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1.
J Natl Compr Canc Netw ; 21(7): 694-704, 2023 07.
Article in English | MEDLINE | ID: mdl-37433432

ABSTRACT

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.


Subject(s)
Bile Duct Neoplasms , Biliary Tract Neoplasms , Cholangiocarcinoma , Gallbladder Neoplasms , Liver Neoplasms , Humans , Biliary Tract Neoplasms/diagnosis , Biliary Tract Neoplasms/therapy , Gallbladder Neoplasms/diagnosis , Gallbladder Neoplasms/therapy , Cholangiocarcinoma/diagnosis , Cholangiocarcinoma/therapy , Liver Neoplasms/diagnosis , Liver Neoplasms/therapy , Bile Ducts, Intrahepatic
2.
Am Surg ; 88(5): 887-893, 2022 May.
Article in English | MEDLINE | ID: mdl-35012359

ABSTRACT

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is associated with significant operative time, hospital resources, and morbidity. We examine factors associated with hospital length of stay (LOS) and early overall survival (OS) after CRS/HIPEC. MATERIALS AND METHODS: Patients who underwent CRS/HIPEC were evaluated for factors associated with LOS. Institutional learning curve influence was addressed by comparing early vs late cohorts. Variables with P < .200 after univariate analysis were considered for inclusion in multivariate linear regression modeling. Independent factors associated with OS were evaluated using the Kaplan-Meier method. RESULTS: Seventy patients underwent CRS/HIPEC (mean age 52.3 years, 64.3% female, and 68.6% Caucasian). Presence of any surgical complication was found in 26 (37.1%), 28 (40%) remained intubated postoperatively, and the mean Peritoneal Carcinomatosis Index (PCI) score was 14.4 (±10.4). Mean intensive care unit and hospital LOS were 2.9 days (±2.3) and 9.6 days (±3.6), respectively. After adjusting for covariates, only shorter time to postoperative ambulation (regression coefficient .92, P = .001) and early extubation (regression coefficient -1.90, P = .018) were associated with decreased hospital LOS on multivariate analysis. Immediate postoperative extubation conferred an independent early survival benefit on Kaplan-Meier analysis (mean OS 714.8 vs 473.4 days, P = .010). There was no difference in hospital LOS or OS between early and late cohorts. CONCLUSION: Early postoperative extubation and shorter time to ambulation are associated with decreased hospital LOS. Moreover, CRS/HIPEC patients extubated immediately postoperatively have an early survival benefit. Every effort should be made to achieve early postoperative extubation and mobilization in CRS/HIPEC patients.


Subject(s)
Hyperthermia, Induced , Peritoneal Neoplasms , Airway Extubation , Combined Modality Therapy , Cytoreduction Surgical Procedures , Female , Hospitalization , Humans , Hyperthermic Intraperitoneal Chemotherapy , Male , Middle Aged , Peritoneal Neoplasms/surgery , Retrospective Studies , Survival Rate
3.
Ann Surg Oncol ; 27(1): 171-178, 2020 Jan.
Article in English | MEDLINE | ID: mdl-30963398

ABSTRACT

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare intra-abdominal soft tissue sarcoma affecting adolescents and young adults. Cytoreduction, hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), and adjuvant radiotherapy may improve local control. We review our experience with patients who undergo CRS/HIPEC and adjuvant radiotherapy for DSRCT. METHODS: A retrospective review was performed for patients with DSRCT from 2013 to 2017 who underwent CRS/HIPEC. Clinicopathologic, operative, and outcome data were reviewed. RESULTS: Ten CRS/HIPEC procedures were performed for nine patients (7 males, 6 Caucasian, median age 19 years (range 10-24)). Four patients presented with extra-abdominal disease; five had liver involvement. The median peritoneal cancer index was 16 (range 5-20). All received neoadjuvant chemotherapy. CCR 0/1 resection was possible in nine patients. Major complications occurred in four with no operative mortalities. All received adjuvant chemotherapy, seven received radiation therapy, and three received stem-cell transplant. All but one patient recurred after treatment. The median recurrence-free and overall survival (OS) were 12 and 45 months (95% confidence interval 35.1-54.9) respectively, with a 3-year OS of 55%. Long-term parenteral nutrition was required in eight for a median of 261 days (range 37-997). Clinically significant long-term complications requiring further surgery included gastroparesis (N = 1), small bowel obstruction (N = 3) and hemorrhagic cystitis (N = 2). CONCLUSIONS: Multimodal therapy for DSRCT consisting of multiagent neoadjuvant chemotherapy, CRS/HIPEC, adjuvant chemotherapy, and radiation therapy is associated with potential cumulative toxicity. Recurrence after resection is common. Prolonged parenteral nutrition may be necessary, and late gastrointestinal and genitourinary complications may require additional treatment.


Subject(s)
Cytoreduction Surgical Procedures/adverse effects , Desmoplastic Small Round Cell Tumor/therapy , Hyperthermia, Induced/adverse effects , Peritoneal Neoplasms/therapy , Adolescent , Antineoplastic Agents/therapeutic use , Chemotherapy, Adjuvant , Child , Combined Modality Therapy/adverse effects , Desmoplastic Small Round Cell Tumor/mortality , Desmoplastic Small Round Cell Tumor/pathology , Female , Follow-Up Studies , Humans , Male , Neoplasm Recurrence, Local , Neoplasm Staging , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/pathology , Postoperative Complications , Retrospective Studies , Survival Rate , Young Adult
4.
Ann Surg Oncol ; 26(1): 131-138, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30353396

ABSTRACT

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive sarcoma. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may improve survival. METHODS: A retrospective review of anesthetic management and postoperative pain control strategies after CRS/HIPEC for DSRCT from 2013 to 2017 was performed. RESULTS: The review analyzed 10 CRS/HIPEC procedures performed for nine DSRCT patients with a median age of 19 years (range 10-24 years). Six of these patients were Caucasian, and seven were men. The median operative duration was 551 min (range 510-725 min), and the median anesthesia duration was 621 min (range 480-820 min). Postoperative mechanical ventilation was necessary in 5 patients for a median duration of 1 day (range 0-2 days). The median intraoperative intravenous fluid administration was 13 ml/kg/h (range 6.3-24.4 ml/kg/h), and the colloid administration was 12 ml/kg (range 0.0-53.0 ml/kg). The median blood loss was 15 ml/kg (range 6.3-77.2 ml/kg). Nine patients received intraoperative transfusion with a median red blood cell transfusion volume of 14 ml/kg (range 10.1-58.5 ml/kg). The median intraoperative urine output was 2 ml/kg/h (range 0.09-8.40 ml/kg/h), and half of the patients received intraoperative diuretics. Cisplatin was used during HIPEC for eight surgeries. Acute kidney injury was observed in two patients, one of whom required short-term dialysis. Epidural infusions were used in eight cases for a median of 4 days (range 3-5 days). Postoperative intravenous opioid use (morphine equivalent) was 0.67 mg/kg/day (range 0.1-9.2 mg/kg/day) administered for a median of 11 days (range 2-35 days). CONCLUSION: Cytoreduction and HIPEC for DSRCT are associated with significant perioperative fluid requirements and potentially challenging pain management. Renal protective strategies should be considered for reduction of cisplatin-associated nephrotoxicity. Further investigation for a more effective, less systemically toxic HIPEC agent is warranted.


Subject(s)
Anesthetics/therapeutic use , Chemotherapy, Cancer, Regional Perfusion/adverse effects , Cytoreduction Surgical Procedures/adverse effects , Desmoplastic Small Round Cell Tumor/therapy , Hyperthermia, Induced/adverse effects , Pain Management , Pain/drug therapy , Adolescent , Adult , Child , Combined Modality Therapy , Desmoplastic Small Round Cell Tumor/pathology , Female , Follow-Up Studies , Humans , Male , Pain/etiology , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/therapy , Prognosis , Retrospective Studies , Young Adult
5.
Surg Oncol Clin N Am ; 20(2): 229-35, vii, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21377580

ABSTRACT

Through 5,000 years of practice, physicians, surgeons, clergy, or lay people have used thermal therapy to treat mass lesions now known as cancer. The methods have changed dramatically over this time span and certainly the techniques have improved the efficacy and safety. Hyperthermia used in combination with chemotherapy or ionizing radiation continues to improve outcomes. The authors briefly describe the historical role of hyperthermia in cancer care as well as modern expectations based on technological advancements. In particular, the article focuses on the role of hyperthermia for cancers that do not have other, more effective treatments.


Subject(s)
Hyperthermia, Induced/history , Neoplasms/history , History, 20th Century , History, 21st Century , History, Ancient , Humans , Neoplasms/therapy
6.
Surgery ; 148(2): 319-24, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20541785

ABSTRACT

BACKGROUND: Gold and carbon nanoparticles absorb nonionizing radio frequency (RF) energy and release heat. Solid gold nanoparticles are delivered to cancer cells via conjugation with targeting antibodies. Here, 20-nm gold particles were conjugated to cetuximab, which is an epidermal growth factor receptor-1 (EGFR-1) antibody. METHODS: A pancreatic carcinoma cell line that highly expresses EGFR-1, Panc-1, and Cama-1, which is a breast carcinoma cell line that minimally expresses EGFR-1, were treated with 100-nmol/L cetuximab-conjugated gold nanoparticles for 3 h (n = 4). Thirty-six hours later, the dishes were placed in an RF field with a generator power of 200 W for 5 min. After another 36 h, cell injury and death were evaluated with flow cytometry. RESULTS: The targeted cell line Panc-1 had a viability of 46% +/- 12%, whereas the Cama-1 cell had a viability of 92% +/- 2% after RF field exposure (P < .008). Transmission electron microscopy showed gold nanoparticle uptake in Panc-1 cells but negligible uptake by Cama-1 cells. Nontargeted cells do not internalize a sufficient amount of antibody-conjugated gold nanoparticles to induce injury in a noninvasive RF field. CONCLUSION: This technique could be useful in cancer treatment if a cancer-specific antibody is used to localize gold nanoparticles to malignant cells.


Subject(s)
Metal Nanoparticles/therapeutic use , Pancreatic Neoplasms/therapy , Radiofrequency Therapy , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Cell Line, Tumor , Cell Survival , Cetuximab , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Gold/administration & dosage , Gold/therapeutic use , Humans , Hyperthermia, Induced , Metal Nanoparticles/administration & dosage , Microscopy, Electron, Transmission , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology
7.
Cancer ; 116(13): 3285-93, 2010 Jul 01.
Article in English | MEDLINE | ID: mdl-20564640

ABSTRACT

BACKGROUND: Nonionizing radiation, such as radiofrequency field and near infrared laser, induces thermal cytotoxicity in cancer cells treated with gold nanoparticles. Quantum dots are fluorescent semiconducting nanoparticles that were hypothesized to induce similar injury after radiofrequency field irradiation. METHODS: Gold nanoparticles and 2 types of quantum dot (cadmium-selenide and indium-gallium-phosphide) conjugated to cetuximab (C225), a monoclonal antibody against human epidermal growth factor receptor (EGFR)-1, demonstrated concentration-dependent heating in a radiofrequency field. The authors investigated the effect of radiofrequency field exposure after targeted nanoparticle treatment in a coculture of 2 human cancer cell lines that have differential EGFR-1 expression (a high-expressing pancreatic carcinoma, Panc-1, and a low-expressing breast carcinoma, Cama-1). RESULTS: Radiofrequency revealed that Panc-1 or Cama-1 cells not containing gold nanoparticles or quantum dots had a viability of > 92%. The viability of Panc-1 cells exposed to the radiofrequency field after treatment with 50 nM Au-C225 was 39.4% +/- 8.3% without injury to bystander Cama-1 cells (viability was 93.7% +/- 1.0%; P approximately .0006). Panc-1 cells treated with targeted cadmium-selenide quantum dots were only 47.5% viable after radiofrequency field exposure (P< .0001 compared with radiofrequency only Panc-1 control cells). Targeted indium-gallium-phosphide quantum dots decreased Panc-1 viability to 58.2% +/- 3.4% after radiofrequency field exposure (P = approximately .0004 compared with Cama-1 and Panc-1 controls). CONCLUSIONS: The authors selectively induced radiofrequency field cytotoxicity in Panc-1 cells without injury to bystander Cama-1 cells using EGFR-1-targeted nanoparticles, and demonstrated an interesting bifunctionality of fluorescent nanoparticles as agents for both cancer cell imaging and treatment.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Antineoplastic Agents/administration & dosage , Hyperthermia, Induced/methods , Pancreatic Neoplasms/therapy , Quantum Dots , Radio Waves , Antibodies, Monoclonal, Humanized , Apoptosis , Cetuximab , Drug Delivery Systems , ErbB Receptors/immunology , ErbB Receptors/metabolism , Fluorescence , Gold/pharmacokinetics , Metal Nanoparticles
8.
Surgery ; 148(2): 310-8, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20466402

ABSTRACT

BACKGROUND: Hepatocellular and pancreatic carcinomas are often auxotrophic for L-arginine, a semi-essential amino acid. The purpose of this study was to investigate cancer cell death using a significantly more active, cobalt-substituted bioengineered arginase. METHODS: Panc-1, a human pancreatic carcinoma cell line, and Hep 3B, a human hepatocellular carcinoma cell line, were exposed to L-arginase. Flow cytometry was used to measure expression of Ki-67, caspase-3, and argininosuccinate synthetase-1 (ASS-1) 4 days after treatment. An MTT assay measured proliferation. The Student t test determined statistical significance. RESULTS: Viability decreased by 31% +/- 2% for Panc-1 cells (P < .0001) and 34% +/- 1% (P < .0001) for Hep 3B cells after treatment. Both cell lines demonstrated a 4-fold increase activated caspase-3 expression after high dose treatment (P < .01), and 5-fold increase in ASS-1 expression (P < .002). Ki-67 expression did not vary in Hep 3B cells but decreased for Panc-1 cells (P < .015). The 50% inhibitory concentration was 8-fold higher for Panc-1 cells than for Hep 3B cells (P < .03). CONCLUSION: Increased ASS-1 expression by these cells, in order to increase L-arginine concentration, is inadequate, suggesting a mechanism by which arginine depletion can be used in multimodality therapy for arginine-dependent cancers.


Subject(s)
Arginase/pharmacology , Argininosuccinate Synthase/biosynthesis , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/enzymology , Caspase 3/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/enzymology , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/enzymology , Apoptosis/drug effects , Apoptosis/physiology , Arginase/administration & dosage , Arginine/metabolism , Carcinoma, Hepatocellular/pathology , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Enzyme Induction/drug effects , Humans , Ki-67 Antigen/metabolism , Liver Neoplasms/pathology , Models, Biological , Pancreatic Neoplasms/pathology , Protein Engineering , Recombinant Proteins/administration & dosage , Recombinant Proteins/pharmacology
9.
J Clin Oncol ; 28(13): 2220-6, 2010 May 01.
Article in English | MEDLINE | ID: mdl-20351325

ABSTRACT

PURPOSE: It is well known that hepatocellular carcinoma (HCC) is an arginine auxotroph due to argininosuccinate synthetase I deficiency. This study's purpose was to evaluate the effects of pegylated arginine deiminase (ADI) in terms of toxicity, tumor response, alpha-fetoprotein (AFP) levels, and serum arginine levels. PATIENTS AND METHODS: Eighty patients were randomly assigned to receive either 80 IU/m(2) or 160 IU/m(2) of ADI weekly for up to 6 months. Adverse events, serum arginine, AFP levels, and antibody production against ADI were measured on a regular basis. In addition, disease response and time to progression according to the Response Evaluation Criteria in Solid Tumors (RECIST) and survival rates were evaluated. RESULTS: Four patients were excluded from the survival analysis because they developed exclusion criteria after randomization, but before first treatment. The number of patients in the two cohorts were similar (n = 37 in the low-dose cohort, n = 39 in the high-dose cohort). Mean (+/-SE) survival for all subjects was 15.8 months (474 days +/- 39 days) from time of diagnosis of unresectable disease. Arginine levels remained below baseline for 50 days while antibodies against ADI reached a plateau at approximately the same time. There were no deaths attributed to ADI treatment. Only two patients were withdrawn for immunogenic-related adverse events. Grade 2, 3, or 4 toxicities were recorded in 92, 19, and 0 patients, respectively. CONCLUSION: Pegylated ADI is a promising drug that capitalizes on a significant enzymatic deficiency in HCC. It is safe, well tolerated, and may benefit patients with unresectable HCC.


Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma, Hepatocellular/drug therapy , Hydrolases/administration & dosage , Liver Neoplasms/drug therapy , Polyethylene Glycols/administration & dosage , Aged , Aged, 80 and over , Antibodies/blood , Antineoplastic Agents/adverse effects , Antineoplastic Agents/immunology , Arginine/blood , Biomarkers/blood , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/secondary , Chi-Square Distribution , Female , Humans , Hydrolases/adverse effects , Hydrolases/immunology , Injections, Intramuscular , Kaplan-Meier Estimate , Liver Neoplasms/metabolism , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Polyethylene Glycols/adverse effects , Time Factors , Treatment Outcome , alpha-Fetoproteins/metabolism
10.
Adv Drug Deliv Rev ; 62(3): 339-45, 2010 Mar 08.
Article in English | MEDLINE | ID: mdl-19909777

ABSTRACT

Despite the use of hyperthermia to treat cancer for thousands of years, the challenge of only heating malignant cells remains daunting. In pre-clinical and early clinical trials, metal nanoparticles induce hyperthermic cytotoxicity when exposed to near-infrared radiation or radiofrequency fields. We discuss the emerging roles of nanoparticles, especially gold, in the hyperthermic treatment of cancer. In addition, we discuss the similarities of radiofrequency ablation and nanoparticle mediated cytotoxicity.


Subject(s)
Hyperthermia, Induced/methods , Metal Nanoparticles/administration & dosage , Neoplasms/therapy , Catheter Ablation/methods , Clinical Trials as Topic , Gold/chemistry , Humans , Nanotechnology/methods
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