was made to standard distal pancreatectomy and splenectomy examining various clinicopathologic variables through retrospective chart review. Twenty-six patients underwent distal pancreatectomy with or without splenectomy between November 2004 and June 2011. Twenty patients underwent standard resection and six patients underwent RAMPS procedures for a variety of histologies. As a result of the heterogeneity of diseases, which included benign lesions, margin status was not applicable in some cases and therefore was not assessed overall. Fisher's exact test and Wilcoxon rank sum tests demonstrated a significant difference in number of lymph nodes removed with mean of 4.3 and 11.2 lymph nodes obtained for standard resection and RAMPS, respectively (P = 0.03). The RAMPS procedure for lesions of the body and tail of the pancreas retrieved significantly more lymph nodes than standard distal pancreatectomy and splenectomy. It should be the preferred surgical approach when lymph node count is important for tumor staging. FOR OVER 100 YEARS distal pancreatectomy has been the standard procedure for tumors in the body of the pancreas. The two goals of pancreatic resection include complete tumor resection with a margin of normal tissue and removal of regional lymph nodes. Tumors of the pancreatic head have been the focus of much innovation in achieving these two goals. Much effort has gone into developing surgical techniques that help eliminate positive margins at the uncinate or posterior border in pancreatic head resections. Exten- sive lymph node mapping has afforded surgeons more opportunity to resect regional nodes as well. Pancreatic body and tail tumors are reported to be just as ag- gressive invading locally and metastasizing through lymph nodes, but very little had been done to address improving these two markers of operative success.1 Radical antegrade modular pancreatosplenectomy (RAMPS) addresses the apparent disparity between pancreaticoduodenectomy and standard distal pancre- atectomy. Strasberg et al.1 describes an operative technique that allows for a more complete dissection posteriorly and incorporates lymph node mapping for resection of all regional nodes. RAMPS differs from a standard approach in that the initial dissection begins medially and the neck of the pancreas is transected early as well as the splenic ves- sels. The dissection continues posteriorly to the aorta at the celiac and superior mesenteric trunks. If the tumor does not break the posterior plane of the pancreatic body, the left adrenal gland is retained and the posterior plane of dissection continues left from medial exposing the left renal vein and clearing Gerota's fascia off the left kidney. When the tumor breaks the posterior plane of the pancreas, the left adrenal is resected en bloc and the dissection continues posteriorly to the diaphragm using the retroperitoneal muscles as the posterior bor- der, diaphragm as the superior border, and renal vein as the inferior border of the dissection plane. The ratio- nale for this approach is to ensure a negative deep margin with complete regional lymph node dissection. Using lymphatic mapping by O'Morchoe,2 it is shown that there are two primary groups of nodes that should be considered N1 or regional (Fig. 1). The first is a ring of lymphatics fed directly by lymphatic drainage from the body and tail of the pancreas. The ring is comprised of gastrosplenic nodes incorporated in the gastrosplenic omentum, splenic nodes in the hilum of the spleen, infrapancreatic nodes deep to the pancreatic body, and gastroduodenal nodes. The sec- ond primary group lies along the aorta, in relation to the celiac and superior mesenteric arteries, and may receive direct lymph drainage from the pancreas and thus must be considered N1. Therefore, to achieve full resection of all potentially N1 nodes, a complete re- section should include all the nodes of the ring de- scribed as well as the celiac lymph nodes and those anterior to and to the left of the superior mesenteric artery. Given the early ligation of the splenic vessels in the medial approach and necessity of removing the nodes in the splenic hilum, all patients undergoing RAMPS also undergo splenectomy. In summation, RAMPS offers improved visualiza- tion of the posterior dissection plane, offers early control of the major blood vessels encountered, early division of the neck of the pancreas, better control of the splenic vessels,3 and the lymph retrieval allows for a more complete regional nodal dissection. Using this technique, improved margin resection and lymph node retrieval for tumors of the body and tail of the pancreas have been reported compared with standard resection. We examined our experience with RAMPS compared with standard resection to determine differences in clinicopathologic outcomes. Methods This study was approved by the Wake Baptist Health Institutional Review Board and Protocol Review Committee of the Wake Forest Comprehensive Cancer Center. Data Collection A prospectively created database of patients under- going standard distal pancreatectomy or RAMPS in- cluded 26 patients between November 2004 and June 2011. The data were acquired from operative notes, anesthesia notes, pathology reports, and follow-up visits. Procedure A standard surgical technique was used for the tra- ditional distal pancreatectomy. This typically consisted of either one of two approaches. Vascular control was then obtained of the splenic artery and vein, which were then serially transected with a vascular stapler. The pancreatic body was then transected with an en- doscopic stapler using a blue, green, or white load depending on the pancreatic body texture. In the other method, the dissection began medially at the proposed site of transection on the pancreatic body. Control is again obtained of the splenic artery and vein and of the pancreatic body. The pancreas is transected first with an endoscopic stapler followed by stapling of the splenic vessels. In both approaches, the dissection posterior to the pancreas follows the natural plane between the retroperitoneum. RAMPS procedures were carried out as previously described and using an anterior or posterior approach (Fig. 2A-B).1 Using RAMPS, the resection of the body and tail of the pancreas was hoped to be achieved with more com- plete N1 node dissection, improved visibility for the posterior margin, and superior blood vessel control. Pathologic Assessment On gross examination, surgical specimens included a segment of distal pancreas and associated peripancreatic soft tissues. Depending on the surgery, a portion of stomach, spleen, and/or adrenal gland would be pres- ent. The pancreatic segment would be serially sectioned to expose the lesion. When applicable, the lesion would get evaluated for extension into peripancreatic soft tis- sues, vasculature, spleen, and/or the adrenal gland with representative sections submitted for microscopic ex- amination. A lymph nodal evaluation would then be performed on the peripancreatic soft tissues with at- tention focused on the posterior pancreatic aspect near vasculature. Lymph node candidates, palpable or ap- preciable visually, are dissected from the adipose tis- sue and submitted for microscopic examination. The microscopic examination would include characteriza- tion of the lesion, a total lymph node count, and as- sessment for possible lymph node metastases. With some cases for malignant tumors with no lymph node candidates found on initial evaluation, the entire peri- pancreatic fat would be submitted for evaluation to obtain more lymph nodes. Data Analysis Notable clinicopathologic variables examined in- cluded: total nodes resected, operative time (OR time), estimated blood loss (EBL), length of stay (LOS), and complications. There was high heterogeneity of dis- ease, including some benign lesions, and therefore the resection margins were not compared in this analysis. For analyzing a small sample size, Fisher's exact test and Wilcoxon rank sum tests were used to measure association between our clinicopathologic variables and the type of surgical resection performed. To assess the difference between patients receiving RAMPS and patients not receiving RAMPS, univariate analyses were performed. Frequencies and percentages were calculated for margin status and complications by RAMPS procedure and statistical significance was assessed using Fisher's exact tests. For total number of lymph nodes, OR time, EBL, and LOS, means and standard deviations were calculated and statistical sig- nificance was assessed using Wilcoxon rank sum tests. All analyses were performed using SAS 9.2 (Cary, NC). Results Twenty-six patients underwent distal pancreatec- tomy with or without splenectomy between November 2004 and June 20, 2011. Twenty patients underwent standard resection for the following histologies: one adenocarcinoma, five mucinous cystic neoplasms, eight neuroendocrine tumors, one serous cystadenoma, three pseudocysts, one intraductal mucinous papillary neo- plasm, and one solid pseudopapillary neoplasm. Six patients underwent RAMPS procedures with the fol- lowing histologies: three adenocarcinomas, one neu- roendocrine tumor, one mucinous cystadenoma, and one serous cystadenoma (Table 1). Table 2 shows clinicopathologic variables measured including total nodes resected, OR time, EBL, and LOS. As a result of the heterogeneity of diseases in- cluding benign lesions, margin status was not com- pared between RAMPS and standard resection. In operations involving cancers, the operative technique for labeling and pathological technique for assessment varied significantly enough during the course of this study to make comparison insignificant. Of the 20 standard resections, nine were for cancer and there was one positive margin. Of the six RAPMS operations, four were performed on cancers with zero positive margins. Four patients who underwent RAMPS procedures had greater than 14 lymph nodes resected, one had seven resected, and one had one node resected. The patient with one resected had undergone octreo- tide therapy for VIPoma before surgical intervention. One standard resection resulted in 20 nodes removed, which was the only traditional approach to achieve more than 12 removed. Six standard resections resul- ted in zero nodes removed. Table 3 shows the difference in approach for the standard resections. Exactly half were performed lap- aroscopically and half were open resections. The re- section direction is also exactly divided in half. There were equal numbers of medial-to-lateral resections as there were lateral to medial. Fisher's exact and Wilcoxon rank sum tests showed no difference in OR time (295.26 vs 300.00 minutes; P 4 0.97), EBL (581.25 vs 500.00 cc; P 4 0.79), or length of hospital stay (6.85 vs 7.67 days; P 4 0.62) for standard resection versus RAMPS, seen in Table 2. A significant difference in number of lymph nodes removed (4.3 vs 11.2; P 4 0.03) was found for stan- dard resection and RAMPS, respectively. Complications also were not significant (11 of 20 vs three of six; P 4 1.00) for standard resection versus RAMPS, seen in Table 4. Complications were cate- gorized and tabulated (Table 5) using the Clavien grading system (Table 6). There were a total of 14 complications with the standard approach versus five total complications with RAMPS. This resulted in 10 Grade I, three Grade II and one Disability Grade for Standard Resection, and four Grade I and one Grade IV complications with RAMPS. Conclusion The RAMPS procedure for lesions of the body and tail of the pancreas retrieved significantly more lymph nodes than standard distal pancreatectomy and sple- nectomy. Margin status was not assessed in this diverse pancreatic resection cohort as a result of the benign nature of some neoplasms. The lymph node resection in RAMPS was aided in large part by O'Morchoe's work in discovering the lymphatic drainage of the human pancreas.2 Strasberg et al. has published data showing their experience with RAMPS over time.1, 4 Their study includes 47 patients who were followed and showed a 35 per cent 5-year survival rate. Con- trasted with a literature review of standard distal pan- createctomies, this is much improved over the reported range of 10 to 19 per cent.4 This study demonstrated increased lymph node yield with RAMPS (mean of 11.2) compared with standard distal pancreatectomy (mean of 4.3) with a P value of 0.03. However, of the 26 operations, 23 margins were negative. All three margins that were not negative were in the standard distal pancreatectomy group. One was a positive retroperitoneal margin in a neuroendocrine tumor, another was a serous microcystic adenoma with equivocal margins, and the last one was a pancreatic intraepithelial neoplasm, which had evidence of PanIN- 1 at the margin. An argument could be made the last two cases really were not positive margins because the lesions were not invasive malignancies. The standard distal pancreatectomies were performed either open or laparoscopic using a medial-to-lateral or lateral-to-medial approach. RAMPS offers improved visualization of the posterior dissection plane, early control of the major blood vessels encountered, and, with early division of the neck of the pancreas, better control of the splenic vessels. RAMPS procedures were performed according the procedure described by Strasberg in 2003. The division of the neck of the pancreas is performed immediately after incision and access to the pancreas. Celiac lymph node dissection is then made and a determination of dissection anterior or posterior to the adrenal gland is made based on whether the tumor breaks the posterior plane of the pancreatic body or tail. This determines the posterior extent of the dissection. The dissection then proceeds laterally to the spleen, mobilizing the tail of the pan- creas along the way.1 Despite the more aggressive dissection in the RAMPS procedure, there was no noted difference in perioperative outcomes. There was no statistical dif- ference in EBL, LOS, or OR time. This is in contrast to the work performed by Bonenkamp examining D2 lymph node dissection in gastric cancer whose radical approach showed significantly higher rates of com- plications than did those in the standard group (43 vs 25%, P < 0.001), more postoperative deaths (10 vs 4%, P 4 0.004), and longer hospital stays (median, 16 vs 14 days; P < 0.001).5 Success of a surgical approach to pancreatic cancer is measured primarily using margin status and lymph node yield. As described previously, margin status was not assessed in this study because not all resections were performed on malignant disease. However, our comparison of RAMPS with standard distal pancrea- tectomy showed a statistically significant increase in lymph node yield using RAMPS. This finding is im- portant and supports the use of RAMPS as the treat- ment of choice for neoplasms in the body and tail of the pancreas. Lymph node resection plays a key role in de- termining the prognosis of pancreatic cancer. Nodal status and number of nodes resected are two major factors considered when assessing the value of a lym- phadenectomy. As described previously, the technique for lymph node resection in RAMPS takes the lym- phatic drainage into account, allowing for complete N1 nodal resection. Therefore, this approach in- herently offers a more complete dissection of poten- tially involved lymphatic tissue. Further supporting this are data suggesting that increased yield in pancreatic lymph node resection improves survival prognosis.1, 4, 6 Huebner et al. showed that in lymphadenectomies in which 11 or more nodes were examined, there is in- creased accuracy of survival prognosis in node-negative patients. Furthermore, it was shown that if less than 11 lymph nodes were examined, the risk of missing one or more positive nodes was between 10 and 41 per cent. Their results showed that patients with suboptimal node removal (less than 11) had worse survival out- comes and suggests that the low yield was responsible for missed metastatic disease.6 Our data showed an average of 11.17 nodes resected in the RAMPS group compared with 4.25 nodes removed in the standard resection group. The anatomic location of lymph node dissection in RAMPS is also superior to the standard approach. Schwarz et al.7 showed that in tumors of the pancreatic head, half of lymph node involvement was on the posterior aspect of the pancreas with one-third lying adjacent to the superior mesenteric artery with one- fifth being paraaortic. The approach taken in the RAMPS lymph node dissection is intended to resect a more posterior fascial plane of tissue to include sentinel nodes, as mapped by O'Morchoe, specifically including superior mesenteric and periaortic nodes. Schwarz goes on to conclude that increased node re- moval and examination influences the quality of staging and overall survival. Specifically their data show that 15 total nodes removed or approximately 10 negative nodes optimized operative benefit.7 To conclude, lymph node yield and status is a sig- nificant factor in pancreatic cancer prognosis and staging. House et al.,8 using data on 696 patients un- dergoing pancreatic resection, concluded that inadequate surgical lymphadenectomy gives an N0 patient similar outcomes as patients with one node positive out of 12 assessed. This finding supports the rationale that a more thorough anatomic dissection will not only in- crease lymph node yield, but in resecting all N1 sites, allow for comprehensive pathologic assessment of all primary sites of metastasis. There were limitations to our study. The sample size is relatively small with only 26 patient experiences to analyze. This is attributable in large part to the fact that all operations were performed by the same surgeon, which is a strength countering the small size. This ensured intraoperative consistency of technique and approach that many other multicenter trials were un- able to achieve. The long specimen collection interval also introduces another confounding factor. Pathologic assessment was not performed by the same patholo- gist. Thus, the pathologic assessment, including lymph node analysis and margin status in particular, may have not been as controlled as if one pathologist evaluated all 26 specimens. Also, the retrospective nature of this study limited our ability to record consistent data re- garding complications and operative/pathologic data. Our study supports the use of RAMPS as the pre- ferred approach to neoplasms of the body and tail of the pancreas. Based on sound anatomic and lymphatic mapping studies, RAMPS resection is actually not a radical procedure, but merely combines a partial pan- createctomy with a complete regional lymphadenec- tomy. There was no increase in perioperative morbidity and mortality and the increased nodal yield may con- tribute to improved staging of disease. We aim to continue studying our experience with RAMPS and evaluate it for future improvements including the po- tential for a laparoscopic approach with or without robotic assistance. REFERENCES 1. Strasberg SM, Drebin JA, Linehan D. Radical antegrade modular pancreatosplenectomy. Surgery 2003;133:521-7. 2. O'Morchoe CC. Lymphatic system of the pancreas. Microsc Res Tech 1997;37:456-77. 3. Fagniez PL, Munoz-Bongrand N. Vascular control during distal pancreatectomy for cancer. Ann Chir 1999;534:632-4. 4. Mitchem JB, Hamilton N, Gao F, et al. Long-term results of resection of adenocarcinoma of the body and tail of the pancreas using radical antegrade modular pancreatosplenectomy procedure. J Am Coll Surg 2012;214:46-52. 5. Bonenkamp JJ, Hermans J, Sasako M, van de Velde CJH. Extended lymph node dissection for gastric cancer. N Engl J Med 1999;340:908-14. 6. Huebner M, Kendrick M, Reid-Lombardo KM, et al. Number of lymph nodes evaluated: prognostic value in pancreatic adeno- carcinoma. J Gastrointest Surg 2012;16:920-6. 7. Schwarz RE, Smith DD. Extent of lymph node retrieval and pancreatic cancer survival: information form a large US population database. Ann Surg Oncol 2006;13:1189-200. 8. House MG, Gönen M, Jarnagin WR, et al. Prognostic sig- nificance of pathological nodal status in patients with resected pancreatic cancer. J Gastrointest Surg 2007;11:1549-55. PAUL TROTTMAN, M.D., KATRINA SWETT, M.S., PERRY SHEN, M.D., JOSEPH SIRINTRAPUN, M.D. From the Department of General Surgery and Biostatistics, Wake Forest School of Medicine, Winston-Salem, North Carolina Abstract data presented at a poster session at Americas Hepatico- Pancreatico-Biliary Association, Miami, FL, March 9, 2012. Address correspondence and reprint requests to Paul Trottman, M.D., Wake Forest University School of Medicine, Department of General Surgery, Surgical Oncology Service, Medical Cen- ter Boulevard, Winston-Salem, NC 27157. E-mail: ptrottma@ wakehealth.edu. (c) 2014 Southeastern Surgical Congress |