Effect of Diabetes on Survival after Resection of Pancreatic Adenocarcinoma. A Prospective, Observational Study

<div><p>Aim</p><p>To investigate the effect of diabetes mellitus (DM) on disease-free and overall post-resection survival of patients with pancreatic ductal adenocarcinoma (PDAC)</p><p>Methods</p><p>Prospective observational study on patients admitted for pancreatic disease from January 2008 to October 2012. DM was classified as recent-onset (<48 months before PDAC diagnosis), longstanding (≥48 months before PDAC) or new onset (after surgery).</p><p>Results</p><p>Of 296 patients, 140 had a diagnosis of DM prior to surgery (26 longstanding, 99 recent-onset, 15 with unknown duration). Median follow-up time was 5.4 ± 0.22 years. Patients with recent onset DM had poorer postoperative survival than patients without DM: disease-free survival and overall survival were 1.14±0.13 years and 1.52±0.12 years in recent onset DM, versus 1.3±0.15 years and 1.87±0.15 years in non-diabetic patients (p = 0.013 and p = 0.025, respectively). Longstanding DM and postoperative new onset DM had no impact on prognosis. Compared to cases without DM, patients with recent onset DM were more likely to have residual disease after surgery and to develop liver metastases during follow-up. Multivariate analysis confirmed recent onset DM was independently associated with PDAC relapse (hazard ratio 1.45 [1.06–1.99]).</p><p>Conclusion</p><p>Preoperative recent onset DM has an impact on survival after the resection of PDAC.</p></div

Patient characteristics by types of preoperative diabetes.

<p>Patient characteristics by types of preoperative diabetes.</p

Effect of pre-operative recent onset DM on PDAC relapse.

<p>Kaplan-Meier estimates of disease free survival and stratified according to seven main recurrence sites for 255 patients (156 no diabetes; 99 recent onset diabetes) with a diagnosis of pancreatic ductal carcinoma submitted to pancreatectomy with radical intent from the Pancreatic Surgery Unit of the S. Raffaele Scientific Institute (2008–2012). The <i>X-axis</i> shows the time since pancreatectomy and the <i>y-axis</i> the PDAC recurrence-free probability. P value of <i>log</i>-<i>rank test</i> vs no diabetes are reported.</p

Ki67 change between 1^st and 2^nd histological evaluation.

<p>SI-NENs = circles. PNENs = squares. Horizontal reference lines refer to Ki67 cut-off levels for G1 NENs (2%) and G2 NENs (20%).</p

Patients characteristics by postoperative diabetic status.

<p>Patients characteristics by postoperative diabetic status.</p

Patients’ general characteristics.

<p>Patients’ general characteristics.</p

Effect of pre-operative DM on PDAC outcome.

<p>Kaplan-Meier estimates of disease-free (left) and overall (right) survival stratified according to pre-operative DM for 281 patients with a diagnosis of pancreatic ductal carcinoma submitted to pancreatectomy with radical intent from the Pancreatic Surgery Unit of the S. Raffaele Scientific Institute (2008–2012). At the time of PDAC diagnosis participants were classified as having: long-standing diabetes if they had a documented diagnosis of DM for ≥48 months; recent onset DM if participants were diagnosed with DM at the time of the diagnosis of PDAC or had a documented diagnosis of DM for <48 months. The <i>X-axis</i> shows the time since pancreatectomy. P value of <i>log</i>-<i>rank test</i> vs no diabetes are reported.</p

Adipophilin immunostain in BL and not-BL cases.

<p>(A) BL is characterized by medium-sized cells with a monotonous cohesive pattern of growth, round nuclei with finely clumped and dispersed chromatin, a high proliferation rate and “starry-sky” appearance [Haematoxilin-eosin (H&E), original magnification (O.M.) ×200). (B) Neoplastic cells show strong positivity to adipophilin with single or multiple droplets in the cytoplasm, sometimes clustering the outer nuclear membrane (inset); the internal positive control is represented by macrophages which show granular positivity in the cytoplasm (arrows) (Adipophilin stain, O.M. ×200; inset, O.M. ×400). (C) An aggressive B-cell lymphoma with diffuse proliferation of medium- to large-sized cells with irregular nuclear contours and relatively large nucleoli corresponding to morphological score 1 according to the Naresh <i>et al.</i> scoring system is shown. Few small lymphocytes and starry-sky macrophages are also present (H&E, O.M. ×200). (D) Adipophilin immunostain on the case depicted in figure C with neoplastic cells showing weak positivity characterized by singly scattered fine lipid droplets in the cytoplasm (Adipophilin stain, O.M. ×200). (E) Morphological features of a diffuse large B-cell lymphoma (H&E, O.M. ×200). (F) Adipophilin immunostain on the case depicted in figure E is entirely negative (Adipophilin stain, O.M. ×200).</p

Classification of cases according to the algorithm proposed by Naresh <i>et al</i>.

<p>After the revision of 43 BL, 30 DLBCL and 7 DLBCL/BL cases, 47 BL and 33 not-BL cases were identified.</p

Genes involved in lipid metabolism in BL other than PLIN2.

<p>Genes involved in lipid metabolism in BL other than PLIN2.</p