Marielda D'Ambra

Pancreatic Endocrine Tumors Less Than 4 cm in Diameter Resect or Enucleate? A Single-Center Experience

Objective: Pancreatic endocrine tumors (PETs) are usually small, benign or low-grade malignant, and surgery should preserve the pancreatic parenchyma as much as possible. The aim of the study was to evaluate the postoperative and long-term survival of patients undergoing enucleation in small PETs. Methods: Of 82 patients having PETs, 46 with tumor less than 4 cm in diameter, without distant metastases and with R0 resection by final pathologic examination, were included in this study. Enucleation was performed when the tumor did not involve the main pancreatic duct and in the absence of peripancreatic lymphadenopathy (group A); a typical resection was carried out in all other cases (group B). The 2 groups were compared regarding postoperative mortality and morbidity, pancreatic fistula, postoperative hospital stay, reoperation, World Health Organization classification, TNM stage, recurrence, and long-term survival. Results: There were 15 patients (32.6%) in group A and 31 (67.4%) in group B. Postoperative and long-term results were similar in the 2 groups, whereas World Health Organization classification was significantly different; enucleation was performed more frequently than typical R0 resection in benign tumors (P = 0.009). Conclusions: Enucleation should be reserved for patients having benign PETs less than 4 cm in diameter and far from the main pancreatic duct.

Are There Prognostic Factors Related to Recurrence in Pancreatic Endocrine Tumors

Aims: The aim of this study was to evaluate the rate, site, time of recurrence and prognostic factors related to the appearance of recurrences in patients affected by pancreatic endocrine tumors (PETs). Methods: Data from 67 consecutive patients with PETs who underwent R0 resection were analyzed. The prognostic factors considered were: gender, age, type of tumor, presence of symptoms, size of tumor, tumor node metastasis (TNM) stage, WHO classification and adjuvant therapy. Results: The recurrence rate was 24.6%, with a mean time of 7.3 ± 4.5 years. The majority were in the liver (75% of cases) and were rarely local (25%). Univariate analysis of the prognostic factors showed that the risk of recurrences is significantly higher in PETs in MEN-1 syndrome, in tumor size ≧4 cm, in the presence of liver metastases, in TNM stages III–IV and, finally, in PD-Cas and WD-Cas. Multivariate Cox regression analysis showed that only MEN-1 syndrome and the WHO classification were independent predictors of an increased risk of recurrence. Conclusions: Several prognostic factors were related to recurrences in PETs. MEN-1 syndrome and the WHO classification can be considered independent factors of an increased risk of recurrence.

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

The Problems of Radiofrequency Ablation as an Approach for Advanced Unresectable Ductal Pancreatic Carcinoma

Advanced ductal pancreatic carcinoma (PC) remains a challenge for current surgical and medical approaches. It has recently been claimed that radiofrequency ablation (RFA) may be beneficial for patients with locally advanced or metastatic PC. Using the MEDLINE database, we found seven studies involving 106 patients in which PC was treated using RFA. The PC was mainly located in the pancreatic head (66.9%) with a median size of 4.6 cm. RFA was carried out in 85 patients (80.1%) with locally advanced PC and in 21 (19.9%) with metastatic disease. Palliative surgical procedures were carried out in 41.5% of the patients. The average temperature used was 90 °C (with a temperature range of 30–105 °C) and the ratio between the number of passes of the probe and the size of the tumor in centimeters was 0.5 (range of 0.36–1). The median postoperative morbidity and mortality were 28.3% and 7.5%, respectively; the median survival was 6.5 months (range of 1–33 months). In conclusion, RFA is a feasible technique: however, its safety and long-term results are disappointing; Thus, the RFA procedure should not be recommended in clinical practice for a PC patient.

Efficacy and Cost-Effectiveness of Immediate Surgery versus a Wait-and-See Strategy for Sporadic Nonfunctioning T1 Pancreatic Endocrine Neoplasms.

Background: Whether patients with small (<2 cm), sporadic nonfunctioning pancreatic endocrine tumors (NF-PETs) should directly undergo pancreatic surgery or should be followed longitudinally to detect growth and malignancy still has to be defined. Study Design: Based on the pertinent literature of the past decade, a Markov model was developed to investigate this issue. In the wait-and-see strategy arm, surgery was performed if the tumor attained a size ≥2 cm or surpassed 20% of the initial size. In a Monte Carlo probabilistic analysis, 100 hypothetical patients undergoing a wait-and-see strategy were compared to 100 patients directly undergoing surgery, with the aim of investigating the efficacy and cost-effectiveness of the two strategies. Results: During the postdiagnostic lifetime, 63 NF-PETs in the wait-and-see group showed significant growth and underwent surgery: 38 were stage I, 10 were stage II, 15 were stage III and none were stage IV. In the base-case scenario, the mean life expectancy and quality-adjusted life expectancy were found to be superior after immediate surgery [26.1 years and 11.8 quality-adjusted life years (QALYs)] than with the wait-and-see strategy (22.1 years and 8.3 QALYs) as the consequence of ageing during the wait-and-see follow-up which increased mortality due to surgery, when surgery was needed. The model was sensitive to starting age and length of follow-up; in particular, for patients >65 years of age, the two strategies provided similar results but the wait-and-see strategy was more cost-effective. Conclusions: The wait-and-see strategy for NF-PETs <2 cm represents a reasonable approach in patients over 65 years of age; otherwise, immediate surgery is preferable.

Characterization of pancreatic ductal adenocarcinoma using whole transcriptome sequencing and copy number analysis by single-nucleotide polymorphism array

The aim of the current study was to implement whole transcriptome massively parallel sequencing (RNASeq) and copy number analysis to investigate the molecular biology of pancreatic ductal adenocarcinoma (PDAC). Samples from 16 patients with PDAC were collected by ultrasound‑guided biopsy or from surgical specimens for DNA and RNA extraction. All samples were analyzed by RNASeq performed at 75x2 base pairs on a HiScanSQ Illumina platform. Single‑nucleotide variants (SNVs) were detected with SNVMix and filtered on dbSNP, 1000 Genomes and Cosmic. Non‑synonymous SNVs were analyzed with SNPs&GO and PROVEAN. A total of 13 samples were analyzed by high resolution copy number analysis on an Affymetrix SNP array 6.0. RNAseq resulted in an average of 264 coding non‑synonymous novel SNVs (ranging from 146‑374) and 16 novel insertions or deletions (In/Dels) (ranging from 6‑24) for each sample, of which a mean of 11.2% were disease‑associated and somatic events, while 34.7% were frameshift somatic In/Dels. From this analysis, alterations in the known oncogenes associated with PDAC were observed, including Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations (93.7%) and inactivation of cyclin‑dependent kinase inhibitor 2A (CDKN2A) (50%), mothers against decapentaplegic homolog 4 (SMAD4) (50%), and tumor protein 53 (TP53) (56%). One case that was negative for KRAS exhibited a G13D neuroblastoma RAS viral oncogene homolog mutation. In addition, gene fusions were detected in 10 samples for a total of 23 different intra‑ or inter‑chromosomal rearrangements, however, a recurrent fusion transcript remains to be identified. SNP arrays identified macroscopic and cryptic cytogenetic alterations in 85% of patients. Gains were observed in the chromosome arms 6p, 12p, 18q and 19q which contain KRAS, GATA binding protein 6, protein kinase B and cyclin D3. Deletions were identified on chromosome arms 1p, 9p, 6p, 18q, 10q, 15q, 17p, 21q and 19q which involve TP53, CDKN2A/B, SMAD4, runt‑related transcription factor 2, AT‑rich interactive domain‑containing protein 1A, phosphatase and tensin homolog and serine/threonine kinase 11. In conclusion, genetic alterations in PDCA were observed to involve numerous pathways including cell migration, transforming growth factor‑β signaling, apoptosis, cell proliferation and DNA damage repair. However, signaling alterations were not observed in all tumors and key mutations appeared to differ between PDAC cases.

Portal/Superior Mesenteric Vein Reconstruction during Pancreatic Resection Using a Cryopreserved Arterial Homograft.

Background: Portal-superior mesenteric vein (PV/SMV) resection during pancreatic resection has been widely applied in clinical practice. Methods: From a prospective data base of pancreatic resections, patients undergoing PV/SMV resection and reconstruction with a cryopreserved arterial homograft were extracted with the aim of evaluating the safety, feasibility and reproducibility of the procedure. Data regarding patient demographics, preoperative staging, surgery, histopathology and postoperative outcomes were analyzed. Results: Five patients were extracted in the last year. Indications for this technique were type IV-V degree of vein involvement and a 3.5 cm median length of vein infiltration. Median operative and clamping times were satisfactory (385 and 27 min, respectively), postoperative outcomes were good and there was no graft infection, thrombosis or stenosis occurred postoperatively and during the follow-up period. Conclusion: The use of a cryopreserved arterial homograft for PV/SMV reconstruction after pancreatic resection seems to be a feasible, safe and easily reproducible surgical technique in high-volume specialized centers and can be added to the pool of surgical solutions in selected patients.

Comparing RECIST and Choi’s Criteria to Evaluate Radiological Response to Chemotherapy in Patients with Advanced Pancreatic Cancer

Context Assessment of response after chemotherapy (CTH) for pancreatic cancer (PC) is currently based on RECIST criteria. In 2007 Choi et al . published a new classification system. Objectives To evaluate the accuracy of the two classification systems for radiological response to CTH in patients affected by advanced PC. Methods From 2006 to 2011, 61 untreated patients affected by advanced pancreatic adenocarcinoma underwent palliative CTH. Thirty-seven (60.7 %) had a locally advanced PC and 24 (39.3%) a metastatic disease. All patients were treated with a bemcitabine-based CTH. We assessed radiological response after three months of first-line therapy applying both RECIST criteria and Choi’s criteria, which consider changes both in size and in density at CT. We evaluated the accuracy in restaging, comparing the class of response with overall survival (OS). OS was calculated with Kaplan-Meier method. The concordance with the two classification systems was evaluated with Kendall’s test. The accuracy in restaging was assessed through log rank test. Results At restaging, using RECIST criteria, we registered 6 (9.8%) patients with partial response (PR), 32 (52.5%) with stable disease (SD), and 23 (37.7%) with disease progression (PD). Instead Choi’s criteria assessed 18 PR (29.5%), 12 SD (19.7%) and 31 PD (50.8%). The concordance test showed that the two systems matched (P<0.001). Comparing each classification with OS, we observed that patients with different prognosis were better stratified with Choi’s criteria. Using RECIST criteria we did not found any significant difference in OS between patients with PR (12 months), SD (16 months) and PD (10 months). Using Choi’s criteria we found that OS in patients with PR was similar to patients with SD with 16 and 19 months (P=0.634). Patients with PR had an OS significantly higher than patients with PD (16 vs . 9 months; P=0.009; RR=2.3). Conclusions Choi’s criteria seem to better assess radiological response of CTH in PC patients than RECIST criteria. Due to the small number of patients, larger prospective studies are needed.

Usefulness of the Clavien–Dindo classification after pancreaticoduodenectomy.

We would like to thank Cornoiu et al. for their article detailing their randomized trial investigating multimedia patient education to assist informed consent for knee arthroscopy. Informed consent is an important issue for any practising surgeon and any process that can improve the conveying of information to the patient is invaluable. As discussed by the authors, previous studies investigating patient recall after verbal-informed consent have shown poor recall results. An article cited by the authors, Hutson and Blaha, found that 82% of patients undergoing total knee arthroplasty could recall the risk of infection immediately after their first informed consent interview. In addition, the rate of recall of the risk of prosthetic loosening and neurovascular damage was only 25 and 11%, respectively, even at this initial interview. In another similar study by Shurnas and Coughlin, investigating the use of a visual aid to assist in informed consent in patients undergoing forefoot surgery, it was found that only a mean of 1 out of 11 risks explained to patients was recalled after 12 weeks. Stanley et al. found a recall rate of only 48% after 6 weeks in patients undergoing vascular surgery. Therefore, to achieve recall rates of above 95% after 6 weeks is a fantastic result. Augmenting verbal consent processes with multimedia should seriously be considered to optimize informed consent.

Safety of Pancreatic Resections in Octogenarians

Context The safety of pancreatic resections in very elderly patients is still controversial. Objective To evaluate postoperative mortality, morbidity, type of discharge and length of hospital stay (LOS) in octogenarians who underwent pancreatic resections for malignancy. Methods From 2004 to 2013, 213 patients underwent pancreatic resections and were recorded in a prospective data base. They were divided in three groups: <70 years, 70-80 years and ≥80 years and were analyzed regarding postoperative course. Multivariate analysis was carried out to verify the impact of age on postoperative results. Results Mortality rate was higher (P=0.029) in patients ≥80 years (16.7%) only when compared with patients <70 years (3.4%). Morbidity rate was similar in the three groups. The discharge home was more frequent in patients <70 years (94.6%) and in those 70-80 years (92.3%) respect on patients ≥80 years (55%; P<0.001). LOS was similar in patients <70 years and in those 70-80 years, while it results higher in those aged ≥80 years (P=0.021). At multivariate analysis, patients aged 70-80 and ≥80 years had an increased risk of postoperative mortality (OR=7.1, P=0.022 and OR=6.3, P=0.050, respectively) as well as malnourishment (OR=4.5, P=0.029). Age did not influence morbidity while ASA score 4 increased risk of complications (OR=7.0, P=0.018). Distal pancreatectomy (DP) or an atypical resection reduced the risk (OR=0.4, P=0.008 and OR=0.1, P=0.049, respectively) respect on major procedures. Discharge to health care facility was more frequent in patients ≥80 years (OR=74.5, P<0.001), with ASA score 4 (OR=48.9, P=0.023), comorbidities (OR=25.4, P=0.011) or jaundice (OR=119.2, P=0.004) and in those performing DP (OR=26.7, P=0.039). Biliary stenting reduced the odds to health care facility (OR=0.1, P=0.041). LOS was increased by comorbidities, chronic renal failure and jaundice by 25% (P=0.039), 64% (P=0.003) and 36% (P=0.010), respectively. Total pancreatectomy reduced LOS by 14% (P=0.036). Conclusions Age ≥80 years increased the risk of postoperative mortality and discharge to health care facility after pancreatic resections.