Nicola Zanini

Analysis of prognostic factors in metastatic tumors of the pancreas: a single-center experience and review of the literature.

Objectives: Pancreatic metastases are rare. The role of surgery is poorly defined, and data on long-term survival are lacking. Methods: Data from patients with pancreatic metastases observed in our division from 2003 to 2008 were retrospectively analyzed. In addition, the recent English medical literature was reviewed regarding series of patients with pancreatic secondary tumors. Results: Data from 234 patients including 9 consecutive patients observed in our division were retrieved. Metastasis from renal cell carcinoma accounted for 67.9% of all cases. Factors predictive of worse survival, as determined by multivariate analysis, were symptoms at diagnosis, synchronous tumors, radical-intent surgery not performed, and pathologic diagnosis of the primary tumor. Compared with pancreatic metastases from renal cell cancer, metastases from melanoma (P < 0.001) and lung cancer (P = 0.002) were associated with worse survival. The differences in survival of patients with renal cell cancer metastases and those with breast cancer, colorectal, or sarcoma metastases did not reach statistical significance. Conclusions: There may be a subset of patients with pancreatic metastases who are able to benefit from surgery with respect to improved long-term survival. Symptoms at diagnosis, presentation with primary tumor, surgical resection, and pathologic diagnosis seem to be important prognostic factors.

Prognostic Factors in Periampullary and Pancreatic Tumor Resection in Elderly Patients

BackgroundMore than half of all patients with pancreatic adenocarcinoma are over 70 years of age. Life expectancy for the elderly population is increasing and currently major pancreatic resection provides the only meaningful chance of cure for periampullary and pancreatic tumors. Controversy over what constitutes the correct treatment of these tumors in elderly patients continues to this day. The aim of our study was to determine whether age alone or age plus some prognostic factors constitute contraindications to major pancreatic resections.MethodsBetween 2000 and 2005, data from 88 consecutive patients who had major pancreatic resection for periampullary or pancreatic tumors were entered into a prospective database. Fifty-three patients under 70 years of age (young patients), and 35 patients 70 years of age or older (elderly patients) were compared with respect to several characteristics and the postoperative course.ResultsPostoperative mortality and morbidity, length of hospital stay, and long-term survival were similar in the two groups. In the elderly group, the mortality rate was significantly higher in patients with chronic obstructive pulmonary disease (COPD), and the morbidity rate was significantly higher in patients with ASA 3 than in patients with ASA 1–2, in whom a pancreaticoduodenectomy or total pancreatectomy had been performed.ConclusionsAge alone is not a contraindication for major pancreatic resection. In elderly patients a careful evaluation of the co-morbidities and of the type of surgical procedure is mandatory in order to allow the proper selection of those patients best suited for surgery in specialized centers.

Serous Cystic Tumors of the Pancreas: When to Observe and When to Operate

Background: Pancreatic serous cystic tumors are considered to have a benign biological and clinical course with only few malignant cases. Methods: We retrospectively analyzed data from 26 patients affected by serous cystic tumors consecutively observed in our Pancreas Unit. We explored the different clinical pictures in operated and nonoperated patients. Results: Eighteen of the 26 patients were female (69%), median age at diagnosis was 61.5 years and 20 patients (77%) underwent surgery. The median diameter of the tumors was greater in patients who underwent surgery than in those who did not (5.5 versus 2.3 cm, p < 0.001). Major pancreatic resections were carried out in 15 of the 20 operated patients (75%). Postoperative morbidity and mortality were 20 and 5%, respectively. During follow-up, there was no observed development of malignancy or any significant increase in the diameter of the lesion among nontreated patients. Conclusions: In asymptomatic patients with a clear imaging diagnosis of serous cystic tumor a wait and see management should be recommended, with a careful follow-up. Surgery should be suggested in symptomatic patients or when the preoperative diagnosis is doubtful.

Very high CEA level in a large pancreatic cyst: Is it a surgical indication by itself?

BACKGROUND Pancreatic mucinous cystic lesions might develop malignancy if untreated, or could harbor malignancy at the time of the diagnosis. Many reports stated that cyst fluid carcinoembryonic antigen is an accurate diagnostic marker of pancreatic mucinous cysts. METHODS A man with a incidental pancretic cystic lesion of 35 mm in diameter was admitted to our Department. CT and EUS did not reveal solid components, main duct was not dilated and cyst fluid CEA was very high (1445 ng/ml). RESULTS The patient underwent a pancreatoduodenectomy and the surgical specimen showed a pseudocyst with columnar mucinous epithelium, consistent with low-grade PanIN. CONCLUSIONS Is it possible that the mucinous epithelium of panIN was responsible for the unexpectedly high CEA value? Clinicians should be aware of the usefulness of the CEA level in cystic fluid but even a very high CEA value should not be considered by itself to be evidence of a mucinous lesion.

Signet Ring Cell Carcinoma of the Ampulla of Vater With Focal Neuroendocrine Differentiation of the Amphicrine Type: Report of a Case With Long-Term Survival

Carcinoma of the ampulla of Vater is an uncommon neoplasm and represents 0.5% of all gastrointestinal malignancies, being less common than carcinoma of the pancreas and bile ducts. The most common ampullary tumor is the adenocarcinoma with tubular growth pattern. Signet ring cell carcinoma is extremely rare. In this article, we report a case of signet ring cell carcinoma of the ampulla of Vater showing focal neuroendocrine amphicrine differentiation and intestinal phenotype, which occurred in a 49-year-old male who is still alive 7 years after surgery, without evidence of recurrence. This long-term survival might be attributed not only to the early stage of the disease but also to the neuroendocrine differentiation and the absence of genetic alterations.

Characterization of malignant gastrointestinal stromal tumors—a single center experience

Background The recurrence rate, related to the unpredictable behavior of gastrointestinal stromal tumors (GISTs), continues to be a major topic of investigation, since no actual risk evaluation scales have proven to be exceedingly effective in predicting prognosis. We therefore focus in this study on investigating the predictive variables of disease recurrence. Methods Between September 2004 and January 2011, 34 patients, 18 males and 16 females with a median age of 62 (range, 27-87) years, underwent operations for primary, localized and advanced GISTs. Immunohistochemical profile, KIT and the platelet-derived growth factor receptor-alpha (PDGFR-α) gene mutations, tumor size, tumor site, mitotic index, synchronous tumors, adjuvant therapy, symptoms and gender were considered and analyzed as predictive variables. The receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off value for tumor dimension to predict recurrence. Results The median follow-up (FU) was 20 months (range, 6-86 months). A first-line adjuvant therapy was performed in nine patients. Disease relapse occurred in five cases. The tumor size and the mitotic index were the strongest predictive factors (P<0.001). The optimal maximum value for the tumor size was 7 cm [area under the curve (AUC) =0.955]. Conclusions In light of the most recent evidence, a tumor size of 7 cm should be considered the threshold value for malignancy, and smaller GISTs with low mitotic counts as tumors with a low-grade risk.

Focal Liver Lesions Suspected of Being Cholangiocarcinomas

To the Editor: It was with great interest that we read the clinical guidelines regarding the management of focal liver lesions that was recently published in the Journal, “ACG Clinical Guideline: The Diagnosis and Management of Focal Liver Lesions” (1).

Surgery for Pancreatic Cancer Liver Metastases. Navigating Uncharted Territory

Context Studies on kinetics of metastases revealed that pancreatic cancer should be considered a systemic disease at the time of diagnosis, regardless of tumor stage at imaging. Surgery is generally not indicated for metastatic pancreatic cancer because it is supposed not to improve survival. Objective Is metastasis from periampullary cancer an absolute contraindication to surgery? Could someone benefit from liver resection? Who? Methods Our prospectively collected database (2003-2012) lists 20 patients who underwent liver resection for metastases from periampullary, non-endocrine cancer. Generally, resection was offered in young patient, fit for surgery, with few metastases. Fourteen patients were affected by synchronous metastases and they underwent simultaneous pancreatectomy and liver resection, 6 patients experienced metachronous metastases. Results Median age was 60 years (IQR: 52-65 years). Pancreatic ductal carcinoma was the primary tumor in 15 patients, the remaining patients were affected by ampullary carcinoma or distal bile duct carcinoma. One right hepatectomy, 2 bisegmentectomies and 17 atypical resections were performed. Simultaneous liver and pancreatic resections did not improve postoperative morbidity and mortality if compared to standard pancreatic resections. Median follow-up was 47 months. Median overall survival (OS) was 15 months (95%CI: 8-22 months). Median OS in patients with synchronous metastases was 12 months (95%CI: 7-17 months). Median OS in patients with metachronous metastases was 28 months (95%CI: 2-55 months) from liver resection, 38 months from pancreatectomy. Conclusion Surgery for liver metastases from periampullary tumors is a minefield. It is a wrong step for most patients and death may occur even earlier if compared to palliative cure. However, a small group of patients could benefit from surgery and find a path to long-term survival.

Three Different Techniques for KRAS Mutational Analysis in EUS-FNA Pancreatic Lesions: Sanger Sequencing, Next Generation Sequencing and Real-Time PCR

Context KRAS is an oncogene frequently mutated in pancreatic carcinomas. 90% of the mutations are localized at the level of codons 12, 13 and 61. Detecting a KRAS mutation could help to distinguish pancreatic cancer from pseudotumoral chronic pancreatitis. Identifying such mutations in preoperative endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) material is an important diagnostic aid. For this reason it is necessary to have highly sensitive and specific molecular techniques. Patients and Methods In 60 consecutive patients, who underwent EUS-FNA for typing of focal lesions of the pancreas, FNA material was processed for routine cytological analysis and an aliquot collected in ethanol for KRAS analysis. The material was used for the analysis of KRAS through: Sanger sequencing (Beckman CEQ2000 platform), Allele specific LNA qPCR (ASLNAqPCR) e Roche 454 GS-Junior sequencer (Next Generation Sequencing; NGS). Results At microscopic examination the cytological diagnosis ranged from malignant to non-neoplastic lesions. The analysis with the Sanger sequencing revealed KRAS mutations in 17/60 samples, using ASLNAqPCR KRAS mutations were detected in 25/60 patients while NGS allowed to detect mutations in 30/60 samples. With regard to cases with cytological diagnosis of primary adenocarcinoma, Sanger sequencing showed KRAS mutations in 6/15 (40%) cases, ASLNAqPCR in 10/15 (66.7%) and NGS in 12/15 (80%). Conclusions ASLNAqPCR and NGS techniques were found to be more sensitive than Sanger sequencing. The NGS allows to detect infrequent mutations and ASLNAqPCR provides data on the fraction of mutated cells in the analyzed sample. The use of one of these two techniques (or both of them) allows to characterize in a very precise way the KRAS molecular status of a pancreatic lesion starting from material obtained with EUS-FNA.

The “Prochronous Metastases” Theory

Context It is known that metastatic process is an early event in the life of a pancreatic ductal adenocarcinoma (PDAC). As soon as cancer cells (cells which became able to pass the basal lamina) are present in the pancreatic gland, maybe that is the moment since the disease should be considered as systemic. A recent study on mouse models revealed that not only PDAC cells can move through basal lamina, but even pre-cancerous cells (pan-IN cells) could do it. This outstanding report gives rise to new possible explanations of some clinical scenarios not fully understood to this day. Case report We report the case a of 70-year-old man who underwent splenectomy for a solid mass of uncertain origin. Pathology revealed a metastasis from undifferentiated adenocarcinoma, biliopancreatic origin was suspected. Extensive sonography, endoscopy, EUS, conventional and nuclear imaging were carried out. No proofs or clues of the primary cancer were found. However, enlarged lymph nodes were visible in the liver hilum, lesser omentum and interaortocaval region. Explorative laparotomy was performed and a small cancer of the pancreatic tail with nodal and peritoneal metastases was found. Conclusion We theorize that PDAC could first arise in distant organs and only later in the pancreas. If pan-IN cells can pass through the basal lamina and reach systemic blood-stream, they could dedifferentiate in distant organs. Could such pan-IN “metastases” give birth to pancreatic cancer before “pancreatic” pan-IN proceed to PDAC? We already deal with sinchronous and metachronous metastases; what if really exist prochronous metastases?