Faculty Bibliography

BACKGROUND:Consensus guidelines discourage resection of poorly differentiated pancreatic neuroendocrine carcinoma (panNEC) given its association with poor long-term survival. This study assessed treatment patterns and outcomes for this rare malignancy using the National Cancer Database (NCDB). METHODS:Patients with non-functional pancreatic neuroendocrine tumors in the NCDB (2004-2016) were categorized based on pathologic differentiation. Logistic and Cox proportional hazard regressions identified associations with resection and overall survival (OS). Survival was compared using Kaplan-Meier and log-rank tests. RESULTS:Most patients (83%) in the cohort of 8560 patients had well-differentiated tumors (panNET). The median OS was 47 months (panNET, 63 months vs panNEC, 17 months; p < 0.001). Surgery was less likely for older patients (odds ratio [OR], 0.97), patients with panNEC (OR, 0.27), and patients with metastasis at diagnosis (OR, 0.08) (all p < 0.001). After propensity score-matching of these factors, surgical resection was associated with longer OS (82 vs 29 months; p < 0.001) and a decreased hazard of mortality (hazard ratio [HR], 0.37; p < 0.001). Surgery remained associated with longer OS when stratified by differentiation (98 vs 41 months for patients with panNET and 36 vs 8 months for patients with panNEC). Overall survival did not differ between patients with panNEC who underwent surgery and patients with panNET who did not (both 39 months; p = 0.294). CONCLUSIONS:Poorly differentiated panNEC exhibits poorer survival than well-differentiated panNET. In the current cohort, surgical resection was strongly and independently associated with improved OS, suggesting that patients with panNEC who are suitable operative candidates should be considered for multimodality therapy, including surgery.

Minimally invasive liver resection (MILR) is increasingly used as a surgical treatment for patients with hepatocellular carcinoma (HCC). However, there is no large scale data to compare the effectiveness of MILR in comparison to open liver resection (OLR). We identified patients with stage I or II HCC from the National Cancer Database using propensity score matching techniques. Overall, 1931 (66%) and 995 (34%) patients underwent OLR or MILR between 2010 and 2015. After propensity matching, 5-year OS was similar in the MILR and OLR group (51.7% vs. 52.8%, p = 0.766). MILR was associated with lower 90-day mortality (5% vs. 7%, p = 0.041) and shorter length of stay (4 days vs. 5 days, p < 0.001), but higher rates of positive margins (6% vs. 4%, p = 0.001). An operation at an academic institution was identified as an independent preventive factor for a positive resection margin (OR 0.64: 95% CI 0.43-0.97) and 90-day mortality (OR 0.61; 95% CI 0.41-0.91). MILR for HCC is associated with similar overall survival to OLR, with the benefit of improved short term postoperative outcomes. The increased rate of positive margins after MILR requires further investigation, as do the differences in perioperative outcomes between academic and nonacademic institutions.

The traditional approach to penetrating injuries to zone II of the neck has included operative neck exploration, extensive enough to allow for proximal and distal vascular control of the potential vascular injury. Few studies have reported cases of entirely endovascular management of penetrating injury to this portion of the neck. In the present case report, we describe the case of a 38-year-old man who had sustained a stab wound to zone II of the neck. The injury to the internal carotid artery was managed endovascularly with placement of a covered stent. The findings from the present case illustrate the potential use of minimally invasive vascular treatment strategies as an alternative to mandated operative intervention.

Objective: The traditional approach to penetrating injuries to zone 2 of the neck includes neck exploration extensive enough to allow proximal and distal vascular control of potential vascular injury.¹ Only a few recent case reports have been published on the use of covered stents in traumatic internal carotid artery (ICA) injury with good functional results.^2,3 Some centers have studied nonoperative management of venous injury in the neck after penetrating trauma, but no reports of endovascular evaluation of the venous system in penetrating neck trauma exist.⁴ Methods: A 38-year-old man presented to the emergency department with a 2-cm laceration to the right posterior triangle of the neck. Glasgow Coma Scale score on presentation was 12. With no overt signs of hemorrhage, a computed tomography angiogram was obtained, showing hematoma surrounding the right ICA with irregularity and tapering of the true lumen at the level of C2 to approximately 70%. Delayed-phase imaging suggested injury to the right internal jugular vein. After the wound was cleaned in the emergency department, a hematoma started to develop along the right jawline with brisk bleeding from the laceration site, and the patient was taken emergently to the operating room.
Result(s): The entire damaged segment of the ICA was stented with a Viabahn covered stent (Figs 1-3). Three segments of the right internal jugular vein (intracranial segment, neck segment, and intrathoracic segment) were imaged through the right femoral vein, which demonstrated no clots or extravasation. The wound was explored locally, and esophagogastroduodenoscopy and bronchoscopy were performed, showing no injury to the esophagus, larynx, or trachea. The patient recovered well without neurologic deficit. Carotid duplex ultrasound performed postoperatively demonstrated no hemodynamically significant flow disturbance in the right ICA.
Conclusion(s): The case demonstrates an opportunity for endovascular evaluation and management of traumatic vascular injury in zone 2 of the neck with close collaboration with trauma surgeons. [Figure presented] [Figure presented] [Figure presented]
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Mainstay treatment for Plasmodium vivax malaria has long relied on chloroquine (CQ) against blood-stage parasites plus primaquine against dormant liver-stage forms (hypnozoites), however drug resistance confronts this regimen and threatens malaria control programs. Understanding the basis of P. vivax chloroquine resistance (CQR) will inform drug discovery and malaria control. Here we investigate the genetics of P. vivax CQR by a cross of parasites differing in drug response. Gametocytogenesis, mosquito infection, and progeny production are performed with mixed parasite populations in nonhuman primates, as methods for P. vivax cloning and in vitro cultivation remain unavailable. Linkage mapping of progeny surviving >15 mg/kg CQ identifies a 76 kb region in chromosome 1 including pvcrt, an ortholog of the Plasmodium falciparum CQR transporter gene. Transcriptional analysis supports upregulated pvcrt expression as a mechanism of CQR.

BACKGROUND:Current readmission rates do not account for readmissions to nonindex hospitals and may underestimate the actual burden of readmissions. OBJECTIVE:Using a nationally representative database, we sought to characterize nonindex readmissions following bariatric surgery and identify risk factors associated with readmission to a nonindex hospital. SETTING/METHODS:Patients in the United States undergoing elective bariatric surgery. METHODS:The Nationwide Readmissions Database was used to identify a weighted sample of 545,377 patients undergoing elective bariatric surgery between 2010 and 2014. Multivariable logistic regression analysis was used to identify factors associated with readmission to a nonindex hospital. RESULTS:Among all patients, 5.6% were readmitted at least once within 30 days. Within the subgroup of patients who were readmitted, 17.6% were readmitted to a different hospital than the index admission hospital. Factors independently associated with higher odds of readmission to a nonindex hospital were primary payor (Medicare: odds ratio [OR] = 1.48, 95% confidence interval [CI]: 1.24-1.75; Medicaid: OR = 1.56, 95% CI: 1.26-1.95), All Patients Refined Diagnosis Related Group severity of illness score (extreme versus minor: OR = 1.48; 95% CI: 1.04-2.09), primary procedure (laparoscopic sleeve gastrectomy versus laparoscopic gastric bypass: OR = 1.23; 95% CI: 1.05-1.44), hospital bed size (reference: small hospital, medium: OR = .52, 95% CI: .39-.70; large: OR = .47, 95% CI: .35-.63), hospital ownership (reference: private, nonprofit hospital, government: OR = 1.77, 95% CI: 1.32-2.37; private, investor-owned: OR = 1.33, 95% CI: 1.07-1.64), and hospital location (reference: metropolitan area >1 million population, metropolitan <1 million population: OR = .44, 95% CI: .34-.56; micropolitan/rural: OR = .44, 95% CI: .27-.73). CONCLUSION/CONCLUSIONS:Failure to account for readmissions to different hospitals may underestimate readmission rates by approximately 18%.

Concerns about malaria parasite resistance to treatment with artemisinin drugs (ARTs) have grown with findings of prolonged parasite clearance t_1/2s (>5 h) and their association with mutations in Plasmodium falciparum Kelch-propeller protein K13. Here, we describe a P. falciparum laboratory cross of K13 C580Y mutant with C580 wild-type parasites to investigate ART response phenotypes in vitro and in vivo. After genotyping >400 isolated progeny, we evaluated 20 recombinants in vitro: IC₅₀ measurements of dihydroartemisinin were at similar low nanomolar levels for C580Y- and C580-type progeny (mean ratio, 1.00; 95% CI, 0.62-1.61), whereas, in a ring-stage survival assay, the C580Y-type progeny had 19.6-fold (95% CI, 9.76-39.2) higher average counts. In splenectomized Aotus monkeys treated with three daily doses of i.v. artesunate, t_1/2 calculations by three different methods yielded mean differences of 0.01 h (95% CI, -3.66 to 3.67), 0.80 h (95% CI, -0.92 to 2.53), and 2.07 h (95% CI, 0.77-3.36) between C580Y and C580 infections. Incidences of recrudescence were 57% in C580Y (4 of 7) versus 70% in C580 (7 of 10) infections (-13% difference; 95% CI, -58% to 35%). Allelic substitution of C580 in a C580Y-containing progeny clone (76H10) yielded a transformant (76H10^C580Rev) that, in an infected monkey, recrudesced regularly 13 times over 500 d. Frequent recrudescences of ART-treated P. falciparum infections occur with or without K13 mutations and emphasize the need for improved partner drugs to effectively eliminate the parasites that persist through the ART component of combination therapy.