JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES Volume 25, Number 4, 2015 ª Mary Ann Liebert, Inc. DOI: 10.1089/lap.2014.0502
Full Report
Long-Term Results of Laparoscopic Pancreaticoduodenectomy for Pancreatic and Periampullary Cancer—Experience of 130 Cases from a Tertiary-Care Center in South India Palanisamy Senthilnathan, MS, DNB, MRCS (Ed), DNB (GI Surgery), FMAS, FACS, Sivakumar Srivatsan Gurumurthy, MS, DNB (GI Surgery), FMAS, Shiekh Imran Gul, MS, Sandeep Sabnis, MS, Anand Vijai Natesan, MS, DNB (GI Surgery), FMAS, Nalankilli V.P., MS, FMAS, P. Praveen Raj, MS, DNB (GI Surgery), FMAS, Rajapandian Subbiah, MS, DNB (GI Surgery), FMAS, Parthasarathi Ramakrishnan, MS, FMAS, and Chinnusamy Palanivelu, MS, MCh, DNB, FACS, FRCS, FICS
Abstract
Background: Laparoscopic pancreaticoduodenectomy (LPD), although an advanced surgical procedure, is being increasingly used for pancreatic head and periampullary tumors. We present our experience of 15 years with the largest series in total LPD for periampullary and pancreatic head tumors with data on oncological outcome and long-term survival. Materials and Methods: Prospective and retrospective data of patients undergoing LPD from March 1998 to April 2013 were reviewed. Of the 150 cases, 20 cases of LPD (7 cases done for chronic pancreatitis and 13 cases for benign cystic tumors of the pancreas) have been excluded, which leaves us with 130 cases of LPD performed for malignant indications. Results: In total, 130 patients were chosen for the study. The male:female ratio was 1:1.6, with a median age of 54 years. We had one conversion to open surgery in our series, the overall postoperative morbidity was 29.7%, and the mortality rate was 1.53%. The pancreatic fistula rate was 8.46%. The mean operating time was 310 – 34 minutes, and the mean blood loss was 110 – 22 mL. The mean hospital stay was 8 – 2.6 days. Resected margins were positive in 9.23% of cases. The mean tumor size was 3.13 – 1.21 cm, and the mean number of retrieved lymph nodes was 18.15 – 4.73. The overall 5-year actuarial survival was 29.42%, and the median survival was 33 months. Conclusions: LPD has evolved over a period of two decades and has the potential to become the standard of care for select periampullary and pancreatic head tumors with acceptable oncological outcomes, especially in high-volume centers. Randomized controlled trials are needed to establish the advantages of LPD.
long-term oncological outcomes, especially overall survival, are lacking. The aim of this retrospective review was to analyze the short-term and long-term outcomes of 130 cases of LPD performed for malignancy, which is the largest singleinstitution series reported to date.
Introduction
S
ince the first description of laparoscopic pancreaticoduodenectomy (LPD) in 1994,1 this technique has evolved considerably over the last two decades. Several singleinstitution series have shown this approach to be technically feasible,2–10 with similar short-term outcomes in comparison with open pancreaticoduodenectomy (OPD). As surgeons’ experience with advanced laparoscopy has increased and data demonstrating technical feasibility have matured, LPD is being done in larger numbers in recent times.11–15 However, data on
Materials and Methods
A retrospective review of a prospectively maintained database was performed. One hundred fifty patients who underwent LPD from March 1998 to April 2013 were identified.
Minimal Access and HPB Surgery, Gem Hospital and Research Centre, Coimbatore, Tamil Nadu, India.
1
2
The inclusion criterion for this study was resection performed for malignant disease on final histopathology (130 cases). All patients who underwent pancreaticoduodenectomy (PD) for benign diseases were excluded from the study (20 cases). All LPD cases were performed by either of the two senior authors (C.P. or P.S.). The standardized surgical technique that has already been published4 was followed for all the cases. Perioperative and follow-up data were collected and analyzed. Preoperative variables included age, gender, body mass index, and indication for surgery. Intraoperative variables included operative time, blood loss, and transfusion requirements. Pancreas-specific complications were assessed and graded according to the recommendations of the International Study Group on Pancreatic Surgery.16 Pathological staging, including retroperitoneal and superior mesenteric artery margin status, was determined from final pathology reports. Patients with T2 and above and node-positive patients received adjuvant chemotherapy. In the earlier phase of our study period a 5-fluorouracil-based regimen was used; however, now a gemcitabine-based regimen is routinely used. Patients were followed up on an outpatient basis after discharge, and re-admissions and complications, if any, were recorded. Patients are advised to complete a follow-up visit 7 days after discharge or earlier if the situation warranted. Apart from the scheduled visits for adjuvant chemotherapy, patients are advised to keep appointments monthly for the first 3 months, every 3 months for the first year, and every 6 months thereafter. At follow-up, patients undergo a detailed clinical examination, blood investigations including cancer antigen 19-9 assay, and imaging in the form of an abdominal computed tomography scan at least once every year. All patients are proactively followed up, including being telephoned if they have not appeared for their scheduled visit. Further follow-up was done through telephone interviews up to 5 years from the initial surgery. Median follow-up was calculated using the median of all the months the patient was traceable for outcomes or until the patient was lost to follow-up. Five-year actuarial survival curves were plotted using the Kaplan–Meier method. The oncological outcomes of LPD were analyzed for several parameters, like size of tumor, overall lymph node harvest, R0/R1 resection status, stage-wise survival, and overall survival. Analysis was done using GraphPad Prism software (version 6 for Windows; GraphPad Software Inc., San Diego, CA).
SENTHILNATHAN ET AL.
of Anesthesiologists score of the patients who underwent LPD was 2 (Table 1). Our series include 72 cases of periampullary and 58 cases of pancreatic head malignancies. The periampullary cases included ampullary (41 cases), cholangiocarcinoma (21 cases), and duodenal adenocarcinoma (10 cases) (Fig. 1). Postoperative outcomes
The overall operative postoperative morbidity was 29.7% as per the Clavien–Dindo classification scheme, of which the majority were minor complications (Clavien–Dindo classes 1 and 2), with major complications (Clavien–Dindo classes 3– 5) occurring in 10.76% of cases overall (14 out of 130 cases). The clinically significant fistula rate (Grade B and C) in this series was 8.46%. The incidence of postpancreatectomy hemorrhage was 4.61%. Re-operation
Re-operation was required in 5 cases (3.84%) (2 with hemorrhage, 1 with jejunal loop obstruction, and 2 with Grade C pancreatic fistula). In all cases re-operation was done by a laparotomy. In 2 cases we had to re-operate owing to hemorrhage following pancreatic leak. In 1 of the cases, the
Table 1. Patient Demographics, Perioperative Variables, and Postoperative Complications in Laparoscopic Pancreaticoduodenectomy Cases Characteristic
Value
Patient demographics
Patient demographics Age (years) [median (range)] 54 (28–76) Male:female ratio 1:1.6 ASA status (median) 2 BMI (kg/m2) [median (range)] 27.85 (22.6–33.8) Perioperative variables [mean – SD (range)] Operative time (minutes) 310 – 34 (238–388) Blood loss (mL) 110 – 22 (75–150) Transfusion requirement (units) 0.64 – 0.5 (0–2) ICU stay (days) 1.84 – 1.35 (1–6) Overall hospital stay (days) 8.06 – 2.61 (6–16) Postoperative complications [% (n)] POPF (Grade B and C) 8.46% (11) Grade B 4.62% (6) Grade C 3.84% (5) Postpancreatectomy hemorrhage 4.61% (6) Grade A 2.32% (3) Grade B 0.76% (1) Grade C 1.53% (2) Delayed gastric emptying 10.76% (14) Grade A 5.38% (7) Grade B 3.07% (4) Grade C 2.31% (3) Cardiac complications 2.3% (3) Pulmonary complications 10.76% (14) Wound infection 3.84% (5) Intraabdominal abscess 1.5% (2) Re-operation rate 3.84% (5) Mortality rate 1.53% (2)
The median age of patients in this study was 54 years, with a male:female ratio of 1:1.6. The median body mass index of the patients was 27.85 kg/m2. The median American Society
ASA, American Society of Anesthesiologists; BMI, body mass index; ICU, intensive care unit; POPF, postoperative pancreatic fistula; SD, standard deviation.
Results
Over the last 15 years, from 1998 to April 2013, in total, 150 LPDs were performed at our center. Among these cases, 65 patients underwent classical Whipple’s PD, and 85 patients underwent pylorus-preserving PD. Of the 150 cases, we have excluded 20 cases of LPD (7 cases done for chronic pancreatitis and 13 cases for benign cystic tumors of the pancreas), which leaves us with 130 cases of LPD performed for malignant indications.
LAPAROSCOPIC PANCREATICODUODENECTOMY
FIG. 1.
3
Tumor location in laparoscopic pancreaticoduodenectomy cases.
bleeding was from the first jejunal branch of the superior mesenteric artery, which was identified and suture-ligated. In the second case, on re-exploration, a large amount of clots was present intraabdominally, no active bleeding vessel was identified, and the pancreatojejunostomy anastomotic site was reinforced. Kinking of the duodenojejunostomy efferent loop with an intestinal obstruction developed in 1 patient, for which he underwent laparotomy with adhesiolysis on postoperative Day 8. Two patients underwent re-operation for pancreatic fistula. In one of the cases with a grade C fistula, the patient underwent drainage of peripancreatic collection and replacement of drains. The other patient developed necrotizing fasciitis of anterior abdominal wall following Grade C pancreatic fistula. The patient initially underwent fasciotomy with wound debridement on postoperative Day 6, and then following re-exploration 3 days later in view of clinical deterioration, the patient underwent drainage of collection and closure of the abdomen with tension sutures. In the immediate postoperative period, the patient developed features of abdominal compartment syndrome, the tension sutures were removed immediately, and the patient’s condition improved. The wound was allowed to heal by secondary intention, and the patient was discharged on postoperative Day 25. Mortality data
The overall 30-day mortality rate was 1.53% (2 cases) in this series. Of the 2 cases, 1 patient died because of postoperative pulmonary complications; the patient developed acute respiratory distress syndrome and died on postoperative Day 14. In the second case, the patient died of sepsis due to a perforation of the jejunal anastomotic limb. At exploration of the jejunal anastomotic limb, congestion with multiple sites of perforation was identified, but its cause could not be determined. Vascular involvement
Patients with known or suspected vascular involvement were preferably not chosen for LPD. However, in one of the recent cases for a patient with a pancreatic head tumor, superior mesenteric vein invasion was identified intraoperatively (it was not picked up on preoperative imaging). Laparoscopic resection and reconstruction of the superior mesenteric vein were done. Postoperative Doppler studies revealed normal patency; the patient had an uneventful recovery and was discharged on postoperative Day 9.
Oncological outcomes
During the initial phase of our LPD experience (1998– 2006), the R1 resection rate was 2.6%. In the subsequent period (from 2006 onwards), a meticulous and detailed evaluation of resected margins, including retroperitoneal margin and superior mesenteric artery margin status, was done as per the American College of Pathology protocol. Our R1 status in the second phase (2006–2013) was 9.23%. The mean tumor size was 3.13 – 1.21 cm. The mean number of nodes retrieved was 18.15 – 4.73, and the overall node positivity rate was 65% (Table 2). Stage-wise survival and follow-up data
Apart from the two deaths in the first 30-day interval, 29 patients were lost to follow-up at various time intervals, bringing the overall follow-up rate down to 77.69%. Median follow-up was 24 months. Median actuarial survivals for different histological subtypes according to their stage are presented in Table 3. The median survival of patients undergoing LPD for adenocarcinoma was 33 months. The 5-year actuarial survival rate was 29.42% estimated from the Kaplan–Meier curve (Fig. 2). Of the total of 130 patients, 27 have completed 5 years of follow-up. Among the survivors, 13 had ampullary adenocarcinomas, 5 had pancreatic head tumors, 6 had cholangiocarcinomas, and 3 had duodenal adenocarcinomas. Of these survivors, metastatic disease developed in 3 cases in the ampullary adenocarcinoma group and 2 of the pancreatic head subgroup. The remaining patients were disease-free until the last follow-up.
Table 2. Tumor Size, Lymph Node Yield, and Resection Margin Status in Our Laparoscopic Pancreaticoduodenectomy Series Characteristic Number of malignancies Tumor size (cm) [mean – SD (range)] Lymph node yield [mean – SD (range)] Node positivity rate R1 status (%) (2006–2013) SD, standard deviation.
Value 130 3.13 – 1.21 (1.1–5.2) 18.15 – 4.73 (11–28) 65% 9.23%
4
SENTHILNATHAN ET AL.
Table 3. Tumor Location and Stage-Wise Actuarial Survival Tumor location, stage (TNM)
Cases (n)
Ampullary carcinoma T1N0M0 16 T2N0M0 19 T2N1M0 6 Total 41 Pancreatic head carcinoma T1N0M0 11 T2N0M0 13 T2N1M0 34 Total 58 Cholangiocarcinoma T1N0M0 3 T2N0M0 10 T2N1M0 8 Total 21 Duodenal carcinoma T1N0M0 6 T2N0M0 2 T2N1M0 2 Total 10 Grand total 130 a
Median survival (months)a
Actuarial 5-year survival (%)a
51 29 19 36
50.55 36.84 16.67 39.07
36 18 11 20
36.36 7.69 2.94 20.91
43 35 19 24
66.67 30.00 20.83 27.82
41 31 19 33 33a
33.33 50 0 33.30 29.42a
Estimated from the Kaplan–Meier curve.
The number of deaths during follow-up was 74, of which 23 (31.08%) were reported to have metastatic disease, mostly in liver and lung, followed by local recurrence in 8 (10.81%). Twenty-five (33.78%) patients supposedly died because of other causes; in the rest the cause could not be determined. Discussion
Our current series of 150 cases of LPD is by far the largest ever reported, both in terms of laparoscopic procedure being successfully done and in the proportion of pancreatic malignancies per se (130 cases). The review by Gumbs et al.17
published in 2011 included 285 cases of LPD overall from the world literature. In our previous two publications on LPDs, in 2007 with 42 patients2 and subsequently in 2009 with 75 patients,4 we had analyzed the outcomes of LPD on several parameters, including oncological outcomes like lymph node harvest, size of tumor, R0/R1 resection status, and overall survival. Kendrick and Cusati14 reported 62 cases of LPD, which included 40 pancreatic head and periampullary carcinomas. Asbun and Stauffer18 published a comparative study with 53 cases of LPD, including 39 malignancies. Kim et al.15 reported a large series of about 100 LPD cases but, however, with a small proportion of malignant cases. Patient selection
Being a tertiary referral center, we cater to a large population with regard to pancreatic malignancies. Previously, periampullary and smaller tumors were selectively chosen for LPD.2 With growing experience, we now offer LPD for most cases of periampullary tumors and tumors in the pancreatic head, with the exceptions being poor performance status, extensive comorbidities, multiple previous abdominal surgeries, borderline resectability, and vascular invasion. In the initial phase, obese patients were preferably chosen for OPD; now, with growing experience, we have found that it is relatively easier to perform LPD for higher body mass index patients also. Conversion rates
The rate of conversions varies in different case series. Zureikat et al.3 reported a 14% conversion, Kendrick and Cusati14 reported a 4.6% conversion, and Kim et al.15 reported a 4.7 % conversion. Reasons for conversion include intraoperative uncontrollable bleeding, difficult operative dissection, vascular injury, or tumor invasion of vascular structures. In our practice, the decision to offer OPD or LPD was carefully taken preoperatively based on parameters like American Society of Anesthesiologists status, comorbidities, stage of the tumour, and presence or absence of vascular involvement. Hence we had only one conversion in our LPD series, where we faced intraoperative difficulty with chronic inflammatory changes near the head of the pancreas due to chronic pancreatitis associated with malignancy. Operative times
FIG. 2. Kaplan–Meier graph showing survival following laparoscopic pancreaticoduodenectomy.
The long operative time taken for the procedure is often cited by critics of the laparoscopic approach as the limiting factor. The operative time for the laparoscopic approach decreases progressively down the learning curve as with any other laparoscopic procedure. The reason for the long duration stems from the need to achieve radicality with extensive dissection and the time taken for a meticulous laparoscopic reconstruction. LPD at our institute has been standardized, and operative times (310 – 34 minutes) are expected to decrease modestly as more experience is gained. Kendrick and Cusati14 mentioned a mean operative time of 7.7 hours for the first 10 patients, which improved to 5.3 hours for the last 10 patients, in their series of 62 patients. Kim et al.15 mentioned a similar improvement in median operative time, from 9.8 hours for the first 33 cases to 6.6 hours for the last 34 cases.
LAPAROSCOPIC PANCREATICODUODENECTOMY Blood loss and transfusion requirements
The magnified view offered by laparoscopy and the use of an energy source like ultrasonic shears or a bipolar coagulation high-frequency electrosurgical unit have resulted in reduced intraoperative blood loss (110 – 22 mL) and lower transfusion requirements (0.6 – 0.5 units). This has been confirmed in similar other studies. Asbun and Stauffer18 quoted a blood loss of 195 – 136 mL and transfusion requirement of 0.64 – 1.5 units. This translates into better outcomes for the patients as they require fewer blood transfusions. Intensive care unit stay and overall stay
Reduced hospital stay with a laparoscopic approach by an average of 3.7 days was recently stated in a meta-analysis comparing OPD versus LPD.19 The duration of intensive care unit stay and the overall hospital stay are lower in uncomplicated cases of LPD; however, this advantage may be negated in cases with postoperative complications. Postoperative morbidity
The postoperative morbidity ranges from about 26% to 40% in various series of LPDs. By and large, a pancreatic fistula is the leading cause of morbidity in these patients. Kendrick and Sclabas20 reported a pancreatic fistula in 17.7% of cases, and Kim et al.15 had pancreatic fistula in 6% of cases. Overall, the clinically significant pancreatic fistula rate in our patients is 8.46%. Our rates of delayed gastric emptying of 10.76% with LPD are comparable to those in the overall world literature.21 Other postoperative complications adding to morbidity in patients of LPD are cardiac, pulmonary, wound infection, and intraabdominal abscess.18
5
a series of major venous resection during LPD in 11 patients with satisfactory results. Oncological outcomes
Regarding the oncological radicality of LPD for pancreatic cancers, the size of the tumor, number of lymph nodes retrieved, resection margins, and short-term outcomes have been studied, although there are limited data in the literature on long-term outcomes.13,22 Our present study, with its large number of patients of malignancy (130 cases) and a long follow-up, tries to abate the shortcomings of the previous reports on LPD in pancreatic malignancy patients. In our practice, especially in the second phase (2006–2013), a meticulous evaluation of resected margins, including retroperitoneal margin status and superior mesenteric artery margin status, was performed as per the American College of Pathology protocol. At the time of surgery, the specimen is inked, and the margins are clearly delineated before it is handed over to the pathologist. Kendrick and Cusati14 reported a median tumor size of 3 cm and the median number of 15 lymph nodes harvested with an R0 resection possible in 89% of patients. Kim et al.15 reported a median tumor size of 2.8 cm with a median number of 13 lymph nodes harvested with 100% margin-free resections. Asbun and Stauffer18 reported a median tumor size of 2.74 cm with a mean number of 23.4 lymph nodes harvested and R0 resection status in 94.9%. Our technique of radical dissection and nodal clearance has been standardized over the years; hence our lymph node yield (18.15) and margin status (90.77%) have been consistently good. Although several other studies have reported 100% R0 resections,17 very few of them have analyzed the uncinate margin and superior mesenteric artery margin positivity, which are very critical aspects of pathological evaluation to achieve oncological radicality.
Re-operation
Re-operation in the early postoperative period has been reported, with the common indications being postoperative leak, bleeding, and obstruction. In our series we had to reoperate on 5 cases (3.84%). We recommend that newer surgeons embarking on this tougher terrain have a low threshold to re-intervene, at the slightest hint or suspicion of clinical deterioration. Mortality
The postoperative mortality in LPD case series is in the range of 1.6%–8%. We have had 2 patients die in the first 30 days (1.53%). Other case series have projected a varying mortality of 7.1% (Zureikat et al.3), 1.5% (Kendrick and Cusati14), 1% (Kim et al.15), and 5.7% (Asbun and Stauffer18). Postoperative leak, hemorrhage, pulmonary complications, myocardial infarction, and sepsis all have been implicated as important causes of mortality.
Long-term survival
In spite of our efforts and constant endeavors to improve oncological radicality, pancreatic cancer still remains a disease with dismal prognosis. Most patients are not candidates for surgical resection and have median survivals of a few months. Our median survival is 33 months, which is less compared with our previous published data of 49 months.2 The reason for decreased survival may be widened criteria of patient selection for LPD with growing expertise, as compared with highly selected cases in earlier series. The actuarial 5-year survival is 29.42%. It should be noted that none of the other publications has mentioned data on long-term survival following LPD.19,22 Our attempt to do so could probably encourage other authors publishing data on LPD to analyze long-term outcomes, which would further substantiate the role of LPD for pancreatic cancer. Conclusions
Vascular invasion
With increasing experience we believe that vascular invasion is only a relative contraindication for LPD. We have recently performed 1 case of laparoscopic superior mesenteric vein resection and reconstruction for a locally advanced pancreatic head tumor. Kendrick and Sclabas20 had published
The initial skepticism associated with LPD has decreased, and many pancreatic surgeons with expertise in minimally invasive surgery are attempting to enter this difficult terrain. Our proportion of LPD cases has gone up considerably in recent years, with growing expertise conferring added advantages of lesser pain, quicker ambulation, faster recovery,
6
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decreased postoperative intensive care unit and hospital stay, and increased lymph node yield. In addition, limited intraoperative blood loss owing to improved energy sources and an oncological clearance comparable to OPD assure that LPD is a suitable, if not a better, alternative for pancreatic malignancy. Unfortunately, extremely limited data are present in the form of comparative studies or randomized controlled trials comparing OPD with LPD. In this process, we have initiated a randomized controlled trial comparing outcomes of OPD versus LPD (PLOT trial NCT02081131), which, when completed, would be the first randomized controlled trial to compare the outcomes in the two groups.
12. 13.
14. 15.
Disclosure Statement
No competing financial interests exist.
16.
References
1. Gagner M, Pomp A. Laparoscopic pylorus-preserving pancreatoduodenectomy. Surg Endosc 1994;8:408–410. 2. Palanivelu C, et al. Laparoscopic pancreaticoduodenectomy: Technique and outcomes. J Am Coll Surg 2007; 205:222–230. 3. Zureikat AH, et al. Can laparoscopic pancreaticoduodenectomy be safely implemented? J Gastrointest Surg 2011; 15:1151–1157. 4. Palanivelu C, et al. Evolution in techniques of laparoscopic pancreaticoduodenectomy: A decade long experience from a tertiary center. J Hepatobiliary Pancreat Surg 2009;16: 731–740. 5. Ammori BJ. Laparoscopic hand-assisted pancreaticoduodenectomy: Initial UK experience. Surg Endosc 2004;18: 717–718. 6. Staudacher C, et al. Laparoscopic assisted duodenopancreatectomy. Surg Endosc 2005;19:352–356. 7. Dulucq JL, Wintringer P, Mahajna A. Laparoscopic pancreaticoduodenectomy for benign and malignant diseases. Surg Endosc 2006;20:1045–1050. 8. Lu B, et al. Laparoscopic pancreaticoduodenectomy to treat cancer of the ampulla of Vater. JSLS 2006;10:97–100. 9. Pugliese R, et al. Laparoscopic pancreaticoduodenectomy: A retrospective review of 19 cases. Surg Laparosc Endosc Percutan Tech 2008;18:13–18. 10. Satyadas T, et al. Evolution in technique of laparoscopic pancreaticoduodenectomy: A decade long experience from a tertiary center. J Hepatobiliary Pancreat Sci 2010;17:367–368. 11. Chalikonda S, Aguilar-Saavedra JR, Walsh RM. Laparoscopic robotic-assisted pancreaticoduodenectomy: A case-matched
17. 18.
19. 20. 21. 22.
comparison with open resection. Surg Endosc 2012;26:2397– 2402. Cho A, et al. Comparison of laparoscopy-assisted and open pylorus-preserving pancreaticoduodenectomy for periampullary disease. Am J Surg 2009;198:445–449. Croome KP, et al. Total laparoscopic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: Oncologic advantages over open approaches? Ann Surg 2014;260: 633–638. Kendrick ML, Cusati D. Total laparoscopic pancreaticoduodenectomy: Feasibility and outcome in an early experience. Arch Surg 2010;145:19–23. Kim SC, et al. Short-term clinical outcomes for 100 consecutive cases of laparoscopic pylorus-preserving pancreatoduodenectomy: Improvement with surgical experience. Surg Endosc 2013;27:95–103. Bassi C, et al. Postoperative pancreatic fistula: An international study group (ISGPF) definition. Surgery 2005;138: 8–13. Gumbs AA, et al. Laparoscopic pancreatoduodenectomy: A review of 285 published cases. Ann Surg Oncol 2011;18: 1335–1341. Asbun HJ, Stauffer JA. Laparoscopic vs open pancreaticoduodenectomy: Overall outcomes and severity of complications using the Accordion Severity Grading System. J Am Coll Surg 2012;215:810–819. Correa-Gallego C, et al. Minimally-invasive vs open pancreaticoduodenectomy: Systematic review and meta-analysis. J Am Coll Surg 2014;218:129–139. Kendrick ML, Sclabas GM. Major venous resection during total laparoscopic pancreaticoduodenectomy. HPB (Oxford) 2011;13:454–458. Li YB, et al. [Delayed gastric emptying after laparoscopic versus open pancreaticoduodenectomy: A comparative study]. Zhonghua Wai Ke Za Zhi 2013;51:304–307. Fisher SB, Kooby DA. Laparoscopic pancreatectomy for malignancy. J Surg Oncol 2013;107:39–50.
Address correspondence to: Palanisamy Senthilnathan, MS, DNB, MRCS (Ed), DNB (GI Surgery), FMAS, FACS Minimal Access and HPB Surgery Gem Hospital and Research Centre Coimbatore, Tamil Nadu, 641045 India E-mail: [email protected]
Full Report
Long-Term Results of Laparoscopic Pancreaticoduodenectomy for Pancreatic and Periampullary Cancer—Experience of 130 Cases from a Tertiary-Care Center in South India Palanisamy Senthilnathan, MS, DNB, MRCS (Ed), DNB (GI Surgery), FMAS, FACS, Sivakumar Srivatsan Gurumurthy, MS, DNB (GI Surgery), FMAS, Shiekh Imran Gul, MS, Sandeep Sabnis, MS, Anand Vijai Natesan, MS, DNB (GI Surgery), FMAS, Nalankilli V.P., MS, FMAS, P. Praveen Raj, MS, DNB (GI Surgery), FMAS, Rajapandian Subbiah, MS, DNB (GI Surgery), FMAS, Parthasarathi Ramakrishnan, MS, FMAS, and Chinnusamy Palanivelu, MS, MCh, DNB, FACS, FRCS, FICS
Abstract
Background: Laparoscopic pancreaticoduodenectomy (LPD), although an advanced surgical procedure, is being increasingly used for pancreatic head and periampullary tumors. We present our experience of 15 years with the largest series in total LPD for periampullary and pancreatic head tumors with data on oncological outcome and long-term survival. Materials and Methods: Prospective and retrospective data of patients undergoing LPD from March 1998 to April 2013 were reviewed. Of the 150 cases, 20 cases of LPD (7 cases done for chronic pancreatitis and 13 cases for benign cystic tumors of the pancreas) have been excluded, which leaves us with 130 cases of LPD performed for malignant indications. Results: In total, 130 patients were chosen for the study. The male:female ratio was 1:1.6, with a median age of 54 years. We had one conversion to open surgery in our series, the overall postoperative morbidity was 29.7%, and the mortality rate was 1.53%. The pancreatic fistula rate was 8.46%. The mean operating time was 310 – 34 minutes, and the mean blood loss was 110 – 22 mL. The mean hospital stay was 8 – 2.6 days. Resected margins were positive in 9.23% of cases. The mean tumor size was 3.13 – 1.21 cm, and the mean number of retrieved lymph nodes was 18.15 – 4.73. The overall 5-year actuarial survival was 29.42%, and the median survival was 33 months. Conclusions: LPD has evolved over a period of two decades and has the potential to become the standard of care for select periampullary and pancreatic head tumors with acceptable oncological outcomes, especially in high-volume centers. Randomized controlled trials are needed to establish the advantages of LPD.
long-term oncological outcomes, especially overall survival, are lacking. The aim of this retrospective review was to analyze the short-term and long-term outcomes of 130 cases of LPD performed for malignancy, which is the largest singleinstitution series reported to date.
Introduction
S
ince the first description of laparoscopic pancreaticoduodenectomy (LPD) in 1994,1 this technique has evolved considerably over the last two decades. Several singleinstitution series have shown this approach to be technically feasible,2–10 with similar short-term outcomes in comparison with open pancreaticoduodenectomy (OPD). As surgeons’ experience with advanced laparoscopy has increased and data demonstrating technical feasibility have matured, LPD is being done in larger numbers in recent times.11–15 However, data on
Materials and Methods
A retrospective review of a prospectively maintained database was performed. One hundred fifty patients who underwent LPD from March 1998 to April 2013 were identified.
Minimal Access and HPB Surgery, Gem Hospital and Research Centre, Coimbatore, Tamil Nadu, India.
1
2
The inclusion criterion for this study was resection performed for malignant disease on final histopathology (130 cases). All patients who underwent pancreaticoduodenectomy (PD) for benign diseases were excluded from the study (20 cases). All LPD cases were performed by either of the two senior authors (C.P. or P.S.). The standardized surgical technique that has already been published4 was followed for all the cases. Perioperative and follow-up data were collected and analyzed. Preoperative variables included age, gender, body mass index, and indication for surgery. Intraoperative variables included operative time, blood loss, and transfusion requirements. Pancreas-specific complications were assessed and graded according to the recommendations of the International Study Group on Pancreatic Surgery.16 Pathological staging, including retroperitoneal and superior mesenteric artery margin status, was determined from final pathology reports. Patients with T2 and above and node-positive patients received adjuvant chemotherapy. In the earlier phase of our study period a 5-fluorouracil-based regimen was used; however, now a gemcitabine-based regimen is routinely used. Patients were followed up on an outpatient basis after discharge, and re-admissions and complications, if any, were recorded. Patients are advised to complete a follow-up visit 7 days after discharge or earlier if the situation warranted. Apart from the scheduled visits for adjuvant chemotherapy, patients are advised to keep appointments monthly for the first 3 months, every 3 months for the first year, and every 6 months thereafter. At follow-up, patients undergo a detailed clinical examination, blood investigations including cancer antigen 19-9 assay, and imaging in the form of an abdominal computed tomography scan at least once every year. All patients are proactively followed up, including being telephoned if they have not appeared for their scheduled visit. Further follow-up was done through telephone interviews up to 5 years from the initial surgery. Median follow-up was calculated using the median of all the months the patient was traceable for outcomes or until the patient was lost to follow-up. Five-year actuarial survival curves were plotted using the Kaplan–Meier method. The oncological outcomes of LPD were analyzed for several parameters, like size of tumor, overall lymph node harvest, R0/R1 resection status, stage-wise survival, and overall survival. Analysis was done using GraphPad Prism software (version 6 for Windows; GraphPad Software Inc., San Diego, CA).
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of Anesthesiologists score of the patients who underwent LPD was 2 (Table 1). Our series include 72 cases of periampullary and 58 cases of pancreatic head malignancies. The periampullary cases included ampullary (41 cases), cholangiocarcinoma (21 cases), and duodenal adenocarcinoma (10 cases) (Fig. 1). Postoperative outcomes
The overall operative postoperative morbidity was 29.7% as per the Clavien–Dindo classification scheme, of which the majority were minor complications (Clavien–Dindo classes 1 and 2), with major complications (Clavien–Dindo classes 3– 5) occurring in 10.76% of cases overall (14 out of 130 cases). The clinically significant fistula rate (Grade B and C) in this series was 8.46%. The incidence of postpancreatectomy hemorrhage was 4.61%. Re-operation
Re-operation was required in 5 cases (3.84%) (2 with hemorrhage, 1 with jejunal loop obstruction, and 2 with Grade C pancreatic fistula). In all cases re-operation was done by a laparotomy. In 2 cases we had to re-operate owing to hemorrhage following pancreatic leak. In 1 of the cases, the
Table 1. Patient Demographics, Perioperative Variables, and Postoperative Complications in Laparoscopic Pancreaticoduodenectomy Cases Characteristic
Value
Patient demographics
Patient demographics Age (years) [median (range)] 54 (28–76) Male:female ratio 1:1.6 ASA status (median) 2 BMI (kg/m2) [median (range)] 27.85 (22.6–33.8) Perioperative variables [mean – SD (range)] Operative time (minutes) 310 – 34 (238–388) Blood loss (mL) 110 – 22 (75–150) Transfusion requirement (units) 0.64 – 0.5 (0–2) ICU stay (days) 1.84 – 1.35 (1–6) Overall hospital stay (days) 8.06 – 2.61 (6–16) Postoperative complications [% (n)] POPF (Grade B and C) 8.46% (11) Grade B 4.62% (6) Grade C 3.84% (5) Postpancreatectomy hemorrhage 4.61% (6) Grade A 2.32% (3) Grade B 0.76% (1) Grade C 1.53% (2) Delayed gastric emptying 10.76% (14) Grade A 5.38% (7) Grade B 3.07% (4) Grade C 2.31% (3) Cardiac complications 2.3% (3) Pulmonary complications 10.76% (14) Wound infection 3.84% (5) Intraabdominal abscess 1.5% (2) Re-operation rate 3.84% (5) Mortality rate 1.53% (2)
The median age of patients in this study was 54 years, with a male:female ratio of 1:1.6. The median body mass index of the patients was 27.85 kg/m2. The median American Society
ASA, American Society of Anesthesiologists; BMI, body mass index; ICU, intensive care unit; POPF, postoperative pancreatic fistula; SD, standard deviation.
Results
Over the last 15 years, from 1998 to April 2013, in total, 150 LPDs were performed at our center. Among these cases, 65 patients underwent classical Whipple’s PD, and 85 patients underwent pylorus-preserving PD. Of the 150 cases, we have excluded 20 cases of LPD (7 cases done for chronic pancreatitis and 13 cases for benign cystic tumors of the pancreas), which leaves us with 130 cases of LPD performed for malignant indications.
LAPAROSCOPIC PANCREATICODUODENECTOMY
FIG. 1.
3
Tumor location in laparoscopic pancreaticoduodenectomy cases.
bleeding was from the first jejunal branch of the superior mesenteric artery, which was identified and suture-ligated. In the second case, on re-exploration, a large amount of clots was present intraabdominally, no active bleeding vessel was identified, and the pancreatojejunostomy anastomotic site was reinforced. Kinking of the duodenojejunostomy efferent loop with an intestinal obstruction developed in 1 patient, for which he underwent laparotomy with adhesiolysis on postoperative Day 8. Two patients underwent re-operation for pancreatic fistula. In one of the cases with a grade C fistula, the patient underwent drainage of peripancreatic collection and replacement of drains. The other patient developed necrotizing fasciitis of anterior abdominal wall following Grade C pancreatic fistula. The patient initially underwent fasciotomy with wound debridement on postoperative Day 6, and then following re-exploration 3 days later in view of clinical deterioration, the patient underwent drainage of collection and closure of the abdomen with tension sutures. In the immediate postoperative period, the patient developed features of abdominal compartment syndrome, the tension sutures were removed immediately, and the patient’s condition improved. The wound was allowed to heal by secondary intention, and the patient was discharged on postoperative Day 25. Mortality data
The overall 30-day mortality rate was 1.53% (2 cases) in this series. Of the 2 cases, 1 patient died because of postoperative pulmonary complications; the patient developed acute respiratory distress syndrome and died on postoperative Day 14. In the second case, the patient died of sepsis due to a perforation of the jejunal anastomotic limb. At exploration of the jejunal anastomotic limb, congestion with multiple sites of perforation was identified, but its cause could not be determined. Vascular involvement
Patients with known or suspected vascular involvement were preferably not chosen for LPD. However, in one of the recent cases for a patient with a pancreatic head tumor, superior mesenteric vein invasion was identified intraoperatively (it was not picked up on preoperative imaging). Laparoscopic resection and reconstruction of the superior mesenteric vein were done. Postoperative Doppler studies revealed normal patency; the patient had an uneventful recovery and was discharged on postoperative Day 9.
Oncological outcomes
During the initial phase of our LPD experience (1998– 2006), the R1 resection rate was 2.6%. In the subsequent period (from 2006 onwards), a meticulous and detailed evaluation of resected margins, including retroperitoneal margin and superior mesenteric artery margin status, was done as per the American College of Pathology protocol. Our R1 status in the second phase (2006–2013) was 9.23%. The mean tumor size was 3.13 – 1.21 cm. The mean number of nodes retrieved was 18.15 – 4.73, and the overall node positivity rate was 65% (Table 2). Stage-wise survival and follow-up data
Apart from the two deaths in the first 30-day interval, 29 patients were lost to follow-up at various time intervals, bringing the overall follow-up rate down to 77.69%. Median follow-up was 24 months. Median actuarial survivals for different histological subtypes according to their stage are presented in Table 3. The median survival of patients undergoing LPD for adenocarcinoma was 33 months. The 5-year actuarial survival rate was 29.42% estimated from the Kaplan–Meier curve (Fig. 2). Of the total of 130 patients, 27 have completed 5 years of follow-up. Among the survivors, 13 had ampullary adenocarcinomas, 5 had pancreatic head tumors, 6 had cholangiocarcinomas, and 3 had duodenal adenocarcinomas. Of these survivors, metastatic disease developed in 3 cases in the ampullary adenocarcinoma group and 2 of the pancreatic head subgroup. The remaining patients were disease-free until the last follow-up.
Table 2. Tumor Size, Lymph Node Yield, and Resection Margin Status in Our Laparoscopic Pancreaticoduodenectomy Series Characteristic Number of malignancies Tumor size (cm) [mean – SD (range)] Lymph node yield [mean – SD (range)] Node positivity rate R1 status (%) (2006–2013) SD, standard deviation.
Value 130 3.13 – 1.21 (1.1–5.2) 18.15 – 4.73 (11–28) 65% 9.23%
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Table 3. Tumor Location and Stage-Wise Actuarial Survival Tumor location, stage (TNM)
Cases (n)
Ampullary carcinoma T1N0M0 16 T2N0M0 19 T2N1M0 6 Total 41 Pancreatic head carcinoma T1N0M0 11 T2N0M0 13 T2N1M0 34 Total 58 Cholangiocarcinoma T1N0M0 3 T2N0M0 10 T2N1M0 8 Total 21 Duodenal carcinoma T1N0M0 6 T2N0M0 2 T2N1M0 2 Total 10 Grand total 130 a
Median survival (months)a
Actuarial 5-year survival (%)a
51 29 19 36
50.55 36.84 16.67 39.07
36 18 11 20
36.36 7.69 2.94 20.91
43 35 19 24
66.67 30.00 20.83 27.82
41 31 19 33 33a
33.33 50 0 33.30 29.42a
Estimated from the Kaplan–Meier curve.
The number of deaths during follow-up was 74, of which 23 (31.08%) were reported to have metastatic disease, mostly in liver and lung, followed by local recurrence in 8 (10.81%). Twenty-five (33.78%) patients supposedly died because of other causes; in the rest the cause could not be determined. Discussion
Our current series of 150 cases of LPD is by far the largest ever reported, both in terms of laparoscopic procedure being successfully done and in the proportion of pancreatic malignancies per se (130 cases). The review by Gumbs et al.17
published in 2011 included 285 cases of LPD overall from the world literature. In our previous two publications on LPDs, in 2007 with 42 patients2 and subsequently in 2009 with 75 patients,4 we had analyzed the outcomes of LPD on several parameters, including oncological outcomes like lymph node harvest, size of tumor, R0/R1 resection status, and overall survival. Kendrick and Cusati14 reported 62 cases of LPD, which included 40 pancreatic head and periampullary carcinomas. Asbun and Stauffer18 published a comparative study with 53 cases of LPD, including 39 malignancies. Kim et al.15 reported a large series of about 100 LPD cases but, however, with a small proportion of malignant cases. Patient selection
Being a tertiary referral center, we cater to a large population with regard to pancreatic malignancies. Previously, periampullary and smaller tumors were selectively chosen for LPD.2 With growing experience, we now offer LPD for most cases of periampullary tumors and tumors in the pancreatic head, with the exceptions being poor performance status, extensive comorbidities, multiple previous abdominal surgeries, borderline resectability, and vascular invasion. In the initial phase, obese patients were preferably chosen for OPD; now, with growing experience, we have found that it is relatively easier to perform LPD for higher body mass index patients also. Conversion rates
The rate of conversions varies in different case series. Zureikat et al.3 reported a 14% conversion, Kendrick and Cusati14 reported a 4.6% conversion, and Kim et al.15 reported a 4.7 % conversion. Reasons for conversion include intraoperative uncontrollable bleeding, difficult operative dissection, vascular injury, or tumor invasion of vascular structures. In our practice, the decision to offer OPD or LPD was carefully taken preoperatively based on parameters like American Society of Anesthesiologists status, comorbidities, stage of the tumour, and presence or absence of vascular involvement. Hence we had only one conversion in our LPD series, where we faced intraoperative difficulty with chronic inflammatory changes near the head of the pancreas due to chronic pancreatitis associated with malignancy. Operative times
FIG. 2. Kaplan–Meier graph showing survival following laparoscopic pancreaticoduodenectomy.
The long operative time taken for the procedure is often cited by critics of the laparoscopic approach as the limiting factor. The operative time for the laparoscopic approach decreases progressively down the learning curve as with any other laparoscopic procedure. The reason for the long duration stems from the need to achieve radicality with extensive dissection and the time taken for a meticulous laparoscopic reconstruction. LPD at our institute has been standardized, and operative times (310 – 34 minutes) are expected to decrease modestly as more experience is gained. Kendrick and Cusati14 mentioned a mean operative time of 7.7 hours for the first 10 patients, which improved to 5.3 hours for the last 10 patients, in their series of 62 patients. Kim et al.15 mentioned a similar improvement in median operative time, from 9.8 hours for the first 33 cases to 6.6 hours for the last 34 cases.
LAPAROSCOPIC PANCREATICODUODENECTOMY Blood loss and transfusion requirements
The magnified view offered by laparoscopy and the use of an energy source like ultrasonic shears or a bipolar coagulation high-frequency electrosurgical unit have resulted in reduced intraoperative blood loss (110 – 22 mL) and lower transfusion requirements (0.6 – 0.5 units). This has been confirmed in similar other studies. Asbun and Stauffer18 quoted a blood loss of 195 – 136 mL and transfusion requirement of 0.64 – 1.5 units. This translates into better outcomes for the patients as they require fewer blood transfusions. Intensive care unit stay and overall stay
Reduced hospital stay with a laparoscopic approach by an average of 3.7 days was recently stated in a meta-analysis comparing OPD versus LPD.19 The duration of intensive care unit stay and the overall hospital stay are lower in uncomplicated cases of LPD; however, this advantage may be negated in cases with postoperative complications. Postoperative morbidity
The postoperative morbidity ranges from about 26% to 40% in various series of LPDs. By and large, a pancreatic fistula is the leading cause of morbidity in these patients. Kendrick and Sclabas20 reported a pancreatic fistula in 17.7% of cases, and Kim et al.15 had pancreatic fistula in 6% of cases. Overall, the clinically significant pancreatic fistula rate in our patients is 8.46%. Our rates of delayed gastric emptying of 10.76% with LPD are comparable to those in the overall world literature.21 Other postoperative complications adding to morbidity in patients of LPD are cardiac, pulmonary, wound infection, and intraabdominal abscess.18
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a series of major venous resection during LPD in 11 patients with satisfactory results. Oncological outcomes
Regarding the oncological radicality of LPD for pancreatic cancers, the size of the tumor, number of lymph nodes retrieved, resection margins, and short-term outcomes have been studied, although there are limited data in the literature on long-term outcomes.13,22 Our present study, with its large number of patients of malignancy (130 cases) and a long follow-up, tries to abate the shortcomings of the previous reports on LPD in pancreatic malignancy patients. In our practice, especially in the second phase (2006–2013), a meticulous evaluation of resected margins, including retroperitoneal margin status and superior mesenteric artery margin status, was performed as per the American College of Pathology protocol. At the time of surgery, the specimen is inked, and the margins are clearly delineated before it is handed over to the pathologist. Kendrick and Cusati14 reported a median tumor size of 3 cm and the median number of 15 lymph nodes harvested with an R0 resection possible in 89% of patients. Kim et al.15 reported a median tumor size of 2.8 cm with a median number of 13 lymph nodes harvested with 100% margin-free resections. Asbun and Stauffer18 reported a median tumor size of 2.74 cm with a mean number of 23.4 lymph nodes harvested and R0 resection status in 94.9%. Our technique of radical dissection and nodal clearance has been standardized over the years; hence our lymph node yield (18.15) and margin status (90.77%) have been consistently good. Although several other studies have reported 100% R0 resections,17 very few of them have analyzed the uncinate margin and superior mesenteric artery margin positivity, which are very critical aspects of pathological evaluation to achieve oncological radicality.
Re-operation
Re-operation in the early postoperative period has been reported, with the common indications being postoperative leak, bleeding, and obstruction. In our series we had to reoperate on 5 cases (3.84%). We recommend that newer surgeons embarking on this tougher terrain have a low threshold to re-intervene, at the slightest hint or suspicion of clinical deterioration. Mortality
The postoperative mortality in LPD case series is in the range of 1.6%–8%. We have had 2 patients die in the first 30 days (1.53%). Other case series have projected a varying mortality of 7.1% (Zureikat et al.3), 1.5% (Kendrick and Cusati14), 1% (Kim et al.15), and 5.7% (Asbun and Stauffer18). Postoperative leak, hemorrhage, pulmonary complications, myocardial infarction, and sepsis all have been implicated as important causes of mortality.
Long-term survival
In spite of our efforts and constant endeavors to improve oncological radicality, pancreatic cancer still remains a disease with dismal prognosis. Most patients are not candidates for surgical resection and have median survivals of a few months. Our median survival is 33 months, which is less compared with our previous published data of 49 months.2 The reason for decreased survival may be widened criteria of patient selection for LPD with growing expertise, as compared with highly selected cases in earlier series. The actuarial 5-year survival is 29.42%. It should be noted that none of the other publications has mentioned data on long-term survival following LPD.19,22 Our attempt to do so could probably encourage other authors publishing data on LPD to analyze long-term outcomes, which would further substantiate the role of LPD for pancreatic cancer. Conclusions
Vascular invasion
With increasing experience we believe that vascular invasion is only a relative contraindication for LPD. We have recently performed 1 case of laparoscopic superior mesenteric vein resection and reconstruction for a locally advanced pancreatic head tumor. Kendrick and Sclabas20 had published
The initial skepticism associated with LPD has decreased, and many pancreatic surgeons with expertise in minimally invasive surgery are attempting to enter this difficult terrain. Our proportion of LPD cases has gone up considerably in recent years, with growing expertise conferring added advantages of lesser pain, quicker ambulation, faster recovery,
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decreased postoperative intensive care unit and hospital stay, and increased lymph node yield. In addition, limited intraoperative blood loss owing to improved energy sources and an oncological clearance comparable to OPD assure that LPD is a suitable, if not a better, alternative for pancreatic malignancy. Unfortunately, extremely limited data are present in the form of comparative studies or randomized controlled trials comparing OPD with LPD. In this process, we have initiated a randomized controlled trial comparing outcomes of OPD versus LPD (PLOT trial NCT02081131), which, when completed, would be the first randomized controlled trial to compare the outcomes in the two groups.
12. 13.
14. 15.
Disclosure Statement
No competing financial interests exist.
16.
References
1. Gagner M, Pomp A. Laparoscopic pylorus-preserving pancreatoduodenectomy. Surg Endosc 1994;8:408–410. 2. Palanivelu C, et al. Laparoscopic pancreaticoduodenectomy: Technique and outcomes. J Am Coll Surg 2007; 205:222–230. 3. Zureikat AH, et al. Can laparoscopic pancreaticoduodenectomy be safely implemented? J Gastrointest Surg 2011; 15:1151–1157. 4. Palanivelu C, et al. Evolution in techniques of laparoscopic pancreaticoduodenectomy: A decade long experience from a tertiary center. J Hepatobiliary Pancreat Surg 2009;16: 731–740. 5. Ammori BJ. Laparoscopic hand-assisted pancreaticoduodenectomy: Initial UK experience. Surg Endosc 2004;18: 717–718. 6. Staudacher C, et al. Laparoscopic assisted duodenopancreatectomy. Surg Endosc 2005;19:352–356. 7. Dulucq JL, Wintringer P, Mahajna A. Laparoscopic pancreaticoduodenectomy for benign and malignant diseases. Surg Endosc 2006;20:1045–1050. 8. Lu B, et al. Laparoscopic pancreaticoduodenectomy to treat cancer of the ampulla of Vater. JSLS 2006;10:97–100. 9. Pugliese R, et al. Laparoscopic pancreaticoduodenectomy: A retrospective review of 19 cases. Surg Laparosc Endosc Percutan Tech 2008;18:13–18. 10. Satyadas T, et al. Evolution in technique of laparoscopic pancreaticoduodenectomy: A decade long experience from a tertiary center. J Hepatobiliary Pancreat Sci 2010;17:367–368. 11. Chalikonda S, Aguilar-Saavedra JR, Walsh RM. Laparoscopic robotic-assisted pancreaticoduodenectomy: A case-matched
17. 18.
19. 20. 21. 22.
comparison with open resection. Surg Endosc 2012;26:2397– 2402. Cho A, et al. Comparison of laparoscopy-assisted and open pylorus-preserving pancreaticoduodenectomy for periampullary disease. Am J Surg 2009;198:445–449. Croome KP, et al. Total laparoscopic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: Oncologic advantages over open approaches? Ann Surg 2014;260: 633–638. Kendrick ML, Cusati D. Total laparoscopic pancreaticoduodenectomy: Feasibility and outcome in an early experience. Arch Surg 2010;145:19–23. Kim SC, et al. Short-term clinical outcomes for 100 consecutive cases of laparoscopic pylorus-preserving pancreatoduodenectomy: Improvement with surgical experience. Surg Endosc 2013;27:95–103. Bassi C, et al. Postoperative pancreatic fistula: An international study group (ISGPF) definition. Surgery 2005;138: 8–13. Gumbs AA, et al. Laparoscopic pancreatoduodenectomy: A review of 285 published cases. Ann Surg Oncol 2011;18: 1335–1341. Asbun HJ, Stauffer JA. Laparoscopic vs open pancreaticoduodenectomy: Overall outcomes and severity of complications using the Accordion Severity Grading System. J Am Coll Surg 2012;215:810–819. Correa-Gallego C, et al. Minimally-invasive vs open pancreaticoduodenectomy: Systematic review and meta-analysis. J Am Coll Surg 2014;218:129–139. Kendrick ML, Sclabas GM. Major venous resection during total laparoscopic pancreaticoduodenectomy. HPB (Oxford) 2011;13:454–458. Li YB, et al. [Delayed gastric emptying after laparoscopic versus open pancreaticoduodenectomy: A comparative study]. Zhonghua Wai Ke Za Zhi 2013;51:304–307. Fisher SB, Kooby DA. Laparoscopic pancreatectomy for malignancy. J Surg Oncol 2013;107:39–50.
Address correspondence to: Palanisamy Senthilnathan, MS, DNB, MRCS (Ed), DNB (GI Surgery), FMAS, FACS Minimal Access and HPB Surgery Gem Hospital and Research Centre Coimbatore, Tamil Nadu, 641045 India E-mail: [email protected]
