A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma

BACKGROUND: 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) is superior to gemcitabine in patients with metastatic pancreatic cancer who have a good performance status. We investigated this combination as neoadjuvant therapy for locally advanced pancreatic cancer (LAPC). METHODS: In this retrospective series, we included patients with unresectable LAPC who received neoadjuvant FOLFIRINOX with growth factor support. The primary analysis endpoint was R0 resection rate. RESULTS: Eighteen treatment-naïve patients with unresectable or borderline resectable LAPC were treated with neoadjuvant FOLFIRINOX. The median age was 57.5 years and all had ECOG PS of 0 or 1. Eleven (61 %) had tumors in the head of the pancreas and 9 (50 %) had biliary stents placed prior to chemotherapy. A total of 146 cycles were administered with a median of 8 cycles (range 3-17) per patient. At maximum response or tolerability, 7 (39 %) were converted to resectability by radiological criteria; 5 had R0 resections, 1 had an R1 resection, and 1 had unresectable disease. Among the 11 patients who remained unresectable after FOLFIRINOX, 3 went on to have R0 resections after combined chemoradiotherapy, giving an overall R0 resection rate of 44 % (95 % CI 22–69 %). After a median follow-up of 13.4 months, the 1-year progression-free survival was 83 % (95 % CI 59-96 %) and the 1-year overall survival was 100 % (95 % CI 85-100 %). Grade 3/4 chemotherapy-related toxicities were neutropenia (22 %), neutropenic fever (17 %), thrombocytopenia (11 %), fatigue (11 %), and diarrhea (11 %). Common grade 1/2 toxicities were neutropenia (33 %), anemia (72 %), thrombocytopenia (44 %), fatigue (78 %), nausea (50 %), diarrhea (33 %) and neuropathy (33 %). CONCLUSIONS: FOLFIRINOX followed by chemoradiotherapy is feasible as neoadjuvant therapy in patients with unresectable LAPC. The R0 resection rate of 44 % in this population is promising. Further studies are warranted

Genetic predisposition to ductal carcinoma in situ of the breast

Background: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci. Methods: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip. Results: Most (67 %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P < 5.0x10-8. Conclusion: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

The response of normal rat hepatocytes when exposed to humoral (regenerating) factor

Evidence for the existence and source of a humoral factor which initiates and controls hepatic regeneration have been reviewed. Collections of this humoral factor have been made by perfusing 24-hour regenerating rat livers. An assay system for this humoral factor has been described which is based on perfusing isolated normal rat livers with the humoral factor, looking for an increase in hepatic DNA synthesis. Autoradiographic studies have revealed that the cells which are synthesizing new DNA in preparation for cell divison are mainly hepatic parenchymal cells (plus an occasional biliary ductal cell) located in all the liver lobules with a distribution primarily in the periportal areas—following the direction of portal and hepatic inflow

A Rapid Technique for Biliary and Duodenal Bypass in Nonresectable Pancreatic Carcinoma

• A technique for biliary and duodenal bypass in patients with metastatic or locally nonresectable pancreatic carcinoma was used in 18 patients. Biliary tract decompression was achieved with a Roux-en-Y cholecystojejunostomy and duodenal bypass with a gastrojejunostomy using an automated stapling device. Although all patients eventually die of this disease, there was no operative mortality and no evidence of anastomotic leak, bleed, or stricture formation in the present series. This procedure reduces the operative time required to perform these anastomoses in poor-risk cases.(Arch Surg 1982;117:375-376

Rapid insulin assay for intraoperative confirmation of complete resection of insulinomas

Solitary insulinomas are usually the cause of organic hypoglycemia, whereas 13% to 24% of patients with hyperinsulinemia have multiple tumors or nesidioblastosis. Intraoperative glucose levels confirming complete excision have variable accuracy. Intraoperative insulin levels have been shown to predict operative outcome. The purpose of this study was to establish criteria for predicting operative success by using a new, rapid insulin assay as an intraoperative adjunct. Eight consecutive patients with organic hypoglycemia underwent pancreatic exploration. With an 8-minute immunochemiluminescent insulin assay, peripheral blood levels were obtained preoperatively, during resection, and at 5-minute intervals after surgical excisions. Operative findings and outcome were compared with intraoperative insulin/glucose ratios (I/G), glucose, and insulin levels. By using the return of insulin levels to normal range and I/G ratios < or = 0.4 15 minutes after tumor(s) resection as criteria to predict operative success, 6 patients had their outcomes correctly predicted (5 true-positive and 1 true-negative). One patient with nesidioblastosis had a false-negative result. One could not be evaluated because of diazoxide medication. These criteria predicted postoperative absence of hypoglycemia with specificity of 100% and accuracy of 89%. These 8-minute insulin assay and criteria can be a useful adjunct for intraoperative assurance of complete insulinoma resection and prediction of postoperative outcome

Focal nodular hyperplasia in identical twins

A unique case of a focal nodular hyperplasia (FNH) in identical twins is presented. The computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen demonstrated in both twins a mass of identical size in the same segment of their liver. Histopathologic examination of both masses confirmed the diagnosis of focal nodular hyperplasia. This case report strongly supports the theory of a congenital vascular anomaly playing a major role in the etiology of focal nodular hyperplasia