Neo-adjuvant FOLFIRINOX in borderline resectable and locally advanced pancreatic adenocarcinoma.

BACKGROUND: Surgery and systemic therapy provide the best option for long-term cancer control in localized resectable pancreas cancer. The present study assessed the efficacy and safety of neoadjuvant treatment with FOLFIRINOX in patients with borderline resectable (BR) and locally advanced (LA) pancreas cancer (PDAC). METHODS: This was a prospective noninterventional observational trial of neoadjuvant FOLFIRINOX in BR and LA PDAC. The primary objective was the R0/R1 surgical resection rate. Secondary objectives included progression free survival (PFS) and overall survival (OS), tolerability, and toxicity. RESULTS: Forty-nine patients were enrolled between 2013 and 2019; the majority had LA disease (59.2%). Median age was 61 years, and median Ca 19-9 level pretreatment was 523.4 µmol/L. Following neoadjuvant FOLFIRINOX, 11 patients (22.5%) underwent surgical resection, the majority of which were BR at diagnosis (72.7%). Median OS and PFS for the entire group were 25 (95% CI: 17.2-32.8) and 12 months (95% CI: 9.7-13.3), respectively. Median PFS in BR patients was 14 (95% CI: 10.5-17.5) compared to 12 months (95% CI: 5.2-18.8) in patients with LA patients. Median OS and PFS were not reached in patients who underwent surgical resection as compared to 22 (95% CI: 18.6-25.4) and 9 months (95% CI: 4.2-13.9) in those who did not, respectively. Grade 3/4 neutropenia, leukopenia, neuropathy, nausea/vomiting, and diarrhea occurred in 6.3%, 2.1%, 10.4%, 4.2%, and 8.3%, respectively. CONCLUSION: Neoadjuvant FOLFIRINOX is an active regimen for patients with LA/BR PDAC with a resection rate of 22.5%. These results are in line with prior data.

New trends in the management of hepatic Echinococcus granulosus.

The liver is the most commonly involved organ in the body by cystic echinococcosis (CE) secondary to infection with Echinococcus granulosus. In this article, the authors discuss the classification, recent advances in magnetic resonance (MR) imaging for the diagnosis of hepatic CE, and approaches for management of hepatic CE using five therapeutic options that include: antihelminthic chemotherapy, surgery, percutaneous treatment, endoscopic approach, and the "watch and wait" approach.

The outcome of cervical exploration for asymptomatic and symptomatic patients with primary hyperparathyroidism.

This study examined the success and safety of cervical exploration in patients with primary hyperparathyroidism (HPT). The presentation, pathologic findings, and outcome of patients with asymptomatic primary HPT were compared with those with symptomatic disease. Records of patients undergoing cervical exploration for primary HPT from January 1993 until December 31, 2003, were reviewed. Information collected consisted of preoperative symptoms, calcium and parathormone (PTH) levels, imaging studies, operative findings, pathology, and outcome of the patients. The groups with asymptomatic and symptomatic primary HPT were compared. In all, 139 patients were studied; 31 (22.3%) were asymptomatic (group I), and 108 (77.7%) had symptoms (group II). The two groups were also comparable regarding mean age, sex, and the yield of the imaging studies. The mean preoperative serum calcium level was comparable in the two groups (11.1 mg/dl versus 11.3 mg/dl). However, PTH levels were significantly lower in group I than in group II (142 pg/dl versus 283 pg/dl, P = 0.01). The weight of the adenoma was also significantly less in group I than in group II (1082 mg versus 1679 mg P = 0.079). The outcome of the surgical exploration was comparable in the two groups with an immediate success rate close to 98% and a long-term success rate of 95.4%. Cervical exploration and parathyroidectomy in patients with primary HPT is a safe procedure with a high success rate and favorable outcome.

Comparative pharmacokinetics and metabolic pathway of gemcitabine during intravenous and intra-arterial delivery in unresectable pancreatic cancer patients.

BACKGROUND: To study the pharmacokinetics and clinical outcome of gemcitabine (2'-2'-difluoro-deoxcytidine [dFdC]) during intra-arterial versus intravenous delivery in locally advanced and regionally metastatic pancreatic cancer. PATIENTS AND METHODS: Seven patients with unresectable pancreatic cancer received escalating intra-arterial doses of gemcitabine ranging from 800 to 1400 mg/m2, after selective embolisation of all pancreatic blood supply, except for the tumour-feeding arteries. Four patients received intravenous gemcitabine (control). Venous blood samples at different time intervals were taken throughout 270 minutes for pharmacokinetic analyses of gemcitabine and its inactive metabolite 2'-2'-difluorodeoxyuridine (dFdU). RESULTS: Pharmacokinetic data revealed differences in plasma concentrations between intra-arterial and intravenous delivery routes. The plasma concentration-time curve of gemcitabine during and after cessation of intra-arterial pancreatic target administration through the proximal splenic artery showed a profile with an area under the plasma concentration-time curve from 0 to 270 minutes (intra-arterial 29.0 +/- 0.4 vs intravenous 331.0 +/- 2.7 ng.min/mL; p < 0.0001) and peak plasma concentration (intra-arterial 1.1 +/- 0.2 vs intravenous 7.6 +/- 2.0 ng/mL; p < 0.0001) significantly lower than that for the corresponding systemic intravenous route. A plot of ln (% of dose) versus time showed a bi-compartmentalised metabolic model for intravenous administration of gemcitabine, one indicating rapid conversion of gemcitabine to dFdU, and another at a significantly lower affinity resulting in no conversion. Hence, this could be the main reason why dFdU was not detected in the systemic circulation during pancreatic intra-arterial target delivery. Furthermore, during intravenous administration a pseudo first-order rate constant ( approximately 0.20 min(-)(1)) for in vivo conversion of gemcitabine to dFdU was estimated, indicating a rapid cellular deamination which was not shown in the intra-arterial route. Clinically, one patient had a partial response and six patients had a stable disease after intra-arterial administration of gemcitabine. The median time to disease progression was 4 months and the median overall survival was 5 months. One patient survived for 26 months. No grade III or IV toxicity was documented. CONCLUSION: Intra-arterial administration of gemcitabine has a major advantage related to reduced toxicity as increasing the dose through this administration route will eventually result in pancreatic cellular drug target delivery prior to systemic availability. Despite the low number of patients recruited, the clinical results are encouraging and this approach should be tested in a randomised study.