A Modified Floxuridine Reduced-Dose Protocol for Patients with Unresectable Colorectal Liver Metastases Treated with Hepatic Arterial Infusion.

BACKGROUND: Most patients treated with the standard dosing protocol (SDP) of hepatic arterial infusion (HAI) floxuridine require dose holds and reductions, thereby limiting their HAI therapy. We hypothesized that a modified dosing protocol (MDP) with a reduced floxuridine starting dose would decrease dose holds, dose reductions, and have similar potential to convert patients with unresectable colorectal liver metastases (uCRLM) to resection. PATIENTS AND METHODS: We reviewed our institutional database of patients with uCRLM treated with HAI between 2016 and 2022. In 2019, we modified the floxuridine starting dose to 50% (0.06 mg/kg) of the SDP (0.12 mg/kg). We compared treatment related outcomes between the SDP and MDP cohorts. RESULTS: Of n = 33 patients, 15 (45%) were treated on the SDP and 18 (55%) with our new institutional MDP. The MDP cohort completed more cycles before a dose reduction (mean 4.2 vs. 2), received more overall cycles (median 7.5 vs. 5), and averaged 39 more days of treatment (all P < 0.05). The SDP experienced more dose reductions (1.4 vs. 0.61) and dose holds (1.2 vs. 0.2; both P < 0.01). Of the patients in each group potentially convertible to hepatic resection, three patients (23%) in the SDP and six patients (35%) in the MDP group converted to resection (P = 0.691). Overall, four patients (27%) in the SDP developed treatment ending biliary toxicity compared with one patient (6%) in the MDP. CONCLUSIONS: A 50% starting dose of HAI floxuridine provides fewer treatment disruptions, more consecutive floxuridine cycles, and a similar potential to convert patients with initially uCRLM for disease clearance.

Safety and Effectiveness of Portal Vein Embolization after Hepatic Arterial Infusion Therapy.

Portal vein embolization (PVE) is a tool potentially useful for inducing future liver remnant (FLR) hypertrophy in patients with advanced hepatic malignancies who are at high risk of hepatic insufficiency if treated with surgical resection. However, the safety and effectiveness of PVE in the context of patients who have undergone hepatic arterial infusion (HAI) are unknown. This retrospective, single-center study identified 9 patients who underwent PVE after HAI between January 2015 and December 2022. There were no major adverse events, including biliary injury or high-grade liver failure. Analysis showed an increase in standardized FLR from 21.1% (SEM ± 2.4) to 34.8% (SEM ± 2.1) over 9.8 weeks (SEM ± 1.2), with a mean kinetic growth rate of 1.9% (interquartile range, 0.9%-2.4%). Patients who have undergone HAI therapy should not be excluded from consideration of PVE as part of their operative clearance strategy.

Adjuvant imatinib in high-risk resected gastrointestinal stromal tumors: Merely delaying the inevitable?

INTRODUCTION: Patients with high-risk resected gastrointestinal stromal tumors (GIST) receiving adjuvant imatinib have improved recurrence-free survival (RFS), however whether a complete cytocidal effect exists is unknown. We investigated this using a normalized recurrence timeline measured from end of oncologic treatment (EOOT), defined as the later of resection or end of adjuvant therapy. METHODS: We reviewed patients with resected high-risk GIST at our cancer center from 2003 to 2018. RFS (measured from resection and EOOT), overall survival (OS), and time to imatinib resistance (TTIR) were analyzed using Kaplan-Meier analysis and multivariable Cox proportional hazards modeling. The performance of the Memorial Sloan Kettering (MSK) GIST nomogram was assessed. RESULTS: We identified 86 patients with high-risk GIST with a median 106 months of postsurgical follow-up. One-third (n = 29; 34%) did not receive adjuvant imatinib, while 57 (66%) did for a median of 3 years. The MSK nomogram-predicted 5-year RFS for patients receiving adjuvant imatinib was similar to those who did not (29% vs. 31%, p = 0.64). When RFS was measured from EOOT, the MSK-predicted RFS was independently associated with EOOT RFS (hazard ratio 0.22, p = 0.02), while adjuvant imatinib receipt and duration were not. Neither receipt nor duration of adjuvant imatinib were associated with TTIR or OS (all p > 0.05). CONCLUSIONS: Treatment with adjuvant imatinib delays, but does not clearly impact ultimate recurrence, TTIR, or OS, suggesting many patients with high-risk GIST may receive adjuvant imatinib unnecessarily. Additional studies are needed to establish the benefit of adjuvant therapy versus initiating therapy at first radiographic recurrence.

The multidisciplinary management of cholangiocarcinoma.

Cholangiocarcinoma is a lethal malignancy of the biliary epithelium that can arise anywhere along the biliary tract. Surgical resection confers the greatest likelihood of long-term survivability. However, its insidious onset, difficult diagnostics, and resultant advanced presentation render the majority of patients unresectable, highlighting the importance of early detection with novel biomarkers. Developing liver-directed therapies and emerging targeted therapeutics may offer improved survivability for patients with unresectable or advanced disease. In this article, the authors review the current multidisciplinary standards of care in resectable and unresectable cholangiocarcinoma, with an emphasis on novel biomarkers for early detection and nonsurgical locoregional therapy options.

Current Practices in Hepatic Artery Infusion (HAI) Chemotherapy: An International Survey of the HAI Consortium Research Network.

BACKGROUND: An increasing number of hepatic artery infusion (HAI) programs have been established worldwide. Practice patterns for this complex therapy across these programs have not been reported. This survey aimed to identify current practice patterns in HAI therapy with the long-term goal of defining best practices and performing prospective studies. METHODS: Using SurveyMonkeyTM, a 28-question survey assessing current practices in HAI was developed by 12 HAI Consortium Research Network (HCRN) surgical oncologists. Content analysis was used to code textual responses, and the frequency of categories was calculated. Scores for rank-order questions were generated by calculating average ranking for each answer choice. RESULTS: Thirty-six (72%) HCRN members responded to the survey. The most common intended initial indications for HAI at new programs were unresectable colorectal liver metastases (uCRLM; 100%) and unresectable intrahepatic cholangiocarcinoma (uIHC; 56%). Practice patterns evolved such that uCRLM (94%) and adjuvant therapy for CRLM (adjCRLM; 72%) have become the most common current indications for HAI at established centers. Referral patterns for pump placement differed between uCRLM and uIHC, with most patients referred while receiving second- and first-line therapy, respectively, with physicians preferring to evaluate patients for HAI while receiving first-line therapy for CRLM. Concern for extrahepatic disease was ranked as the most important factor when considering a patient for HAI. CONCLUSIONS: Indication and patient selection factors for HAI therapy are relatively uniform across most HCRN centers. The increasing use of adjuvant HAI therapy and overall consistency of practice patterns among HCRN centers provides a robust environment for prospective data collection and randomized clinical trials.

Ten-Year Survivorship in Patients with Metastatic Gastrointestinal Stromal Tumors.

INTRODUCTION: Patients developing metastatic gastrointestinal stromal tumors (mGIST) have heterogenous disease biology and oncologic outcomes; prognostic factors are incompletely characterized. We sought to evaluate predictors of 10-year metastatic survivorship in the era of tyrosine kinase inhibitor (TKI) therapy. METHODS: We reviewed patients with mGIST treated at our Comprehensive Cancer Center from 2003 to 2019, including only patients with either mortality or 10 years of follow-up. Ten-year survivorship was evaluated with logistic regression. RESULTS: We identified 109 patients with a median age of 57 years at mGIST diagnosis. Synchronous disease was present in 57% (n = 62) of patients; liver (n = 48, 44%), peritoneum (n = 40, 37%), and liver + peritoneum (n = 18, 17%) were the most common sites. Forty-six (42%) patients were 10-year mGIST survivors. Following mGIST diagnosis, radiographic progression occurred within 2 years in 53% (n = 58) of patients, 2-5 years in 16% (n = 17), and 5-10 years in 16% (n = 17), with median survival of 32, 76, and 173 months, respectively. Seventeen (16%) patients had not progressed by 10 years. Fifty-two (47%) patients underwent metastasectomy, which was associated with improved progression-free survival (hazard ratio 0.63, p = 0.04). In patients experiencing progression, factors independently associated with 10-year survivorship were age (odds ratio [OR] 0.96, p = 0.03) and time to progression (OR 1.71/year, p < 0.001). CONCLUSIONS: Ten-year survivorship is achievable in mGIST in the era of TKIs and is associated with younger age and longer time to first progression, while metastasectomy is associated with longer time to first progression. The role of metastasectomy in the management of patients with disease progression receiving TKI therapy merits further study.

Intensive care unit observation after pancreatectomy: Treating the patient or the surgeon?

BACKGROUND: Routine intensive care unit admission (ICUA) is commonplace following pancreatectomy, particularly pancreaticoduodenectomy. The value of this practice in avoiding failure-to-rescue is poorly studied. METHODS: We queried our institutional National Surgical Quality Improvement Project database for patients undergoing pancreatectomy from 2013 to 2020. Postoperative dispositions, ICU courses, and hospital cost data in United States Dollars (USD) were captured. Data were analyzed with multivariable logistic regression. RESULTS: Six-hundred-thirty-seven patients were identified; 404 (63%) underwent pancreaticoduodenectomy. Postoperatively, 398 (99%) pancreaticoduodenectomies and 110 (47%) distal pancreatectomies had ICUA; two-thirds (n = 318, 63%) did not require immediate postoperative ICU-level interventions at ICUA. Of these, 17 (5.3%) subsequently required ICU-level interventions during initial ICUA, most commonly antiarrhythmic infusion (n = 12). Thirty-day and 90-day mortality in patients requiring immediate ICU-level interventions was 5% (n = 10) and 8% (n = 16) versus 0.3% (n = 1) and 1.2% (n = 4) in those without, respectively. Hospital length of stay was significantly longer with initial ICU-level interventions (median 11 vs. 9 days, p < 0.001), as were total ICU costs (mean 8683 vs. 14611 USD, p < 0.001). CONCLUSION: At high-volume pancreas centers, patients without immediate postoperative ICU-level interventions are very low risk for failure-to-rescue. Ward admission with a low threshold for care escalation presents a significant opportunity for cost-savings and un-burdening ICUs.

Surgical timing after preoperative chemotherapy is associated with oncologic outcomes in resectable colorectal liver metastases.

INTRODUCTION: Preoperative chemotherapy (POC) is often employed for patients with resectable colorectal liver metastasis (CRLM). The time to resection (TTR) following the end of chemotherapy may impact oncologic outcomes; this phenomenon has not been studied in CRLM. METHODS: We queried our institutional cancer database for patients with resected CRLM after POC from 2003 to 2019. TTR was calculated from date of last cytotoxic chemotherapy. Kaplan-Meier analysis and multivariable Cox proportional hazards modeling were used to analyze recurrence-free survival (RFS) and overall survival (OS). RESULTS: We identified n = 187 patients. One hundred twenty-four (66%) patients had a TTR of <2 months, while 63 (33%) had a TTR of ≥2 months. Median follow-up was 36 months. On Kaplan-Meier analysis, patients with TTR ≥ 2 months had shorter RFS (median 11 vs. 17 months, p = 0.002) and OS (median 44 vs. 62 months, p < 0.001). On multivariable analysis, TTR ≥ 2 months was independently associated with worse RFS (hazard ratio [HR] = 1.54, 95% confidence interval [CI] = 1.06-2.22, p = 0.02) and OS (HR = 1.75, 95% CI = 1.11-2.77, p = 0.01). CONCLUSION: TTR ≥ 2 months following POC is independently associated with worse oncologic outcomes in patients with resectable CRLM. We therefore recommend consideration for hepatic resection of CRLM within this window whenever feasible.

Hepatic arterial infusion pump chemotherapy combined with systemic therapy for patients with advanced colorectal liver metastases: Outcomes in a newly established program.

BACKGROUND AND OBJECTIVES: Colorectal liver metastasis (CRLM) is a leading cause of morbidity and mortality in patients with colorectal cancer. Hepatic arterial infusion (HAI) chemotherapy has been demonstrated to improve survival in patients with resected CRLM and to facilitate conversion of technically unresectable disease. METHODS: Between 2016 and 2018, n = 22 HAI pumps were placed for CRLM. All patients received systemic chemotherapy concurrently with HAI floxuridine/dexamethasone. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. RESULTS: HAI pumps were placed in seven patients with completely resected CRLM and 15 patients with unresectable disease. Twenty-one patients received HAI floxuridine with a median of 5 total HAI cycles (interquartile range: 4-7). Biliary sclerosis was the most common HAI-related complication (n = 5, 24%). Of the 13 patients treated to convert unresectable CRLM, 3 (23%) underwent hepatic resection with curative intent after a median of 7 HAI cycles (range: 4-10). For all HAI patients, the mean OS was 26.7 months from CRLM diagnosis, while the median PFS and hepatic PFS from pump placement were 9 and 13 months, respectively. CONCLUSION: Concomitant HAI and systemic therapy can be utilized at multidisciplinary programs for patients with advanced CRLM, both in the adjuvant setting and to facilitate conversion of unresectable disease.

The patient's perspective: a qualitative study of individual experience with decision-making, treatment, and recovery for resectable pancreatic cancer.

INTRODUCTION: Pancreatic ductal adenocarcinoma cancer (PDAC) remains a challenging diagnosis. The likelihood of long-term survival is limited even for patients who undergo maximal medical therapy with systemic chemotherapy and surgical resection. Within this intensive process, there remains limited understanding of patients' pretreatment expectations of PDAC treatment experience and their decision-making process. METHODS: PDAC patients who underwent chemotherapy and surgical resection were retrospectively identified. Semi-structured phone interviews were completed regarding patient experience with therapy. Qualitative descriptive analysis was performed, and categories, subcategories, and themes were determined. RESULTS: Fifteen patients were interviewed regarding their experience with PDAC treatment. An overall personal disease trajectory experience was identified with two phases. The first phase encompassed the patients' treatment. In this phase, patients expressed a choice, non-choice regarding therapy decisions, viewing therapy as the only option. Misconceptions about the roles of therapies and expected experience of treatment were observed. The second phase focused on life after therapy. Patients reported persistent physical changes secondary to therapy. An overall realistic understanding of the patient's limited prognosis was observed, with patients expressing appreciation of the life time gained as a benefit of treatment. CONCLUSIONS: There remains critical areas for improvement in communication and care of patients with PDAC. Physicians should continue to ensure that patient's goals and wishes are respected when making treatment decisions and confirm that patients understand the roles and limitations of prescribed therapies. Additionally, patients continue to have significant physical changes post treatment which should be assessed for and managed as appropriate to maintain quality of life.

Complications in Distal Pancreatectomy versus Radical Antegrade Modular Pancreatosplenectomy: A Disease Risk Score Analysis Utilizing National Surgical Quality Improvement Project Data.

INTRODUCTION: Radical antegrade modular pancreatosplenectomy (RAMPS) was developed to improve R0 resections and lymph node harvests versus distal pancreatectomy (DP) in pancreatic adenocarcinoma (PDAC); relative complication rates are understudied. METHODS: Patients undergoing distal pancreas resections from 2006 to 2020 were identified from our institutional NSQIP database, grouped by resection method, and evaluated for the following outcomes: postoperative pancreatic fistula (POPF), clinically relevant POPF (crPOPF), incisional surgical site infection (iSSI), organ space SSI (osSSI), and Clavien-Dindo grade ≥ 3 (CD ≥ 3) complications using logistic regression. Patients were matched 1:1 based on disease risk score. RESULTS: Two-hundred-thirty-six and 117 patients underwent DP and RAMPS, respectively. POPF, crPOPF, CD ≥ 3 complications, iSSI, and osSSIs occurred in 105 (30%), 43 (12%), 74 (21%), 34 (10%) and 52 (15%) patients, respectively. Disease risk score matching yielded 89 similar patients per group. On multivariable analysis, patients undergoing RAMPS were not significantly more likely to experience POPF (OR 0.69, P = 0.26), crPOPF (OR 0.41, P = 0.72), CD ≥ 3 complication (OR 0.78, P = 0.44), iSSI (OR 0.58, P = 0.27), or osSSI (OR 0.93, P = 0.86). Of patients with PDAC (n = 108) mean nodal harvest were 14.8 (SD 11.30) and 19.4 (SD 7.19) nodes for patients undergoing DP and RAMPS, respectively (P = 0.01). Six patients (20%) undergoing DP had positive margins versus 12 (15%) undergoing RAMPS (P = 0.56). At a median follow-up of 17 months, there was no difference in locoregional recurrence-free survival (P = 0.32) or overall survival (P = 0.92) on Kaplan-Meier analysis. CONCLUSION: RAMPS does not result in increased complications compared to DP and routine use is encouraged in pancreatic malignancies.

Hepatic metastases in gastrointestinal stromal tumors: oncologic outcomes with curative-intent hepatectomy, resection of treatment-resistant disease, and tyrosine kinase inhibitor therapy alone.

BACKGROUND: Hepatic resection for metastatic GIST (mGIST) is often performed with either curative-intent or for tyrosine kinase inhibitor (TKI)-resistant lesions. The efficacy of hepatectomy for treatment-resistant lesions (TRL) is uncertain. METHODS: We reviewed patients with liver-mGIST treated from 2003 to 2018. Oncologic outcomes including overall (OS), post-operative progression-free survival (PFS), and post-progression OS were evaluated using Kaplan-Meier and Cox proportional hazards modeling. RESULTS: We identified n = 91 patients; 31 (34%) underwent curative-intent hepatectomy, 60 (66%) were initially managed with TKI alone, and 17 (19%) had resection of a TRL. The median follow-up for resected patients was 102 months (range 5-209 months) with 23 (25%) managed with a major hepatectomy. Patients having curative-intent hepatectomy had 72% 10-year OS following diagnosis of liver-mGIST, compared with 58% (P = 0.50) for TRL resection and 41% (P = 0.01) for non-resected patients. Curative-intent hepatectomy (HR 0.39, P = 0.03) and age (HR 1.04, P = 0.004) were independently associated with 10-year OS, but not TRL resection. TRL resection was not associated with improved post-progression OS compared to second-line TKI therapy (HR 0.61, P = 0.21). CONCLUSIONS: Curative-intent hepatectomy is associated with improved OS in liver-mGIST. The oncologic benefit of resecting treatment-resistant liver-mGIST compared to second-line TKI therapy alone remains unclear in the era of multi-line TKI therapy.

Patency for autologous vein is superior to cadaveric vein in portal-mesenteric venous reconstruction.

BACKGROUND: Portal venous reconstruction (PVR) is often needed during resection of hepatopancreato-biliary (HPB) malignancies. Primary repair (PR), autologous vein (AV), or cryopreserved cadaveric vein (CCV) are frequently utilized, however relative patency is not well studied. METHODS: All patients undergoing PVR between 2007-2019 at our center were identified. 3-year primary patency (PP), overall survival (OS), and survival-adjusted patency (SAP) were evaluated with Kaplan-Meier and Cox proportional hazards modeling. RESULTS: One-hundred-twenty patients were identified with a median follow-up of 11 months. PR, AV, and CCV reconstruction were used in 28 (23%), 35 (29%), and 57 (48%) patients, respectively, with two (7%), four (11%), and 29 (51%) thromboses, respectively. 3-year PP was greater for both primary repair (90%) and AV (83%) compared to CCV (33%, both p<0.001). On multivariable analysis, CCV had worse 3-year PP (HR 7.89, p=0.005) and SAP (HR 2.09, p=0.02) compared to PR; AV reconstruction had equivalent oncologic and patency-related outcomes to PR (p>0.4 for both comparisons). CONCLUSIONS: Primary patency for PR and AV reconstruction is superior to CCV for PVR during resection of HPB malignancies. AV conduit should be the preferred choice of reconstruction when PR is not achievable. Surgeons should only use CCV when factors preclude PR/AV reconstruction.

Considerations and barriers to starting a new HAI pump program: an international survey of the HAI Consortium Research Network.

BACKGROUND: Widespread implementation of HAI pump chemotherapy has been limited by logistic and feasibility concerns. Recent studies demonstrating excellent outcomes have fueled renewed enthusiasm and multiple new programs have emerged. This survey aims to identify barriers critical to establish a successful HAI program. METHODS: Using SurveyMonkey™, a 17-question survey assessing factors required for establishing a successful program was developed by 12 HAI Consortium Research Network (HCRN) surgical oncologists. Content analysis was used to code textual responses. Frequency of categories and average rank scores for each choice were calculated. RESULTS: Twenty-eight HCRN members responded to the survey. Implementation time varied, with 15 institutions requiring less than a year. Most programs (n = 17) became active in the past 5 years. Medical and surgical oncology were ranked most important for building a program (average ranking scores: 7.96 and 6.59/8). Administrative or regulatory approval was required at half of the institutions. The top 3 challenges faced when building a program were related to regulatory approval (6.65/9), device/equipment access (6.33/9), and drug (FUDR) access (6.25/9). CONCLUSION: Development of successful programs outside of historically established centers is feasible and requires a multidisciplinary team. Future collaborative efforts are critical for sustainability of safe/effective new programs.

Disease-free Interval Is Associated with Oncologic Outcomes in Patients with Recurrent Gastrointestinal Stromal Tumor.

BACKGROUND: Gastrointestinal stromal tumors (GIST) commonly recur following curative-intent resection. Patients with recurrent GIST display heterogeneous outcomes with limited prognostic tools. We investigated factors associated with post-recurrence survival (PRS) and progression-free survival (PFS). METHODS: We performed a review of our institutional cancer registry from 2003 to 2018 for patients with GIST. Clinicopathologic and outcome data were collected. The disease-free interval (DFI) was calculated from the end of curative-intent oncologic therapy until recurrence. Outcomes were evaluated using Kaplan-Meier and Cox proportional hazards modeling. RESULTS: Overall, 254 patients underwent resection of primary, non-metastatic GIST, with 81 (32%) recurrences. The median age was 58 years and more than half of the patients with recurrence (n = 44; 54%) received adjuvant imatinib. Recurrence was most common in the liver (n = 34, 42%), peritoneum (n = 31, 38%), or liver plus peritoneum (n = 10, 12%). The median DFI was 14 months (interquartile range 2-26 months); 51 (63%) patients had a DFI ≤24 months and 30 (37%) had a DFI > 24 months. The median post-recurrence follow-up was 46 months. Compared with a DFI ≤24 months, patients with a DFI >24 months had increased 10-year PRS (77% vs. 41%, p < 0.05) and 10-year PFS (73% vs. 19%, p < 0.001). On multivariable analysis controlling for mutational and clinicopathologic features, a DFI >24 months was independently associated with increased PRS (hazard ratio [HR] 0.24, p < 0.01) and PFS (HR 0.18, p < 0.001). CONCLUSIONS: The DFI is independently associated with oncologic outcomes in recurrent GIST and may be useful in treatment planning. Recurrence after 24 months may signify indolent disease biology that may benefit from additional treatment, including metastasectomy.

Circulating Hybrid Cells: A Novel Liquid Biomarker of Treatment Response in Gastrointestinal Cancers.

BACKGROUND: Real-time monitoring of treatment response with a liquid biomarker has potential to inform treatment decisions for patients with rectal adenocarcinoma (RAC), esophageal adenocarcinoma (EAC), and colorectal liver metastasis (CRLM). Circulating hybrid cells (CHCs), which have both immune and tumor cell phenotypes, are detectable in the peripheral blood of patients with gastrointestinal cancers, but their potential as an indicator of treatment response is unexplored. METHODS: Peripheral blood specimens were collected from RAC and EAC patients after neoadjuvant therapy (NAT) or longitudinally during therapy and evaluated for CHC levels by immunostaining. Receiver operating characteristics (ROCs) and the Kaplan-Meier method were used to analyze the CHC level as a predictor of pathologic response to NAT and disease-specific survival (DSS), respectively. RESULTS: Patients with RAC (n = 23) and EAC (n = 34) were sampled on the day of resection, and 11 patients (32%) demonstrated a pathologic complete response (pCR) to NAT. On ROC analysis, CHC levels successfully discriminated pCR from non-pCR with an area under the curve of 0.82 (95% confidence interval [CI], 0.71-0.92; P < 0.001). Additionally, CHC levels in the EAC patients correlated with residual nodal involvement (P = 0.026) and 1-year DSS (P = 0.029). The patients with RAC who were followed longitudinally during NAT (n = 2) and hepatic arterial infusion therapy for CRLM (n = 2) had CHC levels that decreased with therapy response and increased before clinical evidence of disease progression. CONCLUSION: Circulating hybrid cells are a novel blood-based biomarker with potential for monitoring treatment response and disease progression to help guide decisions for further systemic therapy, definitive resection, and post-therapy surveillance. Additional validation studies of CHCs are warranted.

Geographic Disparities in Referral Rates and Oncologic Outcomes of Intrahepatic Cholangiocarcinoma: A Population-Based Study.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a rare cancer. Patients in rural areas may face reduced access to advanced treatments often only available at referral centers. We evaluated the association of referral center treatment with treatment patterns, outcomes, and geography in patients with ICC. METHODS: We queried the Oregon State Cancer Registry for ICC between 1997 and 2016, collecting clinicopathologic, demographic, and oncologic data. Patients were classified by treatment at a referral center or non-referral center. 'Crowfly' distance to the nearest referral center (DRC) was calculated. Outcomes were evaluated using Kaplan-Meier, Cox proportional hazards modeling, and logistic regression. RESULTS: Over 20 years, 740 patients with ICC had a median age of 66 years. Slightly more than half (n = 424, 57%) were non-referral center treated and 316 (43%) were referral center treated. Referral center treatment increased over time (odds ratio [OR] 1.03/year, p < 0.05). Referral center-treated patients had improved overall survival in all patients (median 9 vs. 4 months, p < 0.001), in the non-metastatic group (median 13 vs. 6 months, p < 0.001), and in patients not receiving liver resection (median 6 vs. 3 months, p < 0.05). On multivariable analysis, referral center-treated patients more often underwent chemotherapy, resection, or radiation (all p < 0.05). Increasing DRC (OR 0.98/20 km, p < 0.05) was independently associated with non-referral center treatment. CONCLUSION: Patients with ICC who are evaluated at a referral center are more likely to receive treatments associated with better oncologic outcomes, including patients who are not managed with hepatic resection. Increasing the DRC is associated with treatment at a non-referral center; interventions to facilitate referral, such as telemedicine, may lead to improved outcomes for patients with ICC in rural states.

Degree of biliary tract violation during treatment of gallbladder adenocarcinoma is independently associated with development of peritoneal carcinomatosis.

BACKGROUND: Gallbladder cancer (GBC) is often incidentally diagnosed after cholecystectomy. Intra-operative biliary tract violations (BTV) have been recently associated with development of peritoneal disease (PD). The degree of BTV may be associated with PD risk, but has not been previously investigated. METHODS: We reviewed patients with initially non-metastatic GBC treated at our institution from 2003 to 2018. Patients were grouped based on degree of BTV during their treatment: major (e.g., cholecystotomy with bile spillage, n = 27, 29%), minor (e.g., intra-operative cholangiogram, n = 18, 19%), and no violations (n = 48, 55%). Overall survival (OS) and peritoneal disease-free survival (PDFS) were evaluated with Kaplan-Meier and Cox proportional hazards modeling. RESULTS: Ninety-three patients were identified; the median age was 64 years (range 31-87 years). Seventy-six (82%) were incidentally diagnosed. The median follow-up was 23 months; 20 (22%) patients developed PD. The 3-year PDFS for patients with major, minor, and no BTV was 52%, 83%, and 98%, respectively (major vs. none: p < 0.001; minor vs. none: p < 0.01). BTV was not associated with 5-year OS (HR 1.53, p = 0.16). CONCLUSION: Increasing degree of BTV is associated with higher risk of peritoneal carcinomatosis in patients with GBC and should be considered during preoperative risk stratification. Reporting biliary tract violations during cholecystectomy is encouraged.

Safety and feasibility of initiating a hepatic artery infusion pump chemotherapy program for unresectable colorectal liver metastases: A multicenter, retrospective cohort study.

INTRODUCTION: Hepatic artery infusion pump (HAIP) chemotherapy is a specialized therapy for patients with unresectable colorectal liver metastases (uCRLM). Its effectiveness was demonstrated from a high volume center, with uncertainty regarding the feasibility and safety at other centers. Therefore, we sought to assess the safety and feasibility of HAIP for the management of uCRLM at other centers. METHODS: We conducted a multicenter retrospective cohort study of patients with uCRLM treated with HAIP from January 2003 to December 2017 at six North American centers initiating the HAIP program. Outcomes included the safety and feasibility of HAIP chemotherapy. RESULTS: We identified 154 patients with HAIP insertion and the median age of 54 (48-61) years. The burden of disease was >10 intra-hepatic metastatic foci in 59 (38.3%) patients. Patients received at least one cycle of systemic chemotherapy before HAIP insertion. Major complications occurred in 7 (4.6%) patients during their hospitalization and 13 (8.4%) patients developed biliary sclerosis during follow-up. A total of 148 patients (96.1%) received at least one-dose of HAIP chemotherapy with a median of 5 (4-7) cycles. 78 patients (56.5%) had a complete or partial response and 12 (7.8%) received a curative liver resection. CONCLUSION: HAIP programs can be safely and effectively initiated in previously inexperienced centers with good response.