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Relatively few imaging and sensing technologies are employed to study human lactation physiology. In particular, human mammary development during pregnancy as well as mammary involution after lactation have been poorly described, despite their importance for breast cancer diagnosis and treatment during these phases. Our case study shows the potential of diffuse optical spectroscopic imaging (DOSI) to uniquely study the spatiotemporal changes in mammary tissue composition during the involution of the lactating breast toward its pre-pregnant state. At nine time intervals over a period of eight months after the cessation of breastfeeding, we reconstructed 2-D maps of mammary water content, lipid content, total hemoglobin (THb) concentration, oxygen saturation (StO2), and tissue optical scattering. Mammary lipid content in the nonareolar region showed a significant relative increase of 59%, whereas water content and THb concentration showed a significant relative decrease of 50% and 48%, respectively. Significant changes were also found in StO2 and tissue optical scattering. Our findings are consistent with the gradual replacement of fibroglandular tissue by adipose tissue and vascular regression during mammary involution. Moreover, our data provide unique insight into the dynamics of breast tissue composition and demonstrate the effectiveness of DOSI as a technique to study human lactation physiology.

Background and Aims Portal hypertension (PH) is a serious adverse event of liver cirrhosis. The hepatic venous pressure gradient or portal pressure gradient (PPG) accurately reflects the degree of PH and is the single best prognostic indicator in liver disease. This is usually obtained by interventional radiology (IR), although it is not routinely performed. Recently, we developed a simple novel technique for EUS-guided PPG measurement (PPGM). Our animal studies showed excellent correlation between EUS-PPGM and IR-PPGM. We present the first human pilot study of EUS-PPGM in patients with liver disease. Methods EUS-PPGM was performed by experienced endosonographers using a linear echoendoscope, a 25-gauge fine-needle aspiration needle, and a novel compact manometer. The portal vein and hepatic vein (or inferior vena cava) were targeted using a transgastric–transduodenal approach. Clinical parameters of PH were evaluated in each patient. Feasibility was defined as successful PPGM in each patient. Safety was based on adverse events captured in a postprocedural interview. Results Twenty-eight patients underwent EUS-PPGM with 100% technical success and no adverse events. PPG ranged from 1.5 to 19 mm Hg and had excellent correlation with clinical parameters of portal hypertension including the presence of varices ( P = .0002), PH gastropathy ( P = .007), and thrombocytopenia ( P = .036). PPG was increased in patients with high clinical evidence of cirrhosis ( P = .005). Conclusion This novel technique of EUS-PPGM using a 25-gauge needle and compact manometer is feasible and appears safe. Given the availability of EUS and the simplicity of the manometry setup, EUS-guided PPG may represent a promising breakthrough for procuring indispensable information in the management of patients with liver disease.

In animal models of hepatocellular carcinoma (HCC), deficiency of S-adenosylmethionine (SAMe) increased the risk of HCC whereas administration of SAMe reduced HCC. The aim of this trial was to determine whether oral SAMe administration to patients with hepatitis C cirrhosis would decrease serum α-fetoprotein (AFP) level, a biomarker of HCC risk in hepatitis C. This was a prospective, randomized, placebo-controlled, double-blind trial of SAMe, up to 2.4 g/d, for 24 weeks as compared with placebo among subjects with hepatitis C cirrhosis and a mildly elevated serum AFP. Primary outcome was change in AFP between baseline and week 24. Secondary outcomes included changes in routine tests of liver function and injury, other biomarkers of HCC risk, SAMe metabolites, markers of oxidative stress, and quality of life. One hundred ten subjects were randomized and 87 (44 SAMe and 43 placebo) completed treatment. There was no difference in the change in AFP during 24 weeks among subjects receiving SAMe as compared with placebo. Changes in markers of liver function, liver injury, and hepatitis C viral level were not significantly different between groups. Similarly, SAMe did not change markers of oxidative stress or serum glutathione level. SAMe blood level increased significantly among subjects receiving SAMe. Changes in quality of life did not differ between groups. Overall, this trial did not find that SAMe treatment improved serum AFP in subjects with advanced hepatitis C cirrhosis and a mildly elevated AFP. SAMe did not improve tests of liver function or injury or markers of oxidative stress or antioxidant potential. Cancer Prev Res; 8(9); 864–72. ©2015 AACR.

Purpose The purpose of this study was to determine locoregional control (LRC), disease-free survival (DFS), and toxicity of high-dose-rate interstitial brachytherapy (HDR-ISBT) in the treatment of locally advanced cervical cancer. Methods and Materials Between March 1996 and May 2009, 116 patients with cervical cancer were treated. Of these, 106 (91%) patients had advanced disease (International Federation of Gynecology and Obstetrics stage IIB-IVA). Ten patients had stage IB, 48 had stage II, 51 had stage III, and 7 had stage IVA disease. All patients were treated with a combination of external beam radiation therapy (EBRT) to the pelvis (5040 cGy) and 2 applications of HDR-ISBT to a dose of 3600 cGy to the implanted volume. Sixty-one percent of patients also received interstitial hyperthermia, and 94 (81%) patients received chemotherapy. Results Clinical LRC was achieved in 99 (85.3%) patients. Three-year DFS rates were 59%, 67%, 71%, and 57% for patients with stage IB, II, III, and IVA disease, respectively. The 5-year DFS and overall survival rates for the entire group were 60% and 44%, respectively. Acute and late toxicities were within acceptable limits. Conclusions Locally advanced cervical cancer patients for whom intracavitary BT is unsuitable can achieve excellent LRC and OS with a combination of EBRT and HDR-ISBT.

Approximately 8–20% of breast cancer patients receiving neoadjuvant chemotherapy fail to achieve a measurable response and endure toxic side effects without benefit. Most clinical and imaging measures of response are obtained several weeks after the start of therapy. Here, we report that functional hemodynamic and metabolic information acquired using a noninvasive optical imaging method on the first day after neoadjuvant chemotherapy treatment can discriminate nonresponding from responding patients. Diffuse optical spectroscopic imaging was used to measure absolute concentrations of oxyhemoglobin, deoxyhemoglobin, water, and lipid in tumor and normal breast tissue of 24 tumors in 23 patients with untreated primary breast cancer. Measurements were made before chemotherapy, on day 1 after the first infusion, and frequently during the first week of therapy. Various multidrug, multicycle regimens were used to treat patients. Diffuse optical spectroscopic imaging measurements were compared with final postsurgical pathologic response. A statistically significant increase, or flare, in oxyhemoglobin was observed in partial responding ( n = 11) and pathologic complete responding tumors ( n = 8) on day 1, whereas nonresponders ( n = 5) showed no flare and a subsequent decrease in oxyhemoglobin on day 1. Oxyhemoglobin flare on day 1 was adequate to discriminate nonresponding tumors from responding tumors. Very early measures of chemotherapy response are clinically convenient and offer the potential to alter treatment strategies, resulting in improved patient outcomes.

The validity of quality of care measurement has important implications for practicing clinicians, their patients, and all involved with health care delivery. The classic strategy for assessing the internal validity of quality of care measures is to examine whether patient outcomes are mediated by process (Donabedian 1982; Field et al. 2001). This can be accomplished either with randomized trials (Antiplatelet Trialists' Collaboration 1994; ISIS-2 [Second International Study of Infarct Survival Collaborative Group] 1988) or, in the case of observational data, with cohort studies. In either case, the fact that sicker patients receive more process, presents challenges in revealing a relationship between process and outcomes. A decade ago, a significant relationship between processes of care and outcomes for hospitalized patients was noted, but even then a paradoxical relationship between process and outcomes for the sickest patients was noted (Kahn, Keeler et al. 1990; Kahn, Rogers et al. 1990). We hypothesize that this paradoxical relationship is a consequence of the association between unmeasured burden of illness and both more process and also worse outcomes. Angrist, Newhouse, McClellan, and Brooks have documented a methodology and a clinical context for using instrumental variables to disentangle the endogeneity of unmeasured burden of illness and both processes and outcomes (McClellan, McNeil, and Newhouse 1994; Angrist, Imbens, and Rubin 1996; Brook, McGlynn, and Cleary 1996; Brooks, McClellan, and Wong 2000; McClellan and Newhouse 2000; Brooks et al. 2003). We applied this methodology to the study of the quality of processes of care to evaluate whether better process was associated with better outcomes. We used empirical data from managed care patients enrolled in west coast physician organizations to test the hypothesis that after adjustment for burden of illness, the changes in health-related quality of life across a 2-year window reflecting process of care. To date, few studies have shown a relationship between explicit process measures and outcomes in the ambulatory setting (Nobrega et al. 1977; Romm and Hulka 1980; Berlowitz et al. 1998; Safran et al. 1998; Asch et al. 2005; Haynes et al. 2005; Higashi et al. 2005), and none have done so for insured managed care patients, or for a health status measure.