Circumstances and implications of conversion from minimally invasive to open liver resection: a multi-center analysis from the AMILES registry.

BACKGROUND: Minimally invasive approaches to liver resection (MILR) are associated with favorable outcomes. The aim of this study was to determine the implications of conversion to an open procedure on perioperative outcomes. METHODS: Patients who underwent MILR at 10 North American institutions were identified from the Americas Minimally Invasive Liver Resection (AMILES) database. Outcomes of patients who required conversion were compared to those who did not. Additionally, outcomes after conversion due to unfavorable findings (poor visualization/access, lack of progress, disease extent) versus intraoperative events (bleeding, injury, cardiopulmonary instability) were compared. RESULTS: Of 1675 patients who underwent MILR, 102 (6.1%) required conversion. Conversion rate ranged from 4.4% for left lateral sectionectomy to 10% for right hepatectomy. The primary reason for conversion was unfavorable findings in 67 patients (66%) and intraoperative adverse events in 35 patients (34%). By multivariable analysis, major resection, cirrhosis, prior liver surgery, and tumor proximity to major vessels were identified as risk factors for conversion (p < 0.05). Patients who required conversion had higher blood loss, transfusion requirements, operative time, and length of stay, (p < 0.05). They also had higher major complication rates (23% vs. 5.2%, p < 0.001) and 30-day mortality (8.8% vs. 1.3%, p < 0.001). When compared to those who required conversion due to unfavorable findings, patients who required conversion due to intraoperative adverse events had significantly higher major complication rates (43% vs. 14%, p = 0.012) and 30-day mortality (20% vs. 3.0%, p = 0.007). CONCLUSIONS: Conversion from MILR to open surgery is associated with increased perioperative morbidity and mortality. Conversion due to intraoperative adverse events is rare but associated with significantly higher complication and mortality rates, while conversion due to unfavorable findings is associated with similar outcomes as planned open resection. High-risk patients may benefit from early conversion in a controlled fashion if difficulties are encountered or anticipated.

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.

Using Experience-Based Design to Improve the Care Experience for Patients With Pancreatic Cancer.

PURPOSE: Despite the importance of the patient care experience to quality and outcome, the literature detailing the care experience in patients with pancreatic cancer is limited. METHODS: To elicit the experience of patients with pancreatic cancer for care redesign, we deployed experience-based design, an emerging methodology based on identification of events of high emotional content, known as touch points, to delineate qualitatively what matters most to patients and families. We defined touch points through direct observations, interviews, and a focus group. We then used experience questionnaires to measure emotional content and develop an experience map to graphically display the fluctuating emotional journey through the care processes. Study subjects were patients with pancreatic cancer who were cared for at Virginia Mason Medical Center, family caregivers, and staff. Redesign was initiated through an all-day improvement event in September 2013. RESULTS: During 2013 and 2014, we cared for 485 new patients with pancreatic cancer, the majority of whom had local disease at diagnosis. The response rate for the experience questionnaire was 23% (117 of 500 questionnaires distributed). The experience-based design results were often contrary to staff preconceptions of the care experience for patients with pancreatic cancer, and contributed to redesign in three key areas: understanding and documenting patient goals and values, providing better resources for caregivers/families, and improving care coordination and support services. CONCLUSION: Experience-based design enabled us to understand the care experience and associated emotional content for patients with pancreatic cancer and their caregivers. This knowledge then supported care redesign targeted at areas of high negative emotional content.

Preoperative computed tomography scan to predict pancreatic fistula after distal pancreatectomy using gland and tumor characteristics.

BACKGROUND: Preoperative risk stratification for postoperative pancreatic fistula in patients undergoing distal pancreatectomy is needed. METHODS: Risk factors for postoperative pancreatic fistula in 220 consecutive patients undergoing distal pancreatectomy at 2 major institutions were recorded retrospectively. Gland density was measured on noncontrast computed tomography scans (n = 101), and histologic scoring of fat infiltration and fibrosis was performed by a pathologist (n = 120). RESULTS: Forty-two patients (21%) developed a clinically significant pancreatic fistula within 90 days of surgery. Fat infiltration was significantly associated with gland density (P = .0013), but density did not predict pancreatic fistula (P = .5). Recursive partitioning resulted in a decision tree that predicted fistula in this cohort with a misclassification rate less than 15% using gland fibrosis (histology), density (HU), margin thickness (cm), and pathologic diagnosis. CONCLUSIONS: This multicenter study shows that no single perioperative factor reliably predicts postoperative pancreatic fistula after distal pancreatectomy. A decision tree was constructed for risk stratification.

The Role of Biliary Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 6 (CEACAM6) as a Biomarker in Cholangiocarcinoma.

OBJECTIVE: The aim of the present study is to determine if CEACAM6 can be detected in the bile of patients with biliary cancer and can serve as a diagnostic biomarker for cholangiocarcinoma. SUMMARY BACKGROUND DATA: Distinguishing bile duct carcinoma from other diagnoses is often difficult using endoscopic or percutaneous techniques. The cell surface protein CEACAM6 is over-expressed in many gastrointestinal cancers and may be selectively elevated in biliary adenocarcinoma. METHODS: Bile from patients with benign biliary disease and cholangiocarcinoma (hilar, intrahepatic and distal) was collected at the time of index operation. The concentration of CEACAM6 was quantified by sandwich enzyme-linked immunosorbent assay (ELISA) and correlated to pathologic diagnosis. Diagnostic capability of CEACAM6 was evaluated by Wilcoxon rank-sum, linear regression, multiple regression, and receiver operating characteristic (ROC) curve analysis. RESULTS: Bile from 83 patients was analyzed: 42 with benign disease and 41 with cholangiocarcinoma. Patients in the benign cohort were younger, predominantly female, and had lower median biliary CEACAM6 levels than patients in the malignant cohort (7.5 ng/ml vs. 40 ng/ml; p = <.001). ROC curve analysis determined CEACAM6 to be a positive predictor cholangiocarcinoma with a CEACAM6 level >14 ng/ml associated with 87.5% sensitivity, 69.1% specificity, and a likelihood ratio of 2.8 (AUC 0.74). Multiple regression analysis suggested elevated alkaline phosphatase and the presence of biliary endoprostheses may influence CEACAM6 levels. CONCLUSION: Biliary CEACAM6 can identify patients with extrahepatic cholangiocarcinoma with a high degree of sensitivity and should be investigated further as a potential screening tool.

Interferon-based Adjuvant Chemoradiation for Resected Pancreatic Head Cancer: Long-term Follow-up of the Virginia Mason Protocol.

OBJECTIVE: To report the long-term impact of adjuvant interferon-based chemoradiation therapy (IFN-CRT) after pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC). BACKGROUND: In 2003, we reported an actuarial 5-year overall survival (OS) of 55% (22 months median follow-up) using adjuvant IFN-CRT after PD. As the original cohort is now 10 years distant from PD, we sought to examine their actual survival, describe patterns of recurrence, and determine prognostic factors. METHODS: From 1995 to 2002, 43 patients underwent PD for PDAC and received adjuvant IFN-CRT consisting of external-beam irradiation, continuous 5-fluorouracil infusion, weekly intravenous bolus cisplatin, and subcutaneous interferon-α. Survival was calculated by the method of Kaplan and Meier, and prognostic factors were compared using a log-rank test and a Cox proportional hazards model. RESULTS: With all patients at least 10 years from PD, the 5-year actual survival was 42% and 10-year actual survival was 28% with median OS of 42 months (95% confidence interval: 22-110 months). Nine patients survived beyond 10 years with 7 currently alive without evidence of disease. Initial recurrence included 4 local, 17 distant, and 4 combined sites at a median of 25 months. IFN-CRT was interrupted in 70% of patients because of grade 3 or 4 toxicity, whereas 42% of patients required hospitalization. Adverse prognostic factors included lymph node ratio of 50% or more, Eastern Cooperative Oncology Group performance status of 1 or higher, and IFN-CRT treatment interruption. CONCLUSIONS: Adjuvant IFN-CRT after PD can provide long-term survival in resected PDAC. Further studies should focus on patient and tumor factors to maximize benefit and minimize toxicity.

Small Bowel Obstruction Is a Surgical Disease: Patients with Adhesive Small Bowel Obstruction Requiring Operation Have More Cost-Effective Care When Admitted to a Surgical Service.

BACKGROUND: Adhesive small bowel obstruction (ASBO), although a potential surgical emergency, is increasingly being managed by medical hospitalists due to the likelihood these patients will not require operation. However, the value of care delivered by medical hospitalists to patients with ASBO has not been reported. STUDY DESIGN: We hypothesized that patients admitted to the medical hospitalist service (MHS) for presumed ASBO have increased length of stay (LOS) and charges compared with patients admitted to the surgical service (SS). There were 555 consecutive admissions with presumed ASBO from 2008 to 2012; these were reviewed and grouped according to admitting service and whether an operation was performed. Group medians were compared and multivariate analysis was performed to identify variables independently associated with increased LOS, time to operation (TTO), and charges. RESULTS: Median LOS among patients whose ASBO resolved nonoperatively was similar for those on SS and MHS (2.85 days vs 2.98 days; p = 0.49). In patients without nonoperative resolution of ASBO, those admitted to MHS had longer median LOS when compared with those admitted to SS (9.57 days vs 6.99 days; p = 0.002) and higher median charges ($38,800 vs $30,100; p = 0.025). Patients admitted to MHS who had an operation, had a greater median TTO than operative patients on SS (51.72 hours vs 8.4 hours; p < 0.001). Multivariate analysis did not identify factors independently predictive of increased LOS, TTO, or charges. CONCLUSIONS: Adhesive small bowel obstruction patients are treated in a heterogeneous fashion in our hospital, causing disparate outcomes depending on admitting service when patients undergo operation. Admitting all suspected ASBO patients to SS has the potential to dramatically decrease LOS and reduce waste in those requiring operation, thereby reducing health care expenditures.

Rare long-term survivors of pancreatic adenocarcinoma without curative resection.

Long-term outcome data in pancreatic adenocarcinoma are predominantly based on surgical series, as resection is currently considered essential for long-term survival. In contrast, five-year survival in non-resected patients has rarely been reported. In this report, we examined the incidence and natural history of ≥ 5-year survivors with non-resected pancreatic adenocarcinoma. All patients with pancreatic adenocarcinoma who received oncologic therapy alone without surgery at our institution between 1995 and 2009 were identified. Non-resected ≥ 5-year survivors represented 2% (11/544) of all non-resected patients undergoing treatment for pancreatic adenocarcinoma, and 11% (11/98) of ≥ 5-year survivors. Nine patients had localized tumor and 2 metastatic disease at initial diagnosis. Disease progression occurred in 6 patients, and the local tumor bed was the most common site of progression. Six patients suffered from significant morbidities including recurrent cholangitis, second malignancy, malnutrition and bowel perforation. A rare subset of patients with pancreatic cancer achieve long-term survival without resection. Despite prolonged survival, morbidities unrelated to the primary cancer were frequently encountered and a close follow-up is warranted in these patients. Factors such as tumor biology and host immunity may play a key role in disease progression and survival.

An analytical review of vasculobiliary injury in laparoscopic and open cholecystectomy.

OBJECTIVES: Biliary injuries are frequently accompanied by vascular injuries, which may worsen the bile duct injury and cause liver ischemia. We performed an analytical review with the aim of defining vasculobiliary injury and setting out the important issues in this area. METHODS: A literature search of relevant terms was performed using OvidSP. Bibliographies of papers were also searched to obtain older literature. RESULTS: Vasculobiliary injury was defined as: an injury to both a bile duct and a hepatic artery and/or portal vein; the bile duct injury may be caused by operative trauma, be ischaemic in origin or both, and may or may not be accompanied by various degrees of hepatic ischaemia. Right hepatic artery (RHA) vasculobiliary injury (VBI) is the most common variant. Injury to the RHA likely extends the biliary injury to a higher level than the gross observed mechanical injury. VBI results in slow hepatic infarction in about 10% of patients. Repair of the artery is rarely possible and the overall benefit unclear. Injuries involving the portal vein or common or proper hepatic arteries are much less common, but have more serious effects including rapid infarction of the liver. CONCLUSIONS: Routine arteriography is recommended in patients with a biliary injury if early repair is contemplated. Consideration should be given to delaying repair of a biliary injury in patients with occlusion of the RHA. Patients with injuries to the portal vein or proper or common hepatic should be emergently referred to tertiary care centers.

Pretreatment assessment of hepatocellular carcinoma: expert consensus statement.

Staging of hepatocellular carcinoma (HCC) is complex and relies on multiple factors including tumor extent and hepatic function. No single staging system is applicable to all patients with HCC. The staging of the American Joint Committee on Cancer / International Union for Cancer Control should be used to predict outcome following resection or liver transplantation. The Barcelona Clinic Liver Cancer scheme is appropriate in patients with advanced HCC not candidate for surgery. Dual phase computed tomography or magnetic resonance imaging can be used for pretreatment assessment of tumor extent but the accuracy of these methods remains poor to characterize < 1 cm lesions. Assessment of tumor response should not rely only on tumor size and new imaging methods are available to evaluate response to therapy in HCC patients. Liver volumetry is part of the preoperative assessment of patients with HCC candidate for resection as it reflects liver function. Preoperative portal vein embolization is indicated in patients with small future liver remnant (≤ 20% in normal liver; ≤ 40% in fibrotic or cirrhotic liver). Tumor size is not a contraindication to liver resection. Liver resection can be proposed in selected patients with multifocal HCC. Besides tumor extent, surgical resection of HCC may be performed in selected patients with chronic liver disease.

Evaluation of a bipolar radiofrequency device for laparoscopic hepatic resection: technique and clinical experience in 18 patients.

BACKGROUND: The increased frequency of laparoscopic hepatic resection as a principal or adjunct component of patient care has driven the need for and development of efficient and safe hepatic parenchymal transection technologies. At present, various devices are available for pre-coagulation transection (PCT) of hepatic parenchyma with the intent of minimizing procedure-associated postoperative haemorrhage and bile leak. This report presents the evaluation of a novel bipolar radiofrequency (RF) energy device for PCT used for laparoscopic hepatic resection. METHODS: Patients undergoing laparoscopic hepatic resection using the Enseal device (SurgRx Inc.) were identified from the prospectively maintained hepatobiliary database. Information on patient demographics, procedures and postoperative complications was collected and analysed; complications were grouped into early (at <30 days) and late (at > or = 30 days) events. RESULTS: A total of 18 patients, of whom 13 had malignant tumours (12 colorectal metastases and one hepatocellular carcinoma) and five had benign tumours (two hepatic adenomas and three haemangiomas) underwent 18 hepatic procedures, including two formal hemi-hepatectomies, four left lateral sections, three posterior sections and nine atypical non-anatomic resections. Estimated blood loss did not differ from institutional historical control data; no postoperative haemorrhage, bile leaks or hepatic abscess or necrosis were identified (n = 18). CONCLUSIONS: This initial experience using the laparoscopic bipolar RF device demonstrates an acceptable safety profile in terms of the outcomes analysed.

Radiofrequency ablation of primary and metastatic liver tumors: a critical review of the literature.

BACKGROUND: Surgical resection is the treatment of choice for hepatic tumors; however, for various reasons, the vast majority of patients are not operative candidates. As a result, several local ablative therapies have emerged as alternatives to resection or as adjuncts in total oncologic care. Presently, the most widely employed liver-directed treatment is radiofrequency thermal ablation. METHODS: To define the current status of radiofrequency ablation (RFA), the authors reviewed available safety and efficacy data from select studies on RFA. A MEDLINE search was performed using the keywords "tumor type" + "radiofrequency ablation" + "survival." Only those studies containing long-term survival data on greater than 50 patients were included in this analysis. CONCLUSIONS: Although RFA has been readily adopted into treatment paradigms, more rigorous trials are needed to solidify its place in the armamentarium of therapeutic strategies for hepatic malignancy.

Lipopolysaccharide-stimulated RAW 264.7 macrophage inducible nitric oxide synthase and nitric oxide production is decreased by an omega-3 fatty acid lipid emulsion.

BACKGROUND: Omega-3 fatty acids (omega-3 FA) have been demonstrated to have anti-inflammatory properties, postulated to occur through several principal mechanisms, including (1) displacement of arachidonic acid from the cellular membrane; (2) shifting of prostaglandin E(2) and leukotriene B(4) production; and (3) molecular level alterations including decreased activation of nuclear factor kappa B and activator protein-1. An additional regulator that is likely associated is the production of nitric oxide (NO) by nitric oxide synthetase. NO is a short-lived free radical involved in many biological functions. However, excessive NO production can lead to complications, suggesting that decreased NO production is a potential target for some inflammatory diseases. We hypothesized that pretreating with an omega-3 FA lipid emulsion would decrease the production of NO in macrophages and that this effect would occur through alterations in inducible nitric oxide synthetase (iNOS). MATERIALS AND METHODS: Greiss reagent was used to assess NO production in RAW 264.7 macrophages following omega-3 or omega-6 FA treatment alone or in combination with lipopolysaccharide (LPS) stimulation for 12 h/24 h. iNOS levels were determined by Western blot. Tumor necrosis factor-alpha levels were determined by enzyme-linked immunosorbent assay. RESULTS: Following LPS-stimulation, omega-3 FA pretreatment at 12 and 24 h produced significantly less NO (P < 0.05) compared to omega-6 FA or media-only conditions. omega-3 FA pretreatment at 12 and 24 h also had less iNOS protein expression compared to omega-6 FA or media-only conditions. Tumor necrosis factor-alpha production was significantly decreased with omega-3 FA treatment compared to omega-6 FA treatment (P < 0.05) after 24 h LPS stimulation. CONCLUSION: These experiments demonstrate that, in addition to other anti-inflammatory effects, omega-3 FA lipid emulsions also significantly lower NO production in LPS-stimulated macrophages through altered iNOS protein expression.

Hepatic and splenic hydatidosis managed with percutaneous aspiration, injection, and reaspiration (PAIR) of the hepatic cyst and laparoscopic splenectomy.

The treatment of hydatidosis traditionally consisted of surgery with a perioperative course of anthelmintic medications. However, percutaneous aspiration, injection, and reaspiration (PAIR) combined with oral albendazole has been recently shown to be as effective as surgery in the treatment of liver hydatidosis. We report a 20-year-old female immigrant from Western Europe who presented with discomfort in her upper abdomen. Computed tomography revealed a 5.7 x 7 x 5.9-cm cyst in segment 7 of the liver and a 17 x 15-cm cyst in the spleen in contiguity with the hilar vessels. Indirect hemaglutination test confirmed hydatidosis. A strategy with two different surgical approaches was designed to treat her condition: laparoscopic splenectomy and ultrasound-guided PAIR of the liver cyst. The patient was discharged on postoperative day 5, and at 18 months follow-up, she is free of symptoms.

A primer on transarterial, chemical, and thermal ablative therapies for hepatic tumors.

BACKGROUND: Surgical resection is the only potentially curative approach for patients with primary and metastatic liver tumors. Unfortunately, most patients with hepatic malignancy are precluded from resection due to multifocal disease, anatomic limitations, inadequate functional liver reserve, extrahepatic metastases, or medical comorbidities. Consequently, several methods of tumor ablation have been developed as alternate treatment strategies for patients with unresectable hepatic tumors or as adjuncts in total cancer therapy. The purpose of this review is to inclusively define the various ablation modalities available (transarterial, chemical, and thermal ablative), and to describe the procedures, general applications, and reported outcomes. DATA SOURCES: A MEDLINE and CINAHL search of the English-language literature was performed on transarterial, chemical, and thermal ablative therapies. CONCLUSIONS: Presently, radiofrequency thermal ablation is the most widely applicable liver-directed modality for hepatic tumor ablation, enabling treatment of primary and metastatic tumors. However, other transarterial and thermoablative techniques are available with accumulating data for their use. Lacking at present are studies that define the role and potential benefit of the various liver-directed modalities in the treatment algorithm for hepatic tumors.

G2/M cell-cycle arrest and apoptosis by n-3 fatty acids in a pancreatic cancer model.

BACKGROUND: n-3 fatty acids (n-3FA) have anti-inflammatory and anti-proliferative effects including modulation of pro-inflammatory cascade mediators and cytokine elaboration (i.e., TNF-alpha, IL-10 and PGE(2)) in many cell lines. However, mechanisms of anti-proliferative effects have not been clearly defined. MATERIALS AND METHODS: MIA PaCa-2 pancreatic cancer cells were treated either with n-3FA (treatment), media (control), or n-6FA (control) for all experiments. Cellular proliferation was evaluated with WST-1 reagent. Cells were stained with propidium iodide and analyzed by flow cytometry for cell-cycle arrest, which was further analyzed by cdc2 expression. Membrane and media lipid concentrations were analyzed by high-performance liquid chromatography. Apoptosis was evaluated by AnnexinV-FITC flow cytometry and reconfirmed by poly (ADP-ribose) polymerase (PARP) cleavage and B(cl)-2 expression. RESULTS: Propidium iodide flow cytometry of MIA PaCa-2 dosed with n-3FA showed a decrease in cells in G1 phase (11-17%) and an increase cells in G2 phase (7-13%) from controls. cdc2 expression was also decreased at 24 h compared to controls. Annexin-V staining of n-3FA-treated cells demonstrated time-dependent increased apoptosis and PARP cleavage was present only in the n-3FA treatment group. Phospho-B(cl)-2 was also decreased in the n-3FA-treated cells compared to controls. CONCLUSIONS: Co-incubation of MIA PaCa-2 cells with n-3FA results in both dose- and time-dependent cell-cycle arrest. Cells also progress to cell death via apoptosis. These data support the potential applicability for n-3FA as an antiproliferative and pro-apoptotic strategy.