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1.
J Am Coll Surg ; 239(1): 61-67, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38770933

ABSTRACT

BACKGROUND: For open minor hepatectomy, morbidity and recovery are dominated by the incision. The robotic approach may transform this "incision dominant procedure" into a safe outpatient procedure. STUDY DESIGN: We audited outpatient (less than 2 midnights) robotic hepatectomy at 6 hepatobiliary centers in 2 nations to test the hypothesis that the robotic approach can be a safe and effective short-stay procedure. Establishing early recovery after surgery programs were active at all sites, and home digital monitoring was available at 1 of the institutions. RESULTS: A total of 307 outpatient (26 same-day and 281 next-day discharge) robotic hepatectomies were identified (2013 to 2023). Most were minor hepatectomies (194 single segments, 90 bi-segmentectomies, 14 three segments, and 8 four segments). Thirty-nine (13%) were for benign histology, whereas 268 were for cancer (33 hepatocellular carcinoma, 27 biliary, and 208 metastatic disease). Patient characteristics were a median age of 60 years (18 to 93 years), 55% male, and a median BMI of 26 kg/m 2 (14 to 63 kg/m 2 ). Thirty (10%) patients had cirrhosis. One hundred eighty-seven (61%) had previous abdominal operation. Median operative time was 163 minutes (30 to 433 minutes), with a median blood loss of 50 mL (10 to 900 mL). There were no deaths and 6 complications (2%): 2 wound infections, 1 failure to thrive, and 3 perihepatic abscesses. Readmission was required in 5 (1.6%) patients. Of the 268 malignancy cases, 25 (9%) were R1 resections. Of the 128 with superior segment resections (segments 7, 8, 4A, 2, and 1), there were 12 positive margins (9%) and 2 readmissions for abscess. CONCLUSIONS: Outpatient robotic hepatectomy in well-selected cases is safe (0 mortality, 2% complication, and 1.6% readmission), including resection in the superior or posterior portions of the liver that is challenging with nonarticulating laparoscopic instruments.


Subject(s)
Ambulatory Surgical Procedures , Hepatectomy , Robotic Surgical Procedures , Humans , Hepatectomy/methods , Middle Aged , Robotic Surgical Procedures/methods , Male , Female , Aged , Adult , Ambulatory Surgical Procedures/methods , Ambulatory Surgical Procedures/statistics & numerical data , Aged, 80 and over , Adolescent , Young Adult , Length of Stay/statistics & numerical data , Treatment Outcome , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Liver Neoplasms/surgery , Liver Neoplasms/mortality , Retrospective Studies
2.
Pancreas ; 53(6): e487-e491, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38460151

ABSTRACT

ABSTRACT: Poorly differentiated pancreatic neuroendocrine carcinomas (pNECs) are rare, highly aggressive neoplasms. Frequently metastatic at diagnosis, prognosis is poor with median overall survival estimated to be less than 1 year. Although multidisciplinary management, including systemic medications and locoregional therapies aimed at reducing and preventing symptoms caused by mass effect, is the mainstay of treatment for patients with metastatic well-differentiated pancreatic neuroendocrine tumors, rapid progression, organ dysfunction, and poor performance status often preclude initiation of even single-modality palliative chemotherapy for patients with metastatic pNEC, limiting the use of and recommendation for multidisciplinary management.We describe the case of a 51-year-old male patient diagnosed with pNEC metastatic to liver and lymph nodes presenting with impending cholestatic liver failure for whom we were able to successfully initiate and dose-escalate cytotoxic chemotherapy with excellent radiographic response. After multidisciplinary review of his case, the patient underwent pancreaticoduodenectomy and hepatic wedge biopsies, with pathology demonstrating a pathologic complete response to chemotherapy in both the pancreas and liver. Surveillance scans at 2 years from initial diagnosis and 1 year from surgery remain without evidence of locoregional or distant recurrence, highlighting the importance and utility of multidisciplinary management in select cases.


Subject(s)
Carcinoma, Neuroendocrine , Liver Neoplasms , Pancreatic Neoplasms , Humans , Male , Pancreatic Neoplasms/therapy , Pancreatic Neoplasms/pathology , Middle Aged , Carcinoma, Neuroendocrine/drug therapy , Carcinoma, Neuroendocrine/therapy , Carcinoma, Neuroendocrine/secondary , Carcinoma, Neuroendocrine/pathology , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Pancreaticoduodenectomy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Treatment Outcome , Lymphatic Metastasis , Combined Modality Therapy
3.
Pancreas ; 52(5): e282-e287, 2023 May 01.
Article in English | MEDLINE | ID: mdl-37782886

ABSTRACT

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDA) is the third most common cause of cancer death in the United States. Most patients who undergo resection develop recurrence. Standard treatment confers a median overall survival (OS) of 24 months. Exposure to alternate regimens may prevent chemoresistance. This study evaluated multiagent perioperative therapy for potentially resectable PDA patients to improve OS. METHODS: A single center, phase 2, trial of patients with resectable or borderline resectable PDA. Patients received neoadjuvant therapy with induction chemotherapy (gemcitabine, docetaxel, capecitabine) for 3 cycles, chemoradiation (intensity-modulated radiation therapy with capecitabine and oxaliplatin) followed by surgery, and 2 months of adjuvant gemcitabine and oxaliplatin and 2 months of gemcitabine. The primary endpoint was OS. The secondary endpoint was recurrence-free survival (RFS). RESULTS: Thirty-two eligible patients were enrolled. Twenty-two patients underwent surgical resection. After a median follow-up of 56.8 months, mOS was 31.6 months (95% confidence interval [CI], 14.2-58.1) for all patients, 58.1 months (95% CI, 31.6 to NR) for those who completed surgery. The mRFS was 31.3 months (95% CI, 12.5 to NR). CONCLUSIONS: Perioperative therapy with GTX, chemoradiotherapy, and adjuvant GemOx/Gem resulted in promising survival of 58 months for patients who underwent resection and may represent another treatment option for PDA.


Subject(s)
Adenocarcinoma , Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/pathology , Capecitabine , Oxaliplatin , Adenocarcinoma/drug therapy , Chemoradiotherapy/methods , Carcinoma, Pancreatic Ductal/surgery , Carcinoma, Pancreatic Ductal/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Neoadjuvant Therapy/adverse effects , Neoadjuvant Therapy/methods , Fluorouracil , Pancreatic Neoplasms
5.
Ann Surg Oncol ; 30(12): 7720-7730, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37488390

ABSTRACT

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.

6.
Am J Surg ; 226(2): 286-289, 2023 08.
Article in English | MEDLINE | ID: mdl-36959023

ABSTRACT

Surgery is considered for patients without metastatic disease and with resectable primary tumor. Pre-operatively, high quality imaging is reviewed to determine the likely extent of resection, specifically including the need for potential en-bloc resection of adjacent organs. In cases where up-front surgical approach would expose the patient to excessive morbidity (such as bilateral nephrectomy, multi-visceral resection, or prohibitively high risk of positive margins), neoadjuvant chemotherapy and/or chemoradiotherapy is considered. Though data are sparse in LMS, a neoadjuvant regimen of doxorubicin and dacarbazine is typically considered for borderline resectable tumors at our institution; patients may be treated for up to 4 months with interval imaging every 2 months to evaluate for tumor response. Postoperatively, adjuvant systemic therapy or radiation may be considered for patients with positive surgical margins or high-grade tumors.


Subject(s)
Leiomyosarcoma , Plastic Surgery Procedures , Humans , Vena Cava, Inferior/surgery , Vena Cava, Inferior/pathology , Leiomyosarcoma/surgery , Nephrectomy , Combined Modality Therapy
7.
Ann Surg Oncol ; 30(3): 1312-1326, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36335273

ABSTRACT

BACKGROUND: The National Comprehensive Cancer Network recommends genetic testing in patients with potentially hereditary breast, ovarian, pancreatic, and prostate cancers (HBOPP). Knowledge of genetic mutations impacts decisions about screening and treatment. METHODS: A retrospective cohort study of 28,586 HBOPP patients diagnosed from 2013 to 2019 was conducted using a linked administrative-cancer database in the Seattle-Puget Sound SEER area. Guideline-concordant testing (GCT) was assessed annually according to guideline updates. Frequency of testing according to patient/cancer characteristics was evaluated using chi-squared tests, and factors associated with receipt of genetic testing were identified using multivariable logistic regression. RESULTS: Testing occurred in 17% of HBOPP patients, increasing from 9% in 2013 to 21% in 2019 (p < 0.001). Ovarian cancer had the highest testing (40%) and prostate cancer the lowest (4%). Age < 50, female sex, non-Hispanic White race, commercial insurance, urban location, family history of HBOPP, and triple negative breast cancer (TNBC) were associated with increased testing (all p < 0.05). GCT increased from 38% in 2013 to 44% in 2019, and was highest for early age at breast cancer diagnosis, TNBC, male breast cancer, and breast cancer with family history of HBOPP (all > 70% in 2019), and lowest for metastatic prostate cancer (6%). CONCLUSIONS: The frequency of genetic testing for HBOPP cancer has increased over time. Though GCT is high for breast cancer, there are gaps in concordance among patients with other cancers. Increasing provider and patient education, genetic counseling, and insurance coverage for testing among HBOPP patients may improve guideline adherence.


Subject(s)
Breast Neoplasms , Genetic Testing , Ovarian Neoplasms , Pancreatic Neoplasms , Prostatic Neoplasms , Female , Humans , Male , Breast Neoplasms/genetics , Genetic Counseling , Ovarian Neoplasms/genetics , Pancreatic Hormones , Prostatic Neoplasms/genetics , Retrospective Studies , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathology , Pancreatic Neoplasms/genetics
9.
Oncologist ; 27(12): 1025-1033, 2022 12 09.
Article in English | MEDLINE | ID: mdl-36124727

ABSTRACT

BACKGROUND: KRAS variant alleles may have differential biological properties which impact prognosis and therapeutic options in pancreatic ductal adenocarcinomas (PDA). MATERIALS AND METHODS: We retrospectively identified patients with advanced PDA who received first-line therapy and underwent blood and/or tumor genomic sequencing at the University of Washington between 2013 and 2020. We examined the incidence of KRAS mutation variants with and without co-occurring PI3K or other genomic alterations and evaluated the association of these mutations with clinicopathological characteristics and survival using a Cox proportional hazards model. RESULTS: One hundred twenty-six patients had genomic sequencing data; KRAS mutations were identified in 111 PDA and included the following variants: G12D (43)/G12V (35)/G12R (23)/other (10). PI3K pathway mutations (26% vs. 8%) and homologous recombination DNA repair (HRR) defects (35% vs. 12.5%) were more common among KRAS G12R vs. non-G12R mutated cancers. Patients with KRAS G12R vs. non-G12R cancers had significantly longer overall survival (OS) (HR 0.55) and progression-free survival (PFS) (HR 0.58), adjusted for HRR pathway co-mutations among other covariates. Within the KRAS G12R group, co-occurring PI3K pathway mutations were associated with numerically shorter OS (HR 1.58), while no effect was observed on PFS. CONCLUSIONS: Patients with PDA harboring KRAS G12R vs. non-G12R mutations have longer survival, but this advantage was offset by co-occurring PI3K alterations. The KRAS/PI3K genomic profile could inform therapeutic vulnerabilities in patients with PDA.


Subject(s)
Neoplasms , Phosphatidylinositol 3-Kinases , Humans , Phosphatidylinositol 3-Kinases/genetics , Retrospective Studies , Genomics , Mutation , Proto-Oncogene Proteins p21(ras)/genetics
10.
HPB (Oxford) ; 24(11): 2029-2034, 2022 11.
Article in English | MEDLINE | ID: mdl-35953409

ABSTRACT

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a significant contributor to morbidity after pancreatectomy. Somatostatin analogues have shown variable efficacy in the prevention of CR-POPF. Lanreotide is a somatostatin analogue ideally suited for perioperative use due to its long half-life and favorable side effect profile. METHODS: We conducted a phase II single-arm trial of a single dose of preoperative lanreotide (120 mg) in patients undergoing either pancreaticoduodenectomy (PD) or distal pancreatectomy (DP). The primary outcome was development of CR-POPF or intra-abdominal abscess. Secondary outcomes included biochemical leak and overall morbidity. RESULTS: A total of 98 patients completed the study. Sixty-two underwent PD (63.3%) and 36 underwent DP (36.7%). The primary outcome was observed in eight (8%) patients in the overall cohort, one from the DP group and seven from the PD group. Biochemical leak was detected in 12 (12.2%) patients in the overall cohort. Twenty-seven (27.5%) patients developed complications, of which 14 (14.2%) were major complications. Drug-related adverse events were limited to mild skin reactions in two (2%) patients. CONCLUSION: Patients who received preoperative lanreotide developed CR-POPF at rates significantly lower than historical controls or published literature. This provides strong justification for a randomized controlled trial.


Subject(s)
Pancreatic Fistula , Postoperative Complications , Somatostatin , Humans , Pancreatectomy/adverse effects , Pancreatic Fistula/etiology , Pancreatic Fistula/prevention & control , Pancreaticoduodenectomy/adverse effects , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Retrospective Studies , Risk Factors , Somatostatin/adverse effects
11.
Lab Anim ; 56(6): 519-527, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35765854

ABSTRACT

While over the past several decades mortality after pancreatic surgery has decreased to <5%, postoperative morbidity remains remarkably high, ranging from 15% to 65%. The development of a postoperative pancreatic fistula (POPF) is a significant contributor to morbidity in patients undergoing pancreatic surgery. POPF can lead to life-threatening conditions such as intra-abdominal abscess, uncontrolled hemorrhage, sepsis, and death. Rates of POPF have not significantly changed over time, despite the introduction of multiple technical and pharmacologic interventions aimed at their treatment and prevention. Unfortunately, there are few POPF experimental models that have been described in the literature and existing models are unable to reliably reproduce the clinical sequelae of POPF, limiting the development of new methods to prevent and treat POPF. Herein, we describe a new rat experimental model that reliably creates a POPF via transection of the common pancreatic duct.


Subject(s)
Pancreatic Fistula , Pancreaticoduodenectomy , Rats , Animals , Pancreatic Fistula/etiology , Pancreatic Fistula/prevention & control , Pancreatic Fistula/surgery , Risk Factors , Pancreas/surgery , Postoperative Complications/etiology
12.
Surg Endosc ; 36(2): 889-895, 2022 02.
Article in English | MEDLINE | ID: mdl-33608766

ABSTRACT

BACKGROUND: Robotic hepatectomy (RH) is increasingly utilized for minor and major liver resections. The IWATE criteria were developed to classify minimally invasive liver resections by difficulty. The objective of this study was to apply the IWATE criteria in RH and to describe perioperative and oncologic outcomes of RH over the last decade at our institution. METHODS: Perioperative and oncologic outcomes of patients who underwent RH between 2011 and 2019 were retrospectively collected. The difficulty level of each operation was assessed using the IWATE criteria, and outcomes were compared at each level. Univariate linear regression was performed to characterize the relationship between IWATE criteria and perioperative outcomes (OR time, EBL, and LOS), and a multivariable model was also developed to address potential confounding by patient characteristics (age, sex, BMI, prior abdominal surgery, ASA class, and simultaneous non-hepatectomy operation). RESULTS: Two hundred and twenty-five RH were performed. Median IWATE criteria for RH were 6 (IQR 5-9), with low, intermediate, advanced, and expert resections accounting for 23% (n = 51), 34% (n = 77), 32% (n = 72), and 11% (n = 25) of resections, respectively. The majority of resections were parenchymal-sparing approaches, including anatomic segmentectomies and non-anatomic partial resections. 30-day complication rate was 14%, conversion to open surgery occurred in 9 patients (4%), and there were no deaths within 30 days postoperatively. In the univariate linear regression analysis, IWATE criteria were positively associated with OR time, EBL, and LOS. In the multivariable model, IWATE criteria were independently associated with greater OR time, EBL, and LOS. Two-year overall survival for hepatocellular carcinoma and intrahepatic cholangiocarcinoma was 94% and 50%, respectively. CONCLUSION: In conclusion, the IWATE criteria are associated with surgical outcomes after RH. This series highlights the utility of RH for difficult hepatic resections, particularly parenchymal-sparing resections in the posterosuperior sector, extending the indication of minimally invasive hepatectomy in experienced hands and potentially offering select patients an alternative to open hepatectomy or other less definitive liver-directed treatment options.


Subject(s)
Bile Duct Neoplasms , Laparoscopy , Liver Neoplasms , Robotic Surgical Procedures , Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic/pathology , Hepatectomy/adverse effects , Humans , Laparoscopy/adverse effects , Length of Stay , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Retrospective Studies , Robotic Surgical Procedures/adverse effects
13.
J Nucl Med ; 63(7): 1033-1038, 2022 07.
Article in English | MEDLINE | ID: mdl-34772791

ABSTRACT

Hepatocellular carcinoma (HCC) is a significant cause of morbidity and mortality worldwide, with limited therapeutic options for advanced disease. Targeted α-therapy is an emerging class of targeted cancer therapy in which α-particle-emitting radionuclides, such as 227Th, are delivered specifically to cancer tissue. Glypican-3 (GPC3) is a cell surface glycoprotein highly expressed on HCC. In this study, we describe the development and in vivo efficacy of a 227Th-labeled GPC3-targeting antibody conjugate (227Th-octapa-αGPC3) for treatment of HCC in an orthotopic murine model. Methods: The chelator p-SCN-Bn-H4octapa-NCS (octapa) was conjugated to a GPC3-targeting antibody (αGPC3) for subsequent 227Th radiolabeling (octapa-αGPC3). Conditions were varied to optimize radiolabeling of 227Th. In vitro stability was evaluated by measuring the percentage of protein-bound 227Th by γ-ray spectroscopy. An orthotopic athymic Nu/J murine model using HepG2-Red-FLuc cells was developed. Biodistribution and blood clearance of 227Th-octapa-αGPC3 were evaluated in tumor-bearing mice. The efficacy of 227Th-octapa-αGPC3 was assessed in tumor-bearing animals with serial measurement of serum α-fetoprotein at 23 d after injection. Results: Octapa-conjugated αGPC3 provided up to 70% 227Th labeling yield in 2 h at room temperature. In the presence of ascorbate, at least 97.8% of 227Th was bound to αGPC3-octapa after 14 d in phosphate-buffered saline. In HepG2-Red-FLuc tumor-bearing mice, highly specific GPC3 targeting was observed, with significant 227Th-octapa-αGPC3 accumulation in the tumor over time and minimal accumulation in normal tissue. Twenty-three days after treatment, a significant reduction in tumor burden was observed in mice receiving a 500 kBq/kg dose of 227Th-octapa-αGPC3 by tail-vein injection. No acute off-target toxicity was observed, and no animals died before termination of the study. Conclusion:227Th-octapa-αGPC3 was observed to be stable in vitro; maintain high specificity for GPC3, with favorable biodistribution in vivo; and result in significant antitumor activity without significant acute off-target toxicity in an orthotopic murine model of HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Animals , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/radiotherapy , Cell Line, Tumor , Glypicans/chemistry , Glypicans/metabolism , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/radiotherapy , Mice , Tissue Distribution , Tumor Burden , Xenograft Model Antitumor Assays
14.
AJR Am J Roentgenol ; 217(5): 1104-1112, 2021 11.
Article in English | MEDLINE | ID: mdl-34467768

ABSTRACT

OBJECTIVE. Pancreatic ductal adenocarcinoma (PDAC) is often a lethal malignancy with limited preoperative predictors of long-term survival. The purpose of this study was to evaluate the prognostic utility of preoperative CT radiomics features in predicting postoperative survival of patients with PDAC. MATERIALS AND METHODS. A total of 153 patients with surgically resected PDAC who underwent preoperative CT between 2011 and 2017 were retrospectively identified. Demographic, clinical, and survival information was collected from the medical records. Survival time after the surgical resection was used to stratify patients into a low-risk group (survival time > 3 years) and a high-risk group (survival time < 1 year). The 3D volume of the whole pancreatic tumor and background pancreas were manually segmented. A total of 478 radiomics features were extracted from tumors and 11 extra features were computed from pancreas boundaries. The 10 most relevant features were selected by feature reduction. Survival analysis was performed on the basis of clinical parameters both with and without the addition of the selected features. Survival status and time were estimated by a random survival forest algorithm. Concordance index (C-index) was used to evaluate performance of the survival prediction model. RESULTS. The mean age of patients with PDAC was 67 ± 11 (SD) years. The mean tumor size was 3.31 ± 2.55 cm. The 10 most relevant radiomics features showed 82.2% accuracy in the classification of high-risk versus low-risk groups. The C-index of survival prediction with clinical parameters alone was 0.6785. The addition of CT radiomics features improved the C-index to 0.7414. CONCLUSION. Addition of CT radiomics features to standard clinical factors improves survival prediction in patients with PDAC.


Subject(s)
Carcinoma, Pancreatic Ductal/diagnostic imaging , Carcinoma, Pancreatic Ductal/mortality , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/mortality , Preoperative Care , Tomography, X-Ray Computed , Adult , Aged , Aged, 80 and over , Carcinoma, Pancreatic Ductal/surgery , Female , Humans , Machine Learning , Male , Middle Aged , Pancreatic Neoplasms/surgery , Prognosis , Retrospective Studies , Survival Analysis , Tumor Burden
15.
HPB (Oxford) ; 23(11): 1716-1721, 2021 11.
Article in English | MEDLINE | ID: mdl-34016543

ABSTRACT

BACKGROUND: Biliary anastomotic stricture (BAS) is an uncommon complication of pancreaticoduodenectomy (PD). As PDs are performed more frequently, BAS may become a more common pathologic entity requiring clinical engagement. The aim of this study was to report the incidence of BAS in the modern era of pancreatic surgery and identify risk factors associated with it. METHODS: Patients undergoing PD at the Johns Hopkins Hospital between 2007 and 2016 were identified using an institutional registry and clinicopathological features were analyzed to identify risk factors associated with BAS. RESULTS: Of 2125 patients identified, 103 (4.9%) developed BAS. Factors independently associated with BAS included laparoscopic approach (HR:2.83,95%CI:1.35-5.92, p = 0.006), postoperative pancreatic fistula (HR:2.45,95%CI:1.56-4.16,p < 0.001), postoperative bile leak (BL) (HR:5.26,95%CI:2.45-11.28,p < 0.001), and administration of adjuvant radiation therapy (HR:6.01,95%CI:3.19-11.34,p < 0.001). Malignant pathology was associated with lower rates of BAS (HR:0.52,95%CI:0.30-0.92, p = 0.025). BL was associated with higher rates of early-BAS (HR:16.49,95%CI:3.28-82.94, p = 0.001) while use of Vicryl suture for biliary enteric anastomosis was associated with lower rates of early-BAS (HR:0.20,95%CI:0.05-0.93, p = 0.041). CONCLUSION: Approximately 5% of patients undergoing PD experience BAS. Multiple factors are associated with the development and timing of BAS.


Subject(s)
Pancreatic Fistula , Pancreaticoduodenectomy , Anastomosis, Surgical/adverse effects , Constriction, Pathologic/surgery , Humans , Pancreatic Fistula/diagnosis , Pancreatic Fistula/epidemiology , Pancreatic Fistula/etiology , Pancreaticoduodenectomy/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Retrospective Studies
16.
Sci Rep ; 11(1): 3731, 2021 02 12.
Article in English | MEDLINE | ID: mdl-33580090

ABSTRACT

Glypican-3 (GPC3) is a tumor associated antigen expressed by hepatocellular carcinoma (HCC) cells. This preclinical study evaluated the efficacy of a theranostic platform using a GPC3-targeting antibody αGPC3 conjugated to zirconium-89 (89Zr) and yttrium-90 (90Y) to identify, treat, and assess treatment response in a murine model of HCC. A murine orthotopic xenograft model of HCC was generated. Animals were injected with 89Zr-labeled αGPC3 and imaged with a small-animal positron emission/computerized tomography (PET/CT) imaging system (immuno-PET) before and 30 days after radioimmunotherapy (RIT) with 90Y-labeled αGPC3. Serum alpha fetoprotein (AFP), a marker of tumor burden, was measured. Gross tumor volume (GTV) and SUVmax by immuno-PET was measured using fixed intensity threshold and manual segmentation methods. Immuno-PET GTV measurements reliably quantified tumor burden prior to RIT, strongly correlating with serum AFP (R2 = 0.90). Serum AFP was significantly lower 30 days after RIT in 90Y-αGPC3 treated animals compared to those untreated (p = 0.01) or treated with non-radiolabeled αGPC3 (p = 0.02). Immuno-PET GTV measurements strongly correlated with tumor burden after RIT (R2 = 0.87), and GTV of animals treated with 90Y-αGPC3 was lower than in animals who did not receive treatment or were treated with non-radiolabeled αGPC3, although this only trended toward statistical significance. A theranostic platform utilizing GPC3 targeted 89Zr and 90Y effectively imaged, treated, and assessed response after radioimmunotherapy in a GPC3-expressing HCC xenograft model.


Subject(s)
Carcinoma, Hepatocellular/therapy , Drug Delivery Systems/methods , Glypicans/immunology , Animals , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Glypicans/metabolism , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Mice , Mice, Nude , Positron-Emission Tomography/methods , Precision Medicine/methods , Radioimmunotherapy , Radioisotopes/pharmacology , Radiopharmaceuticals , Tissue Distribution , Xenograft Model Antitumor Assays , Yttrium Radioisotopes/pharmacology , Zirconium/pharmacology
18.
Lancet Gastroenterol Hepatol ; 5(8): 765-775, 2020 08.
Article in English | MEDLINE | ID: mdl-32511951

ABSTRACT

Around the world, recommendations for cancer treatment are being adapted in real time in response to the pandemic of COVID-19. We, as a multidisciplinary team, reviewed the standard management options, according to the Barcelona Clinic Liver Cancer classification system, for hepatocellular carcinoma. We propose treatment recommendations related to COVID-19 for the different stages of hepatocellular carcinoma (ie, 0, A, B, and C), specifically in relation to surgery, locoregional therapies, and systemic therapy. We suggest potential strategies to modify risk during the pandemic and aid multidisciplinary treatment decision making. We also review the multidisciplinary management of intrahepatic cholangiocarcinoma as a potentially curable and incurable diagnosis in the setting of COVID-19.


Subject(s)
Carcinoma, Hepatocellular/therapy , Coronavirus Infections/epidemiology , Liver Neoplasms/therapy , Pandemics , Pneumonia, Viral/epidemiology , Betacoronavirus , Bile Duct Neoplasms/therapy , COVID-19 , Carcinoma, Hepatocellular/pathology , Cholangiocarcinoma/therapy , Clinical Decision-Making , Humans , Liver Neoplasms/pathology , Neoplasm Staging , Patient Care Team , Risk Factors , SARS-CoV-2
19.
Chin Clin Oncol ; 9(4): 54, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32576018

ABSTRACT

BACKGROUND: Radical antegrade modular pancreatosplenectomy (RAMPS) has been adopted by some surgeons in the treatment of left-sided pancreatic cancer (PDAC). Low disease incidence and heterogenous disease biology make robust prospective comparison of RAMPS and standard distal pancreatosplenectomy (DPS) difficult. METHODS: Consecutive cases of chemo-naïve patients undergoing open RAMPS and DPS for PDAC between 2010-2017 at two international high-volume pancreatectomy centers were compared. Cox proportional hazard modeling was utilized for multivariate analysis. RESULTS: We identified 193 DPS and 253 RAMPS during the study period. DPS was associated with higher rates of median estimated blood loss (500 vs. 300 cc, P<0.001), median total harvested lymph nodes (18 vs. 12, P<0.001) and R0 resection (94.3% vs. 88.9%, P=0.013). There were no differences in rates of postoperative pancreatic fistula (16.5% vs. 17.8%, P=1) or postoperative hemorrhage (5.9% vs. 3.6%, P=0.385) (DPS vs. RAMPS). After controlling for significant clinical pathological parameters, RAMPS was associated with non-superior recurrence-free survival (RFS) (HR 0.29; 95% CI, 0.07-1.27, P=0.101) and overall-survival (HR 1.03; 95% CI, 0.71-1.49, P=0.895) compared with DPS. Similar results were observed in node-positive patients. CONCLUSIONS: RAMPS is safe and effective in the treatment of PDAC, but is not associated with an improvement in either RFS or overall-survival over DPS.


Subject(s)
Pancreatectomy/methods , Pancreatic Neoplasms/surgery , Splenectomy/methods , Aged , Female , Humans , Male , Pancreatic Neoplasms
20.
Surg Oncol ; 28: 158, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30851893

ABSTRACT

BACKGROUND: Laparoscopic anatomical liver resection for posterosuperior lesions is challenging [1,2] A technique of anatomical liver resection with intrahepatic Glissonian approach in open surgery has been published [3]. However, few articles report this technique via the laparoscopic approach [4]. We report a case of laparoscopic anatomical S7 segmentectomy using the Glissonian pedicle approach. VIDEO: A 76-year-old male was admitted for an incidentally detected hepatic mass in segment 7 (S7). Abdominal computed tomography (CT) showed a 5.5 cm solitary tumor. First, the major Glissonian pedicle of the right posterior section was dissected, followed by hepatic parenchymal dissection peripherally until the branches of the Glissonian pedicles of segment 6 and 7 were reached. The S7 Glissonian pedicle was temporarily clamped to confirm demarcation. Dissection was then performed until the right hepatic vein (RHV) was exposed. Further dissection was then continued along the RHV, up to its root. RESULTS: Operative time was 330 minutes. The estimated intraoperative blood loss was 300 mL without a requirement for intraoperative transfusion. On postoperative day 4, the abdominal CT was performed, which revealed no abnormal findings. The patient was discharged on postoperative day 5 without any complications. Pathologic findings demonstrated a 5.2 × 3.8 × 3.1 cm hepatocellular carcinoma (pT1b) with a 2.8-cm tumor-free resection margin. CONCLUSION: Laparoscopic anatomical S7 segmentectomy via the intrahepatic Glissonian approach is a technically demanding procedure and should be adopted for selected patients. However, this technique is feasible with careful dissection and control of the intrahepatic Glissonian pedicle.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy/methods , Laparoscopy/methods , Liver Neoplasms/surgery , Tomography, X-Ray Computed/methods , Aged , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/pathology , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Male , Prognosis
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