Claudio Ricci

Radiofrequency Ablation for Advanced Ductal Pancreatic Carcinoma: Is this Approach Beneficial for Our Patients? A Systematic Review

To the Editor:Radiofrequency ablation (RFA) is a local ablative method used for the palliative treatment of solid tumors, and it should be an attractive approach in patients with unresectable, locally advanced, and nonmetastatic pancreatic cancer. We aimed to systematically review the results of RFA

Late postpancreatectomy hemorrhage after pancreaticoduodenectomy: is it possible to recognize risk factors?

CONTEXTnPost-pancreatectomy hemorrhage is one of the most common complications after pancreaticoduodenectomy.nnnOBJECTIVEnTo evaluate the late post-pancreatectomy hemorrhage rate according to the International Study Group of Pancreatic Surgery criteria and to recognize factors related to its onset.nnnMETHODSnA prospective study of 113 patients who underwent pancreaticoduodenectomy was conducted. Late post-pancreatectomy hemorrhage was defined according to the criteria of the International Study Group of Pancreatic Surgery. Demographic, clinical, surgical and pathological data were considered and related to late post-pancreatectomy hemorrhage.nnnRESULTSnThirty-one (27.4%) patients had a post-pancreatectomy hemorrhage. Twenty-five (22.1%) patients developed late post-pancreatectomy hemorrhage: 19 (16.8%) grade B, 6 (5.3%) grade C. Surgical re-operation was performed in 2 out of the 25 cases with late post-pancreatectomy hemorrhage (8.0%) grade C associated with postoperative pancreatic fistula. At univariate analysis, the only factor significantly related to late post-pancreatectomy hemorrhage was postoperative pancreatic fistula (P<0.001). Multivariate analysis underlined that the severity of postoperative pancreatic fistula (P<0.001) and pancreatic anastomosis (P=0.049) independently increased the risk of late hemorrhage.nnnCONCLUSIONnIn patients undergoing pancreaticoduodenectomy, the criteria introduced by International Study Group of Pancreatic Surgery to define late postpancreatectomy hemorrhage are related to a higher incidence of hemorrhage than previously detected because they considered also mild hemorrhage.

Assessment of Complications According to the Clavien-Dindo Classification After Distal Pancreatectomy

CONTEXTnThe absence of a definition and a widely accepted ranking system to classify surgical complications has hampered proper interpretation of the surgical outcome.nnnPATIENTSnSixty-one patients undergoing distal pancreatectomy.nnnMAIN OUTCOME MEASURESnThe complications were classified according to the Clavien-Dindo classification; each grade was evaluated regarding the length of the postoperative stay and was compared to the most important complications.nnnRESULTSnThirty (49.2%) patients had no complications; out of the thirty-one (50.8%) patients with complications, 9 (14.5%) had grade I, 15 (24.6%) had grade II, 6 (9.8%) had grade III, and 1 (1.6%) had grade IV. There were no postoperative deaths (grade V). A progressive increase in the length of hospitalization from patients with no complications to those having grade IV (P < 0.001) was noted. Postoperative pancreatic fistula and postpancreatectomy hemorrhage rates did not significantly increase from Clavien-Dindo grade I to grade IV (P = 0.118 and P = 0.226, respectively). The severity of a postpancreatectomy hemorrhage, instead, was positively related to the grade of the Clavien-Dindo classification (P = 0.049) while postoperative pancreatic fistula resulted near the significant value (P = 0.058).nnnCONCLUSIONSnThe Clavien-Dindo classification is a simple way of reporting all complications following distal pancreatectomy. It allows us to distinguish a normal postoperative course from any deviation and the severity of complications and it may be useful for comparing postoperative morbidity between different pancreatic centers.

Pancreatic Metastasis From Renal Cell Carcinoma

Background Pancreatic metastases from renal cell carcinoma are uncommon. Methods Retrospective study of 8 patients with a diagnosis of pancreatic metastasis from renal cell carcinoma observed in our Institute. Results Patients were 6 (75%) males and 2 (25%) females. Mean age was 65.3 years. In 5 patients (57.1%), symptoms were present. The median interval of onset from nephrectomy was 10 years. No cases of synchronous pancreatic metastases were observed. Surgical resection was performed in 7 (87.5%) patients. At pathological examination, solitary metastases were identified in 5 patients (71.4%). No post-operative mortality was observed; the morbidity rate was 42.8%. In the group of patients who underwent pancreatic resection, median overall survival was 43.0 months (range 12.9–74.5), median disease-free survival was 23.6 months (range 9.9–74.5). Conclusions Pancreatic metastasis from renal cell carcinoma typically occurs after a long period from the initial nephrectomy, and seems to be related to a good prognosis.

Factors Related to Long-Term Survival in Patients Affected by Well-Differentiated Endocrine Tumors of the Pancreas

Aim. To identify factors related to survival in patients affected by well-differentiated PETs (benign, uncertain behavior, and carcinoma) who underwent R0 pancreatic resection. Methods. Retrospective study of 74 consecutive patients followed up from January 1980 to December 2011. Prognostic factors were sex, age, type of tumor, presence of symptoms, type of surgical procedure, size of tumor, lymph nodes status, WHO classification, and TNM stage. Overall survival was evaluated using the Kaplan-Meier method. Cox regression analyses were used to identify the factors associated with prognosis in univariate and multivariate analysis. Results. The mean follow-up of all the patients was 106 ± 89 months. The 5–10-year long-term survival was 90.9% and 79.1%, respectively. At univariate analysis, patient age <55 years was significantly related to a better long-term survival compared to patients age ≥55 years (307 ± 15 months versus 192 ± 25 months; P = 0.010). Multivariate analysis showed that female gender (P = 0.006), patients without comorbidities (P = 0.033), and patients affected by well-differentiated benign pancreatic endocrine tumors (P = 0.008 and P = 0.002 in relation to tumors with uncertain behavior and carcinomas, resp.) were factors significantly related to a better long-term survival. Conclusions. Patients factors were strongly related to a better long-term survival in patients observed. WHO classification is a very useful prognostic tool for well-differentiated PETs.

Preoperative Gemcitabine and Oxaliplatin in a Patient with Ovarian Metastasis from Pancreatic Cystadenocarcinoma

We describe a case of clinical benefit and partial response with gemcitabine and oxaliplatin (GEMOX) in a young patient with ovarian metastasis from cystadenocarcinoma of the pancreas. A young woman complained of abdominal pain and constipation. Computed tomography (CT) and magnetic resonance imaging scans disclosed two bilateral ovarian masses with pancreatic extension. She underwent bilateral ovarian and womb resection. During surgery peritoneal carcinosis, a pancreatic mass and multiple abdominal lesions were found. The final diagnosis was mucinous pancreatic cystadenocarcinoma with ovarian and peritoneal metastases. She started chemotherapy with GEMOX (gemcitabine 1,000 mg/m2/d1 and oxaliplatin 100 mg/m2/d2 every 2 weeks). After 12 cycles of chemotherapy a CT scan showed reduction of the pancreatic mass. She underwent distal pancreatic resection, regional lymphadenectomy and splenectomy. Pathologic examination documented prominent fibrous tissue and few neoplastic cells with mucin-filled cytoplasm. Chemotherapy was continued with gemcitabine as adjuvant treatment for another 3 cycles. There is currently no evidence of disease. As reported in the literature, GEMOX is associated with an improvement in progression-free survival and clinical benefit in patients with advanced pancreatic cancer. This is an interesting case in whom GEMOX transformed inoperable pancreatic cancer into a resectable tumor.

SNP-Array High Resolution Cytogenetic Analysis of Resectable and Advanced Pancreatic Cancer

Context Pancreatic cancer (PC) is the fourth leading cause of cancer deaths. The molecular mechanisms involved in the high tumorigenicity of PC are not yet well-known. Methods Pancreatic tumor samples from 14 patients were collected by ultrasound-guided biopsy and used for DNA extraction. High resolution copy number analysis was performed on Affymetrix SNP array 6.0 and analyzed with segmentation algorithm against a reference of 270 Ceu HapMap individuals (Partek Genomic Suite). Results Nine out of 14 patients exhibited both macroscopic and cryptic cytogenetic alterations, with a mean of 10 copy number alterations (CNA) per patient, while 5 patients did not show any copy number gain or loss. Deletions outnumbered amplifications by more than 2 folds. The chromosomes showing more copy number gains were chromosomes 12, 18, 19, while chromosomes 6, 9, 17 and 18 were most frequently deleted. In particular, deletions on 9p21 encompassed CDKN2A and 2B tumor suppressor genes, that on chromosome 18q21 overlapped with SMAD4, the one on chromosome 6p21 included RUNX2, while TP53 and MAP2K4 were the target genes deleted on chromosome 17p13. Amplified regions on chromosome 12p12 encompassed KRAS and ETV6 genes, the one on chromosome 18q11 overlapped with GATA6, while that on 19q13 included AKT2. We observed that the number of alterations correlates with the clinical course, and in particular that patients with none to few alterations (≤6) showed a median time to disease progression and a median overall survival significantly longer than those having a high number of CNA (>6), with a time to disease progression of 13.7 vs . 4.1 months (P=0.015) and an overall survival of 14.6 vs . 4.8 months (P=0.035). Conclusions High resolution cytogenetic analysis by SNP-array has the potential to uncover the genetic alterations carried by pancreatic tumors, and find new markers related to patient prognosis.

Are the New IPMN’s Guideline Effective to Predict the Presence of Invasive IPM Carcinoma? A Single Center Experience

Context In 2012 the International Consensus Guidelines for the management of IPMNs changed the criteria for surgery and the definition of “malignancy”, reserving this term only for invasive carcinoma. Objectives To evaluate the accuracy of surgical criteria to predict malignancy. Methods From 2003 to 2012, data regarding 184 patients with IPMNs, were recorded in a prospective database. Forty-two (22.8%) patients, undergoing surgery, were evaluated according to the new guidelines. Criteria for surgery (cyst size, Wirsung dilatation, symptoms andxa0 presence of solid endocystic component) were studied to assess the malignancy in patients affected by IPMNs. Multivariate analysis was carried out comparing the new (only invasive carcinoma) and old definition of malignancy (invasive carcinoma and high grade dysplasia). Results All operated patients presented criteria for surgery: 9 (21.4%) had pancreatitis, 12 (28.6%) showed enhancing solid component (ESC), 28 (66.7%) had main pancreatic duct (MPD) dilated and in 18 (42.9%) cases cystic size was ≥30 mm. Malignancy was recorded in 21 (50.0%) and 17 (40.5%) patients, according to the Sendai and Fukuoka definitions. At multivariate analysis no factors predicted malignancy according to Fukuoka definition, while presence of ESC (RR 14.2; 95% CI 1.8-113.5; P=0.012) and cystic size (RR 1.1; 95%CI 1.02-1.20; P=0.019) were related to malignancy according to Sendai definition. A dimensional cut-off of the cystic lesion of 26 mm was obtained with a ROC curve (AUC=0.724; P=0.013). At the multivariate analysis, this cut-off resulted the strongest independent factor predicting malignancy according to Sendai definition (RR 8.0; 95%CI 1.13-56.95; P=0.037). Conclusion In our experience, surgical criteria seem to be inefficacy to predict presence of invasive carcinoma. ESC and cystic size were the only factors able to detect patients with high grade dysplasia or invasive carcinoma and to suggest the surgical approach.

WHO-2010 and WHO-2000 classifications for pancreatic endocrine tumors. Is it time to change?

Introduction: The long-term results of pancreatic tumors resections are disappointing. In order to increase postoperative survival after resections by surgical control of liver metastasis and peritoneal dissemination no-touch techniques of PD were proposed. Methods: We investigated the results of no-touch PD for malignant periampullary tumors in 31 patients, treated in our clinic in the period of November 20082011 years. In 14 patients tumors of papilla of Vater (PV) were diagnosed, in 12 tumors of the pancreas, 1neuroendocrine tumor, in 3 patientstumors of bile ducts (BD), 1 – gastrointestinal stromal tumor (GIST) of the duodenum. In 19 patients pylorus-preserving PD were done, in 12standard PD. In 3 patients additional resections of the affected portal or superior mesenteric vein were done. Results: Duration of the operation was 440,4 +77,4 minutes (from 340 to 745). Mean blood loss was 575,0 + 320,1 ml (from minimal to 1800). Morbidity was 22,6% (7 patients). Mortality was zero. Median survival in the group of BD cancer patients was 21,5 month. 1and 2year survival in pancreatic cancer patients was 63,5%, maximal follow-up26 months. 1and 2year survival for PV cancer patients was 100%, 3year survival85,7%, disease free 3-year survival57,1%. Patient with GIST is alive 34 months after procedure with metastatic disease from second postoperative year. Patient with neuroendocrine tumor is alive without metastatic disease 26 months after operation. Conclusion: No-touch PD is safe procedure. Further investigations should be done to evaluate potential benefit of the procedure.

Lymph Node Ratio as a Prognostic Factor in Patients with Pancreatic Endocrine Tumours

Context The role of lymph node ratio (LNR) has been recognized as a prognostic factor in several malignancies. Objectives To evaluate the role of LNR in patients affected by pancreatic neuroendocrine tumors (pNETs). Methods Data regarding 45 patients were extracted from a dedicate database containing 92 patients undergone surgical exploration for pNETs. Patients who underwent palliative operation or enucleoresection or without Ki-67 determination were excluded. Sex, age, presence of symptoms, hormonal status, site of tumor, presence of MEN1, surgical procedure, R status, TNM-ENETS stage, WHO 2010 classification, Ki-67, and LNR were studied as possible factors influencing disease free survival (DFS) with univariate and multivariate analyses. Results Mean age of patients was 60±13 years. There were 22 (51.2%) female and 21 (48.8%) male. Symptoms were present in 27 (62.8%) patients. 34 (79.1%) patients had non-functioning pNETs and more frequently the tumor was located in the body (46.5%). Five (11.6%) patients were affected by MEN1. R0 resection was carried out in 38 (88.4%) cases. There were 17 (39.5%) pNETs G1, 24 (55.8%) pNETs G2 and 2 (4.7%) pancreatic neuroendocrine carcinomas (pNECs) G3. Mean Ki-67 was 6±10%. According to TNM-ENETS stage there were 17 (39.5%), 2 (4.7%), 17 (39.5%), and 7 (16.3%) patients in stage I, II, III, and IV, respectively. LNR was 0 in 26 (60.5%) patients, between 0 and 0.2 in 8 (18.6%) patients, and >0.2 in 9 (20.9%) patients. Mean DFS was 48±56 months. Multivariate analysis found that TNM-ENETS stage (HR 5.0; P=0.036) and Ki-67 (HR 1.2; P=0.016) were significantly related to DFS. There were no differences between patients with LNR=0 and LNR between 0 and 0.2 (HR 5.9; P=0.172) while patients with LNR between 0 and 0.2 had better DFS respect to those with LNR >0.2 (HR=0.2; P=0.01). A new cut off for LNR of 0.07 was obtained by ROC curve (AUC 0.771; P=0.008). Considering the new cut off, the multivariate analysis showed that LNR <0.07 was the only independent factor related to DFS (HR=28; P=0.002). Conclusion LNR can be considered an important prognostic factor predicting DFS in patients affected by pNETs.