Does a Laparoscopic Approach to Distal Pancreatectomy for Cancer Contribute to Optimal Adjuvant Chemotherapy Utilization?

BACKGROUND: Although laparoscopic distal pancreatectomy (LDP) versus open approaches (ODP) for pancreatic adenocarcinoma (PDAC) is associated with reduced morbidity, its impact on optimal adjuvant chemotherapy (AC) utilization remains unclear. Furthermore, it is uncertain whether oncologic resection quality markers are equivalent between approaches. METHODS: The National Cancer Database (NCDB) was queried between 2010 and 2016 for PDAC patients undergoing DP. Effect of LDP vs ODP and institutional case volumes on margin status, hospital stay, 30-day and 90-day mortality, administration of and delay to AC, and 30-day unplanned readmission were analyzed using binary and linear logistic regression. Cox multivariable regression was used to correct for confounders. RESULTS: The search yielded 3411 patients; 996 (29.2%) had LDP and 2415 (70.8%) had ODP. ODP had higher odds of readmission [odds ratio (OR) 1.681, p = 0.01] and longer hospital stay [ß 1.745, p = 0.004]. No difference was found for 30-day mortality [OR 1.689, p = 0.303], 90-day mortality [OR 1.936, p = 0.207], and overall survival [HR 1.231, p = 0.057]. The highest-volume centers had improved odds of AC [OR 1.275, p = 0.027] regardless of approach. LDP conferred lower margin positivity [OR 0.581, p = 0.005], increased AC use [3rd quartile: OR 1.844, p = 0.026; 4th quartile; OR 2.144, p = 0.045], and fewer AC delays [4th quartile: OR 0.786, p = 0.045] in higher-volume centers. CONCLUSIONS: In selected patients, LDP offers an oncologically safe alternative to ODP for PDAC independent of institutional volume. However, additional oncologic benefit due to optimal AC utilization and lower positive margin rates in higher volume centers suggests that LDP by experienced teams can achieve best possible cancer outcomes.

Hepatocellular carcinoma: resection with adjuvant hepatic artery infusion therapy vs resection alone. A systematic review and meta-analysis.

Hepatocellular carcinoma (HCC) has a recurrence rate of up to 70% in 5 years after resection, detrimentally lowering survival. The role of adjuvant therapy remains controversial; therefore, the aim of this study was to evaluate the disease-free and overall survival of patients with HCC, not candidates for transplantation, undergoing resection and adjuvant hepatic artery infusion therapy vs resection alone. Our meta-analysis showed that adjuvant HAIC improves overall and disease-free survival after resection, especially in tumors ≥7 cm.

The Role of Surgical Resection for Stage IV Gastric Cancer With Synchronous Hepatic Metastasis.

BACKGROUND: With improved responses to chemotherapy and targeted treatments, the role of surgery in metastatic gastric cancer (MGC) to the liver needs to be revisited. We sought to examine whether surgical resection is associated with improvement of long-term survival. METHODS: The National Cancer Database was queried for MGC to the liver (2010-2014). Survival analysis was performed to compare the effect of gastrectomy and perioperative chemotherapy (G-CT) to palliative chemotherapy (PCT) alone. RESULTS: We identified 3175 patients with MGC to the liver. Most patients (94%, n = 2979) were treated with PCT, whereas 6% (n = 196 patients) underwent G-CT. Overall survival improved in patients treated with G-CT compared to PCT alone (16 versus 9.7 mo, P < 0.001). In patients undergoing G-CT, neoadjuvant chemotherapy was associated with increased overall survival compared to adjuvant chemotherapy (18.9 versus 14.8 mo, P = 0.011). Hazards of death significantly decreased with gastrectomy (hazard ratio [HR]: 0.53, 95% confidence interval [CI]: 0.44-0.63, P < 0.001). Negative prognostic factors included advanced age (HR: 1.10, 95% CI: 1.06-1.14, P < 0.001), treatment at nonacademic institution (HR: 1.23, 95% CI: 1.13-1.33, P < 0.001), and poorly differentiated grade (HR: 1.54, 95% CI: 1.17-2.03, P < 0.001). CONCLUSIONS: G-CT is associated with improved survival in patients with gastric cancer and synchronous liver metastasis. Further experience with well-designed prospective trials may be warranted to confirm these findings.

Global Gene Expression Change Induced by Major Thoracoabdominal Surgery.

OBJECTIVE: To test the hypothesis that major thoracoabdominal surgery induces gene expression changes associated with adverse outcomes. BACKGROUND: Widely different traumatic injuries evoke surprisingly similar gene expression profiles, but there is limited information on whether the iatrogenic injury caused by major surgery is associated with similar patterns. METHODS: With informed consent, blood samples were obtained from 50 patients before and after open transhiatal esophagectomy or pancreaticoduodenectomy. Twelve cases with complicated recoveries (death, infection, venous thromboembolism) were matched with 12 cases with uneventful recoveries. Global gene expression was assayed using human microarray chips. A 2-fold change with a corrected P < 0.05 was considered differentially expressed. RESULTS: In these 24 patients, 522 genes were differentially expressed after surgery; 248 (48%) were upregulated (innate immunity and inflammation) and 274 (52%) were downregulated [adaptive immunity (antigen presentation, T-cell function)]. Hierarchical clustering of the profile reliably predicted pre- and postoperative status. The within-patient change was 3.08 ±â€Š0.91-fold. There was no measurable association with age, malignancy, procedure, surgery length, operative blood loss, or transfusion requirements, but was positively associated with postoperative infection (3.81 ±â€Š0.97 vs 2.79 ±â€Š0.73; P = 0.009) and hospital length of stay (r = 0.583, P = 0.003). Venous thromboembolism and mortality each occurred in one patient, thus no associations were possible. CONCLUSIONS: Major surgery induces a quantifiable pattern of gene expression change that is associated with adverse outcome. This could reflect early impaired adaptive immunity and suggests potential therapeutic targets to improve postoperative recovery.

Distal pancreatectomy for benign and low grade malignant tumors: Short-term postoperative outcomes of spleen preservation-A systematic review and update meta-analysis.

BACKGROUND: The value of spleen preservation with distal pancreatectomy (DP) for benign and low grade malignant tumors remains unclear. The aim of this study was to evaluate the short-term postoperative clinical outcomes in patients undergoing DP with splenectomy (DPS) or spleen preservation (SPDP). METHODS: Online database search was performed (2000 to present); key bibliographies were reviewed. Studies comparing patients undergoing DP with either DPS or SPDP, and assessing postoperative complications were included. RESULTS: Meta-analysis of included data showed SPDP patients had significantly less operative blood loss, shorter duration of hospitalization, lower incidence of fluid collection and abscess, lower incidence of postoperative splenic and portal vein thrombosis, and lower incidence of new onset postoperative diabetes. For the whole group, there was no difference in incidence of postoperative pancreatic fistula (POPF) (RR = 0.95; 95%CI 0.65-1.40, P = 0.80), however, subgroup analysis of studies using ISGPF criteria showed that DPS patients had increased rates of Grade B/C POPF (RR = 1.35; 95%CI 1.08-1.70, P = 0.01). CONCLUSIONS: SPDP for benign and low grade malignant tumors is associated with shorter hospital stay and decreased morbidity compared to DPS. J. Surg. Oncol. 2017;115:137-143. © 2017 Wiley Periodicals, Inc.

Delayed gastric emptying after pancreaticoduodenectomy.

BACKGROUND: Delayed gastric emptying (DGE) remains an unsolved complication after pancreaticoduodenectomy (PD) with conflicting reports of its cause. We aimed to compare the effect of surgical techniques involving the stomach in PD in lowering the risk of postoperative DGE. METHODS: Online search and review of key bibliographies in PubMed, Medline, Embase, Scopus, Cochrane, and Google Scholar was performed. Studies comparing PD surgical techniques were identified. Primary outcome was postoperative DGE. Methodological quality was assessed using Strengthening the Reporting of Observational Studies in Epidemiology and Consolidated Standards of Reporting Trials. Calculated pooled relative risk and odds ratios (ORs) with the corresponding 95% confidence interval (CI) were used in the meta-analyses. RESULTS: Overall, 376 studies were reviewed, of which 22 studies were selected including a total of 5172 patients. The incidence of DGE was lower in antecolic compared with retrocolic gastrojejunostomy (risk ratio [RR], 0.260; CI, 0.157-0.431; P < 0.001; n = 1067 patients) and in subtotal stomach preserving PD compared with pylorus preserving PD (RR, 0.527; CI, 0.363-0.763; P < 0.001; n = 663 patients). There was no significant difference between classic PD versus pylorus preserving PD (OR, 0.64; CI, 0.40-1.00; P = 0.05; n = 1209 patients), pancreaticogastrostomy versus pancreaticojejunostomy (RR, 1.02; CI, 0.62-1.68; P = 0.94; n = 961 patients), Roux-en-Y versus Billroth II gastrojejunostomy (RR, 0.946; CI, 0.788-1.136; P = 0.5513; n = 470 patients), or minimally invasive PD versus open PD (OR, 0.99; CI, 0.62-1.56; P = 0.96; n = 802). CONCLUSIONS: In PD, surgical techniques using antecolic reconstruction route and subtotal stomach preserving PD seem to be associated with a lower risk of DGE. Further randomized controlled trials are necessary to evaluate these results taking other causes into consideration.

Vascular Reconstruction Is Not Warranted in Most Civilian Traumatic Shank Vascular Injuries.

BACKGROUND: Operative management of traumatic shank vascular injuries (SVI) evolved significantly in the past few decades, thereby leading to a dramatic decrease in amputation rates. However, there is still controversy regarding the minimum number of patent shank arteries sufficient for limb salvage. METHODS: Between January 2006 and September 2011, 191 adult trauma patients presented to an urban level I trauma center in Miami, Florida, with traumatic lower extremity vascular injuries. Variables collected included age, gender, mechanism of injury, and clinical status at presentation. Surgical data included vessel injury, technical aspects of repair, associated complications, and outcomes. RESULTS: A total of 48 (25.1%) patients were identified comprising 66 traumatic shank arterial injuries. Mean age was 38.2 ± 13.4 years, and the majority of patients were men (40 patients, 83.3%) presenting with blunt injuries (35 patients, 72.9%). Ligation was performed in 38 injured arteries (57.6%) and no vascular intervention was required in 20% of the patients. Vascular reconstruction was performed in only 6 patients (9.1%): 4 (6.1%) with concurrent popliteal trauma, 1 (1.5%) isolated anterior tibial, and 1 (1.5%) 3-vessel injury. Autogenous venous interposition conduit and polytetrafluoroethylene grafting were performed in 5 (7.6%) and 1 (1.5%) patient, respectively. All amputations (8 patients, 16.7%) occurred in blunt trauma patients presenting with unsalvageable limbs. The overall mortality rate in this series was 2.1%. CONCLUSIONS: Civilian shank arterial injuries are associated with acceptable rates of limb loss. Patients with a single-vessel patent inflow did not require vascular reconstruction in this series. Arterial reconstruction may no longer be determinant for successful management of isolated and double arterial SVI, whereas it is yet essential in the presence of 3-vessel or concurrent above-the-knee vascular injuries. Further investigation including larger number of patients is still warranted to define the role of conservative management in these complex injuries.

Full dose neoadjuvant FOLFIRINOX is associated with prolonged survival in patients with locally advanced pancreatic adenocarcinoma.

BACKGROUND: The efficacy of FOLFIRINOX for metastatic pancreatic cancer has led to its use in patients with earlier stages of disease. This study retrospectively analyzed a cohort of patients with locally-advanced pancreatic cancer (LAPC) treated with FOLFIRINOX. METHODS: Between 2008 and 2013, 51 treatment-naïve patients with LAPC at a single institution received first-line FOLFIRINOX with neoadjuvant intent, at the full dose as described in the PRODIGE 4/ACCORD 11 study. Combined chemoradiation was administered for those who remained unresectable after maximum response to chemotherapy. The primary outcome measure was overall survival (OS), and secondary outcomes were progression-free survival (PFS) and margin-negative (R0) resection rate, and toxicity profile. RESULTS: A total of 429 cycles of FOLFIRINOX were given with a median of 8 cycles (range 2-29) per patient; 66% of cycles were full dose. After chemotherapy, 27 (53%) received chemoradiation. The median OS was 35.4 months (95% CI 25.8-45). Ten (4 borderline resectable and 6 unresectable) patients had successful R0 resections; those who had R0 resections had a significantly longer survival than those who did not (3-year OS rate 67% versus 21%, log rank p = 0.042). Increasing number of full-dose cycles was significantly associated with increased survival. The toxicity profile was similar to previous reports of this regimen. CONCLUSIONS: FOLFIRINOX is feasible as neoadjuvant therapy for LAPC. Although the R0 resection rate was only 20%, the median OS of almost 3 years appears promising. Dose intensity and duration were associated with increased survival in this study, arguing against dose attenuated versions of this regimen.

Minimally invasive spleen-preserving distal pancreatectomy: Does splenic vessel preservation have better postoperative outcomes? A systematic review and meta-analysis.

BACKGROUND: Minimally invasive spleen-preserving distal pancreatectomy (SPDP) can be performed with either splenic vessel preservation (SVP) or resection [Warshaw procedure (WP)]. The aim of this study was to evaluate the postoperative clinical outcomes of patients undergoing both methods. DATA SOURCES: Database search of PubMed, Embase, Scopus, Cochrane, and Google Scholar was performed (2000-2014); key bibliographies were reviewed. Qualified studies comparing patients undergoing SPDP with either SVP or WP, and assessing postoperative complications were included. Calculated pooled risk ratio (RR) with the corresponding 95% confidence interval (CI) by random effects methods were used in the meta-analyses. RESULTS: The search yielded 215 studies, of which only 14 observational studies met our selection criteria. The studies included 943 patients in total; 652 (69%) underwent SVP and 291 (31%) underwent WP. Overall, there was a lower incidence of splenic infarction (RR=0.17; 95% CI: 0.09-0.33; P<0.001), gastric varices (RR=0.16; 95% CI: 0.05-0.51; P=0.002), and intra/postoperative splenectomy (RR=0.20; 95% CI: 0.08-0.49; P<0.001) in the SVP group. There was no difference in incidence of pancreatic fistula (WP vs SVP, 23.6% vs 22.9%; P=0.37), length of hospital stay, operative time or blood loss. There was moderate cross-study heterogeneity. CONCLUSIONS: SVP is a safe, efficient and feasible technique that may be used to preserve the spleen. WP may be more suitable for large tumors close to the splenic hilum or those associated with splenomegaly. Randomized clinical trials are justified to examine the long-term benefits of SVP-SPDP.

The role of MR cholangiopancreatography in preoperative assessment for repair of major iatrogenic biliary injury: 10-year experience.

BACKGROUND/AIMS: Major iatrogenic biliary injury is a potentially life-threatening complication after laparoscopic cholecystectomy. Early diagnosis is essential to improve outcomes, however, to date, there is no consensus regarding the best imaging approach for preoperative assessment of these injuries. METHODOLOGY: From March 2002 to February 2012, 40 patients with postoperative major biliary injury underwent biliary reconstruction at our Institution. Mean age was 51.7 ± 18.1 years (19-86) with 30 (75%) females. Magnetic resonance cholangiopancreatography (MRCP) were compared with different diagnostic modalities and definitive intraoperative findings. RESULTS: Of 40 patients, 10 (25%) had Bismuth type I, 10 (25%) Bismuth type II, 6 (15%) Bismuth type III injury, 10 (25%) Bismuth type IV and, 4 (10%) Bismuth type V. MRCP has similar accuracy to define injury site, but is superior in delineating proximal ductal anatomy that was often not visualized with endoscopic retrograde cholangiopancreatography (ERCP). CONCLUSION: MRCP is a reliable, accurate and readily available diagnostic tool to assess complex biliary injuries. It provides adequate visualization of the proximal and distal biliary trees and may be considered as first-line test in the management of major iatrogenic biliary injuries. Revision of current guidelines for diagnostic approach of this condition is warranted.

Metastatic Pancreatic Adenocarcinoma Downstaged to T0N0 with Chemotherapy and Targeted Therapy, Confirmed by Surgical Pathology: A Case Report.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive human tumor that is typically diagnosed at a later stage when surgery is not possible. Case Presentation: We report the case of a 62-year-old woman who presented to the emergency department with abdominal pain. Computed tomography (CT) revealed a solitary hepatic lesion and a pancreatic body lesion. The pancreatic body lesion was biopsied endoscopically, and a tissue diagnosis was obtained to confirm the diagnosis of PDAC. She was then treated with 12 cycles of FOLFIRINOX with stable disease on CT. Due to the history of a hepatic lesion, she received 11 cycles of gemcitabine/Abraxane and a combination of a MEK inhibitor, Mekinist, and a BRAF inhibitor, BRAFTOVI. Subsequently, the patient underwent a liver biopsy. The biopsy result was negative, and the tumor was deemed resectable. The patient underwent a distal pancreatectomy. Surgical pathology demonstrated a 1.1-cm low-grade papillary mucinous neoplasm with negative margins and lymph nodes, staged T0N0. Adjuvant chemotherapy was not administered. Conclusion: To our knowledge, this is the first report of a patient with metastatic pancreatic adenocarcinoma who received prolonged IV and oral chemotherapy. At the time of the operation, the pathological stage was T0N0. The patient has recently been seen 9 months after surgery with no evidence cancer recurrence. Additionally, ctDNA remains negative.

Biliary-colonic fistula caused by cholecystectomy bile duct injury.

Biliary-colonic fistula is a rare complication after laparoscopic cholecystectomy. We present a case of post-cholecystectomy iatrogenic biliary injury that resulted in a fistula between the common hepatic duct and large bowel. Magnetic resonance cholangiopancreatography provided good visualization of injury even with concurrent normal level of alkaline phosphatase. Radiologic findings and surgical management of this condition are discussed in detail.

Nationwide Outcomes of Pancreaticoduodenectomy for Pancreatic Malignancies: Center Volume Matters.

BACKGROUND: Complex surgeries such as pancreaticoduodenectomies (PD) have been shown to have better outcomes when performed at high-volume centers (HVCs) compared to low-volume centers (LVCs). Few studies have compared these factors on a national level. The purpose of this study was to analyze nationwide outcomes for patients undergoing PD across hospital centers with different surgical volumes. METHODS: The Nationwide Readmissions Database (2010-2014) was queried for all patients who underwent open PD for pancreatic carcinoma. High-volume centers were defined as hospitals where 20 or more PDs were performed per year. Sociodemographic factors, readmission rates, and perioperative outcomes were compared before and after propensity score-matched analysis (PSMA) for 76 covariates including demographics, hospital factors, comorbidities, and additional diagnoses. Results were weighted for national estimates. RESULTS: A total of 19,810 patients were identified with age 66 ± 11 years. There were 6,840 (35%) cases performed at LVCs, and 12,970 (65%) at HVCs. Patient comorbidities were greater in the LVC cohort, and more PDs were performed at teaching hospitals in the HVC cohort. These discrepancies were controlled for with PSMA. Length of stay (LOS), mortality, invasive procedures, and perioperative complications were greater in LVCs when compared to HVCs before and after PSMA. Additionally, readmission rates at one year (38% vs 34%, P < .001) and readmission complications were greater in the LVC cohort. CONCLUSIONS: Pancreaticoduodenectomy is more commonly performed at HVCs, which is associated with less complications and improved outcomes compared to LVCs.

Optimizing Transitions of Care and Enhancing Surgical Education on Acute Care Surgery: A Multi-Institutional Survey Study.

OBJECTIVE: Critically ill and injured patients are routinely managed on the Trauma and Acute Care Surgery (ACS) service and receive care from numerous residents during hospital admission. The Clinical Learning Environment Review (CLER) program established by the ACGME identified variability in resident transitions of care (TC) while observing quality care and patient safety concerns. The aim of our multi-institutional study was to review surgical trainees' impressions of a specialty-specific handoff format in order to optimize patient care and enhance surgical education on the ACS service. DESIGN: A survey study was conducted with a voluntary electronic 20-item questionnaire that utilized a 5 point Likert scale regarding TC among resident peers, supervised handoffs by trauma attendings, and surgical education. It also allowed for open-ended responses regarding perceived advantages and disadvantages of handoffs. SETTING: Ten American College of Surgeons-verified Level 1 adult trauma centers. PARTICIPANTS: All general surgery residents and trauma/acute/surgical critical care fellows were surveyed. RESULTS: The study task was completed by 147 postgraduate trainees (125 residents, 14 ACS fellows, and 8 surgical critical care fellows) with a response rate of 61%. Institutional responses included: university hospital (67%), community hospital-university affiliate (16%), and private hospital-university affiliate (17%). A majority of respondents were satisfied with morning TC (62.6%) while approximately half were satisfied with evening TC (52.4%). Respondees believe supervised handoffs improved TC and prevented patient care delays (80.9% and 74.8%, respectively). A total of 35% of trainees utilized the open-ended response field to highlight specific best practices of their home institutions. CONCLUSIONS: Surgical trainees view ACS morning handoff as an effective standard to provide the highest level of clinical care and an opportunity to enhance surgical knowledge. As TC continue to be a focus of certifying bodies, identifying best practices and opportunities for improvement are critical to optimizing quality patient care and surgical education.

EUS visualization and direct celiac ganglia neurolysis predicts better pain relief in patients with pancreatic malignancy (with video).

BACKGROUND: EUS-guided celiac plexus neurolysis (EUS-CPN) improves pain control in patients with pancreatic cancer. EUS allows visualization of the celiac ganglion. OBJECTIVE: To determine predictors of response to EUS-CPN in a cohort of 64 patients with pancreatic malignancy. DESIGN: Retrospective analysis of prospective database. SETTING: Academic medical center. PATIENTS: Sixty-four patients with pancreatic cancer referred for EUS between March 2008 and January 2010. INTERVENTIONS: EUS-CPN injected directly into celiac ganglia when visible by linear EUS or bilateral injection at the celiac vascular trunk. MAIN OUTCOME MEASUREMENTS: Predictors of pain improvement at week 1 by univariate and multivariate analysis. RESULTS: At week 1, 32 patients (50%) had a symptomatic response. In a multivariate model with 8 potential predictors, visualization of the ganglia was the best predictor of response; patients with visible ganglia were >15 times more likely to respond (odds ratio 15.7; P<.001). Tumors located outside the head of the pancreas and patients with a higher baseline pain level were weakly associated with a good response. LIMITATIONS: Retrospective design and lack of blinding. CONCLUSIONS: Visualization of celiac ganglia with direct injection is the best predictor of response to EUS-CPN in patients with pancreatic malignancy.

EUS-FNA with rescue fluorescence in situ hybridization for the diagnosis of pancreatic carcinoma in patients with inconclusive on-site cytopathology results.

BACKGROUND: Detection of chromosomal abnormalities by fluorescence in situ hybridization (FISH) analysis has not been well-studied in FNA samples of pancreatic masses. Selective use of FISH in patients with inconclusive on-site cytopathology results may improve the sensitivity of EUS for malignancy. OBJECTIVE: To determine the sensitivity and specificity of FISH analysis in patients with inconclusive on-site cytopathology results. DESIGN: Consecutive patients with suspected pancreatic malignancy, nonrandomized cohort study. Final diagnosis was based on either surgical biopsy or disease progression on extended follow-up or death. SETTING: Academic center, tertiary-care referral cancer center. PATIENTS: A total of 212 EUS examinations were performed in 206 patients for solid pancreatic lesions over a 24-month period (January 2009-December 2010). FISH analysis was done for 69 patients with inconclusive or nonavailable on-site cytology results. INTERVENTION: EUS-guided FNA (EUS-FNA) of solid pancreatic masses with cytology and FISH analysis for polysomy of chromosomes 3, 7, and 17 and deletion of 9p21. MAIN OUTCOME MEASUREMENTS: Sensitivity/specificity of cytology, FISH, and a composite of cytology and FISH. RESULTS: Patients with positive on-site cytology (110), neuroendocrine tumors (22), insufficient follow-up (1), FISH not obtained (3), and renal cancer with pancreatic metastasis (1) were excluded. Sixty-nine patients comprised the study cohort, 54 with malignancy and 15 with benign disease. Sensitivity for malignancy of cytology, FISH analysis, and the combination were 61%, 74%, and 85%, respectively (P = .009). FISH detected an additional 13 cases of pancreatic adenocarcinoma missed by cytology. There was no false-positive FISH analysis in 15 patients with benign disease. No major complications occurred from EUS-FNA. LIMITATIONS: Single center, selected patients underwent FISH analysis, limited number of patients with benign disease. CONCLUSION: In patients with suspected pancreatic cancer, FISH analysis can detect additional cases missed by cytology without compromising specificity. FISH analysis to detect polysomy of chromosomes 3, 7, and 17 and deletion of 9p21 should be considered when cytology is negative for malignancy in patients with a known pancreatic mass.

Cobimetinib Plus Gemcitabine: An Active Combination in KRAS G12R-Mutated Pancreatic Ductal Adenocarcinoma Patients in Previously Treated and Failed Multiple Chemotherapies.

Purpose: The KRAS proto-oncogene is involved in the RAS/MAPK pathway. KRAS is present in the wild type or mutated forms. The oncogene KRAS is frequently mutated in various cancers. At the time that amino acid glycine is mutated, KRAS protein acquires oncogenic properties that result in the tumor cell growth, proliferation, and cancer progression. There has been limited understanding of the different mutations at codon 12. The consequences of such mutations is not fully understood. Various G12X mutations in pancreatic cancer patients have been examined, with the most common mutations being G12D (40%), G12V (30%), and G12R (15-20%). Now we are understanding that G12X mutations in the KRAS are not all equal. Methods: In a single-arm exploratory study, we accrued 13 KRAS-G12X-mutated pancreatic patients (KRAS G12D, G12V, and G12R). They were divided into two groups: group 1 consisted of seven patients with G12D and G12V and group 2 included six patients with the KRAS G12R mutation. All patients were treated with the combination of gemcitabine at 1250 mg/m2 intravenous weekly for 3 weeks and oral cobimetinib 20 mg b.i.d. for 3 weeks. This was followed by a week of rest before the initiation of the next cycle. Results: In the first cohort, seven patients were on treatment, all of whom progressed and died within the 2 months of the study. In the second cohort, one of six patients achieved partial response, and five achieved stable disease. Median progression-free survival was 6 months (9% confidence interval 3.0-9.3 months) and overall survival has been reached at 8 months. Common adverse reactions included rash, fatigue, nausea, and vomiting (grades 2 and 3). Cancer antigen CA19-9 decreased by >50% in all group 2 patients. Conclusion: Our pancreatic cancer patients were heavily pretreated (all had received FOLFIRINOX and gemcitabine/nab-paclitaxel) before the entry into our trial. Upon entry into our trial, all patients were treated with the combination of gemcitabine and oral cobimetinib. Therefore, this constituted the second exposure of the patients to gemcitabine. This study illustrates a new discovery, which can potentially target 15-20% of pancreatic cancer patients and allow for a significant improvement in their prognosis. We will be conducting randomized phase II trials to substantiate our findings.

Publication Inaccuracies Listed in General Surgery Residency Training Program Applications.

BACKGROUND: Professionalism is a core competency that is difficult to assess. We examined the incidence of publication inaccuracies in Electronic Residency Application Service applications to our training program as potential indicators of unprofessional behavior. STUDY DESIGN: We reviewed all 2019-2020 National Resident Matching Program applicants being considered for interview. Applicant demographic characteristics recorded included standardized examination scores, gender, medical school, and medical school ranking (2019 US News & World Report). Publication verification by a medical librarian was performed for peer-reviewed journal articles/abstracts, peer-reviewed book chapters, and peer-reviewed online publications. Inaccuracies were classified as "nonserious" (eg incorrect author order without author rank promotion) or "serious" (eg miscategorization, non-peer-reviewed journal, incorrect author order with author rank promotion, nonauthorship of cited existing publication, and unverifiable publication). Multivariate logistic regression analysis was performed for demographic characteristics to identify predictors of overall inaccuracy and serious inaccuracy. RESULTS: Of 319 applicants, 48 (15%) had a total of 98 inaccuracies; after removing nonserious inaccuracies, 37 (12%) with serious inaccuracies remained. Seven publications were reported in predatory open access journals. In the regression model, none of the variables (US vs non-US medical school, gender, or medical school ranking) were significantly associated with overall inaccuracy or serious inaccuracy. CONCLUSIONS: One in 8 applicants (12%) interviewing at a general surgery residency program were found to have a serious inaccuracy in publication reporting on their Electronic Residency Application Service application. These inaccuracies might represent inattention to detail or professionalism transgressions.

Technical skills rotation for general surgery residents.

BACKGROUND: Technical skills are an important part of any general surgery residency curriculum. With the demands of limited work weeks, it is imperative that educators create novel methods of teaching technical skills to their residents. Our program utilizes a dedicated month to help accomplish this. This study hypothesized that general surgery residents would report a positive effect of a dedicated technical skills rotation. METHODS: Residents who had undergone a 1 mo rotation in technical skills during their first year were asked to fill out a survey concerning their experience. During the 1-mo rotation, the residents had almost no clinical responsibilities. Teaching of technical skills was performed with various activities, including video content (VC), virtual reality simulators (VR), open foam procedures (OF), laparoscopic box trainers (BT), surgical equipment in-service (SE), and animate sessions (AS). Responses were given on a Likert scale (1-10) with higher numbers being more positive responses. RESULTS: There were seven residents in this study. The residents gave a very positive response to the overall rotation (9.4) and exposure to laparoscopic procedures (9.6). The other responses were enthusiastic as well: exposure to open procedures (8.9) and preparation for operative room (9.4). After their rotation, the residents were comfortable performing a laparoscopic cholecystectomy (9.2), a hand-sewn anastomosis (8.7), and a stapled anastomosis (9.4). The residents found theses activities helpful in increasing order: VC (7.8), VR (8.0), BT (9.0), ES (9.7), OF (9.8), and AS (9.8). CONCLUSIONS: A 1-mo dedicated technical skills rotations was perceived to be extremely positive by the residents. The residents felt very comfortable performing a laparoscopic cholecystectomy, a hand-sewn anastomosis, and a stapled anastomosis. With the 80-h work week, alternatives to learning technical skills in the operating room are essential. Further studies need to be performed to determine if this rotation aids in accomplishing this goal.

Single-session endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography for evaluation of pancreaticobiliary disorders.

BACKGROUND: Endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) often are required in the evaluation and treatment of patients with pancreaticobiliary disorders. Few reports of single-session EUS-ERCP have raised questions regarding its safety and accuracy or about which procedure should be performed first. METHODS: Data from 2005 to 2009 were reviewed from a prospectively maintained EUS-ERCP database at a single tertiary care cancer center. Sensitivity and specificity of EUS and fine-needle aspiration (FNA), bile duct cannulation rate, duration of procedure, and complications were evaluated. RESULTS: Of the 35 patients (15 men and 20 women) studied, 28 had a final diagnosis of malignancy, and 7 had benign disorders. All the patients underwent ERCP and EUS, with FNA performed for 28 patients (80%). For 22 of the 35 patients (62.8%), EUS was the first procedure performed. The sensitivity of EUS-FNA for malignancy was 96.4%. The bile duct cannulation rate during ERCP was 97.1%. Five patients required a precut sphincterotomy for bile duct access, and one patient with chronic pancreatitis had a failed cannulation despite a EUS-guided rendezvous. A stent was successfully placed in 29 patients (96%). No major complications occurred, and no contrast leak was seen when FNA was performed before the cholangiogram. One patient had periduodenal bleeding after FNA, which was managed conservatively. The mean duration of the procedure was 83.7 min. CONCLUSION: Single-session EUS-ERCP can be performed safely and with efficacy similar to that of the procedures performed separately.