Dietary intake of heterocyclic amines, meat-derived mutagenic activity, and risk of colorectal adenomas.

Meats cooked well-done by high temperature techniques produce mutagenic compounds such as heterocyclic amines (HCAs), but the amounts of these compounds vary by cooking techniques, temperature, time, and type of meat. We investigated the role of HCAs in the etiology of colorectal adenomas and the extent to which they may explain the previously observed risk for red meat and meat-cooking methods. In a case-control study of colorectal adenomas, cases (n = 146) were diagnosed with colorectal adenomas at sigmoidoscopy or colonoscopy, and controls (n = 228) were found not to have colorectal adenomas at sigmoidoscopy. Using a meat-derived HCA and mutagen database and responses from a meat-cooking questionnaire module, we estimated intake of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and mutagenic activity. We calculated odds ratios and 95% confidence intervals using logistic regression adjusting for several established risk factors for colorectal adenomas or cancer. The odds ratios (95% confidence interval; P for trend test) fifth versus first quintiles are: 2.2 (1.2-4.1; P = 0.02) for DiMeIQx; 2.1 (1.0-4.3; P = 0.002) for MeIQx; 2.5(1.1-5.5; P = 0.02) for PhIP; and 3.1 (1.4-6.8; P = 0.001) for mutagenic activity. When the three HCAs were adjusted for the other two, only the trend for MeIQx (P = 0.04) remained statistically significant. When we tried to disentangle the relative contribution of the three HCAs from the meat variables, we found that MeIQx remained significantly associated with risk even when adjusted for red meat but not vice versa. When MeIQx and well-done meat were analyzed in the same model, the risks were attenuated for both. Mutagenic activity from meat remained significantly associated with increased risk even when adjusted for intake of red meat or well-done red meat, whereas the red meat and well-done red meat associations were no longer significant when adjusted for total mutagenic activity. In conclusion, we found an elevated risk of colorectal adenomas associated with high intake of certain HCAS: Further, mutagenic activity from cooked meat consumption, a measure that integrates all of the classes of mutagens, was strongly associated with risk and explained the excess risk with intake of well-done red meat.

Well-done, grilled red meat increases the risk of colorectal adenomas.

Red meat or meat-cooking methods such as frying and doneness level have been associated with an increased risk of colorectal and other cancers. It is unclear whether it is red meat intake or the way it is cooked that is involved in the etiology of colorectal cancer. To address this issue, we developed an extensive food frequency questionnaire module that collects information on meat-cooking techniques as well as the level of doneness for individual meat items and used it in a study of colorectal adenomas, known precursors of colorectal cancer. A case-control study of colorectal adenomas was conducted at the National Naval Medical Center (Bethesda, MD) between April 1994 and September 1996. All cases (n = 146) were diagnosed with colorectal adenomas at sigmoidoscopy or colonoscopy and histologically confirmed. Controls (n = 228) were screened with sigmoidoscopy and found not to have colorectal adenomas. The subjects completed a food frequency questionnaire and answered detailed questions on meat-cooking practices. We used frequency and portion size to estimate grams of meat consumed per day for total meat as well as for meat subgroups defined by cooking methods and doneness levels. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression, adjusted for age, gender, total caloric intake, reason for screening (routine or other), and several established risk factors for colorectal adenomas or cancer, including the use of nonsteroidal anti-inflammatory drugs, physical activity, and pack-years of cigarette smoking. There was an increased risk of 11% per 10 g/day (or 2.5 oz/week) of reported red meat consumption (OR, 1.11; CI, 1.03-1.19). The increased risk was mainly associated with well-done/very well-done red meat, with an excess risk of 29% per 10 g/day (OR, 1.29; CI, 1.08-1.54) versus an excess of 10% per 10 g/day (OR, 1.10; CI, 0.96-1.26) for consumption of rare/medium red meat. High-temperature cooking methods were also associated with increased risk; 26% per 10 g/day (OR, 1.26; CI, 1.06-1.50) of grilled red meat and 15% per 10 g/day (OR, 1.15; CI, 0.97-1.36) of pan-fried red meat consumption. There was an increased risk of colorectal adenomas associated with higher intake of red meat, most of which was due to the subgroup of red meat that was cooked until well done/very well done and/or by high-temperature cooking techniques, such as grilling. These results are consistent with the hypothesis that carcinogenic compounds formed by high-temperature cooking techniques, such as heterocyclic amines and polycyclic aromatic hydrocarbons, may contribute to the risk of developing colorectal tumors.

Spleen-preserving pancreatectomy for cystic pancreatic neoplasms.

Cystic neoplasms of the pancreas are an uncommon entity comprising fewer than 1 per cent of all pancreatic neoplasms. The guidelines for management of these tumors, specifically, the extent of resection, are unclear. Formerly, a distal pancreatectomy including the spleen was performed for tumors in the tail of the pancreas. The importance of preserving the spleen has been well documented; however, there are few reports of spleen-preserving pancreatectomy for cystic neoplasms of the distal pancreas. We report two patients who underwent spleen-preserving pancreatectomy for mucinous cystic neoplasms in the tail of the pancreas. Both patients were female, ages 39 and 65 years. Preoperative preparation included administration of vaccinations and subcutaneous somatostatin. Operative technique emphasized division of the splenic artery and vein beyond the tip of the distal pancreas without mobilization of the spleen. The pancreas was transected with a vascular stapler. Fibrin glue was applied to the margin of the pancreas. The operative blood loss, duration of operation, and postoperative hospital stay were 150 and 250 mL, 150 and 180 minutes, and 7 and 9 days, respectively. The pathology revealed both lesions to be mucinous cystic neoplasms. The patients recovered and at 6-month follow-up were without complaints and in good health. Spleen-preserving pancreatectomy is rapid and associated with minimal morbidity. This procedure should be considered in the surgical management of cystic neoplasms in the tail of the pancreas.

Prognostic significance of DNA replication errors in young patients with colorectal cancer.

OBJECTIVE: To determine the DNA replication error (RER) status in young patients with colorectal cancer (CRC), and to compare the clinical and pathologic characteristics of RER-positive and RER-negative cases. SUMMARY BACKGROUND DATA: Recent studies suggest that patients with RER-positive CRC have an improved prognosis. Further data are required to confirm this observation in young CRC patients. METHODS: All patients 40 years of age and younger with CRC admitted to the National Naval Medical Center between 1970 and 1992 were considered for inclusion in the study. After review, 36 patients for whom the original archived pathology specimen could be retrieved served as the study population. The RER status was determined using a previously described polymerase chain reaction-based assay. The clinical and pathologic features and survival data were compared to RER status. RESULTS: RER-positive tumors were found in 17 cases (47%). There was no significant difference in Dukes' stage or histologic grade at the time of diagnosis between patients with RER-positive tumors compared to RER-negative tumors. Patients with RER-positive tumors were found to have an improved prognosis: the 5-year survival probability for patients with RER-positive tumors was 68%, as compared to 32% for patients with RER-negative tumors (p < 0.05). CONCLUSIONS: RER-positive tumors are common in young patients with CRC, and patients with RER-positive tumors have a significantly improved prognosis. Because of their young age, survival data and prognosis play an important role in the overall treatment plan of young patients with CRC. Therefore, knowledge of RER status could affect initial therapy, postoperative chemotherapy, and follow-up.

Mutations in beta-catenin are uncommon in colorectal cancer occurring in occasional replication error-positive tumors.

Beta-catenin has been identified as an oncogene in colon cancer and melanoma. Phosphorylation of sites in exon 3 of beta-catenin leads to degradation of this protein. These sites are primary targets for activating mutations. The frequency with which oncogenic mutations at these sites are found in colorectal cancer is unknown, as is the frequency of their occurrence in other malignancies. We analyzed 92 colorectal cancers (CRCs) and 57 cancer cell lines (representing a diversity of tumor types) to determine the frequency of activating mutations in this gene. Mutations in exon 3 of beta-catenin were found in 2 of 92 CRCs and in the colorectal cancer cell line HCT 116. Both tumors with beta-catenin mutations exhibited widespread microsatellite instability, which is indicative of a replication error phenotype, a phenotype known to be present in HCT 116. This suggests that mutations in beta-catenin are infrequent in CRC and miscellaneous cancer cell lines and may occur in association with a replication error phenotype.

The influence of a Federal comprehensive health care system on the detection and outcome of primary small bowel malignancies.

Twenty-one cases of primary small bowel malignant tumors treated at our institution from 1983 to 1993 were reviewed. The mean age at diagnosis was 51.6 +/- 16.8 years. Twelve patients (57%) reported symptoms of less than 1 month duration. Diagnosis was made at laparotomy in 13 patients (62%), and nine patients (43%) had three or more preoperative studies. Five patients (24%) presented with abdominal emergencies. The 5-year survival rate for the series was 19 per cent. This study was performed at a tertiary care military hospital where patients and physicians are not subjected to the financial constraints of civilian health care. This system should eliminate delays in seeking medical care and expedite diagnosis. Despite almost immediate medical attention for a majority of the patients, overall survival is not significantly different from that in previous reviews. This study emphasizes that the presentation of small bowel malignancies is indolent and difficult to diagnose. Prognosis remains poor despite the patient cost-free system and almost immediate medical attention. This study suggests that a high index of suspicion and a thorough evaluation, including laparotomy, are required to improve outcome.

Kock pouch dysfunction during pregnancy. Management of a case.

The Kock continent ileostomy is a surgical alternative to a Brooke ileostomy after total proctocolectomy. Complications resulting from an improperly functioning nipple valve are not infrequent and when they occur most often require surgical revision. A 19-year-old female with a functioning Kock pouch of 4 years presented at 6 months of pregnancy with complete bowel obstruction due to nipple valve dysfunction. Operative management was avoided and her bowel obstruction was relieved by endoscopic placement of a stent through the nipple valve and into the abdominal reservoir. The stent was removed at 1 week postpartum with immediate return to normal function of her Kock pouch nipple valve. Temporary malfunction of the Kock pouch nipple valve can occur during pregnancy, probably due to distortion of the valve mechanism by the enlarging uterus. The endoscopic placement of a stent can maintain proper bowel evacuation until delivery and normal Kock pouch function can be expected after stent removal.

Case report. Inflammatory pseudotumor in the retrorectal space: CT and MR appearance.

We report a case of an inflammatory pseudotumor of the retrorectal space, with CT and MRI findings. The imaging findings in this case are consistent with those reported from other anatomic sites, demonstrating the aggressive nature of this histologically benign but frequently invasive mass. Recent discussions in the literature advise close imaging follow-up after surgical excision, particularly in cases in which incomplete resection is deemed preferable to a more mutilating radical resection.

Subcutaneous tissue oxygen pressure: a reliable index of peripheral perfusion in humans after injury.

The usual initial life-threatening effect of injury is hypovolemic shock. In the hierarchical physiologic response to hypovolemia, perfusion of peripheral tissues is sacrificed early and restored late. But the usual hemodynamic and metabolic measurements of blood pressure, urine output, and base deficit are not reliable indices of peripheral perfusion. Although the Clark electrode can quantitate tissue oxygen pressure and thereby serve as an index of perfusion, its use is compromised by several technical deficiencies. Recently, an optical method (optode) using fluorescent technology has been developed for measurement of oxygen tension in subcutaneous tissue (P sgO2). Our studies compared this device with the Clark electrode in the laboratory and tested its value in both animal and clinical studies of hypovolemic shock. The results of these several studies demonstrated that: (1) the new oximeter tracked a rapid fall or rapid rise of oxygen tension between room air (150 mm Hg) and 0 mm Hg ( a glucose oxidase/catalase solution) as well as the Clark electrode without encountering its technical problems; (2) with an acute hemorrhage to 20% of base line, the PsgO2 was found to decline rapidly in parallel with the decline of mean arterial pressure (MAP). Although the MAP rapidly returned to normal after immediate complete return of all shed blood, the PsgO2 did not reach normal levels for at least 2 hours, suggesting persistent peripheral vasoconstriction. (3) Studies in progress suggest that between 35 and 78% of trauma patients (n = 18) adequately resuscitated for hypovolemia b customary criteria have a decreased level of PsgO2 for as long as 60 hours after resuscitation for injury. If care is taken to prevent other causes of catecholamine induced vasoconstriction such as pain, fear, cold, and arterial hypoxia, these several results suggest that a certain number of injured patients are inadequately resuscitated despite the return to normal of conventional hemodynamic measurements. The serial analysis of PsgO2 may assist in managing patients and promote better understanding of the responses to injury.

Sampling lymph node content of human immunodeficiency virus type 1 nucleic acids and p24 antigen by fine-needle aspiration in early-stage patients.

The potential of lymph node fine-needle aspiration (LNFNA) for sampling viral load was evaluated in excised, peripheral lymph nodes from five patients with early-stage human immunodeficiency virus type 1 HIV-1 disease (asymptomatic, CD4 cells > 300/mm3). The preponderance (> 80%) of viral RNA was within follicular germinal centers as noted by in situ hybridization on lymph node frozen sections (LNFSs) as well as within cohesive groups of 10-20 lymphoid cells (microfragments) in LNFNA preparations. Quantification of cells expressing HIV-1 RNA by in situ hybridization, quantification of HIV-1 gag RNA and gag DNA per 10(5) cells by polymerase chain reaction, and measurement of p24 antigen per 10(5) cells yielded similar values for LNFNA, lymph node mononuclear cells (LNMCs) from tissue homogenates by Ficoll-Hypaque separation, and LNFS. Sampling of lymph node viral load by LNFNA appears to capture viral components associated with both individual expressing cells and follicular germinal centers. Due to the advantages in terms of patients' morbidity, repeatability, and cost, assessment of lymphoid tissue viral load by LNFNA warrants an in vivo feasibility trial as an alternative to lymph node biopsy.

Effect of music therapy on state anxiety in patients undergoing flexible sigmoidoscopy.

PURPOSE: Patient anxiety related to flexible sigmoidoscopy can negatively affect acceptability and compliance with screening protocol, complicate and prolong procedure time, and potentially result in prematurely aborted procedures. Music has been recognized through research as a safe, inexpensive, and effective nonpharmaceutical anxiolitic agent. METHODS: An experimental study was performed on 50 adults scheduled for outpatient sigmoidoscopy. The control group received standard sigmoidoscopy protocol. Subjects in the experimental group received the standard protocol with the addition of listening to music throughout the procedure. State-Trait Anxiety Inventory (STAI) measurements were performed on all subjects before and postsigmoidoscopy. Physiologic recordings of heart rate and mean arterial pressure were recorded before and during the procedure. RESULTS: Patients who listened to self-selected music tapes during the procedure had significantly decreased STAI scores (P < 0.002), heart rates (P < 0.03), and mean arterial pressures (P < 0.001) in comparison to the control subjects. CONCLUSION: The results of the study indicate that music is an effective anxiolitic adjunct to flexible sigmoidoscopy.

Massive bleeding from rectal varices.

An elderly female who experienced a life-threatening bleed from an isolated rectal varix is presented. She failed endoscopic injection sclerotherapy but responded to surgical ligation. The literature concerning well-documented bleeding from eight cases of rectal varices is reviewed. Nomenclature, diagnosis, and therapy are emphasized.

Intermittent claudication caused by atherosclerosis in patients aged forty years and younger.

Intermittent claudication may represent a severe limitation in daily life-style for young, active patients and may result in loss of professional career for members of the armed forces. Our recent experience with young patients with atherosclerotic claudication was reviewed to determine whether more liberal use of angioplasty and surgery is warranted in these patients to salvage their military careers and improve their life-styles. A systemic review was made of patients aged 40 years and younger with atherosclerosis who have undergone arteriography at our institution during the past 67 months. From this study, 22 patients were found with the initial complaint of intermittent claudication. Fifteen of these patients (68%) had occlusive disease confined to the iliac arteries, and six (27%) had single-level occlusive disease in a femoropopliteal distribution. Only one patient had multilevel disease. Symptoms of coronary occlusive disease developed in five patients (23%) within 38 months of the onset of claudication, and two of these patients died of myocardial infarctions. Of 19 patients who underwent interventions to correct symptoms of claudication, 16 (85%) had complete relief of symptoms at the end of follow-up, ranging from 6 months to 7 years. Ten of these patients remained symptom free after a single intervention, but six patients had rapid progression of disease and required secondary procedures. These results indicate that a majority of young patients with claudication caused by atherosclerosis can be returned to full active-duty status in the military after angioplasty or surgery. However, some patients may require secondary procedures to relieve recurrent symptoms caused by rapid progression of disease. We believe that an aggressive interventional approach is warranted in the evaluation and treatment of young patients with work-limiting claudication caused by atherosclerosis. These patients are at significant risk of developing premature coronary occlusive disease and should be monitored closely.

Long-term epidural pain relief using a totally implantable access system.

The majority of cancer patients at the terminal stage experience pain as a major symptom, and less than 60% of patients receive adequate pain relief. To relieve this symptom we have placed epidural catheters and attached them to an implantable access system. On this method the patients required 0.4-3.5 mg of morphine per hour with occasional boluses. Catheter life span ranged from 15 to 157 days with an average of 57 days.

Pulse oximetry as a means of assessing bowel viability.

Utilizing a pulse oximeter, oxygen saturation was determined in the periphery (tongue) and compared to the intestinal wall in a canine model. Segmental intestinal ischemia was then produced and the last obtainable pulse oximetry reading was marked with a suture on either end of the ischemic segment. Reexploration was performed within 48 hr and full thickness biopsies were taken in normal intestine and at various distances into the ischemic segment. Blinded evaluation of the biopsies showed that all biopsies taken within 1 cm of a normal pulse oximetry reading were normal, whereas at 3 cm into the ischemic segment 7 of 15 biopsies showed partial necrosis and 5 of 15 showed full thickness necrosis. We conclude that pulse oximetry of the intestinal wall is a valuable method of assessing intestinal viability in this model.

Anorectal abscess and fistula-in-ano.

The etiology of anorectal abscess and fistula-in-ano is discussed. The anatomy, which is vital to the understanding and treatment of the above, is reviewed, with two of the more common classifications of fistula-in-ano presented. The different methods of treating each are discussed, and some of the common complications of the procedure are listed. A true understanding of the disease process and anatomy is needed before treatment of fistulous abscesses is begun, but, with it, successful outcomes will occur in most cases.