**9. Conclusion**

recommend that at least 11 lymph nodes are retrieved and examined. Gleisner and colleagues showed an association between TNLE and overall survival, but the association was not uniform through time at their institution. Standards of care improved. We have found that less than 12

The standard chemotherapy regimen for advanced pancreatic cancer has historically been monotherapy with gemcitabine [49]. In patients with metastatic PDAC, gemcitabine with nab‐ paclitaxel improved median overall survival (8.5 vs 6.7 months, HR = 0.72, *p* < 0.001), one‐year survival (35 vs 22%), two‐year survival (9 vs 4%), and improved objective response rate (23 vs 7%) when compared with gemcitabine alone [50]. The most common Grade 3 or higher toxicity

Given that the majority of patients who undergo resection with curative intent relapse within 2 years [51], the CONKO‐001 trial set to evaluate the efficacy of gemcitabine as adjuvant therapy

follow‐up of 136 months, patients treated with gemcitabine had an increased median disease‐ free survival (13.4 vs 6.7 months, HR, 0.55 [95% CI, 0.44–0.69]; *p* < 0.001) and prolonged overall survival (HR, 0.76 [95% CI, 0.61–0.95]; *p* = 0.01) versus those patients who were only observed after resection. In 2010, a randomized controlled trial compared the use of fluorouracil plus folinic acid versus gemcitabine as adjuvant chemotherapy. There was no difference in survival between the two treatments [52]. Although alternative chemotherapy regimens have since emerged, utilizing other agents as either monotherapy or in combination with gemcitabine,

There has been increased interest in the use of neoadjuvant therapy for the treatment of pancreatic adenocarcinoma given the potential for better treatment tolerance, improved delivery to an undisturbed tumor bed, avoidance of delay in therapy, treatment of occult micrometastatic disease, and the potential of down staging borderline/unresectable tumors. In a meta‐analysis evaluating 14 Phase II trials involving gemcitabine and 5‐FU chemotherapy regimens (either as monotherapy or combination therapy), there was no difference in local recurrence between patients who were initially considered resectable prior to systemic therapy and those who were not. Only 1.8% of patients had a complete tumor response, while 18.8% of all patients had partial tumor response based on RECIST criteria or criteria defined by the authors of each respective study. Pathologic response was not reported. While there was no difference in survival between the groups of patients deemed resectable pretreatment and those determined to be unresectable, approximately one‐third of tumors initially classified as borderline/unresectable were suitable for resection after neoadjuvant therapy

Despite the lack of Phase III trials addressing neoadjuvant therapy, it is important to emphasize its role in selecting patients who will be good surgical candidates once restaged after comple‐ tion of treatment. It not only allows for better patient selection based on tumor biology, but

on day 1, 8, and 15 every 4 weeks for 6 months. After a median

lymph nodes are inadequate lymphadenectomy [48].

events were neutropenia, fatigue, and neuropathy.

few studies have demonstrated significantly improved results [24].

administered as a dose of 1 g/m2

[53].

**8. Therapeutics**

172 Challenges in Pancreatic Pathology

Pancreas adenocarcinoma is an aggressive malignancy. Progression to a multidisciplinary approach to diagnosis, treatment, and perioperative patient management can improve patient outcomes. This can be achieved through the implementation of state‐of‐the‐art diagnostic modalities, including imaging and endoscopic procedures, as well as the application of enhanced recovery pathways that address every aspect of the treatment process from preop‐ erative patient optimization to postoperative rehabilitation. Advances in surgical technique, particularly the use of laparoscopy and robotic‐assisted surgery, also provide benefits to patients without compromising oncologic outcomes. Lastly, advancements in systemic chemotherapy, although slower in progression, have shown some improvement in survival when combined with surgical resection and offer a treatment alternative to patients with advanced disease who are not surgical candidates.
