Sustained Carbohydrate Antigen 19-9 Response to Neoadjuvant Chemotherapy in Borderline Resectable Pancreatic Cancer Predicts Progression and Survival.

BACKGROUND: As neoadjuvant therapy of borderline resectable pancreatic cancer (BRPC) is becoming more widely used, better indicators of progression are needed to help guide therapeutic decisions. MATERIALS AND METHODS: A retrospective review was performed on all patients with BRPC who received 24 weeks of neoadjuvant chemotherapy. Patients with chemotoxicity or medical comorbidities limiting treatment completion and nonexpressors of carbohydrate antigen 19-9 (CA19-9) were excluded. Serum CA19-9 response was analyzed as a predictor of disease progression, recurrence, and survival. RESULTS: One hundred four patients were included; 39 (37%) progressed on treatment (18 local and 21 distant) and 65 (63%) were resected (68% R0). Multivariate logistic regression analysis determined that the percent decrease in CA19-9 from baseline to minimum value (odds ratio [OR] 0.947, p ≤ .0001) and the percent increase from minimum value to final restaging CA19-9 (OR 1.030, p ≤ .0001) were predictive of progression. A receiver operating characteristics curve analysis determined cutoff values predictive of progression, which were used to create four prognostic groups. CA19-9 responses were categorized as follows: (1) always normal (n = 6); (2) poor response (n = 31); (3) unsustained response (n = 19); and (4) sustained response (n = 48). Median overall survival for Groups 1-4 was 58, 16, 20, and 38 months, respectively (p ≤ .0001). CONCLUSION: Patients with initially elevated CA19-9 levels who do not have a decline to a sustained low level are at risk for progression, recurrence, and poor survival. Alternative treatment strategies prior to an attempt at curative resection should be considered in this cohort. IMPLICATIONS FOR PRACTICE: This study identified percent changes in carbohydrate antigen 19-9 blood levels while on chemotherapy that predict tumor growth in patients with advanced pancreas cancer. These changes could be used to better select patients who would benefit from surgical removal of their tumors and improve survival.

Continuous Transversus Abdominis Plane Block for Primary Open Inguinal Hernia Repair: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: Patients undergoing open inguinal hernia repair may experience moderate to severe postoperative pain. We assessed opioid consumption in subjects who received a continuous transversus abdominis plane block in addition to standard multimodal analgesia. DESIGN: Randomized, double-blind, placebo-controlled. SETTING: Tertiary academic medical center. SUBJECTS: Adult patients undergoing open inguinal hernia repair at Virginia Mason Medical Center. A total of 90 patients were enrolled. METHODS: Subjects presenting for surgery were randomized to receive either a continuous transversus abdominis plane block or a subcutaneous sham block. The primary outcome was opioid consumption within the first 48 hours after surgery. Secondary outcomes included pain scores, activities assessment scores, and opioid-related adverse events. Multimodal analgesia utilized in both groups included acetaminophen, nonsteroidal anti-inflammatory drugs, and surgical local anesthetic infiltration. RESULTS: Eighty-two subjects, 42 from the block group and 40 from the sham group, completed the study, per protocol. The intention-to-treat analysis demonstrated no difference in 48-hour postoperative oxycodone equivalent consumption between the block and sham groups (27.8 mg ± 26.8 vs 32 mg ± 39.2, difference -4.4 mg, P = 0.55). There was a statistically significant reduction in pain scores at 24 hours in the block group. There were no other differences in secondary outcomes. CONCLUSIONS: Continuous transversus abdominis plane blocks provide modest improvements in pain after open inguinal hernia repair but fail to significantly reduce opioid consumption or improve functional activity levels in the setting of multimodal analgesia use.

Significance of radiographic splenic vessel involvement in the pancreatic ductal adenocarcinoma of the body and tail of the gland.

BACKGROUND AND OBJECTIVES: Unlike pancreatic head tumors, little is known about the biological significance of radiographic vessel involvement with pancreatic body/tail adenocarcinoma. We hypothesized radiographic splenic vessel involvement may be an adverse prognostic factor. METHODS: All distal pancreatectomies performed for resectable pancreatic adenocarcinoma between 2000 and 2016 were reviewed and clinicopatholgic data were collected, retrospectively. Preoperative computed tomography imaging was re-reviewed and splenic vessel involvement was graded as none, abutment, encasement, or occlusion. RESULTS: Among a total of 71 patients, splenic artery or vein encasement/occlusion was present in 41% (29 of 71) of patients, each. There were no significant differences in tumor size or grade, margin positivity, and perineural or lymphovascular invasion. However, splenic artery encasement/occlusion (P = 0.001) and splenic vein encasement/occlusion (P = 0.038) both correlated with lymph node positivity. Splenic artery encasement was associated with a reduced median overall survival (20 vs 30 months, P = 0.033). Multivariate analysis also showed that splenic artery encasement was an independent risk factor of worse survival (hazard ratio, 2.246; 95% confidence interval, 1.118-4.513; P = 0.023). CONCLUSION: Patients with cancer of the body or tail of the pancreas presenting with radiographic encasement of the splenic artery, but not the splenic vein, have a poorer prognosis and perhaps should be considered for neoadjuvant therapy before an attempt at curative resection.

Gemcitabine and Taxane Adjuvant Therapy with Chemoradiation in Resected Pancreatic Cancer: A Novel Strategy for Improved Survival?

BACKGROUND: Gemcitabine-taxane combination chemotherapy has demonstrated a survival benefit clinically in metastatic pancreatic cancer (PC). The authors present their experience with gemcitabine and docetaxel (gem/tax)-based adjuvant treatment (Rx) after surgery with curative intent. METHODS: Patients with de novo resectable PC from January 2010 to December 2015 were identified from the authors' institutional database and registry. The study included only patients who received gem/tax as their initial Rx administered exclusively at the authors' institution with or without chemoradiation (CRTx). Survival analysis was performed using Kaplan-Meier methods, and prognostic factors were investigated by Cox proportional hazard modeling. RESULTS: Of 102 patients identified, 58 met the study criteria. The median age at diagnosis was 65 years, with 55% of the patients undergoing an R1 resection (margin ≤ 1 mm). Tumor characteristics included a median tumor size of 28 mm, a poor differentiation rate of 54%, and a lymph node positivity of 67%. Most of the patients (90%, 52/58) completed 80% or more of the 24 week Rx. Of these patients, 71% received post-gem/tax CRTx Rx. Grade 3 or 4 toxicity was observed in 52% of the patients. The median follow-up period was 51.2 months, and the observed median overall survival (OS) was 52 months [95% confidence interval (CI) 27.4-not reached]. The actuarial 5-year OS was 49% (95% CI 33.7-63.4%). In the multivariate analysis, an R1 resection and American Joint Committee on Cancer (AJCC) stage 2 versus stage 1 disease were negatively associated with OS, whereas administration of CRTx was positively associated with OS. CONCLUSIONS: Adjuvant gem/tax with or without CRTx is feasible, with a favorable OS. Future prospective studies of gem/taxane-based adjuvant Rx for PC are warranted.

Local resection for duodenal gastrointestinal stromal tumors.

BACKGROUND: Duodenal gastrointestinal tumors (GIST) present infrequently, and surgical resection with negative margins remains the mainstay of therapy; however, given the lack of lymphatic and submucosal spread and anatomic location near the bile duct and pancreas, the optimal approach for resection is unknown. Options include local resection (LR), segmental resection, and pancreaticoduodenectomy (PD). METHODS: All cases of gastrointestinal stromal tumors originating from the duodenum from 2000 to 2015 were identified from administrative databases. Clinical and pathologic information was abstracted from the medical record and compared between patients who received LR vs PD. The chi-square with Fisher's exact test was used to detect differences between groups. RESULTS: Fifteen patients met the inclusion criteria, of which 7 had an LR and 8 had a PD. The second portion of the duodenum was the most common origin of GIST in the PD group, whereas the third portion was most common in the LR group. Patients who underwent LR tended to be younger, but there was no difference in tumor size, mitotic rate, margin positivity, readmission rate, or recurrence. PD was associated with more complications, higher blood loss, and longer length of stay. CONCLUSIONS: Local resection is a reasonable option for resection of duodenal GIST and should be routinely considered if technically feasible.

Expression of vascular endothelial growth factor and receptor flk-1 in colon cancer liver metastases.

BACKGROUND/PURPOSE: This study investigated vascular endothelial growth factor (VEGF) and flk-1 expression in hepatic metastases from colon carcinoma, and their associations with tumor angiogenesis, proliferation, and apoptosis. METHODS: Immunohistochemical studies were performed for VEGF/flk-1, Ki-67, p53, and bcl-2 expression, and microvessel density (MVD) in surgical specimens from 35 patients who underwent hepatectomy for colon cancer liver metastases between 1986 and 2001. RESULTS: VEGF and flk-1 were expressed mainly in the cytoplasm of tumor cells. High VEGF expression was associated with high flk-1 expression (P = 0.043). MVDs of less than 15 and 15 or more were found in 5 (14.3%) and 30 (85.7%) of 35 hepatic metastases, respectively. A Ki-67 index (KI) of 50% or more was detected in 33/35 (94.3%) of tumors, and 23 of these (65.7%) showed a KI of 85% or more. A KI of less than 50% was present in 2/35 (5.7%) of tumors. The expression of VEGF/flk-1 was related to elevated MVD (P < or = 0.026). VEGF was also associated with an increased KI (P = 0.025). Mutant p53 and bcl-2 expressions were detected in 26/35 (74.3%) and 17/35 (48.6%) of liver metastases, respectively. Mutant p53 was not related to VEGF/flk-1 expression, but bcl-2 was highly associated with flk-1 (P = 0.007). The incidences of high flk-1 expression and a KI of 85% or more were significantly higher in tumors which were both p53- and bcl-2-positive (93.3% and 73.3%) than in tumors which were negative for both (42.9% and 14.3%; P < or = 0.021). CONCLUSIONS: The VEGF-flk-1 system takes part in tumor angiogenesis, proliferation, and apoptosis in colon liver metastases. The bcl-2 pathway may upregulate VEGF activity via the flk-1 receptor. These findings are preliminary, requiring a larger sampling in order to elucidate the role of VEGF/flk-1 in metastatic colon cancer.

Outcomes after resection of cholangiocellular carcinoma.

BACKGROUND: Cholangiocellular carcinoma (CCC) is a rare primary liver malignancy that arises from intrahepatic bile duct canaliculi and presents as a liver mass. Our purpose is to report operative morbidity and mortality and to determine long-term survival after resection for CCC. METHODS: Retrospective review of 31 consecutive patients who underwent resection during a 20-year period. RESULTS: Thirty-day hospital mortality was 3%, and postoperative morbidity was 38%. Kaplan-Meier 5-year survival was 35%; mean survival was 37 months; absolute 5-year survival was 33%. Mean survival in stages I, II, IIIA, and IIIC were 57, 33, 26, and 14 months, respectively (P = 0.03 comparing I to >I). Recurrence occurred in 18 patients; 89% were in the liver. Carbohydrate antigen 19-9 >100 U/mL was found to be an indicator of poor prognosis (P = 0.009). CONCLUSIONS: Resection for CCC can be performed with acceptable morbidity and mortality rates and results in good survival and cure. Hepatic recurrence is common. Carbohydrate antigen 19-9 may be useful in determining prognosis.

Learning laparoscopic donor nephrectomy safely: a report on 100 cases.

HYPOTHESIS: There is concern that learning laparoscopic live donor nephrectomy (LLDN) is associated with increased morbidity. We propose that with a team approach LLDN can be learned safely, without increased donor morbidity or graft failure, even during the early portion of a learning curve. DESIGN: Case series with cohort comparison. SETTING: Tertiary referral center. PATIENTS: The laparoscopic group consisted of 100 donors and 100 recipients; the open group, 50 donors and 50 recipients. INTERVENTIONS: A team approach that combines laparoscopic and urologic expertise was used to perform 100 cases of LLDN. MAIN OUTCOME MEASURES: Donor morbidity and graft function in the laparoscopic group were compared with those in the open group. RESULTS: Laparoscopic live donor nephrectomy was completed in 99 patients. One patient required conversion to open donor nephrectomy because of intraoperative hemorrhage. Minor complications occurred in 6 laparoscopic group donors (6%) and 3 open group donors (6%). Laparoscopic and open group donors were of similar age. Operative times were longer for laparoscopic group donors (231 vs 209 minutes). Mean hospital stay was shorter for laparoscopic group donors (3.3 vs 4.7 days). Graft function was comparable between the laparoscopic and open groups, with equivalent postoperative creatinine levels. Graft survival was comparable. Recipient ureteral complications occurred with less frequency (2% vs 6%) in the laparoscopic group. CONCLUSIONS: By forming an operative team that combines expertise in laparoscopy with expertise in live donor nephrectomy, surgeons can learn LLDN safely. Adoption of the techniques developed by those who pioneered the procedure can further minimize the morbidity associated with a learning curve.