The Sticky Standard of Care

The problem at the heart of “Stemming the Standard‐of‐Care Sprawl: Clinician Self‐Interest and the Case of Electronic Fetal Monitoring,” an article by Kayte Spector‐Bagdady and colleagues in the November‐December 2017 issue of the Hastings Center Report, is the persistence of a suboptimal standard of care long after evidence‐driven approaches would dictate a change. That problem is not simply defensive medicine, or what the authors call “standard‐of‐care sprawl.” Instead, it is that, in some cases, the standard of care lags behind best practices. It gets stuck. The authors point to the genesis of the stickiness problem in their passing reference to a core truth: “The problem is that standard of care is not synonymous with best or evidence‐based medicine.” In my view, we might best understand the persistence of ineffective and even harmful medical interventions by acknowledging the regulatory vacuum in which such practices thrive. It is by default, not by design, that the profession relies on medical malpractice law to set the boundaries on acceptable practice.     

Improving pancreas graft utilization through importation

Background

We analyze our outcomes utilizing imported allografts as a strategy to shorten wait list time for pancreas transplantation.

Methods

This is an observational retrospective cohort of 26 recipients who received either a locally procured (n = 16) or an imported pancreas graft (n = 10) at our center between January 2014 and May 2017. Wait list times of this cohort were compared to UNOS Region 9 (New York State and Western Vermont). Hospital financial data were also reviewed to analyze the cost‐effectiveness of this strategy.

Results

Imported pancreas grafts had significantly increased cold ischemia times (CIT) and peak lipase (PL) levels compared to locally procured grafts (CIT 827 vs 497 minutes; P = .001, PL 563 vs 157 u/L; P = .023, respectively). There were no differences in graft or patient survival. The median wait time was significantly lower for simultaneous kidney‐pancreas transplants at our center (518 days, n = 21) compared to Region 9 (1001 days, n = 65) P = .038. Despite financial concerns, the cost of transport for imported grafts was offset by lower standard acquisition costs.

Conclusions

Imported pancreas grafts may be a cost‐effective strategy to increase organ utilization and shorten wait times in regions with longer waiting times.     

Giant-cell tumor of the appendicular skeleton

The common objective of all surgical procedures in the treatment of giant-cell tumor of bone is to minimize the incidence of local recurrence. The purpose of this study was to determine what, if any, patient factors, tumor characteristics, or surgical practices correlate with local recurrence. Seventy-five patients treated for a giant-cell tumor of the appendicular skeleton were followed up for at least 2 years. The mean duration of followup was 62 months (range, 24-224 months). The highest proportion of patients had intralesional curettage, high-speed burring, and adjuvant treatment. Ten patients (13%) had a local recurrence. Bivariate analysis revealed that, with the numbers available, none of the patient variables, tumor variables, or surgical approaches correlated with local recurrence. Post hoc power analysis revealed the power of the study to be 33% to detect a clinically significant difference between treatment groups. The data presented here potentially could contribute to a metaanalysis, which would have the statistical power to determine which tumor-related factors and surgical techniques are most important in predicting recurrence in giant-cell tumor of bone.     

HIF inhibitor 32-134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy

Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide and available therapies, including immunotherapies, are ineffective for many patients. HCC is characterized by intratumoral hypoxia, and increased expression of hypoxia-inducible factor 1α (HIF-1α) in diagnostic biopsies is associated with patient mortality. Here we report the development of 32-134D, a low-molecular-weight compound that effectively inhibits gene expression mediated by HIF-1 and HIF-2 in HCC cells, and blocks human and mouse HCC tumor growth. In immunocompetent mice bearing Hepa1-6 HCC tumors, addition of 32-134D to anti-PD1 therapy increased the rate of tumor eradication from 25% to 67%. Treated mice showed no changes in appearance, behavior, body weight, hemoglobin, or hematocrit. Compound 32-134D altered the expression of a large battery of genes encoding proteins that mediate angiogenesis, glycolytic metabolism, and responses to innate and adaptive immunity. This altered gene expression led to significant changes in the tumor immune microenvironment, including a decreased percentage of tumor-associated macrophages and myeloid-derived suppressor cells, which mediate immune evasion, and an increased percentage of CD8⁺ T cells and natural killer cells, which mediate antitumor immunity. Taken together, these preclinical findings suggest that combining 32-134D with immune checkpoint blockade may represent a breakthrough therapy for HCC.     

A Study of the Growth Patterns of Breast Carcinoma Using 3D Reconstruction: A Pilot Study

Lumpectomy with microscopically clear margins is a safe and effective approach for surgical management of breast carcinoma. Margins are positive for tumor in 18–50% of lumpectomies, as it is not possible to accurately determine the shape or microscopic borders of a tumor preoperatively or intraoperatively. We examined the 3D microanatomy and growth patterns of common breast carcinoma subtypes to provide guidance for lumpectomy surgery. Prospective consent was obtained for the use of excess tissue from patients undergoing lumpectomy or mastectomy for breast carcinoma. Tissue blocks from nine breast carcinomas were serially sectioned. Hematoxylin and eosin‐stained slides at 100 μm intervals were scanned using a Nanozoomer (Hamamatsu, Japan) microscopic‐resolution scanner. Three‐dimensional reconstructions of tumors were created from scanned images using Reconstruct, open‐access software. Breast carcinoma subtypes demonstrated characteristic growth patterns within breast tissue, which may have implications for lumpectomy surgery. Invasive ductal carcinomas showed a spherical shape, with a spiculated surface representing tumor cells infiltrating into surrounding parenchyma. Ductal carcinoma in situ appeared to spread along the duct system, creating dilated, tortuous, tumor‐filled ducts. The invasive lobular carcinomas examined had a haphazard, linear, infiltrative growth pattern, different from the shape seen in ductal carcinomas. Our preliminary work suggests that invasive ductal and invasive lobular carcinomas appear to have distinct growth patterns in three dimensions and ductal carcinoma in situ appears to grow in a linear fashion along the duct network. The microanatomy studies described have the potential to guide refinements in breast lumpectomy technique.     

A population-based study of the extent of surgical resection of potentially curable colon cancer

Background We attempted to determine factors contributing to the extent of initial curative resection for colon cancer in a population-based cohort. Total abdominal colectomy with ileorectal anastomosis (TAC-IR) may be considered for young patients or those with a colorectal cancer family history to prevent metachronous lesions and facilitate surveillance. Methods All Ontario patients newly diagnosed with colon cancer over 12 months beginning in July 1997 were staged at the time of surgery. The extent of resection was compared with variables, including familial risk obtained from the Ontario Familial Colon Cancer Registry. Results Complete staging was possible for 86% of patients. A total of 1223 patients had a potentially curative resection: 17%, 46%, and 36% were stage I, II, and III, respectively. Patients were more likely to receive a TAC-IR if they were ≤50 years old (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.8–6.6), if they had a synchronous lesion (OR, 28.37; 95% CI, 12.2–61.2), or if they were at a teaching hospital (OR, 2.8; 95% CI, 1.6–4.7), but not if they had a family history (OR, 7; 95% CI, 3–1.5). Conclusions Young age, teaching hospital, and multiple cancers but not family history were important factors for performing a TAC-IR.