Original article

Value of peritoneal cytology in potentially resectable pancreatic cancer S. Yamada1 , T. Fujii1 , M. Kanda1 , H. Sugimoto1 , S. Nomoto1 , S. Takeda1 , A. Nakao2 and Y. Kodera1 1

Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, and 2 Department of Surgery, Nagoya Central Hospital, Nagoya, Japan Correspondence to: Dr S. Yamada, Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466–8550, Japan (e-mail: [email protected])

Background: Peritoneal lavage cytology (CY) is used in the diagnosis and staging of various cancers.

The clinical significance of positive cytology results in patients with pancreatic cancer is yet to be determined. Methods: Peritoneal washing samples were collected from consecutive patients with pancreatic cancer between July 1991 and December 2012. The correlations between cytology results, clinicopathological parameters and recurrence patterns were evaluated. The prognostic impact of CY status, regarding resectability and the effectiveness of adjuvant chemotherapy, were analysed. Results: Of 523 included patients, 390 underwent resection. Patients with tumours at least 2 cm in diameter were more likely to have CY+ status than patients with tumours smaller than 2 cm (48 of 312 versus 3 of 78 respectively; P = 0·005) and there was a significant correlation between CY+ status and tumour invasion of the anterior pancreatic capsule (43 of 276 versus 8 of 113 with no invasion of the capsule; P = 0·030). Although the overall survival of patients with resected CY+ tumours was worse than that of patients with resected CY− tumours, it was significantly better than the survival of unresected patients regardless of CY status. Multivariable analysis of all patients who had pancreatectomy did not identify CY+ as an independent prognostic factor. Patients with CY+ tumours tended to develop peritoneal metastasis more often than those with CY− tumours, although not significantly so. The median survival time of 34 patients with resected CY+ tumours who received adjuvant chemotherapy was better than that of 17 patients who had surgery alone, although this was not statistically significant (15·3 versus 10·0 months; P = 0·057). Conclusion: CY+ status is not clinically equivalent to gross peritoneal metastasis in patients with pancreatic cancer. Curative resection is still recommended regardless of CY status. Presented to the 98th Annual Clinical Congress of the American College of Surgeons, Chicago, Illinois, USA, October 2012 Paper accepted 2 August 2013 Published online in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.9307

Introduction

Pancreatic cancer continues to have the worst prognosis of all gastrointestinal malignancies, with complete surgical resection offering the only possibility of a cure. In spite of advances in diagnostic techniques, fewer than 20 per cent of patients have localized, potentially curable, tumours at the time of diagnosis1 and only a moderate improvement in patient outcomes has been achieved2,3 . Peritoneal lavage cytology (CY) has been used widely in the diagnosis and staging of ovarian, endometrial and gastric cancer. Malignant cells can be identified in 7–30  2013 British Journal of Surgery Society Ltd Published by John Wiley & Sons Ltd

per cent of peritoneal washing samples from patients with pancreatic cancer4 – 8 . Recently, the American Joint Committee on Cancer (AJCC) included positive peritoneal washing cytology (CY+) status as indicative of stage IV disease in patients with pancreatic cancer9 . Results from a previous study of 233 patients with pancreatic cancer from the authors’ institution, however, showed that peritoneal washing and CY+ status in the absence of macroscopic peritoneal or liver metastasis was not a contraindication to radical surgery10 . Since that time, the outcome of patients with pancreatic cancer has been improved gradually by effective adjuvant therapies such as gemcitabine11,12 and British Journal of Surgery 2013; 100: 1791–1796

1792

S-1, which is the oral 5-fluorouracil (5-FU) prodrug tegafur combined with oteracil and gimeracil. The effect of multidisciplinary treatment for patients with potential microscopic residual disease may further modify indications for surgical treatment, and a reappraisal of peritoneal cytology as a prognostic factor seemed warranted. The present study examined peritoneal lavage samples from consecutive patients with pancreatic cancer and evaluated the relationship between cytology results, clinicopathological parameters and survival. The study also investigated recurrence patterns and the effectiveness of adjuvant chemotherapy among those patients who underwent pancreatectomy in order to clarify the implications of positive peritoneal cytology results. Methods

Peritoneal washing samples were collected from consecutive patients with pancreatic cancer treated in the Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, between July 1991 and December 2012. All patients considered candidates for curative resection underwent 64-row multidetector computed tomography (MDCT) (Aquilion TM64; Toshiba Medical Systems Corporation, Tochigi, Japan) to look for the extent of local invasion, the presence of liver metastases or evidence of peritoneal deposits. After unenhanced imaging, pancreatic phase, portal venous phase and delayed phase images were acquired and reconstructed with a 1mm section thickness at 0·5- or 0·8-mm intervals, and evaluated by two experienced radiologists. When liver metastasis was suspected strongly, both contrast-enhanced (Sonazoid; Daiichi-Sankyo, Tokyo, Japan) ultrasonography and gadolinium–ethoxybenzyl–diethylenetriamine penta-acetate (Gd-EOB-DTPA)-enhanced (Primovist; Bayer, Osaka, Japan) magnetic resonance imaging were performed to confirm the diagnosis. All patients were followed to March 2013 or until death. Extended radical resection (D2) was performed for all patients without liver or visible peritoneal metastases. Immediately after laparotomy, 200 ml isotonic heparinized saline was introduced into the subhepatic space and pelvis. After gentle agitation, as much fluid as possible was collected using a syringe. Smears were made from the centrifuged deposit and examined by at least two experienced pathologists after conventional Papanicolaou and Giemsa staining. All surgical specimens were examined histopathologically after fixing and staining with haematoxylin and eosin. The tumour node metastasis (TNM) staging system of the International Union Against Cancer (7th edition) was used13 .  2013 British Journal of Surgery Society Ltd Published by John Wiley & Sons Ltd

S. Yamada, T. Fujii, M. Kanda, H. Sugimoto, S. Nomoto, S. Takeda et al.

Table 1

Patient demographics No. of patients* (n = 390)

Age (years)† Sex ratio (M : F) Tumour location Head of pancreas Body/tail of pancreas Entire organ Surgical procedure PD PPPD SSPPD DP TP UICC stage IA IB IIA IIB III IV Adjuvant chemotherapy Intraportal 5-FU Gemcitabine S-1 Gemcitabine + S-1 5-FU + gemcitabine + S-1 Other None

63·9(9·6) 242 : 148 300 81 9 174 43 71 71 31 10 4 98 224 4 50 50 99 34 43 32 14 118

*Unless indicated otherwise; †values are mean(s.d.). PD, pancreatoduodenectomy; PPPD, pylorus-preserving pancreatoduodenectomy; SSPPD, subtotal stomach-preserving pancreatoduodenectomy; DP, distal pancreatectomy; TP, total pancreatectomy; UICC, International Union Against Cancer; 5-FU, 5-fluorouracil.

Correlations between cytology status, clinicopathological variables and patterns of cancer recurrence were evaluated, together with the effects of CY status and adjuvant chemotherapy on overall survival. Gemcitabine (Gemzar; Ell Lilly, Kobe, Japan) and/or S-1 (TS-1; Taiho, Tokyo, Japan) or 5-FU (5-FU; Kyowa-Kirin, Tokyo, Japan) were used as adjuvant chemotherapies, unless contraindicated. Gemcitabine was administered weekly at a dose of 1000 mg/m2 for 3 weeks followed by 1 week of rest. S-1 was administered orally on days 1–14 followed by 1 week of rest. 5-FU was used daily at a dose of 250 mg/m2 for 4 weeks by intraportal administration. Chemotherapy was started within 2 months of surgery in all eligible patients. Patients were followed in outpatients after surgery. Recurrence was detected by 6-monthly MDCT.

Statistical analysis The significance of correlations between CY status and clinicopathological parameters was determined using Fisher’s exact test or the χ2 test. Cox proportional www.bjs.co.uk

British Journal of Surgery 2013; 100: 1791–1796

Peritoneal cytology in pancreatic cancer

1793

Correlation between peritoneal lavage cytology status and clinicopathological parameters

Table 2

Age (years) < 65 ≥ 65 Sex ratio (M : F) Tumour location Head of pancreas Body/tail of pancreas Entire organ Tumour size (cm)

Value of peritoneal cytology in potentially resectable pancreatic cancer.

Peritoneal lavage cytology (CY) is used in the diagnosis and staging of various cancers. The clinical significance of positive cytology results in pat...
134KB Sizes 0 Downloads 0 Views