Pyogenic Liver Abscess: Contemporary Trends in a Tertiary Institute.

Background: Pyogenic liver abscess (PLA) is an uncommon but potentially life-threatening condition. In recent years, advances in diagnostics and management have led to early diagnosis and treatment and decreased mortality. We present recent data from a large series of patients with PLA and examine the trends in the management of PLA over a period of 50 years. Methods: The medical records of all patients admitted to the Shaare Zedek Medical Center, Israel, between January 2011 and December 2021 with a primary or secondary diagnosis of PLA were reviewed retrospectively. Results: : Ninety-five patients with PLA were identified. Thirty-eight (40%) were female. The median patient age was 66 years (range 18-93). The diagnosis of PLA in all patients was confirmed with abdominal computed tomography (CT). In twenty patients (21.1%), PLA was not diagnosed by the initial abdominal US. Most abscesses were right-sided. Biliary tract origin was the most common underlying cause of PLA (n = 57, 60%), followed by cryptogenic etiology (n = 28, 30%). Escherichia coli, Klebsiella pneumoniae, and Streptococcus species were most commonly identified. The most common primary treatment modality was percutaneous drainage (PD), which was performed in 81 patients (85.3%). Fourteen patients (14.7%) were treated medically without intervention, and two patients (2.1%) were treated surgically following a failure of PD. Four patients died as a direct result of PLA. Conclusions: Patients diagnosed with PLA are older, the male predominance is less pronounced, and the offending pathogens are likely to originate from the biliary tract. This study questions the utility of abdominal US as the initial diagnostic imaging in patients with suspected PLA (versus CT) and demonstrates improved outcomes for patients with PLA over the years.

Capillaria hepatica (syn. Calodium hepaticum) as a Cause of Asymptomatic Liver Mass.

Capillaria hepatica (syn. Calodium hepaticum) is a parasitic nematode of rodents, rarely infecting humans. An asymptomatic Israeli adult male with extensive travel history was diagnosed with a liver mass on routine post-thymectomy follow-up. Imaging and computer tomography (CT) guided biopsy were inconclusive. Surgical excision revealed an eosinophilic granuloma with fragments of a nematode suspected to be C. hepatica. Molecular methods verified the diagnosis, and the patient was treated empirically. This is the first case of hepatic capillariasis described in Israel, and the first to be diagnosed using molecular methods.

Increased Rate of Complete Pathologic Response After Neoadjuvant FOLFIRINOX for BRCA Mutation Carriers with Borderline Resectable Pancreatic Cancer.

BACKGROUND: Neoadjuvant FOLFIRINOX is a standard-of-care treatment for BRPC patients. Patients with gBRCAm who have demonstrated improved response to platinum-based chemotherapy may have impaired homologous repair deficiency. This study aimed to describe the pathologic complete response rate and long-term survival for patients with germline BRCA1 or BRCA2 mutation (gBRCAm) and borderline resectable pancreatic cancer (BRPC) treated with neoadjuvant FOLFIRINOX. METHODS: A dual-center retrospective analysis was performed. Patients who had BRPC treated with neoadjuvant FOLFIRINOX followed by curative resection were identified from clinical databases. Pathologic complete response was defined as no viable tumor cells present in the specimen. Common founder Jewish germline BRCA1 or BRCA2 mutation was determined for available patients. RESULTS: The 61 BRPC patients in this study underwent resection after neoadjuvant FOLFIRINOX. Analysis of BRCA mutation was performed for 39 patients, and 9 patients were found to be BRCA2 germline mutation carriers. The pathologic complete response rate was 44.4% for the gBRCAm patients and 10% for the BRCA non-carriers (p = 0.009). The median disease-free survival was not reached for the gBRCAm patients and was 7 months for the BRCA non-carriers (p = 0.03). The median overall survival was not reached for the gBRCAm patients and was 32 months for the BRCA non-carriers (p = 0.2). After a mean follow-up period of 33.7 months, all eight patients with pathologic complete response were disease-free. CONCLUSIONS: The study showed that gBRCAm patients with BRPC have an increased chance for pathologic complete response and prolonged survival after neoadjuvant FOLFIRINOX. The results support the benefit of exposing gBRCAm patients to platinum-based chemotherapy early in the course of the disease. Neoadjuvant FOLFIRINOX should be considered for BRCA carriers who have resectable pancreatic cancer.

Enhanced Recovery Deviation and Failure After Pancreaticoduodenectomy: Causative Factors and Impact.

BACKGROUND: Enhanced recovery after surgery (ERAS) following pancreaticoduodenectomy (PD) is popular and safe. This study aimed to describe the incidence, causative factors, and clinical impact of deviation from and failure of an ERAS protocol. MATERIALS AND METHODS: A prospective cohort analysis of elective PD patients managed according to an ERAS protocol between October 2015 and June 2018 was performed. Univariate and multivariate analyses identified variables associated with protocol deviation and failure. The relationship between protocol deviation and failure was also explored. RESULTS: A total of 97 patients were identified comprising of 46 females and 51 males. The median age was 68 y (range 17-85). Twenty-one patients (21.6%) suffered serious complications, whereas two (2.1%) died perioperatively. The median length of stay (LoS) was 14 d (6-36). In total, 73 (75.3%) patients deviated, whereas 39 (40.2%) failed the protocol. On univariate analysis, protocol deviation was associated with male gender, surgery time ≥270 min, and prolonged LoS. On multivariate analysis only prolonged LoS remained significant. Only serious complications were associated with protocol failure on multivariate analysis. Protocol deviation was not associated with significant complications nor ERAS protocol failure. CONCLUSIONS: ERAS protocol deviation does not alter the course of those destined to protocol failure. Greater understanding into the causative factors of either protocol deviation or failure may be the only way to personalize care and realize the maximal benefit of ERAS in this specific group of patients.

[SARCOPENIA IS AN INDEPENDENT RISK FACTOR FOR DELAYED GASTRIC EMPTYING AFTER PANCREATICODUODENECTOMY].

BACKGROUND: Sarcopenia is defined as the degenerative loss of skeletal muscle and can be measured using the cross-sectional diameter of the psoas muscle on computed tomography. Sarcopenia has been associated with a variety of post-operative complications. We propose that sarcopenia acts as an independent factor predictive of delayed gastric emptying (DGE) after elective pancreaticoduodenectomy (PD). METHODS: A retrospective analysis of a prospectively maintained database of all patients undergoing PD at our tertiary hepatobiliary center was performed for the period December 2014 - March 2017. For each patient, the preoperative cross-sectional diameter of the psoas muscle at the upper border of L4 was calculated. Measurements in the lowest third of gender specific groups were considered to be sarcopenic. The presence of DGE, post-operative pancreatic fistulas (POPF) and major postoperative complications graded as Clavien Dindo III or more were included in the analysis. RESULTS: A total of 40 patients were included, 15 (37.5%) of whom were classified as sarcopenic. Comparison between the sarcopenic and non-sarcopenia groups revealed homogeneity in terms of gender, age, BMI and pre-operative albumin levels. DGE occurred in 11 patients (27.5%) of whom 7 were sarcopenic. Significantly more sarcopenic patients suffered from DGE (7/15 vs 4/25, p = 0.042). Major postoperative complications and POPF occurred in 15 patients each (37.5%). Nevertheless, sarcopenia was not significantly associated with POPF or other complications. The presence of sarcopenia was found to have a significant relationship with the incidence of DGE (OR 4.594, 95% CI 1.052-20.057). DISCUSSION: Sarcopenia acted as an independent risk factor predicting DGE after PD but not for POPF or other major postoperative complications.

[INTRACHOLECYSTIC PAPILLARY-TUBULAR NEOPLASM: A NEW PATHOLOGY OF THE GALLBLADDER?]

INTRODUCTION: The clinicopathologic characterization of tumoral intra-epithelial neoplasms of the gallbladder is fairly limited compared to that of similar tumors of the pancreatobiliary system. Until recently, pre-malignant lesions of the gallbladder were mostly reported as adenomas, which were microscopic and therefore regarded as benign and clinically inconsequential, whereas papillary lesions have been largely regarded as a papillary subtype of gallbladder invasive adenocarcinoma. In an attempt to create a unified terminology for these tumors, the term Intracholecystic papillary-tubular neoplasm (ICPN) was proposed to include all exophytic intra-epithelial tumors of the gallbladder measuring ≥1 cm under one category. A few studies which have retrospectively analyzed tumors fulfilling this category found them to be remarkable analogous to the more well-characterized intra-epithelial tumors of the pancreato-biliary system such as IPMN of the pancreas and IPNB of the bile ducts and as such they also represent an 'adenoma-carcinoma' sequence in the gallbladder. Since then a number of case series have been published which attempted to characterize the clinical and pathological features of these tumors and their relationship with invasive carcinoma. In this paper we report three cases of ICPN which represent different stages of the 'adenoma-carcinoma' sequence.

Sarcopenia is associated with a greater incidence of delayed gastric emptying following pancreaticoduodenectomy.

BACKGROUND AND AIMS: Sarcopenia is the degenerative loss of skeletal muscle and has been associated with a variety of post-operative complications. We propose sarcopenia is associated with delayed gastric emptying (DGE) following elective pancreaticoduodenectomy (PD). METHODS: A retrospective analysis of a computerised database maintained in real time of all patients undergoing PD within our hepatobiliary unit was performed. The cross-sectional area of the psoas muscle at the upper border of L3 was calculated and corrected for patient height. The lowest quartile of gender specific groups was considered to be sarcopenic. RESULTS: 61 patients were included, 32 male and 29 female of whom 8 from each group were sarcopenic (26.2%). Although the sarcopenic and non-sarcopenia groups were found to be comparable, significantly more sarcopenic patients were older (75 vs 64 years, p = 0.003), had a lower body mass index (21.9 vs 25.0 kg/m2, p = 0.003) and suffered from DGE (7/16 vs 8/45, p = 0.045). On multivariate analysis, these variables maintained their significance with DGE having an OR of 6.042 (p = 0.036). CONCLUSION: Sarcopenia is significantly associated with DGE, older age and lower BMI in this specific cohort of patients. Further research into the reversibility of this phenomenon is warranted.

Intrathecal morphine versus intravenous opioid administration to impact postoperative analgesia in hepato-pancreatic surgery: a randomized controlled trial.

PURPOSE: Inadequate analgesia following abdominal surgery may affect outcome. Data in patients undergoing liver surgery suggested that postoperative coagulopathy might delay epidural catheter removal. Thus, alternative analgesic techniques should be evaluated. METHODS: We compared the analgesic efficacy of intraoperative intrathecal morphine [single injection 4 µg/kg before skin incision (ITM group, n = 23)] to intravenous opioids [iv remifentanil infusion during surgery followed by i.v. bolus of morphine, 0.15 mg/kg before the end of surgery (IVO group, n = 26)]. Forty-nine adult patients undergoing elective open resection of liver or pancreas lesions in the Tel Aviv Medical Center were randomized into the two analgesic protocols. Postoperatively both groups received i.v. morphine via a patient-controlled analgesia pump. Follow-up was till the 3rd postoperative day (POD). RESULTS: There was no significant difference in demographics and intraoperative data between groups. The primary outcome, pain scores on movement, was significantly worse in the IVO group when compared with the ITM group at various time points till POD3. In the secondary outcomes - need for rescue drugs - the IVO group required significantly more rescue morphine boluses. Complication related to the analgesia and recovery parameters were similar between groups. CONCLUSIONS: The findings suggest that a single dose of ITM before hepatic/pancreatic surgery may offer better postoperative pain control than i.v. opioid administration during surgery. This beneficial effect is maintained throughout the first three PODs and is not associated with a higher complication rate; neither did it influence recovery parameters. ITM provides an appropriate alternative to i.v. morphine during major abdominal surgery.

Epithelial-to-mesenchymal transition (EMT) in intraductal papillary mucinous neoplasm (IPMN) is associated with high tumor grade and adverse outcomes.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is generally associated with increased tumor aggressiveness and poor prognosis. We evaluated EMT characteristics in intraductal papillary mucinous neoplasm (IPMN) tumor specimens and their potential role as biomarkers for malignancy, metastasis, and adverse patient outcomes. METHODS: IPMN surgical specimens were identified and reviewed by two gastrointestinal pathologists. Immunohistochemical analysis of E-cadherin, vimentin, and ZEB-1 was performed. Samples were linked to clinicopathologic and outcome data for these patients. Western blot test was used to evaluate ZEB-1 expression in IPMN samples; 846 human miRNAs were profiled, and EMT-related differentially expressed miRNAs were validated using quantitative real-time polymerase chain reaction. RESULTS: Fifty-eight IPMN specimens and five normal pancreatic tissue samples were immunohistochemically stained and scored. E-cadherin expression was significantly lower in malignant versus low-grade IPMN (p < 0.05). Vimentin expression was increased in malignant IPMN tumor samples (p < 0.05). EMT was associated with increased lymph node metastasis and decreased survival of malignant IPMN patients (p < 0.05). ZEB-1, an imperative EMT regulator, was exclusively expressed by malignant IPMN tumors. miRNA hierarchical clustering demonstrated grouping of two main IPMN subgroups: low-grade IPMN versus high-grade IPMN and carcinoma. Twenty-four miRNAs were differentially expressed (14 up-regulated, 10 down-regulated). The EMT-regulatory miRNAs, miR-200c and miR-141, were down-regulated (twofold and 1.8-fold decrease, respectively) in malignant versus low-grade IPMN (p < 0.05). CONCLUSIONS: EMT may play a role in IPMN tumorigenesis and metastasis. EMT molecular deregulations could be utilized as potential novel biomarkers for the identification of high-risk IPMN patients.

Pancreaticoduodenectomy in elderly adults: is it justified in terms of mortality, long-term morbidity, and quality of life?

OBJECTIVES: To evaluate long-term morbidity, mortality, and quality of life (QoL) after pancreaticoduodenectomy (PD) in elderly adults. DESIGN: Retrospective cohort study. SETTING: Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. PARTICIPANTS: One hundred and sixty-eight individuals aged 70 and older who underwent PD between 1995 and 2010. MEASUREMENTS: A prospective pancreatic surgery database was analyzed for postoperative morbidity; mortality; intensive care unit (ICU), hospital, and rehabilitation facility stay; and readmissions after surgery. QoL was assessed using a validated questionnaire completed 3, 6, and 12 months after surgery. RESULTS: Seventy-two percent of the participants had an American Society of Anesthesiologists score of 3 or greater. There was no intraoperative death. Thirty- and 60-day postoperative mortality rates were 5.9% and 6.5%, respectively. Median ICU stay was 2 days, and median hospital stay was 22 days. Sixty-four participants (37.5%) were discharged to a rehabilitation facility. The first-year readmission rate was 31%. One- and 2-year overall survival rates were 58% and 36%, respectively. Global QoL scores 3 and 12 months after surgery were 68% and 73%, respectively. Scores were lower yet comparable with those of matched individuals undergoing laparoscopic cholecystectomy. CONCLUSION: Most elderly adults with pancreatic cancer survive longer than 1 year after PD; 36% survive longer than 2 years. These individuals are likely to have acceptable long-term morbidity and overall good QoL, corresponding with their age.

Early and late presentations of graft arterial pseudoaneurysm following pancreatic transplantation.

BACKGROUND: Graft pseudoaneurysm (PSA) following pancreatic transplantation (PT) is a rarely reported complication that has significant morbidity and mortality. Few case reports and small series of this complication exist. METHODS: Retrospective review of files of 106 patients who underwent PT at the Tel-Aviv Sourasky Medical center between 1995 and 2010. Accessible asymptomatic patients (n = 35) were referred for graft PSA screening using ultrasound-Doppler. RESULTS: Eight patients developed graft PSA (8 %). All had early posttransplant sepsis. PSA incidence among patients who had perioperative sepsis is 13 %. Three patients developed early postoperative PSA, presenting as massive abdominal bleeding requiring urgent laparotomy and graft resection. Five patients were diagnosed with late-onset graft PSA between 3 months and 11 years posttransplant: clinical presentations were massive gastrointestinal bleeding (n = 2), acute renal failure (n = 1), and asymptomatic finding on screening ultrasound-Doppler (n = 2, 6 % of screened patients). CONCLUSIONS: PSA following PT occurs in 8 % of patients. Perioperative infection is a risk factor. Early PSAs present as massive intra-abdominal bleeding. PSA may develop years posttransplant, may be asymptomatic, but late rupture is possible and presents as gastrointestinal bleeding. We recommend screening of patients at risk with ultrasound Doppler for early detection and treatment of asymptomatic PSAs.

MicroRNA expression signatures in intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMN) represent a spectrum of tumors that range from low-grade (LG) dysplastic tumors to invasive cancer. Identification of IPMN at high risk for malignant transformation is important for the prevention and early treatment of pancreatic cancer. The roles of microRNA expression in the development of IPMN have not been extensively evaluated. METHODS: Expression patterns of 846 human microRNAs (miRNAs) was analyzed using microRNA microarray in 55 tissues, including LG IPMN (n = 10), moderate-grade (MG) IPMN (n = 5), high-grade (HG) IPMN (n = 5), invasive cancer with IPMN (IPMC; n = 10), pancreatic ductal adenocarcinoma without IPMN (PDA; n = 5), LG IPMN extracted from specimens that contain IPMC (LG_Ca; n = 10), and normal pancreatic tissues (n = 10). RESULTS: Fourteen miRNAs were differentially expressed in all IPMN tissues compared with normal pancreatic tissue. Expression level of 3 miRNAs was proportional to dysplasia level. Hierarchical clustering demonstrated grouping of 2 IPMN subgroups: LG and MG IPMN verses HG IPMN and IPMC. Expression of 15 miRNAs was significantly different between these groups. LG_Ca tissues clustered with the HG IPMC group, and 12 miRNAs were differentially expressed in LG_Ca, HG lesions, and IPMC compared with LG lesions. The expression patterns of selected miRNAs were validated using quantitative reverse-transcription real-time polymerase chain reaction. Hierarchical clustering demonstrated microRNA expression profile in IPMC was significantly different from PDA, suggesting that different pathways are involved in these cancer types. CONCLUSION: This study demonstrates that miRNAs are involved in the development and progression of IPMN. We identified potential targets for diagnosis, prognostication, and treatment of IPMN.

Perioperative complications after neoadjuvant chemotherapy with and without bevacizumab for colorectal liver metastases.

PURPOSE: Bevacizumab has been shown to increase progression free and overall survival in patients with metastatic colorectal cancer. Neoadjuvant bevacizumab is commonly used in patients undergoing liver resection. Our purpose was to evaluate whether bevacizumab is associated with increased rate of perioperative complications in patients undergoing hepatic resection for colorectal liver metastases (CRLM). METHODS: Retrospective analysis of patients undergoing hepatic resection for CRLM who received chemotherapy and bevacizumab (group 1, n = 134), or chemotherapy alone (group 2, n = 57). We compared demographics, surgical characteristics, and perioperative course. RESULTS: Perioperative complications developed in 35 % of patients in group 1, and 47 % in group 2 (p = 0.11). Of those complications, 15 (11.2 %) in group 1, and 5 (8.8 %) in group 2 were considered major (p = 0.617). Four patients, all of whom received preoperative bevacizumab, developed enteric leaks following combined liver and bowel resection. The rate of anastomotic leak in group 1 was 10 %, compared with 0 in group 2, p = 0.56. CONCLUSION: Neoadjuvant chemotherapy along with bevacizumab was not associated with an increased risk of postoperative complications after hepatic resection. Possible association of increased morbidity with simultaneous bowel and liver resections following bevacizumab administration was found and we recommend avoiding such treatment combination.

Intraductal papillary mucinous neoplasm of the pancreas: associated cancers, family history, genetic predisposition?

BACKGROUND: High rates of extrapancreatic malignancies (EPM) have been observed in patients with intraductal papillary mucinous neoplasm (IPMN). IPMN in patients with familial pancreatic cancer have also been reported. Our purpose was to evaluate the association of IPMN with EPM, malignancies in family members, and germline BRCA1 and BRCA2 mutations. METHODS: Using retrospective analysis on prospectively collected data from 82 patients with IPMN and direct contact for familial cancer history, data were compared with those of 150 patients with pancreatic ductal adenocarcinoma (PDAC). The common germline mutations in the BRCA1 and BRCA2 genes were evaluated on available IPMN patients. RESULTS: EPM rates were greater in IPMN than PDAC patients (P = .002). Malignancies in first-degree relatives, specifically pancreatic cancer, were more common among IPMN than PDAC patients (P = .028). IPMN patients with EPM had high rates of relatives with colorectal cancer (31%). Two of the 51 genetically tested patients (4%) were BRCA2 mutation carriers, and both had first-degree relatives with pancreatic cancer. One patient fulfilled the Amsterdam criteria for hereditary nonpolyposis colon cancer; however, the neoplasm was microsatellite stable. CONCLUSION: Our results demonstrated high rates of EPM among IPMN patients. There was an increased rate of cancer in families of IPMN patients, specifically pancreatic cancer. A high rate of colorectal cancer in families of IPMN patients who have EPM was also observed. These findings suggest a genetic component in the pathogenesis of IPMN. Possible genetic changes include BRCA2 mutations, which are found in 25% of IPMN patients with a family history of pancreatic cancer.

[Treatment of colorectal liver metastases: surgical resection vs. local ablative therapy].

INTRODUCTION: Surgical resection of colorectal liver metastases (CRLM) is the most common indication for hepatic resection at the present time and is considered to be the standard of care. However, advancement in imaging and local ablative therapy (LAT) techniques creates an apparently attractive alternative. The utilization of LAT is increasing for the treatment of CRLM in a non-controlled fashion. METHODS: A systematic and critical review of the Literature was undertaken according to the hierarchy of evidence based medicine (EBM). An analysis was conducted of the potential causes of the premature adoption of LAT as the first line treatment of CRLM. RESULTS: There is no level 1a meta-analysis available. A single Level 1b (randomized control study) is poorly presented; 2b cohort studies with some degree of risk adjustment, present a significant superiority to resection over LAT both in local control and in Long term resuLts. A single level 3a review points out a comparable local control following LAT for lesions smaller than 3 cm, but inferior long-term results, which may be biased by patient selection. Level 3b and 4 series point to different and contradicting results, prohibiting any conclusions. CONCLUSIONS: Based on the current knowLedge, LAT cannot replace surgical resection as the treatment of choice for CRLM. The increasing application of LAT in this setting is based on Level 5 evidence and is therefore inappropriate.

Contemporary surgical approach to hilar cholangiocarcinoma.

BACKGROUND: The diagnostic and therapeutic approach to hilar cholangiocarcinoma and thus the prognosis have changed significantly over the last two decades. Nonetheless, hilar cholangiocarcinoma presents a complex surgical challenge. OBJECTIVES: To assess the outcome of the radical approach for the management of types III and IV hilar cholangiocarcinoma. METHODS: We conducted a retrospective single-center study. Preoperative diagnosis was based on ultrasound, computed tomography and selective percutaneous cholangiography without tissue diagnosis. Surgery was radical and included en-bloc liver, extrahepatic biliary tree and hilar lymph nodes resection, followed by biliary reconstruction with hepaticojejunostomy. RESULTS: Fifteen patients (mean age 49 years, range 24-72) were managed accordingly. Anatomic classification of the biliary involvement was Bismuth-Corlette type IIIA (n=4), type IIIB (n=3) and type IV (n=8). The surgical procedures performed included four right hepatic lobectomies, five left hepatic lobectomies and six trisegmentectomies (all extended to the caudate lobe). Complete negative resection margins (RO) were accomplished in 12 cases (80%). Regional lymph node metastases were detected in five cases. There were two perioperative mortalities. Long-term follow-up (mean 30 months, range 6-72) revealed local recurrences in two cases, distant metastases in three, and both local and distant in two cases. Eleven patients are alive and 6 are without evidence of disease. The overall 2- and 5-year survival is 78% and 38% respectively. CONCLUSIONS: In selected patients the aggressive surgical approach to hilar cholangiocarcinoma is justified and can result in long-term survival.

Pancreatic cancer: surgery is a feasible therapeutic option for elderly patients.

BACKGROUND: Compromised physiological reserve, comorbidities, and the natural history of pancreatic cancer may deny pancreatic resection from elderly patients. We evaluated outcomes of elderly patients amenable to pancreatic surgery. METHODS: The medical records of all patients who underwent pancreatic resection at our institution (1995-2007) were retrospectively reviewed. Patient, tumor, and outcomes characteristics in elderly patients aged ≥ 70 years were compared to a younger cohort (<70 y). RESULTS: Of 460 patients who had surgery for pancreatic neoplasm, 166 (36%) aged ≥ 70 y. Compared to patients < 70 y (n = 294), elderly patients had more associated comorbidities; 72% vs. 43% (p = 0.01) and a higher rate of malignant pathologies; 73% vs. 59% (p = 0.002). Operative time and blood products consumption were comparable; however, elderly patients had more post-operative complications (41% vs. 29%; p = 0.01), longer hospital stay (26.2 vs. 19.7 days; p < 0.0001), and a higher incidence of peri-operative mortality (5.4% vs. 1.4%; p = 0.01). Multivariable analysis identified age ≥ 70 y as an independent predictor of shorter disease-specific survival (DSS) among patients who had surgery for pancreatic adenocarcinoma (n = 224). Median DSS for patients aged ≥ 70 y vs. < 70 y were 15 months (SE: 1.6) vs. 20 months (SE: 3.4), respectively (p = 0.05). One, two, and 5-Y DSS rates for the cohort of elderly patients were 58%, 36% and 23%, respectively. CONCLUSIONS: Properly selected elderly patients can undergo pancreatic resection with acceptable post-operative morbidity and mortality rates. Long term survival is achievable even in the presence of adenocarcinoma and therefore surgery should be seriously considered in these patients.

High-throughput mutation profiling in intraductal papillary mucinous neoplasm (IPMN).

BACKGROUND: Specific mutations leading to the development of various histological grades of intraductal papillary mucinous neoplasm (IPMN) have been partially characterized. METHODS: Analysis of 323 oncogenic mutations in 22 tumor-related genes was conducted, using a chip-based matrix-assisted laser desorption time-of-flight mass spectrometer of DNA extracted from microdissected cells of low-grade (n = 14), borderline (n = 6), and invasive IPMN (n = 7). Additional assays were performed on the DNA extracted from dyplastic cells found in the background of the adenocarcinoma. RESULTS: We identified 9 K-ras mutations (low grade, 2/14; borderline, 1/6; invasive, 6/7), 3 p53 mutations (low grade, 1/14; invasive 2/7), and 2 PIK3CA mutations (low grade, 1/14; invasive, 1/7). K-ras, p53, and PIK3CA mutations present in the invasive cancer were absent in the adjacent precursor cells in 50% of the cases. In one patient, K-ras mutation was present in the precursor lesion and absent in the adjacent invasive lesion. CONCLUSIONS: Of the 22 screened tumor-related genes, only K-ras, p53, and PIK3CA mutations were found in IPMN. K-ras mutations are more prevalent in invasive than premalignant IPMN. The variable coexistence of mutations in the invasive cancer and in the adjacent precursor cells may point to the heterogeneous nature of this tumor.

Clinical presentation can predict disease course in patients with intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND: Preoperative diagnosis of malignancy within intraductal papillary mucinous neoplasm of the pancreas (IPMN) solely by clinical or radiological findings is not always possible. We sought a correlation between preoperative clinico-radiological findings and outcome. METHODS: A prospective database of pancreatic resections for IPMN (2002-2008) and a retrospective pathological revision of all pancreatic cancer specimens (1995-2001) were analyzed. The patients were grouped into asymptomatic with preoperative diagnosis of IPMN (group 1), symptomatic with a preoperative diagnosis of IPMN (group 2), and those with a preoperative diagnosis of pancreatic cancer whose specimen revealed a background of IPMN (group 3). The groups were compared for demographics, clinical presentation, pathological findings, and outcome. RESULTS: Of the 62 patients with IPMN, 19 were in group 1, 23 in group 2, and 20 in group 3. Their median age (range) was 65.6 (46-80), 67 (50-84), and 73.4 (57-86) years, respectively. The clinical presentation for groups 2 and 3 included abdominal pain (56% vs. 32 %), weight loss (8% vs. 52%), obstructive jaundice (4% vs. 57%), pancreatitis (22% and 5%), and new onset of diabetes (14% and 44%). Invasive cancer was found in one patient in group 1 (5.2%), two patients in group 2 (8.7%), and all patients in group 3. IPMN was present in 23 of 217 (10.6%) of all resected pancreatic cancer specimens. Five year survival for patients with invasive disease was 47% and 92% for patients with noninvasive disease (mean follow-up 37.6 months). CONCLUSIONS: Benign IPMN can usually be differentiated from adenocarcinoma preoperatively. The clinical presentation is highly indicative of disease course.