Diabetes mellitus affects response to neoadjuvant chemoradiotherapy in the management of rectal cancer.

INTRODUCTION: Although diabetic patients with rectal cancer have poorer outcomes than their nondiabetic counterparts, few studies have looked at diabetics' response to therapy as an explanation for this disparity. This study compares the neoadjuvant chemoradiotherapy (CRT) response in diabetic and nondiabetic patients with locally advanced rectal cancers. METHODS: This is a single-institution, retrospective review of rectal cancer patients who received CRT followed by resection from 1995 to 2006. Pretreatment tumor-node-metastasis (TNM) staging was determined using endorectal ultrasound, computed tomography (CT) scan, and magnetic resonance imaging (MRI); post-treatment staging was determined by pathological review. RESULTS: 110 patients were included; seventeen had diabetes and 93 were nondiabetics. Pretreatment staging was similar in both groups. Sixteen of the diabetics (94%) completed CRT compared to 92% (86/93) of the nondiabetics. Tumor downstaging rates were similar in the two groups (53% in diabetics, 52% in nondiabetics). Nondiabetic patients had a higher rate of nodal downstaging although not statistically significant (67% versus 27%, P = 0.80). While none of the diabetics patients achieved a pathologic complete response (pCR), 23% (21/93) of the nondiabetics did (P = 0.039). Local progression rates were higher in the diabetic group (24% versus 5%, P = 0.046). CONCLUSION: Our study shows that neoadjuvant chemoradiotherapy in rectal cancer is less effective in diabetic patients than in nondiabetics. While minimal differences are found in the rate of downstaging, the rate of achieving a complete pathologic response was significantly higher in nondiabetic patients, and in fact was not seen in any of our diabetic patients. This may explain the poorer outcomes seen in diabetic patients with rectal cancer.

In vitro-in vivo correlation of hepatobiliary drug clearance in humans.

The biliary clearance (Cl(biliary)) of three compounds was estimated using sandwich-cultured human hepatocytes (SCHH) and compared with Cl(biliary) values measured in vivo. Tc-99m sestamibi (MIBI) Cl(biliary) was determined in seven healthy volunteers using an oroenteric catheter to aspirate duodenal secretions, and gamma scintigraphy to determine gallbladder contraction; this technique was used previously to determine Tc-99m mebrofenin (MEB) and piperacillin (PIP) in vivo Cl(biliary). In vitro Cl(biliary) of MEB, MIBI, and PIP was quantified in SCHH as the ratio of mass excreted into bile canaliculi and area under the blood concentration-time curve (AUC) in medium. MIBI Cl(biliary) in vivo was 5.5+/-1.2 mL/min/kg (mean+/-SD). The rank order of Cl(biliary) predicted from SCHH corresponded well with the in vivo Cl(biliary) values in mL/min/kg for MEB (7.44 vs 16.1), MIBI (1.20 vs 5.51), and PIP (0.028 vs 0.032). In conclusion, the methods developed allowed for reproducible quantification of Cl(biliary) of drugs in healthy humans and prediction of Cl(biliary) from in vitro data.

Expression of 15-lipoxygenase-1 in human colorectal cancer.

Recently, we reported the induction of reticulocyte type 15-lipoxygenase (15-Lox-1) in a human colorectal carcinoma cell line that had been stimulated by butyrate to undergo apoptosis and cell differentiation (H. Kamitani et al., J. Biol. Chem., 273: 21569-21577, 1998). To determine if 15-Lox-1 is expressed in human colorectal cancer tissue, 21 matched pairs of colorectal tumor and adjacent normal tissue were examined by immunoblot analysis using specific antibodies for human 15-Lox-1, prostaglandin H synthase (also called cyclooxygenase, Cox)-1 and Cox-2. Eighteen of the 21 were found to have 15-Lox-1 in both tumor tissue and matched adjacent normal tissue, with the 15-Lox-1 expression being significantly higher in most of the tumor tissue. The expression of Cox-2 was also elevated in most tumors, whereas Cox-1 was frequently expressed at lower levels in the tumor tissue than in the paired normal tissue. Reverse-phase high-performance liquid chromatography analysis of arachidonate metabolites, formed on incubation of arachidonic acid with a crude enzyme preparation from the colon samples, revealed the formation of 15-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid with a much lower level of 12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (15-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid:12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid, 6.5:1) which also indicate the presence of 15-Lox-1. Furthermore, reverse transcription-PCR with primers specific for human 15-Lox-1 or 15-Lox-2 cDNA indicated that 15-Lox-1 mRNA was present in the colorectal tumors. The sequence of the PCR product was identical to the human 15-Lox-1. Immunohistochemical studies showed 15-Lox-1 localization in the glandular epithelium of human colorectal tumor tissue. These results suggest that 15-Lox-1 is highly expressed in human colorectal cancer epithelial cells and that its expression may have a role in colorectal carcinogenesis.

Metastatic gastric leiomyoblastoma: a case report.

Gastric leiomyoblastoma is a rare entity. In this report, we describe the magnetic resonance (MR) appearance of a recurrent gastric leiomyoblastoma 14 years after initial presentation. This tumor was heterogeneous and moderately low signal intensity on T1-weighted images and heterogeneous and moderately high signal intensity on T2-weighted images. The tumor also contained foci of low signal intensity on the post gadolinium images, consistent with areas of necrosis. The mass enhanced mildly and increased in enhancement on the delayed images, consistent with a hypovascular mass. Multiple liver metastases were noted. Magnetic resonance findings were confirmed with surgical specimens.

Cholangiocarcinoma: spectrum of appearances on MR images using current techniques.

This study describes the spectrum of appearances of cholangiocarcinoma on magnetic resonance (MR) sequences, including gadolinium-enhanced, fat-suppressed spoiled gradient echo images and MR cholangiography. Fifteen patients were included in the study. Histologic diagnosis was established in 11 patients by surgical resection (6 patients), percutaneous biopsy (4 patients), and open liver biopsy (1 patient). The final diagnosis was determined by correlation of the MR findings with cholangiographic studies and laboratory studies in 4 patients. MR studies were performed at 1.5 T, and the following sequences were obtained: T1-weighted spoiled gradient echo (SGE), T1-weighted fat-suppressed spin echo or SGE, T2-weighted fat-suppressed conventional or turbo spin echo, MR cholangiography, and gadolinium-enhanced T1-weighted fat-suppressed SGE images. The following determinations were made: tumor location, tumor extent, ductal dilatation, ductal wall thickness, signal intensity, enhancement pattern, and associated findings. Mass-like neoplasms were peripheral (6 patients), hilar (1 patient), and extrahepatic (2 patients). Circumferential tumors were hilar (2 patients) and extrahepatic (4 patients). All peripheral tumors were multifocal. Mass-like tumors were well-defined, rounded, and ranged from 1 to 14 cm in diameter. Circumferential tumors had less well-defined margins and measured from 3 to 15 mm in thickness. All mass-like tumors were moderately hypointense on T1-weighted images and mildly to moderately hyperintense on T2-weighted images. The circumferential tumors were iso- to moderately hypointense on T1-weighted images and iso- to mildly hyperintense on T2-weighted images. Mass-like tumors were generally well shown on non-contrast and immediate gadolinium-enhanced images, whereas circumferential tumors were poorly seen on non-contrast images and best shown on gadolinium-enhanced T1-weighted fat-suppressed images. The degree of enhancement ranged from minimal to intense on immediate gadolinium-enhanced images, with all tumors becoming more homogeneous in signal intensity on images obtained between 1 and 5 min following contrast administration. Tumor-containing lymph nodes greater than or equal to 1 cm in diameter were demonstrated in 11 out of 15 patients (73.3%). These were best shown on T2-weighted fat-suppressed images and gadolinium-enhanced fat-suppressed SGE images. MR cholangiography demonstrated the level of obstruction and degree of dilatation of the proximal biliary system in 5 out of 6 patients who underwent MR cholangiography. The spectrum of appearances of cholangiocarcinoma is demonstrable on MR images. Mass-like tumors are well shown on both pre- and post-gadolinium sequences. Circumferential tumors may cause minimally increased duct wall thickness and are most clearly shown on gadolinium-enhanced fat-suppressed SGE images obtained 1 to 5 min following gadolinium administration.

Beyond anatomy: MR imaging as a molecular diagnostic tool.

Technical advances in software and hardware make MR imaging competitive with CAT scanning as an anatomic imaging tool. Although anatomic relationships remain important, increased understanding of cell structure and function is rapidly moving us toward diagnosis and treatment at the cellular level. By virtue of its reliance on nuclear magnetic spin moment, MR imaging is responsive to real time physico-chemical characteristics of cells and tissues being imaged. This intrinsic advantage of MR imaging is being rapidly developed through the use of targeted imaging agents and magnetic resonance spectroscopy. Imaging agents that target specific cell populations have been prepared by using monoclonal antibodies, liposomes, and short peptides bound to chelates containing paramagnetic atoms. Using magnetic resonance spectroscopy, the chemical composition of tumors can be analyzed and compared with normal tissues in vivo and in vitro. Areas of possible clinical usefulness for magnetic spectral analysis include: (1) in vitro or in vivo characterization of lesions as benign or malignant, (2) differentiation between in situ and invasive carcinomas, (3) determination of responsiveness to specific chemotherapeutic regimens before their institution, (4) study of in vivo drug metabolism by neoplasms, and (5) assessment of response to therapy and of residual disease at the completion of therapy. Early experiences in these parallel fields show great promise, with widespread clinical applications expected in the near future.

Peritoneovenous shunting for nongynecologic malignant ascites.

BACKGROUND: The development of malignant ascites has been associated with a poor prognosis. Previous reports have documented high morbidity rates associated with placement of palliative peritoneovenous shunts (PVS). Most study series have included gynecologic malignancies in their analysis, and wide variations in survival time have been reported. Reported data from nongynecologic malignancies and identification of preoperative factors associated with improved outcome were the concerns of the current study, which attempted to identify patients with malignant ascites who might have benefitted from PVS. METHODS: A retrospective chart review was performed and data including age, gender, weight, preoperative laboratory values, cytology on peritoneal fluid aspirates, and complications within 30 days of the operative procedure were obtained and recorded. Discharge date and follow-up status were obtained for all patients. Statistical analysis was done for categorical values by comparing survival times from date of procedure with follow-up times using the log rank test. Significance for numeric values was determined with Cox regression analysis. Multivariate analysis using Cox regression was performed for those values found to be significant on univariate analysis. RESULTS: Fifty- five patients who had undergone PVS from 1980-1996 for ascites on the Gastric and Mixed Tumor service at the Memorial Sloan-Kettering Cancer Center were identified. Two patients with benign disease and two patients with ovarian malignancies were excluded. The remaining 51 patients underwent placement of 53 PVSs for palliation. Median survival time for the entire group was 52 days. Univariate analysis identified preoperative blood urea nitrogen (BUN), creatinine (Cr), BUN to Cr ratio, and diagnosis as significant factors. Preoperative BUN emerged as an independent predictor of survival by multivariate analysis, and those patients who had a BUN value of < = 17 demonstrated a survival advantage over those with a BUN of > 17. The assessable palliation factors were hospital discharge (80% of patients) and weight loss after shunting (68% of patients lost > 1 kg). Ninety-six percent of patients (24 of 25) with a preoperative BUN of < or = 17 were discharged. CONCLUSIONS: The development of nongynecologic malignant ascites is an end stage event for most patients. The placement of PVS for those patients with nongastrointestinal tumor etiologies, a BUN of < 17, a Cr of < or = 1.1, and a BUN to Cr ratio of < 19 yielded the best results. In the current study, palliation was difficult to assess accurately, although most patients were discharged or lost > 1kg of weight after shunting.