Publications

BACKGROUND

In addition to lower operative mortality, patients undergoing selected cancer operations at high volume centers have improved longterm survival. We sought to determine the overall effect of hospital volume on life expectancy after cancer surgery.

STUDY DESIGN

We used a Markov decision analysis model to estimate life expectancy for patients undergoing resection for pancreatic, lung, or colon cancer. Model inputs included probabilities of operative mortality and longterm survival. For input data, we examined operative mortality (in-hospital or within 30 days) stratified by volume in over 400,000 patients undergoing resection for these three cancers using the national Medicare database (1994-1999). Risks of late mortality were abstracted from published studies (MEDLINE, 1966 to present) to model the effect of hospital volume on longterm survival. In analysis, we first calculated life expectancy for patients undergoing surgery at very low, low, medium, high, and very high volume hospitals. We then explored the effects of various regionalization strategies.

RESULTS

Life expectancy increased steadily with hospital volume for all three cancers. Life expectancy after pancreatic cancer resection increased linearly with hospital volume: from 1.9 years at very low volume centers to 3.6 years at very high volume centers. For lung cancer, life expectancy ranged from 5.4 to 6.6 years. Increases in life expectancy for colon cancer were not as dramatic: from 6.8 at very low volume hospitals to 7.4 years at very high volume hospitals. Differences in life expectancy across volume strata were largely attributable to differences in longterm survival, not operative mortality. From a policy perspective, regionalizing surgery for colon cancer would produce the greatest overall life-expectancy gains, but it would require moving most patients.

CONCLUSIONS

Patients aged 65 and older with pancreatic, lung, and colon cancer have substantially greater life expectancy after cancer resection at higher volume hospitals. Further work is needed to understand the mechanisms underlying differences in performance across hospitals in cancer care.

BACKGROUND

Although initiatives to regionalize cancer surgery are already under way, the relative importance of volume in cancer surgery is disputed.

HYPOTHESIS

We examined surgical mortality with 8 cancer resections in the US population to better quantify the influence of hospital volume.

METHODS

Using information from the all-payer Nationwide Inpatient Sample (1995-1997), we examined mortality with 8 cancer resections (N = 195 152). After dividing patients into 3 evenly sized volume groups based on hospital procedure volume (low, medium, and high), we used regression techniques to describe relationships between hospital volume and in-hospital mortality, adjusting for patient characteristics.

RESULTS

Trends toward lower operative risks at high-volume hospitals were observed for 7 of the 8 procedures. However, differences between low- and high high-volume hospitals were statistically significant for only 3 operations (esophagectomy, 15.0% vs 6.5%; pancreatic resection, 13.1% vs 2.5%; and pulmonary lobectomy, 10.1% vs 8.9%, respectively). Although they did not reach statistical significance, absolute differences in mortality between low- and high-volume hospitals were greater than 1% for the following 3 procedures: gastrectomy, 8.7% vs 6.9%; cystectomy, 3.6% vs 2.5%; and pneumonectomy, 10.6% vs 8.9%, respectively. Mortality reductions for nephrectomy and colectomy were small. In general, in terms of absolute differences in mortality, the effect of volume was greatest in elderly patients.

CONCLUSIONS

Operative mortality decreases with increasing hospital volume for several cancer resections. However, volume may be most important in patients who are older and at higher risk.

OBJECTIVE

Aimed at reducing surgical deaths, several recent initiatives have attempted to establish volume-based referral strategies in high-risk surgery. Although payers are leading the most visible of these efforts, it is unknown whether volume standards will also reduce resource use.

METHODS

We studied postoperative length of stay and 30-day readmission rate after 14 cardiovascular and cancer procedures using the 1994-1999 national Medicare database (total n = 2.5 million). We used regression techniques to examine the relationship between length of stay, 30-day readmission, and hospital volume, adjusting for age, gender, race, comorbidity score, admission acuity, and mean social security income.

RESULTS

Mean postoperative length of stay ranged from 3.4 days (carotid endarterectomy) to 19.6 days (esophagectomy). There was no consistent relationship between volume and mean length of stay; it significantly increased across volume strata for 7 of the 14 procedures and significantly decreased across volume strata for the other 7. Mean length of stay at very-low-volume and very-high-volume hospitals differed by more than 1 day for 6 procedures. Of these, the mean length of stay was shorter in high-volume hospitals for 3 procedures (pancreatic resection, esophagectomy, cystectomy), but longer for other procedures (aortic and mitral valve replacement, gastrectomy). The 30-day readmission rate also varied widely by procedure, ranging from 9.9% (nephrectomy) to 22.2% (mitral valve replacement). However, volume was not related to 30-day readmission rate with any procedure.

CONCLUSION

Although hospital volume may be an important predictor of operative mortality, it is not associated with resource use as reflected by length of stay or readmission rates.

Differential diagnosis of hypoglycemic patients should include insulinoma. Plasma insulin-to-glucose ratio greater than 0.3 or C-peptide levels of 2 nmol/L or greater suggest insulinoma. Abdominal CT scan can exclude metastatic disease and identify uncommonly large islet cell tumors, but has poor sensitivity for localizing insulinomas; transgastric endoscopic ultrasound is the most sensitive technique. Palpation combined with intraoperative ultrasound identifies most tumors at operation and gives vital information about surrounding structures. If no tumor is found, blind distal pancreatectomy should not be performed, and the patient should be referred to an endocrinologist or endocrine surgeon for diagnostic confirmation and further localization. Laparoscopy is a viable alternative to open tumor resection; laparoscopic ultrasound can facilitate localization and guide safe resection.

Since the first minimally invasive colon resection 15 years ago, laparoscopic colectomy has been implemented as techniques have evolved. Like the laparoscopic approach for other operations, minimally invasive colectomy has potential benefits of improved short-term outcomes. Questions have been raised, however, regarding its use for colorectal cancer resection. Until recently, it was unclear whether minimally invasive surgery for colonic malignancies would achieve adequate oncologic resection. This review provides an overview of laparoscopic colectomy and techniques and examines recent data from randomized, controlled trials that report the short- and long-term outcomes after laparoscopic colectomy for cancer.

BACKGROUND

Current information about outcomes in octogenarians undergoing cancer operations is limited largely to case series from selected centers. Population-based data can provide more realistic estimates of the risks and benefits of operations in this group.

STUDY DESIGN

We performed a retrospective cohort study of patients undergoing major resections for lung, esophageal, and pancreas cancer. Using the Nationwide Inpatient Sample (1994 to 2003), we examined operative mortality and discharge disposition in octogenarians (aged 80+ years), relative to younger patients (aged 65 to 69 years) (n = 272,662). We then used the Surveillance and End Results-Medicare-linked database (1992 to 2001) to measure late survival in the elderly (n = 14,088).

RESULTS

Operative mortality among octogenarians was substantially higher than that of younger patients (aged 65 to 69 years) for all three cancers (esophagectomy, 19.9% versus 8.8%, p < 0.0001; pancreatectomy, 15.5% versus 6.7%, p < 0.0001; lung resection, 6.9% versus 3.7%, p < 0.0001). A large proportion of octogenarians were transferred to extended care facilities after operation, ranging from 24% after lung resection to 44% after esophagectomy. Five-year survival in octogenarians was low for all three cancers: 11% after pancreatectomy, 18% after esophagectomy and 31% after lung cancer resection. Survival among octogenarians with two or more comorbidities was worse than those with fewer comorbid diagnoses--10% versus 14% for pancreatectomy, 15% versus 23% for esophagectomy, and 27% versus 37% for lung resection.

CONCLUSIONS

Population-based outcomes after high-risk cancer operation in octogenarians are considerably worse than typically reported in case series and published survival statistics. Such information might better inform clinical decision making in this high-risk group.

Activated T cells may express FOXP3. It is thought that FOXP3 is not a specific marker to determine regulatory T cells (Treg) in humans. Here, we examined the functional phenotype and cytokine profile of the in vitro induced FOXP3(+) T cells, primary FOXP3(+) and FOXP3(-) T cells in patients with ulcerative colitis and tumors including colon carcinoma, melanoma, hepatic carcinoma, ovarian carcinoma, pancreatic cancer, and renal cell carcinoma. We observed similar levels of suppressive capacity of primary FOXP3(+) T cells in blood, tumors, and colitic tissues. Compared with primary FOXP3(-) T cells in the same microenvironment, these primary FOXP3(+) T cells expressed minimal levels of effector cytokines, negligible amount of cytotoxic molecule granzyme B, and levels of suppressive molecules interleukin-10 and PD-1. Although the in vitro activated T cells expressed FOXP3, these induced FOXP3(+) T cells expressed high levels of multiple effector cytokines and were not functionally suppressive. The data reinforce the fact that FOXP3 remains an accurate marker to define primary Tregs in patients with cancer and autoimmune disease. We suggest that the combination of FOXP3 and cytokine profile is useful for further functionally distinguishing primary Tregs from activated conventional T cells.

BACKGROUND

Patients with obstructive sleep apnea syndrome (OSAS) are known to have an increased risk for motor vehicle crashes. They suffer from sleep-related respiratory abnormality causing repetitive arousal leading to daytime sleepiness. In turn, it has been demonstrated that sleepiness can impair human psychomotor performance causing slowing of reaction times (RTs). Patients with OSAS present with RTs comparable to young adults under the influence of blood alcohol concentrations above the legally permitted level to drive a motor vehicle. Vigilance related risk levels in patients with upper airway resistance syndrome (UARS) and potential deficits in psychomotor performance are unknown.

METHODS

We designed a study to compare psychomotor performance in UARS and compared it to patients with OSAS. Forty-seven UARS patients were matched by gender and age with 47 OSAS patients. All subjects completed a standardized vigilant attention task utilizing reaction time before undergoing polygraphic sleep studies.

RESULTS

Patients with UARS presented worse psychomotor performance on most test metrics than patients with OSAS.

CONCLUSIONS

Our study results may suggest that patients with UARS may also present an increased risk for motor vehicle crashes as previously demonstrated in OSAS patients.

Th17 cells play an active role in autoimmune diseases. However, the nature of Th17 cells is poorly understood in cancer patients. We studied Th17 cells, the associated mechanisms, and clinical significance in 201 ovarian cancer patients. Tumor-infiltrating Th17 cells exhibit a polyfunctional effector T-cell phenotype, are positively associated with effector cells, and are negatively associated with tumor-infiltrating regulatory T cells. Tumor-associated macrophages promote Th17 cells through interleukin-1beta (IL-1beta), whereas tumor-infiltrating regulatory T cells inhibit Th17 cells through an adenosinergic pathway. Furthermore, through synergistic action between IL-17 and interferon-gamma, Th17 cells stimulate CXCL9 and CXCL10 production to recruit effector T cells to the tumor microenvironment. The levels of CXCL9 and CXCL10 are associated with tumor-infiltrating effector T cells. The levels of tumor-infiltrating Th17 cells and the levels of ascites IL-17 are reduced in more advanced diseases and positively predict patient outcome. Altogether, Th17 cells may contribute to protective human tumor immunity through inducing Th1-type chemokines and recruiting effector cells to the tumor microenvironment. Inhibition of Th17 cells represents a novel immune evasion mechanism. This study thus provides scientific and clinical rationale for developing novel immune-boosting strategies based on promoting the Th17 cell population in cancer patients.