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Pancreaticoduodenectomy in elderly patients: a special place for minimally invasive surgery?

To the Editor:

We read with keen interest the recent paper by El Nakeeb et al,[1]and the subsequent editorial published by Dudeja and Livingstone.[2]Globally, the authors have correctly and timely portrayed the current role of pancreaticoduodenectomy in the elderly. Actually, most patients are expected to succumb a few years after surgery, being the overall survival slightly enhanced by adjuvant treatments. Moreover, even in the case of benign or borderline malignancy, despite the substantive advances that have been achieved in the perioperative management, surgery is still burdened by some potential lifethreatening complications.[1,2]In this view, we believe that the well-known benefits of minimally invasive surgery can offer aged patients are to be taken into consideration while evaluating quality rather than quantity of life.[1-4]Indeed, in recent years, minimally invasive surgery has proven to have the potential of providing elderly undergoing major visceral surgery with diminished postoperative complications and shorter hospitalization, with faster return to ambulation and daily activities compared to conventional surgery.[3]

Although the recent years have seen a dramatic penetration of minimally invasive surgery in daily surgical practice, pancreaticoduodenectomy has been historically considered a relative contraindication to the application of laparoscopy.[4,5]This is essentially due to the deep, retroperitoneal localization of the pancreas, its intrinsic connection with major vasculature and the technical difficulty of the reconstructive phase of the intervention, which requires at least three anastomoses.[5]Nonetheless, approximately two decades after its first appearance, the application of minimally invasive methods for pancreatic surgery is becoming more widespread, mostly due to increased experience in laparoscopic surgery and the availability of new and sophisticated technologies.[4,5]Currently, in a progressively growing number of experienced centers, both conventional laparoscopy and robotassisted surgery can be employed in performing pancreaticoduodenectomy competently, with expected rates of morbidity and mortality while maintaining oncological adequacy.[4-7]

Of note, increasing evidence exists proving not only the surgical efficacy and safety of minimally invasive pancreaticoduodenectomy, but also suggesting significant advantages over conventional surgery on intraoperative blood loss, length of intensive care unit and hospital stay, postoperative wound infection and time to return to daily activities.[4-7]Several uncertainties on oncological adequacy essentially connected with an appropriate lymphadenectomy and the rates of R0 resection margins have now been allayed.[5-9]Interestingly, probably due to the enhanced postoperative recovery and lowered rates of postoperative morbidity and wound infection, also a potential role in increasing the percentage of patients being able to receive adjuvant therapies at appropriate timing has been put in connection with minimally invasive surgery.[5-7]

Indeed, in a comprehensive and intriguing review of the literature including twenty-two studies and more than six thousands patients, the comparison between conventional open and minimally invasive pancreaticoduodenectomy did not elicit any statistically significant difference in terms of mortality (0-37.5%), morbidity (26.5%-58.3%), pancreatic fistula or bile leakage.[6]Contrariwise, minimally invasive surgery was favorably associated with intraoperative blood loss, wound infection rates, duration of hospital stay and oncological outcomes. Despite some selection bias due to surgical difficulty (such as vascular encasement or tumor size), nearly all the comparative studies in the analysis reported on groups of patients that were matched for demographics characteristics. Particularly, in more than half of the studies the mean age was higher in the minimally invasive group.

It is noteworthy that in a number of single experiences worldwide several advantages in particular frailty subgroups have been noticed. Of note, the abovementioned advantages of laparoscopy over traditional surgery were also confirmed by Kuroki et al in a specific matched comparison between patients undergoing laparoscopic or traditional pancreaticoduodenectomy, with a mean age of 71.2±8.8 and 73.5±7.3 years, respectively.[8]Interestingly, geriatric surgical patients were even considered comparatively more appropriate candidates to laparoscopic pancreaticoduodenectomy.[9]Similarly, it has been suggested that, regardless of chronologic age, patients with severe pulmonary dysfunction are likely to take advantages from a laparoscopic procedure.[10]

Definitive conclusions cannot be drawn on the basis of the current knowledge essentially due to the lack of

well-conducted, randomized trials. Nevertheless, the current available evidence from the literature suggests that pancreaticoduodenectomy can be performed in a minimally invasive manner competently, even in aged population.[4-9]

While we congratulate with the authors on their elegant and timely papers, we believe that the decision whether to offer pancreaticoduodenectomy should now be taken according to how much has changed through the last years also with reference to surgical approaches. This is particularly the case of the elderly, who represent the subgroup of patients that may potentially benefit the most from the limited surgical and immunologic trauma and enhanced postoperative recovery connected with minimally invasive surgery.[2-6]

Francesco Guerra and Lapo Bencini Division of Oncological and Robotic General Surgery, Careggi University Hospital, Florence, Italy

Email: fra.guerra.mail@gmail.com Giovanni Battista Levi Sandri Division of General Surgery and Liver Transplantation, San Camillo Hospital, Rome, Italy

1 El Nakeeb A, Atef E, El Hanafy E, Salem A, Askar W, Ezzat H, et al. Outcomes of pancreaticoduodenectomy in elderly patients. Hepatobiliary Pancreat Dis Int 2016;15:419-427.

2 Dudeja V, Livingstone A. Is age just a number: pancreaticoduodenectomy in elderly patients? Hepatobiliary Pancreat Dis Int 2016;15:346-347.

3 Wang JF, Zhang SZ, Zhang NY, Wu ZY, Feng JY, Ying LP, et al. Laparoscopic gastrectomy versus open gastrectomy for elderly patients with gastric cancer: a systematic review and meta-analysis. World J Surg Oncol 2016;14:90.

4 Bencini L, Annecchiarico M, Farsi M, Bartolini I, Mirasolo V, Guerra F, et al. Minimally invasive surgical approach to pancreatic malignancies. World J Gastrointest Oncol 2015;7:411-421.

5 Guerra F, Levi Sandri GB, Amore Bonapasta S, Farsi M, Coratti A. The role of robotics in widening the range of application of minimally invasive surgery for pancreaticoduodenectomy. Pancreatology 2016;16:293-294.

6 Zhang H, Wu X, Zhu F, Shen M, Tian R, Shi C, et al. Systematic review and meta-analysis of minimally invasive versus open approach for pancreaticoduodenectomy. Surg Endosc 2016; Mar 22.

7 Croome KP, Farnell MB, Que FG, Reid-Lombardo KM, Truty MJ, Nagorney DM, et al. Total laparoscopic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: oncologic advantages over open approaches? Ann Surg 2014;260:633-640.

8 Kuroki T, Adachi T, Okamoto T, Kanematsu T. A nonrandomized comparative study of laparoscopy-assisted pancreaticoduodenectomy and open pancreaticoduodenectomy. Hepatogastroenterology 2012;59:570-573.

9 Battal M, Yilmaz A, Ozturk G, Karatepe O. The difficulties encountered in conversion from classic pancreaticoduodenectomy to total laparoscopic pancreaticoduodenectomy. J Minim Access Surg 2016;12:338-341.

10 Li H, Peng B. Total laparoscopic pancreaticoduodenectomy may benefit patients with severe impaired pulmonary function. Surg Laparosc Endosc Percutan Tech 2015;25:266.

Published online November 4, 2016.

The Author Reply:

We thank the authors for their commentary on our paper.[1]Pancreaticoduodenectomy can be performed safely in selected elderly patients. Advanced age alone should not be a contraindication to do pancreaticoduodenectomy. Careful patient selection is the cornerstone to improve the outcome of pancreaticoduodenectomy in elderly. An aggressive approach to pancreatic cancer in the elderly can be justified in high volume centers in order to optimize resectability, and minimize morbidity and mortality. The elderly may potentially benefit from minimally invasive pancreaticoduodenectomy due to limited surgical and immunologic trauma and enhanced postoperative recovery.[2,3]In this view, we believe that the well-known benefits the minimally invasive surgery offered to elderly patients are to be taken into consideration in decision making.

Ayman El Nakeeb Gastroenterology Surgical Center, Mansoura University, Mansoura 35516, Egypt

Email: elnakeebayman@yahoo.com

References

1 El Nakeeb A, Atef E, El Hanafy E, Salem A, Askar W, Ezzat H, et al. Outcomes of pancreaticoduodenectomy in elderly patients. Hepatobiliary Pancreat Dis Int 2016;15:419-427.

2 Zhang H, Wu X, Zhu F, Shen M, Tian R, Shi C, et al. Systematic review and meta-analysis of minimally invasive versus open approach for pancreaticoduodenectomy. Surg Endosc 2016; Mar 22.

3 Croome KP, Farnell MB, Que FG, Reid-Lombardo KM, Truty MJ, Nagorney DM, et al. Total laparoscopic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: oncologic advantages over open approaches? Ann Surg 2014;260:633-640.

(doi: 10.1016/S1499-3872(16)60150-9)

Published online November 4, 2016.

Preoperative pancreatic resection score: a preliminary prospective validation from Spain

To the Editor:

We read with outstanding interest the article by Celik et al.[1]It is the first external description of the Hamburg’ s preoperative pancreatic resection (PREPARE) score since it was published in 2014 by Uzunoglu et al.[2]According to the latter authors, it is necessary to stratify risk of major morbidity and mortality before performing a pancreatic resection, and PREPARE score is a simple index, validated in a multicenter cohort of patients undergoing this group of technically demanding procedures.

With the aim of contributing to external validation of this score as well, we designed an observational prospective study immediately after publication of PREPARE score, carried out in our Hepato-pancreato-biliary Unit. Among all evaluated individuals with pancreatic or periampullary lesions (benign and malignant) at our institution, those patients between 18 and 80 years old who underwent major pancreatic resection (Whipple’s procedure as well as distal or total pancreatectomy) were included for this study. Exclusion criteria: patients with unresectable pancreatic or periampullary malignacies in whom operation was aborted or a palliative procedure without pancreatic resection was performed. After selection, 18 patients have been enrolled for this study from January 2015 to March 2016 in whom we calculated PREPARE score. A blood analysis was obtained immediately before operation but blood pressure and cardiac rate were registered upon hospital admission, the afternoon before surgery.

In our series, mean age was 63.8±8.1 years (range 45-75) and 15 patients were male. Two patients were American Society of Anesthesiologists (ASA) score I, 11 were ASA score II and 5 were ASA score III. Mean albumin was 3.5 ±0.5 g/dL (range 2.7-4.8); mean hemoglobin was 13.7 ±1.6 g/L (range 11.1-17.2); mean systolic blood pressure was 124.7±16.3 mmHg (range 98-155); mean cardiac rate was 76.7±13.8 beats/min (range 55-97). Whipple’s procedure was performed in 15 patients, while one individual underwent total pancreatectomy as well other 2 distal pancreatectomies (elective surgery in all cases). Two thirds of the individuals were diagnosed of pancreatic entity. According to these items, PREPARE score was calculated, obtaining a mean value of 6.8±3.9 points (range 0-14), classifying 8 individuals as low risk category, 5 as intermediate risk and 5 as high risk.

Major complications (Clavien ≥III) occurred in 5 patients (27.8%), with the following distribution: IIIa 5.6%, IIIb 5.6%, IV 11.1% and V 5.6%. Our only death corresponded to a female patient with Child-Pugh grade A liver cirrhosis due to hepatitis C virus, who developed progressive multiorgan failure without any evidence of technical complications. Pancreatectomy specific morbidities were: hemorrhage[3](grade A 5.6%, grade B 5.6%, grade C 11.1%), delayed gastric emptying[4](grade A 16.7%, grade B 11.1%) and fistula[5](grade A 5.6%, grade B 5.6%). Mean hospital stay was 16.6±11.2 days (range 6-47).

Statistical analysis (SPSS 18.0, IBM corporation) showed a significant higher proportion of severe postoperative complications (Clavien ≥III) in those patients included in the PREPARE intermediate risk group (2/5, 40.0%) and high risk group (3/5, 60.0%), though subjects classified as low risk did not suffer major morbidity (0%; P=0.02). Consequently, we obtained a relative risk of 0.200 (95% CI: 0.058-0.691) and 0.270 (95% CI: 0.104-0.716) for those patients with low risk versus those in the intermediate and high risk cohorts, respectively. However, we found no statistical differences in terms of postoperative hospital stay between the three groups (16.1 versus 18.6 versus 18.5 days, respectively).

The score proposed by Uzunoglu et al[2]in 2014 seems to be easy-to-use, since it only includes 8 variables, and accurate (75.0%) as reported by the authors. To date, only the article by Celik et al[1]has externally evaluated PREPARE score in a retrospective study, including patients operated from 2010 to 2015 in Turkey. Consequently, our preliminary study is the first prospective cohort of patients, specifically designed in order to validate this index, and we keep on recruiting patients. Currently, we have obtained statistical differences in terms of risk prediction for severe morbidity and mortality (0%, 40% and 60%, for low, intermediate and high risk groups, respectively) despite an extremely low number of patients. These figures are similar to those published when the score was described, excepting for the low risk cohort (18%, 40% and 66%, respectively), what might be explain due to our short series. Global major morbidity and mortality rates in our study do not differ much from the figures reported by Uzunoglu et al.[2]On the contrary, PREPARE score does not statistically correlate with postoperative hospital stay in our series, what has not been previously evaluated.

We conclude that our preliminary results, as well as those reported by Celik et al,[1]support the use of PREPARE score, though more large studies are still required. Hence, obtaining ＜6 points implies, in our series, a protective clinical context against major morbidity in those patients undergoing pancreatic resection, as defined for this index. Theoretically, the albumin value, which is weighted as the most important variable of this

score (5 points), might be improved preoperatively by nutritional support. This reflects the capital importance of preoperative nutritional status as a factor associated with surgical complications after pancreatectomy.[6]

Mario Rodriguez-Lopez, Martin Bailon-Cuadrado, Francisco J Tejero-Pintor, Baltasar Perez-Saborido, Enrique Asensio-Diaz and Asterio Barrera-Rebollo General and Digestive Surgery Department, Rio Hortega University Hospital, Dulzaina 2, 47012, Valladolid, Spain

Email: mariorodriguezlopez@gmail.com

Acknowledgments: Authors are thankful to all consultant surgeons from our HPB Surgery Unit, to the rest of surgeons and residents at the General and Digestive Surgery Department (Rio Hortega University Hospital, Valladolid, Spain) as well as to our OR and ward teams of nurses. Besides, RLM thanks his colleagues from the General, Visceral and Thoracic Surgery Department at the University Medical Center Hamburg-Eppendorf (leaded by Prof. Jakob R Izbicki), where he attended an Observership in 2014, and particularly to Dr. Matthias Reeh, who first provided the paper of the PREPARE score.

Disclosures: The results herein presented have been accepted for oral presentation at the Spanish National Surgical Congress, which takes place in Madrid (Spain) in November 2016. Authors declare that no financial support has been provided for this study.

References

1 Celik H, Kilic MO, Erdogan A, Ceylan C, Tez M. External validation of PREPARE score in Turkish patients who underwent pancreatic surgery. Hepatobiliary Pancreat Dis Int 2016;15:108-109.

2 Uzunoglu FG, Reeh M, Vettorazzi E, Ruschke T, Hannah P, Nentwich MF, et al. Preoperative pancreatic resection (PREPARE) score: a prospective multicenter-based morbidity risk score. Ann Surg 2014;260:857-864.

3 Wente MN, Veit JA, Bassi C, Dervenis C, Fingerhut A, Gouma DJ, et al. Postpancreatectomy hemorrhage (PPH): an International Study Group of Pancreatic Surgery (ISGPS) definition. Surgery 2007;142:20-25.

4 Wente MN, Bassi C, Dervenis C, Fingerhut A, Gouma DJ, Izbicki JR, et al. Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). Surgery 2007;142:761-768.

5 Bassi C, Dervenis C, Butturini G, Fingerhut A, Yeo C, Izbicki J, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery 2005;138:8-13.

6 Shirakawa H, Kinoshita T, Gotohda N, Takahashi S, Nakagohri T, Konishi M. Compliance with and effects of preoperative immunonutrition in patients undergoing pancreaticoduodenectomy. J Hepatobiliary Pancreat Sci 2012;19:249-258.

(doi: 10.1016/S1499-3872(16)60151-0)

Published online November 4, 2016.

10.1016/S1499-3872(16)60149-2)