Predictors of Timely Initiation and Completion of Adjuvant Chemotherapy in Stage II/III Colorectal Adenocarcinoma.

Background: Adjuvant chemotherapy (AC) for colorectal cancer (CRC) has led to substantial improvement in survival. Several clinical trials advocate the initiation of AC within 6-8 weeks of surgical resection based on evidence of improved survival with early initiation of AC. We aim to evaluate factors that predict initiation and completion of AC, subsequently improving survival. Methods: We identified 451 patients who underwent resection for CRC between 2014 and 2022. One hundred ten patients had stage II/III colorectal cancer who underwent resection followed by AC. Multivariable logistic regression analysis was performed to identify factors significantly predicting delay in AC >8 weeks. Secondary outcomes included chemotherapy completion rate, recurrence-free survival, and overall survival. Results: The final analysis included 110 patients. The median time to initiation of adjuvant chemotherapy (TIAC) was 6.9 weeks (IQR: 5.8-9.5). In total, 36.4% of patients had a delay >8 weeks to initiation of AC, and only 40% completed treatment. The surgical approach (open vs laparoscopic vs robotic) had no effect on the TIAC. On multivariable logistic regression analysis, preoperative albumin ≥3.5 (OR = .31; 95% CI: .12-.80) was an independent predictor of timely initiation of AC. Completion of AC was associated with a higher overall survival. Discussion: Preoperative nutritional status predicted delay in initiation of AC. Patients with a delay in AC beyond eight weeks had a lower rate of AC completions and worse survival. It is imperative to optimize this aspect of treatment as it correlates with survival.

Low Rates of Colorectal Cancer Screening in Our Patients' First-Degree Relatives: Are We Failing Them?

BACKGROUND: Guidelines recommend screening those with a family history of early-onset colorectal cancer at age 40 or 10 years before the age of their relative's diagnosis. Currently, there is no literature reporting the screening rate in these individuals and no protocols are in place to identify and target this population for screening awareness. OBJECTIVE: Assess adherence to current screening guidelines among FDRs of patients with early-onset colorectal cancer. DESIGN: Retrospective and qualitative study involving a telephone survey where patients were asked about relative's screening status and barriers to screening. SETTINGS: Two community-based institutions between January 2018-December 2021. PATIENTS: Individuals diagnosed with early-onset colorectal cancer who had undergone surgery at our institutions. MAIN OUTCOME MEASURES: Rate of screening in first-degree relatives of our patients with early-onset colorectal cancer. Other factors measured included demographics, clinicopathologic characteristics and screening barriers. RESULTS: Thirty-six patients were identified. Survey response rate was 66.6% (n=24). A total of 88 first-degree relatives who met criteria for screening resulted, with 67.1% (n=59) having a known screening status. Of the 59 with known screening status, it was reported that only 44% (n=26) have undergone screening. Patients of African American race, stage III/IV disease, Medicare/Medicaid and living within Baltimore City County were more likely to have family members with unknown or no screening. Lack of insurance coverage was the most common barrier noted 12.5% (n=3); whereas 54.1% (n=13) reported no barriers to screening. LIMITATIONS: Retrospective design. CONCLUSIONS: Most first-degree relatives of patients diagnosed with early-onset colorectal cancer do not undergo colorectal cancer screening. This could be attributed to the lack of protocols that could guarantee these individuals are informed of their elevated risk and the different options available for screening. Furthermore, our study suggests that racial and socioeconomic disparities exist among high-risk patients who should pursue screening. See Video Abstract.

Risk factors for post-operative VTE following colorectal surgery: Is caprini score enough?

BACKGROUND: Post-operative colorectal venous thromboembolism (VTE) rates range between 1 and 3%. Often, surgeons utilize risk assessment models, like the modified Caprini, to determine need for prophylaxis. However, studies reveal additional unaccounted risk factors like preoperative serum albumin level, perioperative blood transfusion, emergency surgery, and preoperative steroid use. METHODS: This was a multicenter, retrospective study conducted between January 2021-December 2021. The primary endpoint was to assess the VTE rate within 30 days post-operatively. RESULTS: Overall, incidence rate was 1.75%. Of these, 53% underwent urgent/emergent surgery and 60% had perioperative blood transfusions. Twelve patients had a known preoperative serum albumin level, with 66% being less than 3.5 â€‹g/dL. Only 30% of patients had a high Caprini risk score. No patient had preoperative steroid use. CONCLUSION: The study suggests considering urgent/emergent surgeries, low preoperative albumin levels, and blood transfusions for enhanced VTE screening and prophylaxis in post-operative colorectal patients.

Intraoperative Radiation Therapy as a Safe Alternative to Whole Breast Radiation for Treatment of Minimally Invasive Breast Cancers: A Retrospective Cohort Study.

BACKGROUND: Intraoperative radiation therapy (IORT) in select populations is a viable alternative to whole breast radiation therapy (WBRT) in the treatment of biopsy-proven localized invasive and non-invasive breast cancer. We aim to assess recurrence and complication rates following IORT in lumpectomy patients at a community hospital in Baltimore City. METHODS: An IRB-approved retrospective cohort study was conducted on consecutive cases of lumpectomy with IORT from 2013 through 2020 by a single surgeon. Patient demographics, tumor and operative characteristics, and complications were retrieved from electronic medical records. Primary outcomes were postoperative complications and local recurrence rates. RESULTS: The final cohort included 117 patients with mean follow-up time of 2.60 + 1.78 years. Mean age was 69.84 + 8.77 years. Thirty-three (28.21%) of patients developed a seroma. Odds of seroma formation were mildly significant for skin spacing [OR: 1.18, 95% CI: (1.02-1.37)] and balloon fill volume [1.04 (1.00-1.08)], but not for age, BMI, diabetes, former or current smoking status, history of WBRT, tumor size, or balloon size. Three (2.6%) patients had local recurrence. Odds of local recurrence were mildly significant for increased tumor size [1.14 (1.04-1.24)] and not significant for any other covariates. CONCLUSIONS: IORT exposure did not confer higher rates of complications and the local recurrence rate mirrored that of the general population undergoing lumpectomy and WBRT. This study demonstrates the need for equitable treatment options based on individual needs: IORT is a safe alternative to WBRT in certain subpopulations, especially those with physical, social, or personal limitations preventing participation in a 3- to 7-week time commitment of WBRT.

Impact of Surgical Resident Education and EMR Standardization in Enhancing ERAS Adherence and Outcomes in Colorectal Surgery.

OBJECTIVE: Our study aimed at investigating the degree of adherence to ERAS pathway at our institution and to evaluate the role of providing resident education and a standardized EMR order set in improving adherence and patient surgical outcomes. DESIGN: The study is prospective in nature and consists of two phases with a preintervention cohort to assess adherence to ERAS protocol and a postintervention cohort to evaluate improvement in adherence and patient outcomes. Adherence with the ERAS protocol was assessed across preoperative, intraoperative, and postoperative phases. SETTING: The study took place at MedStar Franklin Square Medical Center in Baltimore, Maryland, involving inpatient care at a surgical ward. PARTICIPANTS: During the preintervention phase, patients undergoing elective colorectal surgery were identified over 6 months (N = 77), and their adherence to the ERAS protocol was assessed. Following the intervention of surgical resident and faculty education sessions on the ERAS protocol and the implementation of a standardized order set in the Electronic Medical Record, a postintervention cohort (N = 54) was selected for comparison over another 6 months. RESULTS: Among 77 patients who underwent elective colorectal surgery, the adherence rate to ERAS protocol was notably below 80% for most elements of the postoperative phase. When pre- and postintervention cohorts were compared, there were no significant differences in the baseline demographics and perioperative variables. After the implementation of our intervention, adherence rates were significantly improved in 7 out of 8 ERAS protocol elements of the postintervention phase. Among primary outcome measures, readmission rate (24.7% vs.9.4%; p = 0.022) and length of stay (7.3 ± 4.5 vs. 5.5 ± 3.6; p = 0.014) were significantly lower in the postintervention cohort. Although the rate of postoperative complications did not decrease significantly (33.8% vs. 31.5%; p = 0.284), there were fewer patients with postoperative ileus and surgical site infections. Outcomes were evaluated based on an 8-point score of postoperative ERAS elements. A significant decrease in mean length of stay and readmission rates is observed when at least 5 elements are completed, emphasizing the ERAS pathway's importance as a complementary bundle. CONCLUSION: Our study highlights the impact of resident education and electronic medical record standardization on ERAS adherence in colorectal surgery. This multidisciplinary approach improves adherence, reduces hospital stay, and enhances communication among healthcare providers for better patient outcomes.

Detecting Somatic Mutations for Well-Differentiated Pancreatic Neuroendocrine Tumors in Endoscopic Ultrasound-Guided Fine Needle Aspiration with Next-Generation Sequencing.

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) exhibit heterogenous behavior, whereby some small tumors are aggressive with a propensity for metastasis. Detection of somatic mutations associated with aggressive biology may help with patient stratification and surgical decision-making in patients with well-differentiated PanNETs. Using next-generation sequencing (NGS), we investigated the feasibility of detecting somatic mutations in endoscopic ultrasound-guided, fine-needle aspiration (EUS-FNA) specimens and determining the mutational concordance between the EUS-FNA specimens and the primary tumors. METHODS: Thirty-eight patients with well-differentiated, nonfunctioning PanNETs were obtained from two tertiary referral centers. Patient demographic characteristics and tumor, clinicopathologic features were collected. Tissue from both the EUS-FNA specimen and the primary tumor was extracted from archival tissue blocks. NGS using a panel of ten genes was performed on both samples. RESULTS: In our series, the median age was 61.1 years. Tumors were predominantly left-sided (60.5%) and unifocal (94.7%). The median tumor size was 2.2 cm. NGS detected somatic mutations in 29% of primary tumors and 36.8% of EUS-FNA specimens. In primary tumors, DAXX/ATRX mutations were predominantly detected (63.6%). In EUS-FNA specimens, MEN1 mutations were predominantly detected (64.3%). Among non-wild-type specimens, mutational concordance was achieved in 31.6% of cases. In 11 patients with a detectable mutation in the primary tumor, a mutation was detected in the EUS-FNA specimen in 45.5% of cases, with a mutational concordance of 54.5%. CONCLUSIONS: NGS can detect somatic mutations in EUS-FNA specimens of well-differentiated PanNETs. Efforts to improve detection sensitivity and mutational concordance are required to overcome current technical limitations.

Robot-Assisted Diagnostic Laparoscopy: A Safe and Feasible Adjunct to the Management of Massive Spontaneous Pneumoperitoneum.

Pneumoperitoneum is the abnormal presence of free air in the peritoneal cavity. Oftentimes, it is a surgical emergency requiring exploratory laparotomy as most cases of pneumoperitoneum are due to perforated hollow viscus. However, not all pneumoperitoneum cases are surgical; nonsurgical pneumoperitoneum can arise from thoracic, abdominal, gynecologic, and other causes. We present a case of a 35-year-old male who developed a non-surgical pneumoperitoneum in the setting of drug overdose. The patient underwent robot-assisted diagnostic laparoscopy without findings of perforation or other pathology. Resolution of pneumoperitoneum was evidenced on follow-up computed tomography scan. This case emphasizes the importance of diagnostic laparoscopy in the setting of a confusing clinical picture and the feasibility of utilizing the robotic approach in hemodynamically stable patients.

Cancer-cell-derived sialylated IgG as a novel biomarker for predicting poor pathological response to neoadjuvant therapy and prognosis in pancreatic cancer.

BACKGROUND: Neoadjuvant therapy (NAT) is increasingly applied in pancreatic ductal adenocarcinoma (PDAC); however, accurate prediction of therapeutic response to NAT remains a pressing clinical challenge. Cancer-cell-derived sialylated immunoglobulin G (SIA-IgG) was previously identified as a prognostic biomarker in PDAC. This study aims to explore whether SIA-IgG expression in treatment-naïve fine needle aspirate (FNA) biopsy specimens could predict the pathological response (PR) to NAT for PDAC. METHODS: Endoscopic ultrasonography-guided FNA biopsy specimens prior to NAT were prospectively obtained from 72 patients with PDAC at the Johns Hopkins Hospital. SIA-IgG expression of PDAC specimens was assessed by immunohistochemistry. Associations between SIA-IgG expression and PR, as well as patient prognosis, were analyzed. A second cohort enrolling surgically resected primary tumor specimens from 79 patients with PDAC was used to validate the prognostic value of SIA-IgG expression. RESULTS: SIA-IgG was expressed in 58.3% of treatment-naïve FNA biopsies. Positive SIA-IgG expression at diagnosis was associated with unfavorable PR and can serve as an independent predictor of PR. The sensitivity and specificity of SIA-IgG expression in FNA specimens in predicting an unfavorable PR were 63.9% and 80.6%, respectively. Both positive SIA-IgG expression in treatment-naïve FNA specimens and high SIA-IgG expression in surgically resected primary tumor specimens were significantly associated with shorter survival. CONCLUSIONS: Assessment of SIA-IgG on FNA specimens prior to NAT may help predict PR for PDAC. Additionally, SIA-IgG expression in treatment-naïve FNA specimens and surgically resected primary tumor specimens were predictive of the prognosis for PDAC.

Tailoring Adjuvant Chemotherapy to Biologic Response Following Neoadjuvant Chemotherapy Impacts Overall Survival in Pancreatic Cancer.

BACKGROUND: The role of postoperative chemotherapy in patients with resected pancreatic cancer who receive neoadjuvant treatment is unknown. Clinicians use changes in CA19-9 and histopathologic scores to assess treatment response. We sought to investigate if CA19-9 normalization in response to NAT can help guide the need for postoperative treatment. METHODS: Patients with elevated baseline CA19-9 (CA19-9 > 37U/mL) who received NAT followed by surgery between 2011 and 2019 were retrospectively reviewed. Treatment response was determined by CA19-9 normalization following NAT and histopathologic scoring. The role of postoperative chemotherapy was analyzed in light of CA19-9 normalization and histopathologic response. RESULTS: We identified and included 345 patients. Following NAT, CA19-9 normalization was observed in 125 patients (36.2%). CA19-9 normalization was associated with a favorable histopathologic response (41.6% vs 23.2%, p < 0.001) and a lower ypT (p < 0.001) and ypN stage (p = 0.003). Receipt of adjuvant chemotherapy was associated with improved overall survival in patients in whom CA19-9 did not normalize following NAT (26.8 vs 16.4 months, p = 0.008). In patients who received 5FU-based NAT and in whom CA19-9 did not normalize, receipt of 5FU-based adjuvant chemotherapy was associated with improved OS (p = 0.014). CONCLUSION: CA19-9 normalization in response to NAT was associated with favorable outcomes and can serve as a biomarker for treatment response. In patients where CA19-9 did not normalize, receipt of postoperative chemotherapy was associated with improved OS. These patients also benefited from additional 5FU-based postoperative chemotherapy following 5FU-based NAT.

Resected Early-Onset Pancreatic Cancer: Practices and Outcomes in an International Dual-Center Study.

BACKGROUND: Early-onset pancreatic cancer (EOPC), defined as age ≤ 45 years at diagnosis, accounts for 3% of all pancreatic cancer cases. Although differences in tumor biology have been suggested, available data are sparse and specific treatment recommendations are lacking. This study explores the clinicopathological features and oncologic outcomes of resected EOPC. PATIENTS AND METHODS: Patients with EOPC undergoing resection between 2002 and 2018 were identified from the Heidelberg University Hospital and Johns Hopkins University registries. Median overall survival (OS) and recurrence-free survival (RFS) were analyzed, and prognostic factors were identified. RESULTS: The final cohort included 164 patients, most of whom had pancreatic ductal adenocarcinoma (PDAC, n = 136; 82.9%) or IPMN-associated pancreatic cancer (n = 17; 10.4%). Twenty (12.1%) patients presented with stage 1 disease, 42 (25.6%) with stage 2, 75 (45.7%) with stage 3, and 22 (13.4%) with oligometastatic stage 4 disease. Most patients underwent upfront resection (n = 113, 68.9%), whereas 51 (31.1%) individuals received preoperative treatment. Median OS and RFS were 26.0 and 12.4 months, respectively. Stage-specific median survival was 70.6, 41.8, 23.8, and 16.9 months for stage 1, 2, 3, and 4 tumors, respectively. Factors independently associated with shorter OS and RFS were R1 resections and AJCC stages 3 and 4. Notably, AJCC 3-N2 and AJCC 3-T4 tumors had a median OS of 20 months versus 29.5 months, respectively. CONCLUSION: Despite frequently presenting with advanced disease, oncologic outcomes in EOPC patients are satisfactory even in locally advanced cancers, justifying aggressive surgical approaches. Further research is needed to tailor current guidelines to this rare population.

Primary Balloon Angioplasty Versus Hydrostatic Dilation for Arteriovenous Fistula Creation in Patients with Small-Caliber Cephalic Veins: A Systematic Review and Meta-Analysis.

BACKGROUND: For arteriovenous fistula (AVF) presence of a venous segment with adequate diameter is essential which is lacking in many patients. To find the optimal augmentation technique in patients with small-caliber cephalic vein (i.e., cephalic vein diameter <3 mm), studies compared primary balloon angioplasty (PBA) versus hydrostatic dilation (HD); however, it remained debatable. This systematic review seeks to determine which technique is preferable. METHODS: We searched MEDLINE, PubMed, Embase, and Google Scholar. Primary outcomes were 6-month primary patency, reintervention, and working AVF. Secondary outcomes were immediate success, the AVF's maturation time (day), and surgical site infection. RESULTS: Three randomized controlled trials yielding 180 patients were included, of which 89 patients were in the PBA group. The odds ratio (OR) of primary patency was significantly higher in the PBA group (OR 6.09, 95% confidence interval [CI], 2.36-15.76, P = 0.0002), the OR of reintervention was significantly lower in the PBA group (OR 0.16, 95% CI, 0.06-0.42, P = 0.0002), and the OR of working AVF was greater in PBA group (OR 4.22, 95% CI, 1.31-13.59, P = 0.02). The OR of immediate success was significantly greater in the PBA group (OR 11.42, 95% CI, 2.54-51.42, P = 0.002), and the AVF maturation time was significantly shorter in patients who underwent PBA (mean difference -20.32 days, 95% CI, -30.12 to -10.52, P = 0.0001). The certainty of the evidence was high. CONCLUSIONS: PBA of small cephalic veins with diameter ≤2.5 cm is a safe, feasible, and efficacious augmentation method for AVF creation. This technique achieves favorable maturation outcomes, and PBA is superior to the standard hydrostatic dilatation technique.

Predictors, Patterns, and Timing of Recurrence Provide Insight into the Disease Biology of Invasive Carcinomas Arising in Association with Intraductal Papillary Mucinous Neoplasms.

OBJECTIVES: To identify predictors, patterns, and timing of recurrence after resection of invasive carcinomas arising in association with an IPMN. BACKGROUND: Postoperative management of an invasive carcinoma arising in association with an intraductal papillary mucinous neoplasm (IPMN), a biologically distinct entity from PanIN-derived pancreatic ductal adenocarcinoma (PDAC), remains largely based on guidelines for PanIN-derived PDAC. To minimize treatment failure and inform disease-specific management, cancer recurrence must be better characterized. METHODS: Patients were identified from a prospectively maintained registry between 1996 and 2018. Predictors of recurrence were evaluated by employing Cox regression models to determine risk-adjusted hazard ratios (HR) with 95% confidence intervals (95%CI). The patterns and timing of recurrence were recognized and compared utilizing a log-rank test, respectively. RESULTS: Of the 213 patients included, 92 (43.2%) recurred with a median RFS of 23.7 months (16.7-30.7). The predominant pattern of recurrence included any systemic (65.2%). The median time to local recurrence was longer than systemic (21.6 versus 11.4 months, p = 0.05). Poor differentiation [HR: 3.01, 95%CI (1.06-8.61)] and nodal disease [N1, HR: 2.23, 95%CI (1.12-4.60); and N2, HR: 5.67 95%CI (2.93-10.99)] emerged as independent predictors of systemic recurrence. For local-specific recurrences, poor differentiation [HR: 3.73, 95%CI (1.04-13.45)] and an R1 margin [high-grade dysplasia or invasive carcinoma; HR: 2.66, 95%CI (1.14-6.21)] emerged as independent predictors. CONCLUSIONS: The predominant pattern of recurrence after resection of invasive carcinomas arising in association with IPMNs is systemic, and occurs earlier than local recurrence. Poor differentiation and nodal disease are associated with systemic recurrence while poor differentiation and an R1 margin are associated with local recurrence. Future studies should investigate the role of systemic (chemotherapy) versus local (radiation) therapies and surveillance strategies in a personalized manner.

Postoperative Chemotherapy is Associated with Improved Survival in Patients with Node-Positive Pancreatic Ductal Adenocarcinoma After Neoadjuvant Therapy.

BACKGROUND: Postoperative chemotherapy following pancreatic cancer resection is the standard of care. The utility of postoperative chemotherapy for patients who receive neoadjuvant therapy (NAT) is unclear. METHODS: Patients who underwent pancreatectomy after NAT with FOLFIRINOX or gemcitabine-based chemotherapy for non-metastatic pancreatic adenocarcinoma (2015-2019) were identified. Patients who received less than 2 months of neoadjuvant chemotherapy or died within 90 days from surgery were excluded. RESULTS: A total of 427 patients (resectable, 22.2%; borderline resectable, 37.9%; locally advanced, 39.8%) were identified with the majority (69.3%) receiving neoadjuvant FOLFIRINOX. Median duration of NAT was 4.1 months. Following resection, postoperative chemotherapy was associated with an improved median overall survival (OS) (28.7 vs. 20.4 months, P = 0.006). Risk-adjusted multivariable modeling showed negative nodal status (N0), favorable pathologic response (College of American Pathologists score 0 & 1), and receipt of postoperative chemotherapy to be independent predictors of improved OS. Regimen, duration, and number of cycles of NAT were not significant predictors. Thirty-four percent (60/176) of node-positive and 50.1% (126/251) of node-negative patients did not receive postoperative chemotherapy due to poor functional status, postoperative complications, and patient preference. Among patients with node-positive disease, postoperative chemotherapy was associated with improved median OS (27.2 vs. 10.5 months, P < 0.001). Among node-negative patients, postoperative chemotherapy was not associated with a survival benefit (median OS, 30.9 vs. 36.9 months; P = 0.406). CONCLUSION: Although there is no standard NAT regimen for patients with pancreatic cancer, postoperative chemotherapy following NAT and resection appears to be associated with improved OS for patients with node-positive disease.

Association of Matrix Metalloproteinase 7 Expression With Pathologic Response After Neoadjuvant Treatment in Patients With Resected Pancreatic Ductal Adenocarcinoma.

Importance: The use of neoadjuvant therapy (NAT) in resectable pancreatic ductal adenocarcinoma (PDAC) remains controversial. A favorable pathologic response (complete or marked tumor regression) to NAT is associated with better outcomes in patients with resected PDAC. The role of NAT for early systemic control compared with immediate surgical resection for PDAC is under investigation. In the era of precision medicine, biomarkers for patient selection and prediction of therapy response are crucial. Objective: To evaluate the use of assessment for protein expression on fine-needle aspiration (FNA) biopsy specimens in predicting pathologic response to NAT in treatment-naive patients. Design, Setting, and Participants: This was a single-institution prognostic study from a high-volume center for pancreatic cancer. All specimens were obtained between January 1, 2009, and December 31, 2018, with a median (SE) follow-up of 20.2 (1.4) months. Analysis of the data was performed from October 1, 2019, to April 30, 2021. Targeted RNA sequencing of frozen FNA biopsy specimens from a discovery cohort of 23 patients was performed to identify genes with aberrant expression that was associated with patients' pathologic response to NAT. Immunohistochemical staining was performed on an additional 80 FNA biopsy specimens to assess expression of matrix metalloproteinase 7 (MMP-7) and its association with pathologic response. Receiver operating characteristic curves for prediction of favorable pathologic response were determined. Results: In the discovery cohort (12 [52.1%] male; 3 [13.0%] Black and 20 [86.9%] White), RNA sequencing showed that lower MMP-7 expression was associated with favorable pathologic response (College of American Pathologists system scores of 0 [complete response] and 1 [marked response]). In the validation cohort (40 [50.0%] female; 9 [11.3%] Black and 71 [88.7%] White), patients with negative MMP-7 expression were significantly more likely to have a favorable pathologic response (odds ratio, 21.25; 95% CI, 6.19-72.95; P = .001). Receiver operating characteristic curves for prediction of favorable pathologic response from multivariable Cox proportional hazards regression modeling showed that MMP-7 expression increased the area under the curve from 0.726 to 0.906 (P < .001) even after stratifying by resectability status. The positive predictive value and negative predictive value of MMP-7 protein expression on FNA biopsy specimens in predicting unfavorable pathologic response (scores of 2 [partial response] or 3 [poor or no response]) were 88.2% and 73.9%, respectively. Conclusions and Relevance: Assessment of MMP-7 expression on FNA biopsy specimens at the time of diagnosis may help identify patients who would benefit the most from NAT.

Germline Variants in DNA Damage Repair Genes: An Emerging Role in the Era of Precision Medicine in Pancreatic Adenocarcinoma.

Pancreatic adenocarcinoma is a lethal disease that is projected to become the second most common cause of cancer deaths by 2030. The role of adjuvant therapy after surgical resection has been established by several clinical trials to prolong survival and improve outcomes. Multiagent chemotherapy seems to be the most promising approach to counteract early recurrence and improve survival; however, in the era of precision medicine, patient selection and individualized therapy seems to hold the key to desirable superior outcomes. Several cancer susceptibility genes have been proven to be associated with an increased risk of pancreatic cancer, both familial and sporadic cases. The role of genomic profiling for germline variants has been extensive and of limited clinical value, considering their low prevalence in pancreatic ductal adenocarcinoma (PDAC). However, an accumulating body of evidence from several studies in the past decade have successfully shown a recognizable value of germline variants in risk assessment and patient stratification. Recently, anti-PD-1 therapy (pembrolizumab) has been FDA-approved for use in solid malignancies with a Mismatch repair deficiency or high Microsatellite instability. Several trials have evaluated the role of poly (ADP-ribose) polymerase (PARP) inhibitors in patients harboring germline BRCA1/2 mutations. Finally, germline variants in DNA damage response genes and particularly deleterious ones have the potential to guide therapy after surgical resection and serve as biomarkers to predict survival. The dire need to address challenges for applying precision medicine in real-life clinical settings for PDAC patients lies in further characterizing the genetic and molecular processes through translational research.