Abstract
Background/Aim: Preoperative evaluation of resectability of pancreatic cancer (PC) is difficult, so that staging laparoscopy (SL) has come to be used for detecting occult metastases. We aimed to evaluate the prognostic impact of SL in comparison with exploratory laparotomy (EL) in unresectable PC. Patients and Methods: Between 2010 and 2016, 57 patients with PC underwent SL after conventional tumor staging. Patient characteristics, operative findings and survival rates were compared between SL and EL group. Results: Twenty patients (35%) were identified as having unresectable factors in SL group. In contrast, laparotomy showed unresectable factors in 8 patients who did not receive preoperative SL (EL group). The time between the surgery to the induction of chemotherapy was significantly shorter in the SL group (mean=6 days, range=2-17) than in the EL group (mean=10 days, range=6-15). There was no significant difference in overall survival between the two groups; however, EL was associated with shorter survival in the early postoperative period. Conclusion: SL was associated with a shorter time interval to chemotherapy and lead to the prevention of unnecessary laparotomy.
Pancreatic cancer (PC) is a highly lethal disease with a very poor prognosis (1). In spite of the advancements in diagnostic techniques and treatments, the 5-year overall survival in patients with resected PC remains low, with only a 20%-30% survival rate (2-4). The recent development of radiographic modalities such as computed tomography (CT) and positron emission tomography (PET) offers higher sensitivity in identifying peritoneal metastasis than ever before (5); however, it is often inadequate in determining resectability (6, 7). Laparotomy after conventional preoperative staging occasionally discovers metastases during abdominal exploration. Along with the development of laparoscopic surgery, staging laparoscopy (SL) in pancreatic cancer surgery has become more common due to its feasibility and utility, which has been reported in several studies (8-12). However, the prognostic impact of SL in PC remains unclear. The aim of this retrospective, single-institutional cohort study is to test the efficacy of SL when compared with exploratory laparotomy in unresectable PC.
Patients and Methods
Patients and operation. This retrospective study included patients with pancreatic cancers admitted to the Department of Gastroenterological Surgery, Kumamoto University Hospital, between 2005 and 2016. The study protocol conformed to the ethical guidelines of the Declaration of Helsinki in 1995 (as revised in Brazil 2013) and was approved by the Institutional Review Board of Kumamoto University Hospital. Conventional preoperative diagnostic evaluation was performed routinely with triple-phase helical CT, enhanced magnetic resonance imaging (MRI), PET-CT, endoscopic ultrasonography (with fine-needle aspiration biopsy; EUS-FNA), and endoscopic retrograde cholangiopancreatography (ERCP). A total of 195 patients were diagnosed PC without obvious unresectable locally advanced and/or metastatic tumor by conventional diagnostic evaluation (Figure 1). The indication of SL in this study was undeniable possibility of micro-metastasis, such as abdominal dissemination or locally advanced tumor, at the clinical decision of the attending surgeon. Among the 195 patients, 57 patients underwent SL, while 138 patients did not (Figure 1). SL was performed in 3-port under general anesthesia for intraoperative cytology and biopsy. Laparoscopic ultrasonography was performed in cases of suspected vascular invasion, para-aortic lymph node metastasis, and small liver metastasis. The lesser sac was routinely opened. SL with or without ultrasonography did not reveal any findings of unresectability in 37 patients, and they underwent immediate or two-stage pancreatic resection (Figure 1). On the other hand, SL confirmed unresectable factors, such as peritoneal dissemination, micro-liver metastasis, and tumor invasion in the superior mesenteric artery or portal vein in 20 patients (SL group, Figure 1). During the same period, laparotomy was performed on 138 patients who were considered to have a resectable PC without SL. Of these patients, unresectable factors were found during laparotomy in 8 cases (exploratory laparotomy; EL group), while 130 patients underwent pancreatic resection (Figure 1). Patient characteristics, operative findings, and prognosis after surgery of SL group and EL group were reviewed.
Statistical analysis. Descriptive statistics are presented as the median (range) or number. Data were analyzed using SAS software (Release 10.1, SAS Institute Inc., Cary, NC, USA). Parameters were compared between patient subgroups using Mann–Whitney U-tests or the chi-square test. Survival probabilities were estimated by the Kaplan–Meier method and compared using generalized log-rank and Wilcoxon test. Differences were considered statistically significant at p<0.05.
Ethical standards. The study protocol was approved as number 1120 by the Institutional Review Board of Kumamoto University Hospital.
Results
Result of staging laparoscopy and comparisons of clinicopathological features between SL and EL groups. Of the patients with PC who underwent SL (SL group; n=57), 20 (35%) were identified as having unresectable factors or metastases. The 37 patients without any unresectable tumors or metastases underwent curative resection, including one-stage operation (n=6) or two-stage operation (n=31) following SL. On the other hand, 8 of the 138 patients (6%) who did not receive SL were identified as having an unresectable PC during laparotomy. Patient characteristics in both groups are shown in Table I. There were no significant differences in clinicopathological features such as age, sex, location, or tumor markers.
Comparison of perioperative findings and surgical factors between SL and EL groups. To investigate the benefits of SL in PC in contrast with EL, the operative findings and clinical courses were compared (Table II). The operating time was significantly shorter in the SL group than in the EL group (mean=84 min, range=49-159 vs. mean=229 min, range=100-347; p=0.0008). Additionally, there was a significant difference in intraoperative bleeding between the SL group and the EL group (mean=0 g, range=0-100 vs. mean=213 g, range=10-2258; p<0.0001). For one patient, radical resection was attempted at the beginning of surgery; however, it was unsuccessful because of the local invasion of cancer. As a consequence, the operating time was long (347 min) and resulted in a large amount of bleeding (2,258 g). None of the patients in this study underwent biliary or duodenal bypass with EL. White blood cell (WBC), C-reactive protein (CRP), and serum albumin (Alb) are known as markers of surgical invasiveness; in Figure 2 the perioperative changes of WBC, CRP, and Alb in both groups are shown. The number of WBC at postoperative day 1 (POD 1) was significantly lower in the SL group than those in the EL group (p=0.037). There were also significant differences in CRP and Alb between the two groups at POD1, 3, and 7 (CRP: p=0.0003, p=0.0006, p=0.0003; Alb: p=0.0003, p=0.0005, p=0.0024, respectively) (Figure 2). These findings indicate that SL is much less invasive than EL. The most common unresectable factor in the SL group was peritoneal dissemination. Liver metastasis and local advancement including arterial invasion were the most common unresectable factors in the EL group (Table II). The incidence of postoperative complication was not significantly different between the two groups. The SL group showed no complication, and aspiration pneumonia was observed in one case (10%) of the EL group. This patient could not undergo the following course of chemotherapy due to this complication. Furthermore, the time between the operation to the induction of chemotherapy was significantly shorter in the SL group than in the EL group (mean=6 days, range=2-17 vs. mean=10 days, range=6-15; p=0.03) (Table II). There was no significant difference of overall survival between the SL and EL groups in a log-rank test (p=0.27); however, patients with EL had nominally worse outcomes than patients with SL did when compared by the generalized Wilcoxon test (p=0.046) (Figure 3).
Clinicopathological features.
Perioperative findings and surgical outcomes.
Patient flow diagram of this study. SL, Staging laparoscopy; EL, exploratory laparotomy.
Discussion
Despite the recent advances of imaging studies, approximately 20-40% of patients with PC will have occult metastasis identified in the operation (13, 14). The purpose of SL is to avoid unnecessary laparotomies in patients who appear to have resectable abdominal malignancies after conventional preoperative examinations. In the present study, 35% (20 of the 57 cases) of patients in the SL group had metastasis or unresectable factors, suggesting that SL could prevent 35% of patients with PC from an unnecessary laparotomy. Additionally, this study showed that SL is less invasive and can lead to the start of chemotherapy sooner for patients with unresectable PC when compared to patients receiving EL.
Overall survival in patients with unresectable PC is quite poor (15, 16), thus a rapid induction of chemotherapy may be necessary for improving survival. Kaito et al. studied gastric cancer patients and demonstrated that patients, who underwent a laparoscopic gastrectomy, were able to start chemotherapy significantly sooner compared to those who underwent an open gastrectomy (17). In PC, Sell NM et al. has reported that SL not only saves patients an incision but it may also help them live longer. They attributed this survival advantage to the shorter time period for palliative chemotherapy of SL compared to EL (18). Our study had similar results in the Asian race. These findings suggest that not only the length of the time until the induction of chemotherapy but also higher surgical stress itself could affect prognosis in the early postoperative period. In addition, the time from operation to chemotherapy in our study was less than that in the study by Sell NM et al. Less invasive surgery and better perioperative care may be important for rapid induction of chemotherapy. However, further studies are needed to identify factors that could be associated with a higher postoperative survival rate.
Although we received promising results, our study had some limitations. First, the sample size is small, so further large prospective studies – such as a multicenter study – is required to confirm our results. Second, it is necessary to establish an adequate indication criterion of SL candidates in patients with PC, because SL would be time-consuming and requires additional medical cost.
Perioperative changes of white blood cell (WBC), C-reactive protein (CRP) and albumin (Alb) after staging laparoscopy or exploratory laparotomy. Graph shows median values with 25%-75% quartile. POD, Post-operative day.
Overall, this study provided evidence of SL being associated with a shorter time period to chemotherapy for unresectable PC, and it also leads to the prevention of unnecessary laparotomy.
Kaplan–Meier curves of overall survival for patients with SL or EL after surgeries. SL, Staging laparoscopy; EL, exploratory laparotomy.
Acknowledgements
The Authors thank Lauren J. Patterson for providing English editing.
Footnotes
Authors' Contributions
K. Yamamura: Study concept and design, acquisition of clinical data, analysis and interpretation of data; statistical analysis, drafting of the manuscript; D. Hashimoto: Study concept and design, analysis and interpretation of data; N. Umezaki: Acquisition of data, participation in drafting the article, T. Yamao: Acquisition of data, participation in drafting the article; D. Kuroda: Acquisition of data, participation in drafting the article; T. Eto: Acquisition of data, participation in drafting the article; Y. Kitano: Acquisition of data, participation in drafting the article; K. Arima: Acquisition of data, participation in drafting the article; T. Miyata: Acquisition of data, participation in drafting the article; S. Nakagawa: Acquisition of data, participation in drafting the article; H. Okabe: Acquisition of data, participation in drafting the article; H. Nitta: Acquisition of data, participation in drafting the article; Y. Yamashita: Study concept and design, drafting of the manuscript and revising it critically; H. Baba: Study concept and design, drafting of the manuscript and revising it critically.
Conflicts of Interest
The Authors have no competing interest to declare.
- Received November 23, 2019.
- Revision received December 20, 2019.
- Accepted December 21, 2019.
- Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
In this issue
Jump to section
Related Articles
Cited By...
- No citing articles found.