
==== Front
Ann Surg Open
Ann Surg Open
AS9
Annals of Surgery Open
2691-3593
Wolters Kluwer Health, Inc. Two Commerce Square, 2001 Market Street, Philadelphia, PA 19103

AOSO-D-24-00129
00035
10.1097/AS9.0000000000000487
3
Original Study
Effects of Minimally Invasive Versus Open Pancreatoduodenectomy on Short-Term Surgical Outcomes and Postoperative Nutritional and Immunological Statuses: A Single-Institution Propensity Score-Matched Study
Yumoto Shinsei MD *
Hayashi Hiromitsu MD, PhD *
Mima Kosuke MD, PhD *
Ogawa Daisuke MD *
Itoyama Rumi MD, PhD *
Kitano Yuki MD, PhD *
Nakagawa Shigeki MD, PhD *
Okabe Hirohisa MD, PhD *
Baba Hideo MD, PhD *
* From the Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Reprints: Hiromitsu Hayashi, MD, PhD, Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan. Email: hhayasi@kumamoto-u.ac.jp.
30 8 2024
9 2024
5 3 e487e487
12 6 2024
7 8 2024
Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Objective:

To evaluate the feasibility and clinical impact of minimally invasive pancreatoduodenectomy (MIPD) versus open pancreatoduodenectomy (OPD) on postoperative nutritional and immunological indices.

Background:

The surgical advantages of MIPD over OPD are controversial, and the postoperative nutritional and immunological statuses are unknown.

Methods:

In total, 306 patients who underwent MIPD (n = 120) or OPD (n = 186) for periampullary tumors from April 2016 to February 2024 were analyzed. Surgical outcomes and postoperative nutritional and immunological indices (albumin, prognostic nutritional index [PNI], neutrophil-to-lymphocyte ratio [NLR], and platelet-to-lymphocyte ratio [PLR]) were examined by 1:1 propensity score matching (PSM) with well-matched background characteristics.

Results:

PSM resulted in 2 balanced groups of 99 patients each. Compared with OPD, MIPD was significantly associated with less estimated blood loss (P < 0.0001), fewer intraoperative blood transfusions (P = 0.001), longer operative time, shorter postoperative hospital stay (P < 0.0001), fewer postoperative complications (P = 0.001) (especially clinically relevant postoperative pancreatic fistula [P = 0.018]), and a higher rate of textbook outcome achievement (70.7% vs 48.5%, P = 0.001). The number of dissected lymph nodes and the R0 resection rate did not differ between the 2 groups. In elective cases with textbook outcome achievement, the change rates of albumin, PNI, NLR, and PLR from before to after surgery were equivalent in both groups.

Conclusions:

MIPD has several surgical advantages (excluding a prolonged operative time), and it enhances the achievement of textbook outcomes over OPD. However, the postoperative nutritional and immunological statuses are equivalent for both procedures.

minimally invasive pancreatoduodenectomy
nutritional and immunological status
open pancreatoduodenectomy
pancreatic fistula
postoperative complications
textbook outcome
OPEN-ACCESSTRUE
SDCT
==== Body
pmcINTRODUCTION

Pancreatoduodenectomy (PD) is the classic curative surgery for resectable periampullary tumors. Despite the recent development of surgical instruments and improvement of surgical techniques for pancreatic surgery, PD is still associated with a high risk of postoperative complications such as pancreatic fistula or bleeding, with incidence rates reaching 50%.1,2

Minimally invasive PD (MIPD), including laparoscopic, robot-assisted, and hybrid techniques, has been widely implemented during the past decade. Several studies, including 4 randomized clinical trials (RCTs), have been performed in an attempt to elucidate the clinical benefits of MIPD. In systematic reviews and meta-analyses of nonrandomized retrospective studies or nationwide studies between MIPD and open PD (OPD), MIPD showed better short-term nononcologic outcomes (such as lower blood loss and shorter hospital stay) as well as oncological noninferiority compared with OPD.3–11 Additionally, 2 single-center and 1 multicenter RCT comparing laparoscopic PD (LPD) versus OPD for periampullary tumors revealed a shorter length of hospital stay (LOS) in the laparoscopic approach and equivalent pancreas-specific morbidity between the 2 approaches.12–14 However, the LEOPARD-2 trial was prematurely ended because of the higher 90-day complication-related mortality rate with LPD than with OPD.15 Thus, the true impact of MIPD on surgical outcomes remains unclear. OPD is still one of the most invasive gastrointestinal surgeries. If MIPD provides benefits of decreased pain, shorter hospitalization, reduced postoperative complications, and enhanced recovery after surgery, the postoperative nutritional and immunological statuses also may be enhanced. Unfortunately, studies focusing on postoperative nutritional and immunological statuses are lacking.

In the present study, we compared MIPD and OPD for periampullary tumors with respect to the short-term surgical outcomes and clinical impact on the postoperative nutritional and immunological statuses using a propensity score-matching (PSM) analysis.

METHODS

Study Design

We conducted a single-center retrospective study comparing MIPD and OPD in a PSM cohort. All patients provided written informed consent, and the Ethics Committee of Kumamoto University approved the study protocol. The institutional ethical review board approved this study (IRB no. 1800), and all procedures were performed in accordance with the guidelines of the Declaration of Helsinki.

Eligibility and Data Collection

This study involved 334 consecutive patients with periampullary tumors who underwent MIPD or OPD at Kumamoto University Hospital from April 2016 to February 2024. The indications for MIPD in our institution were as follows: body mass index (BMI) of <30 kg/m2, no severe organ disorders (eg, cardiopulmonary dysfunction, blood disorders, dialysis), no history of upper mesocolic abdominal surgeries, no evidence of major vascular involvement on preoperative imaging, and no need for combined resection of other organs. OPD did not have such a limited operative indication. Patients who underwent conversion from MIPD to OPD were included in the OPD group. The exclusion criteria were combined resection for lesions in other organs, combined artery resection with revascularization, emergency PD, a history of pancreatectomy, insufficient baseline data, or missing primary outcome data.

Variables and Definitions

The patients’ baseline characteristics, operation-related parameters, short-term surgical outcomes, and nutritional and immunological status indices were collected from the medical records.

The resection margins were defined by the pathologists in our institution. The margin status was considered R1 when the distance between the tumor and any resection margins was ≤1 mm and R2 when macroscopic tumor tissue remained. Pathological TNM and stage were classified according to the 8th edition of the Union for International Cancer Control staging system. Resectability (resectable, borderline resectable, or unresectable) of pancreatic ductal adenocarcinoma (PDAC) was assessed according to the National Comprehensive Cancer Network guidelines (version 2.2021). Postoperative complications were defined as Clavien–Dindo classification (CD-c) grade ≥IIIa complications occurring within 90 days after surgery.16 Pancreas-specific complications, including postoperative pancreatic fistula (POPF), postpancreatectomy hemorrhage (PPH), and delayed gastric emptying (DGE), were defined in accordance with the International Study Group of Pancreatic Surgery,17–19 which defines clinically relevant POPF (CR-POPF) as grade B or C.17 Bile leakage was defined according to the International Study Group of Liver Surgery.20 Postoperative mortality was defined as the number of deaths occurring within 30 days after surgery.

Indices of the nutritional and immunological statuses were defined as the albumin concentration, postoperative prognostic nutritional index (PNI),21 neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). Postoperative albumin, PNI, NLR, and PLR were calculated from the blood tests that were performed when the patients visited our hospital for the first routine follow-up after surgery (approximately 30–60 days postoperatively). To assess changes in the nutritional and immunological statuses from before to after surgery, the percent change in the preoperative and postoperative nutrition scores was calculated as follows: percent change (%) = (postoperative score − preoperative score)/preoperative score. Albumin, PNI, NLR, and PLR index were defined as the percent change in each. Textbook outcomes were defined according to a previous report.22

Statistical Analysis

Continuous variables are expressed as mean ± SD or median with interquartile range according to the data type (parametric or nonparametric, respectively) and analyzed using the Wilcoxon signed-rank test or Mann–Whitney test. Categorical variables were evaluated using the chi-square test or Fisher exact test as appropriate. To reduce the bias arising from patient selection and lack of randomization, PSM was performed with 1:1 nearest-neighbor matching23 using a caliper width of 0.2. A logistic regression model with well-known variables potentially affecting the outcomes was used to estimate the propensity score. The outcomes were then compared between the OPD and MIPD groups in the matched cohort.

We calculated the 95% confidence intervals, and P < 0.05 was considered statistically significant. All statistical analyses were performed using JMP Pro software version 16.0.0 (SAS Institute, Cary, NC).

RESULTS

Clinicopathological Characteristics and Perioperative Outcomes Before PSM

A total of 306 patients met the inclusion criteria and were analyzed (Fig. 1). Among these patients, MIPD was planned for 128, but 8 (6.3%) required conversion to OPD. Therefore, we analyzed 186 (60.8%) patients who underwent OPD and 120 (39.2%) who underwent MIPD. The reasons for conversion were the need for vascular resection (n = 5, 62.5%), treatment of inflammation-induced peripancreatic adhesions (n = 2, 25.0%), and management of intraoperative bleeding (n = 1, 12.5%). In the MIPD group, LPD and robot-assisted PD (RPD) were performed in 81 (67.5%) and 39 (32.5%) patients, respectively.

FIGURE 1. Flowchart of surgical outcomes analysis. PPPD indicates pylorus-preserving pancreatoduodenectomy; SSPPD, subtotal stomach-preserving pancreatoduodenectomy.

The demographics, clinicopathological characteristics, and perioperative outcomes in the unmatched cohort are summarized in Table 1. There were no differences in sex, age, BMI, Eastern Cooperative Oncology Group performance status (ECOG PS), American Society of Anesthesiologists (ASA) score, history of diabetes, cholangitis, pancreatitis, preoperative biliary drainage, or preoperative chemotherapy between the 2 groups. Compared with the OPD group, the MIPD group had a higher incidence of soft pancreas (75.8% vs 47.3%, P < 0.0001) and a lower incidence of concomitant vascular resection (7.5% vs 23.1%, P < 0.0001). The details of vascular resection were as follows: segmental resection with end-to-end anastomosis (n = 43), wedge resection with primary closure (n = 5), reconstruction using venous interposition allograft (n = 2), and other procedures (n = 2) in our cohort. Regarding postoperative outcomes, the MIPD group had a significantly longer median operative time (524 [476–591] vs 473 [411–554] min, P < 0.0001) and significantly lower median estimated blood loss (EBL) (303 [150–543] vs 612 [356–1057] g, P < 0.0001) than the OPD group. Moreover, a shorter LOS was seen in the MIPD group (15.0 [11.0–23.0] vs 25.0 [17.0–38.3] days, P < 0.0001). The total postoperative complication rate (CD-c grade ≥IIIa) was lower in the MIPD group (29.2% vs 41.4%, P = 0.030); however, pancreas-specific complications were comparable between the 2 groups, including the rates of CR-POPF (28.3% vs 36.0%, P = 0.163), PPH (6.7% vs 5.9%, P = 0.790), and DGE (1.7% vs 4.3%, P = 0.206). Postoperative pathologic examination revealed lower rates of malignancies (74.2% vs 88.7%, P = 0.001) and PDAC (23.3% vs 39.3%, P = 0.004) as well as smaller tumors in the MIPD than OPD group. No mortality occurred within 30 days postoperatively in either group.

TABLE 1. Clinicopathological Characteristics and Perioperative Outcomes Before PSM

Characteristic	OPD
n = 186	MIPD
n = 120	P	
Male (%)	115 (61.8%)	69 (57.5%)	0.450	
Age (yr), mean ± SD	68.9 ± 9.5	67.9 ± 12.3	0.831	
BMI, mean ± SD	22.5 ± 3.4	23.0 ± 3.4	0.106	
ECOG PS ≤1 (%)	179 (96.2%)	116 (96.7%)	0.844	
ASA score ≤2 (%)	154 (82.8%)	106 (88.3%)	0.188	
Surgical approach			—	
 Laparoscopic (%)	—	81 (67.5%)		
 Robotic (%)	—	39 (32.5%)		
History of diabetes (%)	69 (37.1%)	46 (38.3%)	0.827	
History of cholangitis (%)	31 (16.7%)	22 (18.3%)	0.707	
History of pancreatitis (%)	8 (4.3%)	7 (5.8%)	0.544	
Preoperative biliary drainage (%)	75 (40.3%)	39 (32.5%)	0.167	
Preoperative chemotherapy (%)	32 (17.2%)	23 (19.2%)	0.663	
Malignancy (%)	165 (88.7%)	89 (74.2%)	0.001	
PDAC (%)	73 (39.3%)	28 (23.3%)	0.004	
Other malignancy			0.479	
 Pancreatic cancer (excluding PDAC) (%)	30 (16.1%)	13 (10.3%)		
 Biliary tract cancer (%)	53 (28.5%)	42 (35.0%)		
 Duodenal cancer (%)	9 (4.8%)	6 (5.0%)		
Tumor diameter (mm), median (IQR)	30.0 (19.0–40.0)	24.0 (13.0–33.0)	0.002	
Soft pancreas (%)	88 (47.3%)	91 (75.8%)	<0.0001	
Vascular resection (%)	43 (23.1%)	9 (7.5%)	<0.0001	
Operative time (min), median (IQR)	473 (411–554)	524 (476–591)	<0.0001	
Estimated blood loss (g), median (IQR)	612 (356–1057)	303 (150–543)	<0.0001	
Intraoperative blood transfusion (%)	44 (23.7%)	6 (5.0%)	<0.0001	
Number of dissected lymph nodes, median (IQR)	20 (10–27)	17 (9–27)	0.335	
R0 resection (%)	154 (82.8%)	110 (91.7%)	0.028	
Length of hospital stay (d), median (IQR)	25.0 (17.0–38.3)	15.0 (11.0–23.0)	<0.0001	
Postoperative complications (CD-c ≥IIIa) (%)	77 (41.4%)	35 (29.2%)	0.030	
CR-POPF (%)	67 (36.0%)	34 (28.3%)	0.163	
PPH (%)	11 (5.9%)	8 (6.7%)	0.790	
DGE (%)	8 (4.3%)	2 (1.7%)	0.206	
Bile leakage (%)	1 (0.5%)	0 (0.0%)	0.421	
30-d mortality (%)	0 (0.0%)	0 (0.0%)	1.0	
Textbook outcomes achieved (%)	109 (58.6%)	85 (70.8%)	0.030	
IQR indicates interquartile range; PPH, postpancreatectomy hemorrhage.

Clinicopathological Characteristics and Perioperative Outcomes After PSM

The following variables, well known to affect outcomes, were used for PSM: sex, age, BMI, ECOG PS, ASA score, preoperative chemotherapy, pathological malignancy, pathological PDAC, tumor diameter, soft pancreas, and concomitant vascular resection. After PSM, 198 patients were correctly matched (99 patients in each group) (Fig. 1). The clinicopathological characteristics and perioperative outcomes in the matched cohort are shown in Table 2. No significant differences were evident between the 2 groups in the matched cohort in terms of baseline characteristics, postoperative pathological diagnosis, concomitant vascular resection, and pancreatic texture. All vascular resections were segmental resections of portal vein/superior mesenteric vein (9 cases in MIPD and 8 cases in OPD). In the PDAC patients, stage classifications and resectability (resectable/borderline resectable/unresectable) are also not significantly different in both groups after PSM (Supplemental Table 1, see http://links.lww.com/AOSO/A399). In the MIPD group, LPD and RPD were performed in 70 (70.7%) and 29 (29.3%) patients, respectively. Regarding postoperative outcomes, the median operative time was significantly longer (523 [476–594] vs 458 [342–549] min, P = 0.001) and the median EBL was significantly lower (330 [175–550] vs 611 [350–1060] g, P < 0.001) in the MIPD than OPD group. Additionally, the MIPD group was less likely to require intraoperative blood transfusion (6.1% vs 23.2%, P = 0.001). Moreover, the MIPD group had a shorter LOS (15.0 [11.0–23.0] vs 27.0 [17.0–41.0] days, P < 0.0001) and lower total postoperative complication rate (CD-c grade ≥IIIa) (29.3% vs 51.5%, P = 0.001). In particular, the CR-POPF rate was significantly lower in the MIPD group (28.3% vs 44.4%, P = 0.018). The incidence of PPH (8.1% vs 10.1%, P = 0.621), DGE (2.0% vs 3.0%, P = 0.312), and bile leakage (0.0% vs 1.0%, P = 0.316) were comparable between the 2 groups. The number of dissected lymph nodes (18.0 [10.5–27.5] vs 19.0 [9.0–27.0], P = 0.834) and the rate of R0 resection (91.9% vs 85.9%, P = 0.175) were also comparable, suggesting that the oncological outcomes of MIPD are comparable to those of OPD. No 30-day mortality was seen in either group. Additionally, higher rates of achieving textbook outcomes were observed in the MIPD group (70.7% vs 48.5%, P = 0.018).

TABLE 2. Clinicopathological Characteristics and Perioperative Outcomes After PSM

Characteristic	OPD
n = 99	MIPD
n = 99	P	
Male (%)	55 (55.6%)	61 (61.6%)	0.387	
Age (yr), mean ± SD	69.5 ± 9.3	68.4 ± 11.6	0.566	
BMI, mean ± SD	23.1 ± 3.6	23.0 ± 3.1	0.934	
ECOG PS ≤1 (%)	96 (97.0%)	95 (96.0%)	0.700	
ASA score ≤2 (%)	84 (84.9%)	86 (86.9%)	0.683	
Surgical approach			—	
 Laparoscopic (%)	—	70 (70.7%)		
 Robotic (%)	—	29 (29.3%)		
History of diabetes (%)	30 (30.3%)	37 (37.4%)	0.293	
History of cholangitis (%)	17 (17.2%)	21 (21.2%)	0.470	
History of pancreatitis (%)	5 (5.1%)	5 (5.1%)	1.0	
Preoperative biliary drainage (%)	37 (37.4%)	37 (37.4%)	1.0	
Preoperative chemotherapy (%)	19 (19.2%)	21 (21.2%)	0.723	
Malignancy (%)	83 (83.8%)	84 (84.9%)	0.845	
PDAC (%)	24 (24.2%)	27 (27.3%)	0.626	
Other malignancy			0.684	
 Pancreatic cancer (excluding PDAC) (%)	18 (18.2%)	13 (13.1%)		
 Biliary tract cancer (%)	33 (33.3%)	38 (38.4%)		
 Duodenal cancer (%)	8 (8.1%)	6 (6.1%)		
Tumor diameter (mm), median (IQR)	28.0 (17.0–40.0)	25.0 (14.0–35.0)	0.400	
Soft pancreas (%)	69 (69.7%)	70 (70.7%)	0.877	
Vascular resection (%)	8 (8.1%)	9 (9.1%)	0.800	
Operative time (min), median (IQR)	458 (342–549)	523 (476–594)	0.001	
Estimated blood loss (g), median (IQR)	611 (350–1060)	330 (175–550)	<0.0001	
Intraoperative blood transfusion (%)	23 (23.2%)	6 (6.1%)	0.001	
Number of dissected lymph nodes, median (IQR)	19.0 (9.0–27.0)	18.0 (10.5–27.5)	0.834	
R0 resection (%)	85 (85.9%)	91 (91.9%)	0.175	
Length of hospital stay (d), median (IQR)	27.0 (17.0–41.0)	15.0 (11.0–23.0)	<0.0001	
Postoperative complications (CD-c ≥IIIa) (%)	51 (51.5%)	29 (29.3%)	0.001	
CR-POPF (%)	44 (44.4%)	28 (28.3%)	0.018	
PPH (%)	10 (10.1%)	8 (8.1%)	0.621	
DGE (%)	3 (3.0%)	2 (2.0%)	0.312	
Bile leakage (%)	1 (1.0%)	0 (0.0%)	0.316	
30-d mortality (%)	0 (0.0%)	0 (0.0%)	1.0	
Textbook outcomes achieved (%)	48 (48.5%)	70 (70.7%)	0.001	
IQR indicates interquartile range; PPH, postpancreatectomy hemorrhage.

Comparison of Postoperative Nutritional and Immunological Statuses Between MIPD and OPD

We assessed the postoperative nutritional and immunological statuses in patients who achieved textbook outcomes to exclude the effect of postoperative complications (Fig. 2).22 For this purpose, we focused on the percent change of well-known nutritional indices (albumin, PNI, NLR, and PLR) before and after surgery. The following variables, well known to affect outcomes, were used for PSM: sex, age, BMI, ECOG PS, ASA score, preoperative chemotherapy, pathological malignancy, pathological PDAC, and concomitant vascular resection.

FIGURE 2. Flowchart of textbook outcome analysis.

The clinical characteristics and perioperative outcomes before and after PSM are summarized in Supplemental Table 2, see http://links.lww.com/AOSO/A399 and Table 3, respectively. The baseline characteristics were not different between the 2 groups in the matched cohort. Interestingly, the data regarding the achievement of textbook outcomes also demonstrated the superiority of MIPD over OPD in terms of EBL and LOS, suggesting that these advantages of MIPD do not depend on the rate of postoperative complications. However, despite the advantages of MIPD, no significant difference in any nutritional score was found between the 2 groups (albumin index: P = 0.911, PNI: P = 0.895, NLR index: P = 0.935, PLR index: P = 0.626) (Fig. 3). Additionally, in the PSM analysis of the total cohort, the postoperative nutritional and immunological status indices were also comparable between the 2 groups (data not shown).

TABLE 3. Post-PSM Clinicopathological Characteristics and Perioperative Outcomes in Patients Who Achieved Textbook Outcomes

Characteristic	OPD
n = 66	MIPD
n = 66	P	
Male (%)	37 (56.1%)	37 (56.1%)	1.0	
Age (year), mean ±SD	69.4 ± 9.2	70.1 ± 8.7	0.911	
BMI, mean ± SD	22.4 ± 3.2	22.5 ± 3.3	0.875	
ECOG PS ≤1 (%)	63 (95.5%)	64 (97.0%)	0.648	
ASA score ≤2 (%)	61 (92.4%)	61 (92.4%)	1.0	
Surgical approach			—	
 Laparoscopic (%)	—	40 (60.6%)		
 Robotic (%)	—	26 (39.3%)		
Preoperative diabetes (%)	42 (63.6%)	36 (54.6%)	0.288	
Preoperative chemotherapy (%)	16 (24.2%)	15 (22.7%)	0.837	
Malignancy (%)	59 (89.4%)	57 (86.4%)	0.594	
PDAC (%)	20 (30.3%)	21 (31.8%)	0.851	
Other malignancy			0.215	
 Pancreatic cancer (excluding PDAC) (%)	19 (28.8%)	10 (15.2%)		
 Biliary tract cancer (%)	18 (27.3%)	21 (31.8%)		
 Duodenal cancer (%)	2 (3.0%)	5 (7.6%)		
Vascular resection (%)	11 (16.7%)	9 (13.6%)	0.627	
Operative time (min), median (IQR)	456 (406 to 539)	522 (476 to 569)	0.002	
Estimated blood loss (g), median (IQR)	556 (317 to 934)	301 (122 to 550)	<0.0001	
Intraoperative blood transfusion (%)	14 (21.2%)	3 (4.6%)	0.004	
Length of hospital stay (d), median (IQR)	18.0 (14.0 to 23.3)	14.0 (11.0 to 17.3)	<0.0001	
Albumin index (%), median (IQR)	−6.4 (−16.7 to 3.3)	−6.5 (−16.3 to 3.3)	0.911	
PNI index (%), median (IQR)	−4.0 (−13.8 to 3.5)	−3.2 (−15.3 to 4.2)	0.895	
NLR index (%), median (IQR)	−4.7 (−30.4 to 56.6)	0.2 (−37.2 to 50.4)	0.935	
PLR index (%), median (IQR)	13.2 (−17.8 to 57.3)	12.9 (−17.6 to 49.1)	0.626	
IQR indicates interquartile range.

FIGURE 3. Preoperative and postoperative changes in nutritional and immunological statuses.

DISCUSSION

This single-center PSM study revealed that MIPD had better short-term surgical outcomes than OPD in terms of EBL, intraoperative blood transfusion, LOS, postoperative complications (especially CR-POPF), and achievement of textbook outcomes. Moreover, MIPD was equivalent to OPD in oncologic outcomes such as the number of dissected lymph nodes and the rate of R0 resection. Unexpectedly, despite these advantages of MIPD, no advantages were found in terms of the postoperative nutritional and immunological statuses, even in the cohort that achieved textbook outcomes. These results suggest the importance of not only the surgical approach but also the use of alternative therapeutic strategies to achieve enhanced postoperative nutritional and immunological statuses after PD.

Many recent studies have compared the surgical outcomes between MIPD and OPD. However, the advantages of MIPD in terms of postoperative surgical outcomes remain controversial. Previous studies, including single-institution reports, systematic reviews, and meta-analyses, have produced varying results. Some have shown that MIPD has advantages in terms of LOS, EBL, and postoperative complications,4,10,11 whereas others did not show all of these advantages.5–8,24–30 Notably, 3 RCTs revealed advantages of MIPD in terms of LOS and EBL,12–14 whereas only one study showed an advantage of MIPD in terms of postoperative complications.13 The abovementioned RCTs and the present PSM analysis suggest that MIPD facilitates shorter LOS and less EBL. Additionally, the present study suggests that postoperative complications, including POPF, are less likely to occur with MIPD. We consider there are 3 reasons why MIPD has better short-term surgical outcomes than OPD. First, MIPD provides a magnified view and enables precise tissue manipulation in anastomosis. Second, MIPD can reduce the development of bowel wall edema after laparoscopy compared to OPD,31 resulting in better anastomotic healing. Moreover, a reduction in the development of bowel wall edema can lead to enhanced gastrointestinal peristalsis and oral intake early after surgery. Third, a smaller skin incision in MIPD can reduce postoperative pain and promote early postoperative rehabilitation, which also contributes to preventing POPF formation. Interestingly, MIPD was associated with a higher rate of achieving textbook outcomes than was OPD in the present study, suggesting that MIPD enhances social reintegration. The MIPD procedures in the present study included both LPD and RPD, whereas the abovementioned RCTs only included LPD. This difference may have contributed to the minor discrepancy in surgical outcomes between the present study and the above RCTs. Unfortunately, the LEOPARD-2 trial,15 a multicenter RCT, was prematurely terminated because of the higher 90-day complication-related mortality rate among the patients undergoing LPD than OPD. Given this outcome, the role of MIPD remains a subject of debate. Although no RCTs to date have focused on RPD, a recent systematic review and meta-analysis showed no difference in surgical outcomes between RPD and LPD.32–34 Further multicenter RCTs that include RPD may be required to elucidate the true superiority of MIPD over OPD. In our series, the conversion rate was 6.8%, which was much lower than that of many other series (3.8%–26.0%).13,15,26,32,35–38 Moreover, the reasons for conversion to OPD in the present study were mainly adhesion and tumor-related factors such as vascular invasion. Only one (0.78%) patient required conversion because of intraoperative bleeding. These results indicate that MIPD is feasible. However, it is still difficult to discern the necessity of vascular resection on preoperative images, especially in cases of PDAC with preoperative chemotherapy. RPD with vascular resection and reconstruction may be the next step to decrease the need for conversion to OPD in the near future.

With respect to oncological outcomes, the number of dissected lymph nodes and the rate of R0 resection were comparable between the 2 groups in the matched cohort. However, no strong conclusions regarding oncologic outcomes can be drawn from this study because of its limited power and the heterogeneity of the patients’ diseases, including benign tumors and malignancies.

Achievement of textbook outcomes as a novel quality measure in pancreatic surgery has recently become a research hotspot.22 In previous studies, textbook outcomes were achieved in 58.3% to 59.0% of patients with every PD approach, 55.0% with OPD, and 46.4% to 85.0% with MIPD.22,39–41 In our unmatched cohort, 60.7% of patients who underwent all PD approaches, 55.7% of those who underwent OPD, and 69.2% of those who underwent MIPD achieved textbook outcomes. In our matched cohort, the rate of textbook outcome achievement was 47.4% in OPD and 71.1% in MIPD. The rate of textbook outcome achievement with OPD in the matched cohort was inferior to that in the unmatched cohort. This may have occurred because the OPD group in the matched cohort included more patients with benign tumors than did OPD groups in previous reports. Indeed, PDAC was associated with a higher rate of achieving textbook outcomes.22 Collectively, our results revealed a significantly higher rate of textbook outcome achievement with MIPD than with OPD, which might enhance social reintegration after surgery.

Such enhanced recovery with MIPD over OPD led us to hypothesize that MIPD improves postoperative nutritional and immunological statuses. Few studies have investigated the advantages of MIPD in terms of the postoperative nutritional status. Chen et al42 showed that 60 patients who underwent RPD exhibited significantly faster nutritional status recovery in terms of serum total protein and prealbumin as well as hemoglobin within 2 weeks after surgery compared with 120 patients who underwent OPD. They stated that this benefit might have resulted from earlier resumption of oral intake, less incisional pain, and a more relaxed psychological status, especially after parenteral nutrition was switched to enteral nutrition on postoperative day 5 to 7.42 However, during the early postoperative phase (within 2 weeks), nutritional status indicators such as serum total protein, prealbumin, and hemoglobin can show high variability due to postoperative infection, intraoperative blood loss, use of perioperative blood transfusion and plasma fractionators, or morbidity. The abovementioned study by Chen et al42 lacked a discussion of these points. In the present study, we analyzed nutritional and immunological indices in the postoperative medium-term period (4–8 weeks postoperatively) using cases in which textbook outcomes had been achieved to minimize the influence of infections, transfusion, or postoperative complications. Contrary to our hypothesis, the postoperative nutritional and immunological status indices (albumin, PNI, NLR, and PLR index) were equivalent between MIPD and OPD. To the best of our knowledge, this is the first study to compare the postoperative nutritional and immunological statuses of MIPD versus OPD in the postoperative medium-term period. From the study results, we inferred alternative therapeutic strategies to improve the nutritional and immunological statuses after PD. PD is accompanied by loss of pancreatic function and the need for gastrointestinal reconstruction, which results in pancreatic exocrine insufficiency and malnutrition. To recover the nutritional and immunological statuses as soon as possible postoperatively, comprehensive management and care such as gastrointestinal prokinetic agents, pancrelipase, or rehabilitation might be more important than the surgical approach.

Several limitations of this study should be considered. First, this was a single-center retrospective analysis and was therefore inherently susceptible to potential treatment selection bias and many unknown confounders. PSM was conducted to minimize the potential for selection bias and adjust for cofounders. A multicenter RCT is required to validate our findings. Second, our initial consecutive experience of MIPD and the learning curves for both LPD and RPD are underlying factors. Third, the timing of the first routine outpatient follow-up during which blood tests were performed to calculate the nutritional and immunological indices slightly differed among individual patients because of the retrospective nature of the study. The blood data were obtained at approximately 30 to 60 days postoperatively (median: 43 days, interquartile range: 39–50 days). In a future study, nutritional and immunological assessment using prospective data collection after PD may elucidate the true impact of MIPD on postoperative nutritional and immunological statuses.

CONCLUSIONS

MIPD for periampullary tumors may contribute to better surgical outcomes with less EBL, fewer intraoperative blood transfusions, shorter LOS, decreased postoperative complications (especially CR-POPF), and a higher achievement rate of textbook outcomes compared with OPD. The exception to these advantages is a prolonged operative time. MIPD and OPD were found to be comparable in terms of the number of dissected lymph nodes, R0 resection rate, and mortality rate. Taken together, these findings indicate that MIPD is a feasible procedure. However, despite these advantages of MIPD over OPD, no advantage with respect to the postoperative nutritional and immunological statuses was detectable even in the cohort that achieved textbook outcomes. Not only the surgical approach but also alternative therapeutic strategies such as comprehensive management and care to ameliorate pancreatic exocrine insufficiency or enhance rehabilitation may be important to improve the postoperative nutritional and immunological statuses after PD.

ACKNOWLEDGMENTS

We thank Angela Morben, DVM, ELS, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Supplementary Material

Disclosure: The authors declare that they have nothing to disclose.

S.Y.: conceptualization, data curation, investigation, methodology, analysis and interpretation of data, writing–original draft preparation, and writing–review and editing. H.H.: conceptualization, project administration, investigation, methodology, analysis and interpretation of data, validation, and writing–review and editing. K.M., R.I., Y.K., S.N., and H.O.: validation and writing–review and editing. D.O.: acquisition of data writing–review and editing. H.B.: conceptualization, project administration supervision, and writing–review and editing.

The datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

The protocol for this retrospective research has been approved by a suitably constituted Ethics Committee of the institution, and it conforms to the provisions of the Declaration of Helsinki. The Ethics Committee of the Graduate School of Medicine, Kumamoto University (Kumamoto, Japan).

Informed consent was obtained from all human subjects according to institutional guidelines.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.annalsofsurgery.com).
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