April 2023

This cohort study found that patients with multifocal intrahepatic cholangiocarcinoma had similar overall survival after hepatic artery infusion pump (HAIP) therapy with floxuridine chemotherapy as compared to resection.  

Summary: 

Background
Intrahepatic cholangiocarcinoma (iCCA) is a highly fatal primary liver malignancy with poor prognosis, namely due to the multifocal nature at presentation. Most guidelines recommend palliative chemotherapy for multifocal iCCA and surgical resection is only considered in patients with limited multifocal disease. However, hepatic artery infusion pumps (HAIP) have been shown to improve overall survival in patients with iCCA as it delivers high dose chemotherapy directly to the liver while reducing systemic toxic effects. The aim of this study was to compare overall survival of patients with multifocal iCCA treated with HAIP chemotherapy versus surgical resection. 

Methods
This is a prospective cohort study comparing patients with multifocal iCCA who underwent HAIP placement to those who underwent surgical resection. The HAIP cohort consisted of unresectable (determined by multidisciplinary group), multifocal iCCA treated with HAIP floxuridine chemotherapy between 2001-2018 at Memorial Sloan Kettering Cancer Center. The surgical resection cohort consisted of patients undergoing surgical resection for multifocal iCCA between 1990-2017 at 12 major hepatobiliary centers across the US, Australia, Asia, and Europe. Patients were excluded from both cohorts if they had distant metastatic disease. The primary outcome was overall survival (OS), defined as the time interval between date of HAIP placement or surgical resection and date of death or last follow up which was analyzed using Cox proportional hazards models. 

Results
319 patients with multifocal iCCA were included with 141 patients in the HAIP cohort and 178 patients in the surgical resection cohort. Compared with the HAIP cohort, the surgical resection cohort had higher rates of major postoperative complications (25.3% vs 6.4%, P=0.04) and 30-day mortality (6.2% vs 0.8%, P = .01). Median OS did not significantly differ between HAIP (20.3 months) and surgical resection (18.9 months, P = .32). Crude five-year OS in the HAIP cohort was 12.5% (95% CI, 7.4%-21.1%) compared with 20.7% (95% CI, 14.4-29.7%) in the surgical resection cohort. No significant differences in median OS or 5-year OS were observed between HAIP and surgical resection. Risk factors for decreased OS were tumor diameter (HR, 1.74; 95% CI, 1.20-2.52; P < 0.01), number of tumors (HR, 1.84, 95% CI, 1.39-2.44; P < 0.01), and regional nodal disease (HR, 1.51, 95% CI, 1.17-1.96, P < 0.01). After adjustment for these risk factors, the HR for HAIP versus resection was 0.75 (95% CI, 0.55-1.03), although not significant (p=0.07). 

Limitations
There are several limitations worth noting. Although this study adjusted for known variables associated with decreased survival, there is still a risk for unmeasured confounding in the setting of non-randomization. Second, the HAIP patients all received care at one institution, which may limit the generalizability of the findings – more importantly, the definitions of unresectable and resectable may vary from institution to institution based on resource availability, surgeon experience, etc and thus, these results should be interpreted with caution. Third, and most notably, results should be interpreted with caution when comparing overall survival in patients with resectable to those with unresectable disease; certain data was not collected, such as distribution of liver lesions or genomics of the tumors, both of which may mediate propensity to get resection and response to treatment. Fourth, while most patients in the HAIP cohort received systemic treatment, a minority in the surgical resection cohort also received systemic treatment (neoadjuvant and/or adjuvant). Given most patients with iCCA die from distant metastatic disease, it is possible that OS in the resection group would have been improved if a larger proportion of resection patients received systemic treatment. 

Bottom Line
Similar median overall survival was observed in patients with multifocal iCCA treated with HAIP chemotherapy or surgical resection. Five-year overall survival was greater for patients who underwent surgical resection compared with HAIP, and although it didn’t reach statistical significance, it suggest that select patients with multifocal iCCA, particularly those with good performance status and only 2-3 tumors, may benefit from surgical resection in the long term if feasible. Alternatively, HAIP may offer similar survival to those who undergo resection and thus could be considered for patients with poor performance status or higher risk disease.

The majority of residents feel unprepared to manage their finances and want formal financial education to be incorporated into residency. Educating residents has the potential to reduce financial stress and improve physician wellbeing.

Summary:
Personal physician finance is an often overlooked and underdiscussed source of stress that impacts resident wellbeing and success. The average student loan debt has reached over $215,000 and most residents feel unprepared to manage their finances.

The authors evaluated perceptions of financial literacy among residents, the level of financial education incorporated across programs, and the resources that residents utilize to obtain information about personal finance. To answer these questions, they performed a systematic review of articles published between 2012-2022; they ended up with 23 studies evaluating a total of 5146 residents.

14 studies evaluated resident perceptions of their financial literacy. 42-79% of residents reported a “below average” understating of finance and felt unprepared to handle future financial decisions. Deficiencies included investing, retirement, negotiating salaries, mortgages, insurance, and tax planning.

In addition, 80% of residency program directors believed that their residents were unprepared to handle personal and professional financial decisions after graduation. 79-95% of residents agreed that personal finance should be taught during residency. Despite this, only up to 36.7% of programs provided financial education, depending on the study. In the absence of formal curricula, residents turned to personal research, family members or outside financial planning seminars.

Options for financial education interventions included financial workshops and lectures on topics ranging from debt repayment, billing compliance, medical malpractice, contract negotiation, financial management and many other topics. When administered, these interventions were well received by residents with over 95% of participants recommending continued programming.  In addition, pre- and post-tests showed significant improvements in financial literacy knowledge. More work needs to be done to tie these interventions with financial outcomes, such as retirement savings program participation, insurance coverage, and financial planning.

This article in Nature Medicine offers conclusions from a unique Jury-based consensus conference seeking to provide a framework for evaluating surgical outcomes and future research priorities that reflects the perspectives of research experts, patients, providers, and other stakeholders. 

Summary: In 2008, the WHO recognized that surgical complications are a significant global public health and economic burden on both an individual and societal level. Unfortunately, efforts to improve postoperative complications through research have been limited by heterogeneity in terms of end points and outcomes evaluated. Ideally, these outcomes should reflect the priorities of the main stakeholders involved i.e. the patient and provider, but also consider the goals the hospital, payers, regulatory agencies, and government.   

With these goals in mind, the authors sought to develop a framework for surgical outcomes assessment that reflects the multi-faceted priorities of the patient, provider, and society. To do this, they used the Zurich-Danish model for consensus building. This approach has previously been used to provide recommendations in hepatocellular carcinoma and liver metastases. Briefly, the model relies on the creation of two groups – the Experts who select the topics and evidence for possible solutions and the Jury who challenges and finalizes the recommendations. Experts consisted of leaders in patient outcomes-related research, while the Jury consisted of individuals with sufficient background knowledge in the topics compiled by the experts, but not directly involved in outcomes research. Once the topics were selected, the Experts work in panels to generate evidence-based solutions to the topics selected which are ultimately presented to the Jury at the final Consensus Conference. Here the Jury and audience can ask questions and offer comments. Uniquely, it is the Jury who finalizes the consensus recommendations that are ultimately reported to the public.   

Through this approach, the Experts selected 9 topics - five focusing on stakeholders priorities and six focusing on outcome measurement, analysis and interpretation. Notable areas of emphasis included what outcomes should we be measuring to reflect patient priorities, how often should we be measuring them, and how do we better use benchmarking or individual risk to better interpret individual surgical complications. The Jury then developed a series of recommendations outlined in Box 2 which emphasize using patient reported clinical and experience outcomes at standardized timepoints and the optimal utilization of M&M conferences, data integrity, benchmarking, and patient risk classification tools to interpret and improve complication incidence. They also offer a series of research priorities that will help the field to meet these recommendations and potentially direct the future of outcomes research, listed in Box 4 and included below.