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Metastasectomy with curative intent has become standard practice for the management of some malignancies. Resection of isolated metastatic colorectal cancer, gastrointestinal stromal tumours, neuroendocrine cancers, renal-cell cancer and sarcoma is associated with longer survival or even cure. The strongest evidence in favour of metastasectomy exists for colorectal cancer, in which resection of limited metastatic disease in some patients is associated with 5-year survival rates of more than 50%. 1–3 High incidence of the disease, predictable tumour biology, and development of successful chemotherapies have encouraged metastasectomy. Furthermore, improved safety of complex surgeries over the past several decades has lowered the threshold for more aggressive surgical intervention. Most literature on metastasectomy pertains to the resection of disease involving the liver, lung, and brain. However, metastasectomy has been described for almost every organ system, including the pancreas. In this Review, we discuss resection of isolated cancer metastases to the pancreas. Pancreatic metastasectomy is most often done through a formal pancreatic resection such as pancreaticoduodenectomy or distal pancreatectomy. Less often, pancreatic metastasectomy is done by enucleation or a pancreas sparing operation such as a central pancreatectomy.

Pancreatic cystic neoplasms (PCN) are a heterogeneous group of pancreatic cysts that include intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, serous cystic neoplasms and other rare cystic lesions, all with different biological behaviours and variable risk of progression to malignancy. As more pancreatic cysts are incidentally discovered on routine cross-sectional imaging, optimal surveillance for patients with PCN is becoming an increasingly common clinical problem, highlighting the need to balance cancer prevention with the risk of (surgical) overtreatment. This Review summarizes the latest developments in the diagnosis and management of PCN, including the quality of available evidence. Also discussed are the most important differences between the PCN guidelines from the American Gastroenterological Association, the International Association of Pancreatology and the European Study Group on Cystic Tumours of the Pancreas, including diagnostic and follow-up strategies and indications for surgery. Finally, new developments in the management of patients with PCN are addressed.

Objective: Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy, due in large part to its resistance to conventionaltherapies, including radiotherapy (RT). Despite RT exerting a modest antitumor response, it has also been shown to promote animmunosuppressive tumor microenvironment. Previous studies demonstrated that focal adhesion kinase inhibitors (FAKi) inclinical development inhibit the infiltration of suppressive myeloid cells and T regulatory (T regs) cells, and subsequently enhanceeffector T cell infiltration. FAK inhibitors in clinical development have not been investigated in combination with RT in preclinicalmurine models or clinical studies. Thus, we investigated the impact of FAK inhibition on RT, its potential as an RT sensitizer andimmunomodulator in a murine model of PDAC. Methods: We used a syngeneic orthotopic murine model to study the effect of FAKi on hypofractionated RT. Results: In this study we showed that IN10018, a small molecular FAKi, enhanced antitumor response to RT. Antitumor activity ofthe combination of FAKi and RT is T cell dependent. FAKi in combination with RT enhanced CD8+ T cell infiltration significantlyin comparison to the radiation or FAKi treatment alone (P < 0.05). FAKi in combination with radiation inhibited the infiltrationof granulocytes but enhanced the infiltration of macrophages and T regs in comparison with the radiation or FAKi treatment alone(P < 0.01). Conclusions: These results support the clinical development of FAKi as a radiosensitizer for PDAC and combining FAKi with RT toprime the tumor microenvironment of PDAC for immunotherapy.

Pancreatic cancer is currently one of the deadliest of the solid malignancies. However, surgery to resect neoplasms of the pancreas is safer and less invasive than ever, novel drug combinations have been shown to improve survival, advances in radiation therapy have resulted in less toxicity, and enormous strides have been made in the understanding of the fundamental genetics of pancreatic cancer. These advances provide hope but they also increase the complexity of caring for patients. It is clear that multidisciplinary care that provides comprehensive and coordinated evaluation and treatment is the most effective way to manage patients with pancreatic cancer. [PUBLICATION ABSTRACT]

Background While sarcopenia is typically defined using total psoas area (TPA), characterizing sarcopenia using only a single axial cross-sectional image may be inadequate. We sought to evaluate total psoas volume (TPV) as a new tool to define sarcopenia and compare patient outcomes relative to TPA and TPV. Method Sarcopenia was assessed in 763 patients who underwent pancreatectomy for pancreatic adenocarcinoma between 1996 and 2014. It was defined as the TPA and TPV in the lowest sex-specific quartile. The impact of sarcopenia defined by TPA and TPV on overall morbidity and mortality was assessed using multivariable analysis. Result Median TPA and TPV were both lower in women versus men (both P  < 0.001). TPA identified 192 (25.1 %) patients as sarcopenic, while TPV identified 152 patients (19.9 %). Three hundred sixty-nine (48.4 %) patients experienced a postoperative complication. While TPA-sarcopenia was not associated with higher risk of postoperative complications (OR 1.06; P  = 0.72), sarcopenia defined by TPV was associated with morbidity (OR 1.79; P  = 0.002). On multivariable analysis, TPV-sarcopenia remained independently associated with an increased risk of postoperative complications (OR 1.69; P  = 0.006), as well as long-term survival (HR 1.46; P  = 0.006). Conclusion The use of TPV to define sarcopenia was associated with both short- and long-term outcomes following resection of pancreatic cancer. Assessment of the entire volume of the psoas muscle (TPV) may be a better means to define sarcopenia rather than a single axial image.

Pancreatic neuroendocrine tumors (PanNETs) are a rare but clinically important form of pancreatic neoplasia. To explore the genetic basis of PanNETs, we determined the exomic sequences of 10 nonfamilial PanNETs and then screened the most commonly mutated genes in 58 additional PanNETs. The most frequently mutated genes specify proteins implicated in chromatin remodeling: 44% of the tumors had somatic inactivating mutations in MEN1, which encodes menin, a component of a histone methyltransferase complex, and 43% had mutations in genes encoding either of the two subunits of a transcription/chromatin remodeling complex consisting of DAXX (death-domain-associated protein) and ATRX (α thalassemia/mental retardation syndrome X-linked). Clinically, mutations in the MEN1 and DAXX/ATRX genes were associated with better prognosis. We also found mutations in genes in the mTOR (mammalian target of rapamycin) pathway in 14% of the tumors, a finding that could potentially be used to stratify patients for treatment with mTOR inhibitors.

Introduction Assessing patient-specific risk factors for long-term mortality following resection of pancreatic adenocarcinoma can be difficult. Sarcopenia—the measurement of muscle wasting—may be a more objective and comprehensive patient-specific factor associated with long-term survival. Methods Total psoas area (TPA) was measured on preoperative cross-sectional imaging in 557 patients undergoing resection of pancreatic adenocarcinoma between 1996 and 2010. Sarcopenia was defined as the presence of a TPA in the lowest sex-specific quartile. The impact of sarcopenia on 90-day, 1-year, and 3-year mortality was assessed relative to other clinicopathological factors. Results Mean patient age was 65.7 years and 53.1 % was male. Mean TPA among men (611 mm 2 /m 2 ) was greater than among women (454 mm 2 /m 2 ). Surgery involved pancreaticoduodenectomy (86.0 %) or distal pancreatectomy (14.0 %). Mean tumor size was 3.4 cm; 49.9 % and 88.5 % of patients had vascular and perineural invasion, respectively. Margin status was R0 (59.0 %) and 77.7 % patients had lymph node metastasis. Overall 90-day mortality was 3.1 % and overall 1- and 3-year survival was 67.9 % and 35.7 %, respectively. Sarcopenia was associated with increased risk of 3-year mortality (HR = 1.68; P  < 0.001). Tumor-specific factors such as poor differentiation on histology (HR = 1.75), margin status (HR = 1.66), and lymph node metastasis (HR = 2.06) were associated with risk of death at 3-years (all P  < 0.001). After controlling for these factors, sarcopenia remained independently associated with an increased risk of death at 3 years (HR = 1.63; P  < 0.001). Conclusions Sarcopenia was a predictor of survival following pancreatic surgery, with sarcopenic patients having a 63 % increased risk of death at 3 years. Sarcopenia was an objective measure of patient frailty that was strongly associated with long-term outcome independent of tumor-specific factors.

Background The impact of postoperative complications on the administration of adjuvant therapy following pancreaticoduodenectomy (PD) for adenocarcinoma is still unclear. Methods A retrospective review of all patients undergoing PD at our institution between 1995 and 2011 was performed. Clinicopathological data, including Clavien–Dindo complication grade, time to adjuvant therapy (TTA), and survival, were analyzed. Results A total of 1,144 patients underwent PD for adenocarcinoma between 1995 and 2011. The overall complication rate was 49.1 % and clinically severe complications (≥IIIb) occurred in 4.2 %. Overall, 621 patients (54.3 %) were known to have received adjuvant therapy. The median TTA was 60 days. Although the presence of a complication was associated with a delay in TTA ( p   =  0.002), the grade of complication was not ( p   =  0.112). On multivariate analysis, only age > 68 years ( p   <  0.001) and length of stay >9 days ( p   =  0.002) correlated with no adjuvant therapy. Patients with postoperative complications were more likely to receive single adjuvant chemotherapy or radiation therapy (31.4 %) than were patients without complications (17.1 %; p   <  0.001). Patients without a complication had a longer median survival compared with patients who experienced complications (19.5 vs. 16.1 months; p   =  0.001). Patients without complications who received adjuvant therapy had longer median survival than patients with complications who received no adjuvant therapy (22.5 vs. 10.7 months; p   <  0.001). Multivariate analysis demonstrated that complications [hazard ratio (HR) 1.16; p   =  0.023] and adjuvant therapy (HR 0.67; p   <  0.001) were related to survival. Conclusion Complications and no adjuvant therapy are common following PD for adenocarcinoma. Postoperative complications delay TTA and reduce the likelihood of multimodality adjuvant therapy. Identifying patients at increased risk for complications and those unlikely to receive adjuvant therapy warrants further investigation as they may benefit from a neoadjuvant approach.

Introduction Robotic pancreaticoduodenectomy is slowly gaining acceptance within pancreatic surgery. Advantages have been demonstrated for robotic surgery in other fields, but robust data for pancreaticoduodenectomy is limited. The aim of this study was to compare the short-term outcomes of robotic pancreaticoduodenectomy (RPD) to open pancreaticoduodenectomy (OPD) and laparoscopic pancreaticoduodenectomy (LPD). Methods Patients who underwent a pancreaticoduodenectomy between January 2011 and July 2019 at the Johns Hopkins Hospital were included in this retrospective propensity-matched analysis. The RPD cohort was matched to patients who underwent OPD in a 1:2 fashion and LPD in a 1:1 fashion. Short-term outcomes were analyzed for all three cohorts. Results In total, 1644 patients were included, of which 96 (5.8%) underwent RPD, 131 (8.0%) LPD, and 1417 (86.2%) OPD. RPD was associated with a decreased incidence of delayed gastric emptying (9.4%) compared to OPD (23.5%; P = 0.006). The median estimated blood loss was significantly less in the RPD cohort (RPD vs OPD, 150 vs 487 mL; P < 0.001, RPD vs LPD, 125 vs 300 mL; P < 0.001). Compared to OPD, the robotic approach was associated with a shorter median length of stay (median 8 vs 9 days; P = 0.014) and a decrease in wound complications (4.2% vs 16.7%; P = 0.002). The incidence of other postoperative complications was comparable between RPD and OPD, and RPD and LPD. Conclusion In the hands of experienced surgeons, RPD may have a modest yet statistically significant reduction in estimated blood loss, postoperative length of stay, wound complications, and delayed gastric emptying comparing to OPD in similar patients.

BackgroundAfter radical resection of pancreatic ductal adenocarcinoma (PDAC), approximately 80% of patients will develop disease recurrence. It remains unclear to what extent the location of recurrence carries prognostic significance. Additionally, stratifying the pattern of recurrence may lead to a deeper understanding of the heterogeneous biological behavior of PDAC.ObjectiveThe aim of this study was to characterize the relationship of recurrence patterns with survival in patients with resected PDAC.MethodsThis single-center cohort study included patients undergoing pancreatectomy at the Johns Hopkins Hospital between 2000 and 2013. Exclusion criteria were neoadjuvant therapy and incomplete follow-up. Sites of first recurrence were stratified into five groups and survival outcomes were estimated using Kaplan–Meier curves. The association of specific recurrence locations with overall survival (OS) was analyzed using Cox proportional-hazards models with and without landmark analysis.ResultsAccurate follow-up data were available for 877 patients, 662 (75.5%) of whom had documented recurrence at last follow-up. Patients with multiple-site (n = 227, 4.7 months) or liver-only recurrence (n = 166, 7.2 months) had significantly worse median survival after recurrence when compared with lung- (n = 93) or local-only (n = 158) recurrence (15.4 and 9.7 months, respectively). On multivariable analysis, the unique recurrence patterns had variable predictive values for OS. Landmark analyses, with landmarks set at 12, 18, and 24 months, confirmed these findings.ConclusionsThis study demonstrates that specific patterns of PDAC recurrence result in different survival outcomes. Furthermore, distinct first recurrence locations have unique independent predictive values for OS, which could help with prognostic stratification and decisions regarding treatment after the diagnosis of recurrence.