Surgery-first Research Articles

Impact of Neoadjuvant Therapy on Oncological Outcomes of Patients With Distal Pancreatic Adenocarcinoma.

Distal pancreatic ductal adenocarcinoma (D-PDAC) often presents at an advanced stage. The efficacy of neoadjuvant therapy (NAT) in improving outcomes for D-PDAC is not well-established. This study evaluates the impact of NAT on the oncological outcomes of patients with D-PDAC. A retrospective cohort study of consecutive patients with resectable and borderline-resectable D-PDAC treated at a single center from 2012 to 2020 was performed. Stratification was based on initial treatment-NAT or surgery first (SF). Survival analysis, following intention-to-treat framework, used Kaplan-Meier and Cox regression to assess NAT's impact on progression-free survival (PFS) and overall survival (OS) of D-PDAC. Among 141 patients (median age 69.8 years, 51.8% females) included in the study, 71 (50.4%) received NAT and 70 (49.6%) were planned for SF. Patients receiving NAT were younger (65.9 vs. 72.6 years) and had higher incidence of borderline-resectable disease (31% vs. 4.3%) (both p < 0.05) than those undergoing SF. Thirteen patients (18.3%) undergoing NAT and five (7.1%) in SF group, failed to undergo resection. Univariate comparison showed no difference in the PFS (SF:13.97 vs. NAT:17.00 months, p = 0.6), and OS (SF:23.73 vs. NAT:32.53 months, p = 0.35). Multivariate Cox regression analysis noted significantly improved PFS (HR = 0.64, 95%CI = 0.42-0.96, p = 0.031) and OS (HR = 0.60, 95%CI = 0.39-0.93, p = 0.021) with NAT. NAT is associated with improved PFS and OS in patients with -D-PDAC. Further randomized controlled trials are warranted to confirm these findings.

Multi-institutional Analysis of Choledocholithiasis in Pediatric vs Adult Patients

BackgroundIn adults, upfront intraoperative cholangiogram with laparoscopic common bile duct exploration (LCBDE) is well accepted for management of choledocholithiasis. Despite recent evidence supporting LCBDE utility in children, there has been hesitation to adopt this surgery first (SF) approach over ERCP first (EF) due to perceived technical challenges. We compared rates of successful stone clearance during LCBDE between adult and pediatric patients to evaluate if pediatric surgeons could anticipate similar rates of successful clearance. MethodsA multicenter, retrospective review of pediatric (<18 years) and adult patients with choledocholithiasis managed from 2018 to 2024 was performed. Demographic and clinical data were obtained. Rate of successful duct clearance with LCBDE was compared. Surgical and endoscopic complications (infections, bleeding, pancreatitis, bile leak) were also compared. Results724 patients, 333 (45.9%) pediatric and 391 (54.0%) adults, were included. The median age of pediatric vs adult patients was 15.2 years [13.1, 16.6] vs 55.5 years [34.1, 70.5], respectively. Of these, 201 (60.4%) pediatric vs 169 (43.2%) adult patients underwent SF, p < 0.001. LCBDE was attempted in 84 (41.7%) pediatric vs 140 (82.8%) adults, p = 0.002. LCBDE success was higher in pediatric vs adult patients (82.1% vs 71.4%, p = 0.004). Complications rates were similar however, pediatric patients who underwent EF had higher endoscopic complications (9.1% vs 3.6%, p = 0.03). ConclusionLCBDE is highly successful in children vs adults with no increased surgical complications. This data, coupled with the limited ERCP access for children, supports that LCBDE is an equally effective tool for managing choledocholithiasis in children as is accepted in adults. Level of EvidenceLevel III.

Reducing MRCP Utilization Through a “Surgery First” Approach for Pediatric Choledocholithiasis: A CARES Working Group Retrospective Study

BackgroundCholedocholithiasis in children is rising and frequently managed with an endoscopy-first (EF) approach that utilizes endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy (LC). Magnetic resonance cholangiopancreatography (MRCP) is a resource intensive modality that often precedes ERCP to gain further assurance of choledocholithiasis prior to intervention. MRCP can lead to a longer length of stay (LOS) and strain healthcare resources. We hypothesized that the use of MRCP is decreased with a surgery-first (SF) approach. MethodsThe Choledocholithiasis Alliance for Research, Education, and Surgery (CARES) Working Group conducted this retrospective study on pediatric patients with suspected choledocholithiasis. SF patients underwent LC + intraoperative cholangiogram (IOC) ± laparoscopic common bile duct exploration (LCBDE). Imaging studies included ultrasound (US), MRCP, and computed tomography (CT). ResultsFrom seven institutions, 357 pediatric patients were identified. The SF (n = 220) group received fewer imaging studies then EF (n = 137) (1.29 vs. 1.62; p < 0.05). US was more commonly employed and the number of US and CT scans was similar. The SF group had lower MRCP utilization than EF (29% vs. 59%; p < 0.05). EF patients that received an MRCP had the longest LOS (4.0 d [2.4, 6.3]) compared to SF that did not (1.9 d [1.2, 3.2]) (p < 0.05). ConclusionChildren with choledocholithiasis managed with an EF approach receive more diagnostic imaging, especially MRCP. While MRCP remains a powerful diagnostic tool, a surgery-first approach can minimize the resource utilization and LOS associated with magnetic resonance imaging. Level of EvidenceLevel III.

No survival benefit with suboptimal CA19-9 response: defining effective neoadjuvant chemotherapy in resectable or borderline resectable pancreatic cancer

Background/purposeNeoadjuvant chemotherapy (NAC) is gaining popularity over a surgery-first (SF) approach in treating resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC). However, what constitutes effective neoadjuvant chemotherapy is unknown. MethodsWe retrospectively analyzed resectable and borderline resectable PDAC patients who underwent pancreaticoduodenectomy (2010–2019) at a single institution. Optimal CA19-9 response was defined as normalization AND >50% reduction. We utilized Kaplan-Meier and multivariable-adjusted Cox models and competing risk subdistribution methods for statistical analysis. Results586 patients were included in this study. The multivariable-adjusted analysis demonstrated OS benefit in the NAC group only when OS was calculated from diagnosis (HR = 0.72, p = 0.02), but not from surgery (HR = 0.81, p = 0.1). However, in 59 patients who achieved optimal CA19-9 response, OS is significantly longer than the 134 patients with suboptimal CA19-9 response (39.3 m vs. 21.5 m, p = 0.005) or the 117 SF patients (39.3 m vs. 19.5 m, p < 0.001). Notably, a suboptimal CA19-9 response conferred no OS advantage compared to SF patients. The accumulative incidence of liver metastases (but not other metastases) was significantly reduced only in patients with optimal CA19-9 response to NAC (multivariable-adjusted subdistribution HR = 0.26, p = 0.03). ConclusionCA19-9 response to NAC may serve as the marker for effective NAC. These findings warrant validation in a multi-institutional study.

Total Neoadjuvant Treatment for Pancreatic Ductal Adenocarcinoma Is Associated With Limited Lymph Node Yield but Improved Ratio

IntroductionThe lymph node yield (LNY) and lymph node ratio (LNR) of nodal metastases following pancreatoduodenectomy (PD) have been reported as prognostic parameters in patients with pancreatic ductal adenocarcinoma (PDAC). However, they have not been compared in the setting of various neoadjuvant therapy modalities. MethodsA single institutional retrospective study identified 134 patients diagnosed with resectable, BLR- and LA-PDAC who underwent PD at Fox Chase Cancer Center between 2010 and 2019. Patients were categorized based on first-line treatment as follows: surgery first (SF), total neoadjuvant therapy (TNT), and single modality neoadjuvant therapy (SMNT). The histopathological reports of the surgical specimens were examined to obtain LNY and determine the counts of lymph nodes with metastases. Subsequently, LNR was calculated as the number of positive lymph nodes divided by the number of lymph nodes examined. ResultsOverall, 49, 38, 27, 12, and 8 patients underwent SF approach, SMNT, incomplete TNT, induction TNT, and consolidation TNT, respectively. There was no difference in R0 resection and vascular resection between the groups (P = 0.096 and 0.794, respectively). The median counts of LNY were 22, 15, 21, 11.5, and 10, respectively (P < 0.001). The average LNR was 0.16, 0.07, 0.03, 0.02, and 0.02, respectively (P < 0.001). There were statistically significant differences in overall survival in the TNT groups (log-rank test P = 0.030). ConclusionsPDAC patients who undergo the TNT modality exhibit lower LNY and improved LNR compared with the SF approach and SMNT neoadjuvant therapy groups. This is likely explained by the increased treatment response and lymph node obliteration associated with the TNT approach. Our results question the minimal requirement of 11-18 harvested lymph nodes for PD following TNT.

Comparable Skeletal and Dental Movements Achieved Using Conventional and Surgery-First Techniques in Class III Patients

The surgery-first (SF) approach to orthognathic surgery has been proposed as a more efficient method to correct the dentofacial deformity. This study aimed to evaluate if the magnitude of skeletal and dental changes achieved in Class III patients treated with either conventional orthognathic surgery (COS) or SF techniques differ. A retrospective cohort study of Class III orthognathic surgery patients between January 2006 and May 2020 with available pre- and post-treatment lateral cephalograms was conducted at an academic institution. The primary predictor variable was surgery technique: COS or SF. Assessed outcome variables included cephalometric skeletal parameters: SNA, SNB, ANB, Wits Appraisal, Sn-GoGn, and FMA; and dental parameters: U1-SN, U1-NA (°), U1-NA (mm), L1-NB (°), L1-NB (mm), and overjet. Within-group posttreatment parameters were analyzed with paired t tests. Pretreatment, posttreatment, and between-group parameter changes were analyzed by 2-sided 2-sample independent t tests. Potential covariates, including gender, surgical procedure, previous conventional treatment, extractions (excluding 3rd molars), crowding, and midline discrepancy, were analyzed using Fisher exact tests. Thirty-nine subjects were included in this study: 1) 21 COS (age: 20.9±8.7years) and 2) 18 SF (age: 19.6±5.0years). Cohorts were comparable (P>.05) for all analyzed covariates. COS showed statistically significant increases in L1-GoGn (3.31±6.23°; P=.024), overjet (4.26±3.99mm; P<.001), ANB (3.5±2.79°; P<.001), SNA (3.5±1.85°; P<.001), and Wits Appraisal (3.78±4.97mm; P=.002). SF showed statistically significant increases in L1-GoGn (4.19±4.85°; P=.002), L1-NB (3.08±4.13°; P=.006), L1-NB (0.79±1.35mm; P=.023), overjet (5.82±2.96mm; P<.001), ANB (5.51±3°; P<.001), SNA (4.13±2.38°; P<.001), and Wits Appraisal (5.92±3.42mm; P<.001) and statistically significant decreases in U1-NA (-3.69±7.35°; P=.048) and SNB (-1.38±2.14°; P=.014). There were no statistically significant differences in skeletal or dental parameters between groups when adjusted for pretreatment levels of that parameter. The mean treatment duration was 38months (standard deviation=12.7) in COS and 17.6months (standard deviation=5.2) in SF. The results show that skeletal and dental changes between groups were not statistically different, despite an average 20-month difference in treatment duration. This suggests that either technique can be used to achieve comparable degrees of skeletal and dental movement in Class III patients.

Patient Preferences for Neoadjuvant Therapy in Pancreatic Ductal Adenocarcinoma.

Physicians are increasingly recommending neoadjuvant therapy (NT) before surgery for pancreatic ductal adenocarcinoma (PDAC). However, patient preferences for and opinions regarding NT are poorly understood. Survivors and caregivers from a national PDAC patient advocacy organization completed an online survey assessing preferences for NT versus surgery first (SF) and factors influencing their decision making. Among 54 participants, 74.1% had a personal history of PDAC. While most patients preferred SF for resectable disease, NT was the preferred treatment approach for borderline resectable, locally advanced, and resectable cancers with high carbohydrate antigen 19-9. The most important factor influencing patient decision making regarding NT was its impact on overall survival while the least important was published national guidelines. The most preferred rationale for NT was ability to downstage to surgical resection and early treatment of micrometastatic disease. Among a national cohort of PDAC survivors and caregivers, the majority preferred SF for resectable PDAC, whereas NT was preferred when the resectability of a tumor was in question. The impact of NT on quantity and quality of life, as well as the likelihood of achieving surgical resection, was most highly valued by participants.

Prognostic significance of preoperative and postoperative CA 19-9 normalization in pancreatic adenocarcinoma treated with neoadjuvant therapy or surgery first.

Normal(ization) of serum carbohydrate 19-9 (CA19-9) before/after surgery has not been compared in patients with pancreatic adenocarcinoma (PDAC) treated with neoadjuvant therapy (NT) versus surgery-first (SF). Characteristics for patients with PDAC who underwent resection from July 2011 to October 2018 were collected. Patients with pre-/postoperative CA19-9, bilirubin <2 mg/dL, and initial CA19-9 > 1 U/ml were included. Overall survival (OS) and recurrence-free survival (RFS) were compared by pre-/postoperative CA19-9. In patients receiving NT, normal pre/postoperative CA19-9 ("NTnl/nl ") was associated with median RFS and OS (26 and 77mo), followed by those who normalized after surgery ("NTabnl/nl " 16 and 44mo). For SF patients, normal pre-/postoperative CA19-9 ("SFnl/nl ") was associated with median RFS and OS (115 and not estimable mo), followed by those who normalized after resection ("SFabnl/nl " 18 and 49mo). Groups "NTabnl/abnl " and "SFabnl/abnl " with elevated CA19-9 both before and after resection had the worst median RFS and OS durations. While a normal(ized) postoperative CA19-9 may result in similar survival as preoperative normal(ization), postoperative normalization failed to occur in nearly 30% of SF patients. NT should be considered in patients presenting with elevated CA19-9. If considering SF, ideal patients may include those with normal CA19-9 at presentation.

Total neoadjuvant therapy is associated with improved overall survival and pathologic response in pancreatic adenocarcinoma.

Few studies have evaluated outcomes of total neoadjuvant therapy (TNT) compared with single modality neoadjuvant therapy (SMNT) or surgery first (SF) for pancreatic ductal adenocarcinoma (PDAC). A single-institution retrospective review of PDAC patients who underwent pancreatectomy was conducted (1993-2019). Overall survival (OS) estimates from diagnosis and from surgery were determined using Kaplan-Meier methods; Cox proportional hazards models adjusted for covariates. Surgery was performed upfront (SF) in 168 (46.9%), while 111 (31.0%) had chemotherapy or chemoradiation before resection (SMNT), and 79 (22.1%) underwent TNT (chemotherapy and chemoradiation). Resection margins were more frequently R0 in the TNT group (86.1%) compared with SMNT (64.0%) and SF (72%) (p < 0.001). Complete pathologic response was more common in the TNT group (10.1%) compared with SMNT (3.6%) or SF (0.6%) (p = 0.001), resulting in prolonged survival (median OS = 100.2 months). TNT patients demonstrated longer median OS from surgery (33.6 months) compared with SF (19.1 months) and SMNT (17.4 months) (p = 0.010), which persisted after controlling for covariates. TNT is associated with more frequent complete pathologic response, a higher rate of margin negative resection, and prolonged OS as compared with SF or SMNT. Additional studies to identify subgroups that derive the greatest benefit are warranted.

Redefining our protocol of the orthognathic surgery-first approach after 10 years of experience

The objective of this study was to update and redefine some concepts of the surgery-first (SF) approach, regarding its indications and contraindications, virtual planning work-up, surgical tips, and postoperative orthodontic benefits, after 10 years of experience. A retrospective analysis was made of orthognathic surgical procedures following the SF protocol between January 2010 and December 2019 to review inclusion and exclusion criteria, diagnostic workflow, surgical tips, and postoperative outcomes. A total of 148 SF procedures were performed during this period, which corresponded to only 9.2% of the total orthognathic surgeries performed, which means that we have broadened the exclusion criteria instead of reducing them. Surgical tips include interdental corticotomies solely in cases of anterior crowding and leaving the intermaxillary fixation miniscrews in place postoperatively for orthodontic skeletal anchorage. The mean duration of postoperative orthodontic treatment was reduced in comparison to conventional surgery (36.8 vs 87.5 weeks). The overall degree of satisfaction was high not only for the patients, but also for the orthodontists and surgeon. SF is especially indicated for patients who desire an immediate aesthetic result, with short-term orthodontics, or for treatment of sleep-related breathing disorders, if they meet the established criteria.

Comparing Post-Operative Outcomes of Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma: Neoadjuvant Therapy Versus Surgery First Approach.

Optimal use of surgery first (SF) vs neoadjuvant therapy (NAT) for localized pancreatic ductal adenocarcinoma (PDAC) is still unclear. There is concern that NAT may result in worsened post-operative outcomes. Our study objectives were to show the impact of NAT on post-operative morbidity and mortality. All patients undergoing resection for PDAC between 1/1/2010 and 12/31/2020 were reviewed and those who underwent pancreaticoduodenectomy (PD) were included. Demographics, perioperative details, and pathology details were gathered. Data pertaining to 90-day complications were obtained and graded according to international consensus guidelines. Those undergoing SF were compared to those who had NAT. Categorical variables were compared by Fisher's exact test and continuous variables by Student's t-test. Two hundred and forty-one subjects who underwent PD for PDAC were included in this review. There was no significant difference in the rate of major morbidity between subjects who received NAT vs SF (19.4 vs 20.3%, P = 1.0). Similarly, there were no significant differences in the rates of mortality (3.1 vs 4.2%, P = .742), post-operative pancreatic fistula (8.2 vs 10.5%, P = .658), or post-pancreatectomy hemorrhage (7.1 vs 7.7%, P = 1.0), respectively. Post-operative outcomes are not worsened by the use of the NAT approach prior to PD for PDAC. Further investigation is needed to reveal which patient subgroups may benefit from the use of NAT, especially regarding survival.

Neoadjuvant Chemotherapy Resulting in Suboptimal CA19-9 Response is Associated with No Survival Benefit Compared to Surgery First Approach in Resectable or Borderline Resectable Pancreatic Cancer

Introduction: Neoadjuvant chemotherapy (NAC) is gaining popularity over surgery-first (SF) approach in treating resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC). Although CA19-9 change during NAC predicts oncological outcomes among NAC patients, how patients with suboptimal CA19-9 response compare to SF patients is unknown. Methods: We retrospectively analyzed resectable and borderline resectable PDAC patients who underwent pancreaticoduodenectomy (2010-2019) at a single institution. Optimal CA19-9 response was defined as normalization and >50% reduction. We utilized Kaplan-Meier and multivariate-adjusted Cox models for statistical analysis. Overall survival (OS) was calculated from both diagnosis and surgery to account for the immortal time bias of receiving NAC. Results: 488 patients were included in this study. The multivariate-adjusted analysis demonstrated OS benefit in the NAC group only when OS was calculated from diagnosis (HR=0.77, p=0.034), but not from surgery (HR=0.89, p=0.369). However, in 57 patients who achieved optimal CA19-9 response, OS is significantly longer than the 106 patients with suboptimal CA19-9 response (39.5m vs 21.3m, p=0.004) or the 110 SF patients (39.5m vs 20.1m, p=0.001). Importantly, a suboptimal CA19-9 response conferred no OS advantage compared to SF patients in both unadjusted and multivariate-adjusted models, even when calculating OS from diagnosis (HR=0.91, p=0.601). Conclusions: Suboptimal CA19-9 NAC responses correlated with no survival benefit when compared to SF approach, even when accounting for the NAC immortal-time. This result should be verified in a multi-institutional study. Nevertheless, we underlined a possible threshold of NAC response to achieve superior survival and highlighted the necessity of efficacy assessment during NAC.

Prognostic Significance of Preoperative and Postoperative CA 19-9 Normalization in Pancreatic Adenocarcinoma Treated with Neoadjuvant Therapy or Surgery First

Background: Normal(ization) of serum carbohydrate 19-9 (CA 19-9) before/after surgery has not been compared between patients with pancreatic adenocarcinoma (PDAC) treated with neoadjuvant therapy (NT) vs. surgery-first (SF). We hypothesized that postoperative normalized CA 19-9 is associated with dissimilar outcomes compared to normal(ization) before surgery. Methods: Clinicopathologic characteristics for patients with PDAC who underwent resection from July 2011 to October 2018 were abstracted from a prospective database. Patients with pre-/post-operative CA 19-9, total bilirubin <2mg/dL, and initial CA 19-9 >1 U/mL were included. Overall survival (OS) and recurrence-free survival (RFS) were compared among groups when stratified by pre-/post-operative CA 19-9. Results: In patients receiving NT (N = 171), normal pre-/post-operative CA19-9 (group “NT-1”) had the best median RFS and OS (26 and 77mo), followed by those who finally normalized after surgery (“NT-2,” 16 and 39mo). For SF patients (N = 57), normal pre-/post-operative CA19-9 (“SF-1”) had the best median RFS and OFS (28 and 57mo), followed by those who immediately normalized after resection (“SF-2,” 18 and 49mo). Groups “NT-3” (n=36) and “SF-3” (n=11) with elevated CA 19-9 both before and after resection had the worst median RFS and OS durations (Figure 1). Conclusion: While a normal(ized) postoperative CA 19-9 may result in similar survival as preoperative normal(ization), postoperative normalization failed to occur in 28.9% of SF patients, despite careful selection. Thus, NT should be considered in patients presenting with elevated CA 19-9. If considering surgery-first, the ideal patients are those with normal pre-operative CA 19-9.

AJCC 8th edition pathologic nodal staging of resected pancreatic adenocarcinoma predicts survival regardless of treatment sequencing

ObjectiveThe primary aim was to compare overall survival (OS) between neoadjuvant therapy (NT) and surgery-first (SF) patients with pancreatic adenocarcinoma (PDAC) by nodal stage using the American Joint Commission on Cancer 8th Edition (AJCC8). BackgroundRates of nodal positivity are consistently lower following NT versus SF sequencing. It's unclear whether post-NT nodal stage (ypNx) has similar survival compared to SF (pNx) using AJCC8. MethodsThis is a single-institution retrospective cohort study with routine consideration of NT. Patients undergoing PDAC resection from 2010 to 2018 were analyzed and OS compared by nodal stage using AJCC8. ResultsOf 450 total patients, 24% were treated with SF and 76% NT. SF patients had potentially resectable disease in 97% of the cases, whereas NT patients had more advanced clinical stages at diagnosis: borderline resectable 34%, locally advanced 5%. NT patients had higher rates of node-negativity (52.4% vs 22.7%) and lower rates of pathologic N2 disease (19.1% vs 43.6%) vs. SF (p < 0.001). For each pathologic nodal stage, SF and NT groups had similar 5-year OS [pN0/ypN0 52.7% vs. 53.6%, p = 0.723], [pN1/ypN1 37.0% vs. 36.7%, p = 0.872], and [pN2/ypN2 16.6% vs. 21.0%, p = 0.508]. ConclusionsAJCC8 stratifies outcomes for each post-NT nodal stage similar to SF counterparts. Despite presenting with more advanced clinical stage, NT patients had lower rates of nodal metastases yet comparable OS when stratified by final nodal status. These data provide both hope for patients with obvious radiographic nodal disease at presentation and further support for considering NT sequencing for most patients diagnosed with localized PDAC.

Comparison of Pre-operative and Postoperative Skeletal and Dental Movements in Class III Patients Treated with Conventional and Surgery-first Techniques

The conventional orthognathic-surgery technique involves lengthy pre-surgical orthodontic interventions, while invoking a surgery-first technique eliminates this necessity. Previous studies have reported the degree of skeletal and dental movements achieved using the conventional approach compared to orthodontic camouflage. However, none has directly compared the conventional orthognathic-surgery and surgery-first techniques. The objective of this study was to determine the magnitude of skeletal and dental changes achieved in class III patients with conventional orthognathic surgery (COS) and surgery-first (SF) techniques.In total, 82 lateral cephalograms for class III patients (n = 41) were analyzed for 2 groups: 1) COS (20.9±8.7 years) and 2) SF (20.7±6.6 years). Skeletal parameters such as SNA, SNB, ANB, Wits Analysis, Sn-GoGn, FMA, and lower anterior facial height and dental parameters such as U1-SN, U1-NA (°), U1-NA (mm), L1-NB (°), L1-NB (mm), and overjet were analyzed. Paired T-test analyses were performed to analyze the changes between pre-treatment and post-treatment parameters within the 2 groups, and 2-sample T-tests were used to compare the pre-treatment and post-treatment changes between the 2 groups.COS showed significant increase in L1-GoGn, overjet, ANB, SNA, and Wits analysis. SF showed significant increase in L1-GoGn, L1-NB (°), L1-NB (mm), overjet, ANB, SNA, and Wits analysis and significant decrease in U1-NA (°) and U1-NA (mm). The comparison between COS and SF showed that there was no statistically significant difference in the skeletal and dental parameters between the 2 groups.The results indicate that orthognathic surgery in class III patients with conventional orthognathic-surgery and surgery-first techniques does not produce a difference in results among the skeletal and dental parameters, suggesting that either technique can be used to achieve similar results with a comparable degree of skeletal and dental movement in patients with class III malocclusion.

GRP78 expression and prognostic significance in patients with pancreatic ductal adenocarcinoma treated with neoadjuvant therapy versus surgery first

BackgroundGlucose-regulated protein 78 (GRP78) plays an essential role in protein folding, transportation, and degradation, thus regulates ER homeostasis and promotes cell survival, proliferation and invasion. GRP78 expression in PDAC patients who received neoadjuvant therapy has not been reported. MethodsThis retrospective study of resected PDAC patients included 125 patients treated with neoadjuvant therapy (NAT) and 140 patients treated with surgery first (SF). The expression of GRP78 was evaluated by immunohistochemistry on tissue microarrays and the results were correlated with clinicopathologic parameters and survival. ResultsGRP78 expression was higher in SF patients compared to NAT patients (P < 0.001). In SF cohort, the median disease-free survival (DFS) and overall survival (OS) for patients with GRP78-positive tumors were 11.2 months and 25.0 months, respectively, compared to DFS of 52.1 months (P = 0.008) and OS of 69.5 months (P = 0.02) for those with GRP78-negative tumors. GRP78 expression correlated with higher frequency of recurrent/metastasis (P = 0.045). In NAT cohort, GRP78 expression correlated with shorter OS (P = 0.03), but not DFS (P = 0.08). GRP78 expression was an independent prognosticator for both DFS (P = 0.02) and OS (P = 0.049) in SF cohort and was an independent prognosticator for OS (P = 0.03), but not for DFS (P = 0.06) in NAT cohort by multivariate analysis. ConclusionsOur study showed that GRP78 expression in NAT cohort is lower than that in SF cohort. GRP78 expression correlated with shorter survival in both SF and NAT patients. Our findings suggest that targeting GRP78 may help to improve the prognosis in PDAC patients.

"Surgery First" vs "Traditional Sequence" Surgery: A Qualitative Study of Health Experiences in 46 Bimaxillary Orthognathic Patients.

Orthognathic patients are advocating an active role in selecting their appropriate ortho-surgical treatment, between the surgery first (SF) and the traditional sequence (TS) approaches. The aim of this study was to evaluate, through qualitative analysis, the subjective perceptions of the outcomes of each protocol. In-depth interviews were conducted with 46 (10 male and 36 female) orthognathic patients (23 SF and 23 TS) treated with bimaxillary orthognathic surgery by the same surgeon, between 2013 and 2015. Average treatment duration was 6.5months for SF and 12months for TS. Inclusion criteria were: the presence of Class III or Class II asymmetries and open bite. Patients were excluded if they refused interviews or stopped attending post-treatment follow-up. Investigated health experiences included overall satisfaction with appearance, self-confidence after surgery, perceived treatment time, functional recovery, and diet restrictions. All SF and TS patients showed overall satisfaction with their appearance (though TS showed more enthusiastic tones) and approved their degree of functional recovery after surgery. Class III SF patients had earlier improvements in self-confidence after surgery. Orthodontics was considered enduring by both SF and TS patients. SF patients expressed a higher degree of satisfaction with the reduction in overall treatment time and with the early psychological benefit deriving therefrom. Both SF and TS patients completely approved of the aesthetic outcomes and the functional recovery from which they benefitted due to the entire procedure.

Therapeutic Strategy of Colorectal Liver Metastasis Using Modified-JHBPS Nomogram.

We attempted to stratify prognosis using the modified Journal of Hepato-Biliary-Pancreatic Sciences (mJHBPS) nomogram upon identification of colorectal liver metastasis (CRLM) and to investigate which strategy is better, surgery first (SF) or chemotherapy first (CF), in each risk group. A total of 137 patients with CRLM who underwent resection of the primary tumor were included. Patients with brain, bone, or perihilar lymph node metastases were excluded. Patients were scored using the mJHBPS nomogram upon identification of CRLM. Prognosis was investigated using event-free survival (EFS) and overall survival (OS). The nomogram allowed stratification of patients using EFS and OS: low-risk (0-6 score, n=38), medium-risk (7-11 score, n=42), and high-risk (12≥ score, n=57). In the low-risk group, the EFS and OS of the CF group were significantly poorer than those of the SF group (p=0.019 and p=0.014, respectively). CF was an independent prognostic factor for both EFS and OS. The mJHBPS nomogram can stratify CRLM patients with sufficient differences in EFS and OS. SF was recommended for patients in the low-risk group.

Optimal Management of Resectable Pancreatic Head Cancer in the Elderly Patient: Does Neoadjuvant Therapy Offer a Survival Benefit?

Neoadjuvant therapy (NAT) is a growing strategy for patients with resectable pancreatic ductal adenocarcinoma (PDAC). Elderly patients are at increased risk of treatment withdrawal due to functional decline, and the benefit of NAT in this cohort remains to be studied. The objective of this study was to compare outcomes of elderly patients with resectable head PDAC who underwent NAT or a surgery-first (SF) approach. All patients 75 years of age and older with radiographically resectable (National Comprehensive Cancer Network criteria) PDAC who underwent pancreaticoduodenectomy at a single institution from 2008 to 2017 were analyzed. Baseline characteristics and perioperative outcomes were compared between the SF and NAT cohorts. Recurrence-free survival and overall survival (OS) were analyzed by treatment strategy. Overall, 158 patients were identified: SF cohort=90 (57%) and NAT cohort=68 (43%). Patients in the SF cohort were older (80 vs. 78 years; p=0.01) but there were no differences in preoperative comorbidities or frailty indices. SF patients had a trend toward higher rates of major complications (38% vs. 24%; p=0.06) with higher Comprehensive Complication Index totals (20.9 vs. 20; p=0.03). There were similar rates of adjuvant therapy. NAT was associated with significantly longer OS (24.6 vs. 17.6 months; p=0.01) in both the intent-to-treat and resected cohorts. On multivariable analysis (MVA), NAT remained an independent predictor of OS (hazard ratio 0.60; p=0.02). NAT is safe and effective for elderly patients with PDAC. This study suggests NAT is associated with fewer complications after surgery, equal rates of adjuvant therapy receipt, and increased OS over a surgery-first approach.

Neoadjuvant therapy versus surgery first for ampullary carcinoma: A propensity score-matched analysis of the NCDB.

The role of neoadjuvant therapy (NT) for ampullary carcinoma (AC) has not been clearly established. Patients who underwent pancreatoduodenectomy for AC between 2004 and 2016 were identified in the National Cancer Database. Overall survival (OS) was compared between those who received NT before resection and those who underwent surgery first (SF). Propensity score matching (PSM) was performed using age, pathologic T and N stage, and tumor differentiation. Among 8688 patients with AC, 175 (2.0%) received NT before surgery. While patients who received NT were younger (p = .022) and more likely to have nodal metastasis (43.3% vs. 35.1%, p < .001), there was no difference in OS on univariate (43 vs. 33 months; hazard ratio [HR]: 1.10, 95% confidence interval [CI]: 0.88-1.37, p = .401) or multivariate (HR: 1.09, 95% CI: 0.88-1.36, p = .416) analysis between groups. After PSM, there remained no difference in OS between NT or SF groups on univariate (37 vs. 32 months; HR: 1.20, 95% CI: 0.87-1.64, p = .350) or multivariate (HR: 0.99, 95% CI: 0.71-1.38, p = .943) analysis. NT followed by surgery was not associated with improved survival outcomes compared with SF among patients with localized AC. While NT is an acceptable alternative for patients with advanced disease, SF should remain the standard of care.