Faculty Bibliography

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer type in which the mortality rate approaches the incidence rate. More than 85% of PDAC patients experience a profound loss of muscle mass and function, known as cachexia. PDAC patients with this condition suffer from decreased tolerance to anti-cancer therapies and often succumb to premature death due to respiratory and cardiac muscle wasting. Yet, there are no approved therapies available to alleviate cachexia. We previously found that upregulation of the metal ion transporter, Zip14, and altered zinc homeostasis are critical mediators of cachexia in metastatic colon, lung, and breast cancer models. Here, we show that a similar mechanism is likely driving the development of cachexia in PDAC. In two independent experimental metastasis models generated from the murine PDAC cell lines, Pan02 and FC1242, we observed aberrant Zip14 expression and increased zinc ion levels in cachectic muscles. Moreover, in advanced PDAC patients, high levels of ZIP14 in muscles correlated with the presence of cachexia. These studies underscore the importance of altered ZIP14 function in PDAC-associated cachexia development and highlight a potential therapeutic opportunity for improving the quality of life and prolonging survival in PDAC patients.

INTRODUCTION:Modern-era systemic therapy for locally advanced pancreatic adenocarcinoma (LAPC) offers improved survival relative to historical regimens but not necessarily improved radiographic downstaging to allow more patients to undergo resection. The aim of this study was to evaluate the survival, progression, and pathologic outcomes after resection of LAPC that did not regress from > 180 degrees arterial encasement after neoadjuvant therapy. METHODS:Sixty-one LAPC patients were brought to the operating room after neoadjuvant therapy for NCCN-defined unresectable pancreatic cancer between 2012 and 2017. Pts were explored with intent of pancreatectomy and irreversible electroporation for margin extension; 5 (8%) had metastatic lesions on exploratory laparoscopy and were excluded from analyses. Imaging was re-examined to confirm LAPC prior to surgery. Data were analyzed from a prospective pancreatic cancer database. RESULTS:Patients had arterial involvement of the celiac axis (37.5%) and/or superior mesenteric artery (42.9%) and/or an extended length of the common hepatic (n = 44.6%) artery. Twenty-nine males and 27 females, median 65 years of age, received neoadjuvant gemcitabine-based (58.9%) or FOLFIRINOX (35.7%) chemotherapy and stereotactic body (42.9%) or intensity-modulated (51.8%) radiation therapy. Median months from initiation of neoadjuvant therapy to surgery was 7.5. Sixty-one percent underwent Whipple, 21% distal, and 18% modified Appleby procedures; 57% patients underwent venous reconstruction. Ninety-day mortality was 2%. An R0 margin was achieved in 80%, and 53% were N0. Median overall and progression-free survival was 18.5 (95%CI 12.27-32.33) and 8.5 months (95%CI 6.0-15.0), respectively. One- and 3-year survival from surgery was 68.5% (95%CI 53.0-79.7) and 39.0% (95%CI 23.7-53.8), respectively. CONCLUSION:With modern-era neoadjuvant therapy, R0 resections can be achieved in a majority of non-metastatic patients with locally advanced, unresectable disease based on cross-sectional imaging.

In this review, we will focus on rare pancreatic tumors. Most of these tumors do not have distinct characteristic appearances so the key to diagnosis requires a combination of imaging appearance, laboratory data, patient demographics, and associated medical syndromes in order to narrow the differential diagnosis. Nonetheless, imaging plays a vital role in narrowing the differential and guiding management. While there are many variant pathologic entities that cannot be encompassed by a single review, we aim to illustrate the imaging appearance of less common pancreatic tumors highlighting key distinctive diagnostic characteristics and discuss the implications for management. While there is overlap in the imaging appearances of many of these entities, for educational purposes, lesions will be categorized into solid (hypoenhancing and hyperenhancing), cystic lesions, mesenchymal neoplasms, and neoplasms seen in younger patients (< 40 years).

Irreversible electroporation (IRE) is increasingly used for the ablation of unresectable locally advanced pancreatic adenocarcinoma. Unlike other ablation technologies that cannot be safely used around critical vasculature or ducts for risk of thermal damage, IRE uses high-voltage pulses to disrupt cellular membranes. This causes cell death by apoptosis and inflammation. IRE has been deployed by both open and percutaneous approaches. Generator parameters are the same for both approaches, and settings are pancreas specific. Variations in settings, probe placement, and probe exposure can result in thermal damage or reversible electroporation and resultant treatment failure, morbidity, or mortality. When used properly, IRE appears to improve overall survival and local recurrence, but does not influence the rate of distant recurrence. However, studies of both open and percutaneous approaches have been relatively small, non-controlled, and without appropriate comparisons. It is challenging for the radiologist to interpret treatment effects after IRE because of a dearth of guiding literature and pathologic correlates. This primer describes technical aspects, pathology correlates, post-IRE imaging, and outcomes for percutaneous and open approaches.

BACKGROUND:Central venous catheters (CVC) can be useful for perioperative monitoring and insertion has low complication rates. However, routine post insertion chest X-rays have become standard of care and contribute to health care costs with limited impact on patient management. METHODS:200 patient charts who underwent pancreaticoduodenectomy with central line placement and early line removal were reviewed for clinical complications related to central line placement as well as radiographic evidence of malpositioning. A cost analysis was performed to estimate savings if CXR had not been performed across routine surgical procedures requiring central access. RESULTS:In 200 central line placements for Whipple procedures, 198 lines were placed in the right internal jugular and 2 were placed in the subclavian. No cases of pneumothorax or hemothorax were identified and 30 (15.3%) of CVCs were improperly positioned. Only 1 (0.5%) of these was deemed clinically significant and repositioned after the CXR was performed. CONCLUSION:Routine CXR consumes valuable time and resources (≅$155,000 annually) and rarely affects management. Selection should be guided by clinical factors.

Pancreatic cancer is the fourth leading cause of cancer-related death. Early detection is challenging because symptoms are relatively nonspecific. Imaging is vital in detecting and staging pancreatic tumors, and management depends on imaging findings. Radiologists should be aware of current surgical treatments for pancreatic neoplasms, as surgeons rely on interpretation of cross-sectional imaging for presurgical planning. Understanding postsurgical anatomy is critical to assess for complications and recurrence. This review will emphasize the role of the radiologist in planning for surgery and will review postoperative changes based on surgical intervention and common complications.

Paraneoplastic neurological syndromes are rare autoimmune manifestations of malignancies associated with specific antibodies. Anti-Hu associated brainstem encephalitis, a well-described syndrome, usually presents subacutely with preferential involvement of the medulla. Anti-Hu antibodies target intraneuronal antigens and are therefore highly correlated with neurological syndromes when present concomitantly with a neoplasm. Reported is a case of anti-Hu brainstem encephalitis associated with a pancreatic neuroendocrine tumor (PNET) presenting with central hypoventilation. This is the first described case of brainstem encephalitis associated with a well-differentiated PNET as well as the first case of Anti-Hu antibodies associated with a PNET. There are no standardized protocols for the treatment of paraneoplastic brainstem encephalitis however, as in the present case, surgical resection and oncological treatment of the tumor is the first line treatment.

OBJECTIVES:To evaluate postoperative pain management (POPM) practices by anesthesiologists caring for patients with chronic kidney disease (CKD). DESIGN:Prospective one-time survey endorsed by the French Society of Anesthesia and Intensive Care (SFAR). SETTING:A self-administered online questionnaire was distributed to members of SFAR nationally. PARTICIPANTS:Three hundred seven SFAR members participated in the study. INTERVENTION:Close-ended questions concerned: standard test used to assess renal function, analgesic agent selection and dose adjustment based on the CKD functional stage, and the availability of standard operating procedures. MAIN OUTCOMES MEASURES:The primary end-point was to identify the most frequently prescribed analgesics in case of CKD, variations in practice based on different stages of CKD, and drug dosing adjustments. The secondary end-point was to identify the most commonly used tests to evaluate kidney function. RESULTS:The most commonly used postoperative analgesics were paracetamol (acetaminophen) and morphine. The most commonly used opioid was morphine, relative to oxycodone and sufentanil. Modification of diet in renal disease (MDRD) and Cockcroft equations were used by 39 and 40 percent of anesthesiologists, respectively, to measure kidney function. Six percent of anesthesiologists declared following standard operating procedures for POPM in patients with CKD. CONCLUSIONS:There is considerable variability in POPM practices for patients with all stages of CKD. Morphine is favored even in end-stage renal disease. Departments of anesthesiology are insufficiently involved in drafting standard operating procedures.

BACKGROUND:The prognosis for patients with diffuse malignant peritoneal mesothelioma has dramatically improved with cytoreductive surgery and intraperitoneal chemotherapy. Little is known about disease recurrence after treatment. We analyzed the time to and predictors of recurrence in a large cohort of optimally treated patients. METHODS:We examined 113 patients completing a two-stage cytoreduction and intraperitoneal chemotherapy protocol. All patients achieved optimal surgical resection with completeness of cytoreduction (CC) score ≤ 1 and were divided into two groups based on absence (Group A) or presence (Group B) of gross disease at the outset of the second operation. Predictors of disease recurrence and recurrence-free survival (RFS) were determined using Cox proportional hazard regression modeling, and estimates were obtained by using the Kaplan-Meier method. RESULTS:Forty-six percent of patients had no gross evidence of disease at the second operation; the remaining 54% were cytoreduced to CC ≤ 1 (Group B). Forty-two percent of patients developed disease recurrence with a median recurrence-free survival of 38.5 months for the cohort; 79% of these received a form of iterative treatment. There was no statistically significant difference in recurrence-free survival between Group A (median RFS: 44.6 months) and B (median RFS: 35.5 months) (log-rank test, p = 0.06). Additionally, the only variable significantly associated with RFS was male gender (hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.16-3.38). CONCLUSIONS:Absence of gross disease at the second operation was not statistically protective against recurrence compared with presence of quantifiable residual disease (Group B) that was effectively cytoreduced. Long-term disease surveillance is recommended, because recurrence continues years after treatment. Where a question of recurrence arises on surveillance, males may benefit from a higher degree of suspicion.

Asymptomatic pancreatic cysts are a common clinical problem but only a minority of these cases progress to cancer. Our aim was to compare the accuracy to detect malignancy of the 2015 American Gastroenterological Association (AGA), the 2012 International Consensus/Fukuoka (Fukuoka guidelines [FG]), and the 2010 American College of Radiology (ACR) guidelines.We conducted a retrospective study at 3 referral centers for all patients who underwent resection for an asymptomatic pancreatic cyst between January 2008 and December 2013. We compared the accuracy of 3 guidelines in predicting high-grade dysplasia (HGD) or cancer in resected cysts. We performed logistic regression analyses to examine the association between cyst features and risk of HGD or cancer.A total of 269 patients met inclusion criteria. A total of 228 (84.8%) had a benign diagnosis or low-grade dysplasia on surgical pathology, and 41 patients (15.2%) had either HGD (n = 14) or invasive cancer (n = 27). Of the 41 patients with HGD or cancer on resection, only 3 patients would have met the AGA guideline's indications for resection based on the preoperative cyst characteristics, whereas 30/41 patients would have met the FG criteria for resection and 22/41 patients met the ACR criteria. The sensitivity, specificity, positive predictive value, negative predictive value of HGD, and/or cancer of the AGA guidelines were 7.3%, 88.2%, 10%, and 84.1%, compared to 73.2%, 45.6%, 19.5%, and 90.4% for the FG and 53.7%, 61%, 19.8%, and 88% for the ACR guidelines. In multivariable analysis, cyst size >3 cm, compared to ≤3 cm, (odds ratio [OR] = 2.08, 95% confidence interval [CI] = 1.11, 4.2) and each year increase in age (OR = 1.07, 95% CI = 1.03, 1.11) were positively associated with risk of HGD or cancer on resection.In patients with asymptomatic branch duct-intraductal papillary mucinous neoplasms or mucinous cystic neoplasms who underwent resection, the prevalence rate of HGD or cancer was 15.2%. Using the 2015 AGA criteria for resection would have missed 92.6% of patients with HGD or cancer. The more "inclusive" FG and ACR had a higher sensitivity for HGD or cancer but lower specificity. Given the current deficiencies of these guidelines, it will be important to determine the acceptable rate of false-positives in order to prevent a single true-positive.