Ki-67 protein expression and tumor associated inflammatory cells (macrophages and mast cells) in canine colorectal carcinoma.

BACKGROUND: Ki67 index, tumor associated macrophages (TAMs) and mast cells (MCs) are associated with malignancies in animal and human neoplasms including colorectal carcinomas (CRC). This has not been assessed in canine CRC. Given similar genetic abnormalities between human and canine CRC, we assessed Ki-67 and mitotic indices, TAMs and MC count (MCC) in canine CRC (n = 17). TAMs and MCC were compared with those in adenomas (n = 13) and control (n = 9). RESULTS: Ki-67 index in CRC (17.13 ± 11.50) was strongly correlated (r = 0.98, p < 0.05) with mitotic index (3.52 ± 1.80). MCC was higher (p < 0.05) in CRC (6.30 ± 3.98) than in adenomas (0.78 ± 0.77) and control (0.35 ± 0.33). The results suggest that Ki-67 index and MCC are associated with malignancy in canine CRC. Higher average TAMs were counted in adenomas (21.30 ± 20.70) and in CRC (11.00 ± 9.82) than in the control (7.69 ± 7.26), although the differences were not significant (p > 0.05). CONCLUSION: Ki-67 index, TAMs and MCC in canine CRC were recorded for the first time in this study. Ki-67 index and MCC are associated with malignancy in canine CRC. Quantitative assessment of MCs and Ki-67 coupled with mitotic index and other clinical parameters may help in evaluating malignancy in canine CRC. TAMs likely play a role in the development of canine colorectal tumors. Further studies to determine the clinical significance of these parameters for prognostic, chemo-preventive and chemotherapeutic purposes in canine colorectal tumors are recommended.

Cutaneous and renal glomerular vasculopathy as a cause of acute kidney injury in dogs in the UK.

To describe the signalment, clinicopathological findings and outcome in dogs presenting with acute kidney injury (AKI) and skin lesions between November 2012 and March 2014, in whom cutaneous and renal glomerular vasculopathy (CRGV) was suspected and renal thrombotic microangiopathy (TMA) was histopathologically confirmed. The medical records of dogs with skin lesions and AKI, with histopathologically confirmed renal TMA, were retrospectively reviewed. Thirty dogs from across the UK were identified with clinicopathological findings compatible with CRGV. These findings included the following: skin lesions, predominantly affecting the distal extremities; AKI; and variably, anaemia, thrombocytopaenia and hyperbilirubinaemia. Known causes of AKI were excluded. The major renal histopathological finding was TMA. All thirty dogs died or were euthanised. Shiga toxin was not identified in the kidneys of affected dogs. Escherichia coli genes encoding shiga toxin were not identified in faeces from affected dogs. CRGV has previously been reported in greyhounds in the USA, a greyhound in the UK, without renal involvement, and a Great Dane in Germany. This is the first report of a series of non-greyhound dogs with CRGV and AKI in the UK. CRGV is a disease of unknown aetiology carrying a poor prognosis when azotaemia develops.

Comparison of human papillomavirus genotypes in archival cervical cancer specimens from Alaska natives, Greenland natives and Danish Caucasians.

Archival, formalin-fixed, paraffin-embedded cervical cancer specimens from 53 Alaska natives, 32 Greenland natives and 34 Danish Caucasians were analyzed for human papillomavirus (HPV) genotypes 16, 18, 31, 33, 35 and 45 and unidentified genotypes (HPV X) using PCR. The specimens were from the time period 1980-1989. No significant differences were observed in the overall HPV detection rates among cases from Alaska (98.1%), Greenland (84.4%) and Denmark (85.3%). HPV genotype 16 was the most prevalent type: 78.8% in Alaska natives, 96.3% in Greenland natives and 82.8% in Danish Caucasians. A prevalence of 21.2% HPV 31 and 30.8% HPV 33 was found in Alaska natives, of which most were coinfections with HPV 16. Only 3.7% HPV 31 and 3.7% HPV 33 were found in Greenland natives and no HPV 31 and 6.9% HPV 33 were found in Danish Caucasians. HPV 18 was only detected in Alaska natives and HPV 35 and 45 were not detected in any of the three populations. Infections with multiple genotypes were prevalent in Alaskan (36.5%) but not in Greenland natives (3. 7%) and Danish Caucasians (6.9%). The Eskimo subgroup of the Alaska native population has a significantly higher prevalence of HPV genotypes 31 and 33 associated with mixed infections in invasive cancer than the two other native subgroups (P = 0.04) and Greenland and Danish populations, reflecting genotype distributions in dysplasia and normal cervical cytology. The reason for HPV genotype diversity, although unknown, may be relevant to the current development of HPV vaccines.

Complications of mitral valve prolapse. Disproportionate occurrence in men and older patients.

To determine factors influencing the strength of association between mitral valve prolapse and mitral regurgitation, ruptured chordae tendineae, and infective endocarditis, the prevalence of mitral prolapse in patients with disease was compared with both clinical and population control groups. The prevalence of mitral valve prolapse was 4 percent among population and clinical control groups (eight of 196 and 84 of 2,146, respectively) and was significantly higher (p less than 0.001) in patients with endocarditis (11 of 67, 16 percent), mitral regurgitation (17 of 31, 55 percent, and ruptured chordae (27 of 43, 63 percent). Odds ratios for complications in persons with mitral valve prolapse ranged from 4.6 for endocarditis to 41.4 for ruptured chordae in overall analyses, and from 6.8 for endocarditis to 53.0 for ruptured chordae based on age- and sex-matched case-control triplets (p less than 0.001 for each). All complications occurred disproportionately in men with mitral valve prolapse, in whom odds ratios ranged from 2.5 to 7.4 compared with an additional control group of unselected subjects with mitral valve prolapse. Compared with this control group, patients with mitral valve prolapse and endocarditis were slightly more likely to have a previously known heart murmur (odds ratio 3.2, difference not significant) but significantly more likely to have murmurs at the time of evaluation (odds ratio 8.5, p less than 0.01). Patients with mitral valve prolapse and mitral regurgitation and ruptured chordae tendineae were also significantly older than the unselected subjects with mitral valve prolapse (48 +/- 14 and 55 +/- 16 versus 38 +/- 14 years, p less than 0.005 for both). The concentration of risk of endocarditis in men with mitral valve prolapse and patients with antecedent murmur suggests that antibiotic prophylaxis is warranted in these groups but not in women without a murmur of mitral regurgitation.

Carbon dioxide as an angioscopic medium. Comparison to various methods of saline delivery.

The limitations of angiography, when it is used as the sole method of vascular assessment, are increasingly apparent as vascular intervention becomes more sophisticated. Angioscopy could be an adjunctive diagnostic modality by differentiating among thrombus, dissection, and atheroma, and by monitoring the response to therapy. However, angioscopy requires a blood-free field for adequate visibility, and this may be difficult to obtain. The feasibility of carbon dioxide (CO2) and various saline delivery methods for clarifying the viewing field for percutaneous angioscopy was investigated. Angioscopy of femoral and iliac arteries on nine dogs was performed. Saline was infused by hand injection, pressure bag infusion, or mechanical power injection, and CO2 gas was injected using a special gas injector. The clarity of the viewing field was graded for each medium and method. Excellent quality antegrade femoral angioscopy was obtained with CO2. The superiority of CO2 injection in comparison with power-injected saline approached statistical significance (P = .06). Power-injected CO2 and power saline were superior to hand-injected or pressure bag-injected saline for maintaining sufficient visibility. Retrograde iliac angioscopy was possible without inflow occlusion, but required high flow rates (only possible with power-injected saline or CO2). CO2 injected under controlled circumstances holds promise as a medium to improve angioscopic visibility.

Effects of carbon dioxide arterial infusion on hepatic biochemistry and histology in a rabbit model.

RATIONALE AND OBJECTIVES: The objective of this study was to determine the effect of carbon dioxide (CO2) infusion on hepatic biochemistry and histology in a rabbit model. METHODS: The study population consisted of 24 anesthetized rabbits that received hepatic infusion of either CO2 or saline (control) at doses of 10 mL/kg, comparable with those doses used in human clinical trials. Blood for clinical chemistry analysis was collected at baseline, 1 hour, 24 hours, and 168 hours (7 days) postprocedure. The rabbits were killed at 7 days postprocedure and the liver examined histologically for hepatic damage. RESULTS: There were no significant differences between the CO2 and the control groups in dorsal, ventral, and dorsal/ventral scores. Increases in alanine, an important indicator of hepatocellular membrane injury, in the CO2 group were significantly greater at 1 hour and 24 hours posttreatment (P = 0.037 and 0.013). However, the mean levels at 168 hours (7 days) were not significantly different (P = 0.22). The increases at 1 and 24 hours were small, transient, and considered clinically insignificant. CONCLUSION: No long-term hepatic effects in these animals were suggested by biochemical and histological examinations.

Incidence of invasive cervical cancer preceded by negative screening in high-risk Alaska Native women.

BACKGROUND: Alaska Native women experience higher invasive cervical cancer incidence and mortality rates than US whites despite a long-standing cancer screening programme including recommendations for annual Pap smears. METHODS: To determine the frequency and results of cytological screening preceding their diagnoses, a histological and medical record review was completed for 44 of 46 Alaska Native cases of invasive cervical cancer from a defined population. An interval cancer (no prior dysplasia and a negative screening report within 3 years of diagnosis) was determined for 23 women. Mean number of negative reports during the 3- and 5-year intervals before diagnosis was 1.7 and 2.6 respectively. The age-adjusted incidence rate for all cervical cancer was 24.0/100,000 women/year and for interval cancer with single and multiple negative reports during the 3-year interval before diagnosis it was 11.6, and 9.6 respectively. Sensitivity of a Pap smear to demonstrate dysplasia during the year before diagnosis was 51%. CONCLUSIONS: Annual cytological screening of all Alaska Native women with current methods would provide earlier diagnoses for only an additional 15% of cervical cancer cases. Plausible but unproven explanations include rapid progression through precursor stages of neoplasia or random screening errors. Improved or ancillary screening methods appear necessary.

Standardized measurement of the future liver remnant prior to extended liver resection: methodology and clinical associations.

BACKGROUND: There is no agreement regarding the preoperative measurement of liver volumes and the minimal safe size of the liver remnant after extended hepatectomy. METHODS: In 20 patients with hepatobiliary malignancy and no underlying chronic liver disease, volumetric measurements of the liver remnant (segments 2 and 3 +/- 1) were obtained before extended right lobectomy (right trisegmentectomy). The ratios of future liver remnant to total liver volume were calculated by using a formula based on body surface area. In 12 patients, response to preoperative right trisectoral portal vein embolization was evaluated. In 15 patients who underwent the planned resection, preoperative volumes were correlated with biochemical and clinical outcome parameters. RESULTS: The future liver remnants increased after portal vein embolization (26% versus 36%, P < .01). Smaller size liver remnants were associated with an increase in postoperative liver function tests (P < .05) and longer lengths of hospital stay (P < .02). Preliminary data indicates an increase in major complications for liver volumes < or = 25% (P = .02). CONCLUSIONS: A simple method of measurement provides an assessment of the liver remnant before resection. It is useful in evaluating response to portal vein embolization and in predicating the outcome before extended liver resections.

New monofilament basket for bladder calculi.

Successful stone manipulation was facilitated with the new monofilament basket in experimental situations and in patients. Advantages over other baskets include: in vivo adjustability, reduced mucosal trauma, ability to irrigate and aspirate through the basket, and ability to pass lithotriptor electrodes within the basket. Basket modifications under study might prove useful within the ureter, renal pelvis, and biliary tree.

Hawkins-Hunter retrograde transcutaneous nephrostomy: a new technique.

Retrograde nephrostomy, a new technique to aid in stone management, has been performed successfully in dogs. It has also been used without complication in a human patient to help remove a renal stone percutaneously under local anesthesia. The technique consists of placing a coaxial catheter over a guidewire under fluoroscopy into the exact calyx desired and advancing a long needle out to the skin to establish a transcutaneous tract. The advantages of the technique include increased control and precision of tract placement, efficient working angles for percutaneous stone removal, and the ability to perform the procedure under local anesthesia.

Absolute ethanol renal angioinfarction for control of hypertension.

Six patients (11 renal units) underwent ethanol renal angioinfarction for medically uncontrollable hypertension. The mean preablation blood pressure was 175/112 mm Hg despite antihypertensive medications. Five of the patients demonstrated elevated renal vein renin levels prior to angioinfarction. Hypertension was improved in all 6 patients, during a mean follow-up period of fifty-one months. Systemic hypertension was completely eliminated in 4 patients. Two patients continue to require antihypertensive medication to control their hypertension. There were no major complications directly related to intra-arterial injection of ethanol. Transcatheter renal ablation employing intra-arterial injection of absolute ethanol for control of severe hypertension appears to be a safe and efficacious procedure. It should be considered an alternative to nephrectomy in selected high-risk patients.

Current status of carbon dioxide angiography.

The current status of carbon dioxide as an angiographic contrast agent is reviewed in this article. The physical characteristics of intravascular carbon dioxide, pertinent physiology, and principles of imaging are discussed. In addition, the advantages and limitations of carbon dioxide are compared with those of iodinated contrast. Examples of diagnostic and therapeutic procedures in both the arterial and venous systems show the utility of carbon dioxide angiography.

Percutaneous cholecystostomy for acute cholecystitis in high-risk patients.

Seventeen high-risk critically ill patients with suspected cholecystitis underwent percutaneous transhepatic cholecystostomy between 1981 and 1986 using Hawkins' needle guide system for gallbladder intubation. Acute cholecystitis was documented in 15 patients, including 1 with common bile duct obstruction. Two other patients had common bile duct obstruction secondary to metastatic cancer (one patient) and chronic pancreatic fibrosis (one patient). There was rapid resolution of the signs and symptoms of cholecystitis, sepsis, or both in 16 of the 17 patients. One critically ill patient with positive findings on blood culture and an organism resistant to triple antibiotic therapy died soon after percutaneous cholecystostomy. In the entire group of 17 patients, there was no evidence of bile leaks or other catheter complications. Six patients subsequently underwent successful cholecystectomy and two underwent common bile duct exploration without complications. One patient underwent cholecystojejunostomy, and in three patients, the catheter was removed with no sequelae of cholecystitis. Two remaining patients had the catheter in place and were awaiting operation at last follow-up. Three of four patients who died within 30 days of percutaneous transhepatic cholangiographic cholecystostomy died either from the terminal malignant condition (two patients) or from arrhythmia (one patient with cirrhosis). This review suggests that percutaneous cholecystostomy is a safe and effective procedure for resolving acute cholecystitis in high-risk patients. In addition, the technique of percutaneous transhepatic cholangiographic cholecystostomy appears well suited for percutaneous dissolution of stones, sclerosis of the gallbladder, or both in selected high-risk critically ill patients.

Evaluation of percutaneous transhepatic balloon dilatation of benign biliary strictures in high-risk patients.

During the period from 1979 through 1984, 17 patients with benign biliary strictures underwent percutaneous transhepatic balloon dilatation. All patients presented with either hyperbilirubinemia and acute cholangitis, a history of intermittent chills and fever, or both. Balloon dilatation was most successful in those patients with intrahepatic strictures, sclerosing cholangitis, strictured biliary enteric anastomoses, and distal common bile duct strictures with retained calculi. Two patients with postsurgical common bile duct injury had treatment failure 3 and 18 months after dilatation and subsequently underwent elective hepaticojejunostomy. Although our longest treatment success is now more than 4 1/2 years in an 83 year old woman who is 15 years posthepaticojejunostomy, the mean follow-up of the entire group has only been 2 years. On the basis of our early experience and that of others, we now recommend an initial attempt at balloon dilatation in most patients with postsurgical benign biliary strictures. Further technical advances and longer follow-up in present and future series may certainly broaden the appeal of this nonoperative procedure.

Angiography of the lower extremity in atherosclerotic vascular disease. Current techniques.

With the vast array of technology available, detailed diagnostic information is now routinely obtained in patients with peripheral vascular disorders. In addition, percutaneous intervention and advanced surgical techniques now safely permit the patient to return to an active life, and in advanced vascular disease, the extremity can be salvaged when previously the only option was amputation. We feel strongly that the maximum amount of information about the arterial system should be obtained throughout the patient's management. In addition, these complex procedures require considerable experience and judgment, and our practice of ongoing communication with the vascular surgery staff during both the diagnostic and the therapeutic phases of the patient's treatment has been extremely beneficial.

Angiography with carbon dioxide (CO2).

CO2 possesses many advantages over conventional iodinated contrast agents used for arteriography. It is nonallergic and lacks renal toxicity. Its unique properties permit use of smaller catheters in diagnostic and therapeutic angiographic procedures, allow optimal vascular imaging of various neoplasm, assist in detection of occult gastrointestinal bleeding, and facilitate TIPS procedures. With digital subtraction techniques and stacking programs, CO2 arteriography is as accurate as iodinated contrast studies in most patients and thus is the preferred arterial imaging technique in patients with contrast allergy and renal insufficiency. CO2 is also extremely inexpensive compared with available contrast agents. Understanding of the effects of buoyancy and compressibility is necessary for safe, controlled delivery of CO2 during arteriography, but only rare complications have occurred in our large experience with CO2 angiography. Thus, use of CO2 as an arterial contrast agent significantly expands the safety and utility of arterial imaging in patients with peripheral vascular disease.

Endoscopic balloon dilation of outlet stenosis after gastric bypass.

Eighteen of 22 patients with stenotic gastrojejunostomies following gastric bypass surgery were successfully corrected by endoscopically placing a guidewire through the narrowed outlet and then passing a dilating balloon catheter over the wire. No complications occurred. All procedures were done without general anesthesia, and 64 per cent were done without hospitalization. This procedure can spare patients prolonged hospitalization for nasogastric decompression or reoperation, the two standard approaches to this problem. Successful use of this technique to dilate obstructed gastric partitions and distal esophageal strictures suggests that it may be considered for any gastrointestinal stenosis within reach of the endoscope.

Angiographic findings in some rare pancreatic tumors.

Angiographic findings in one giant cell carcinoma, one cystadenocarcinoma, one poorly vascularized mucinous cystadenocarcinoma, as well as in two avascular (gastrin- and glucagon-producing) islet-cell tumors of the pancreas are described. Two hypervascularized islet-cell tumors are presented for comparison and a case of tumorous chronic pancreatitis in a child is reported because ot its rarity. The aggressiveness of the giant cell carcinoma of the pancreas was demonstrated by its expansive growth. In the case of cystadenocarcinoma angiography revealed the tumor with hepatic metastases not diagnosed at explorative laparotomy. The relative hypovascularity in the case of mucinous cystadenocarcinoma was unusual. Both avascular islet-cell tumors simulated a pancreatic pseudocyst and the final diagnosis was made only by immunoassay. Chronic pancreatitis in a child presented with marked hypervascularization.

Prognostic value of angiography in management of severe acute renal transplant rejection.

Angiograms of 34 kidney transplant patients with progressive decrease in renal function after multiple doses of intravenous methylprednisolone (MP) were evaluated retrospectively in regard to the prognostic value of angiography. The following parameters were included in evaluation: prolonged arterial washout time, large vessel vasculitis, presence of arteriovenous shunting, poor cortical perfusion as evidenced by non-filling of cortical vessels, poor definition of cortico-medullary junction, and a poor nephrogram. When 1 to 3 of these abnormalities existed in angiogram, 67% of living related donor transplants (LRD) recovered under continued MP-therapy. With 4-6 angiographic abnormalities the recovery rate was reduced to 30%. The overall recovery rate for LRD transplants was 44%. Cadaveric transplants (CAD) had a statistically significant poorer prognosis as evidenced by only 8% recovery rate under continued MP-therapy.

Evolution of hepatocellular carcinoma associated with chronic hepatitis B virus infection in Alaskan Eskimos.

Hepatocellular carcinoma (HCC) associated with chronic hepatitis B virus (HBV) infection in Yupik Eskimos in southwestern Alaska, detected in early stages as a result of screening, appears to be more frequently associated with variants of chronic portal inflammation in the noninvolved liver than with fully developed cirrhosis, otherwise common in HBV-associated HCC from other geographic areas. Of 38 patients diagnosed with HCC since 1969, adequate tissue was available from both the tumor and nontumorous liver in 17. Of the 17 specimens, 14 had chronic portal inflammation and three had advanced cirrhosis; 12 of the 14 were from hepatitis B surface antigen carriers. These 12 cases were studied in detail to examine the features accompanying the development of HCC unobscured by cirrhotic transformation. In the noninvolved parenchyma they included hepatocytic nodules as apparent precursors to HCC and, as markers of phenotypic alterations, dysplastic hepatocytes and hepatitis B surface antigen-laden ground-glass hepatocytes. The latter were observed in eight instances and often accumulated in nodules. Parenchyma within 1 mm of the HCC exhibited increased confluent hyperplasia and frequently conspicuous necroinflammation associated with pericellular and periductular fibrosis, which contributed, in addition to fibrous connections between displaced and heavily inflamed portal tracts, to the capsule that was forming in all cases to varying degrees in the pericarcinomatous region. The HCC was uniformly trabecular and in a few specimens, a continuous transition from hyperplasia and dysplasia near the periphery of the tumor to increasing anaplasia in the center could be made out in addition to pressure effects of the HCC. The pericarcinomatous changes, including hyperplasia progressing to neoplasia and necroinflammation, are also observed in experimental models, particularly the woodchuck HCC induced by a hepadna virus related to HBV. Coordinated morphologic and molecular biologic studies on such animal models and on human HCC detected by screening, as for instance in Eskimos, neither complicated by cirrhosis, should elucidate the direction of the evolution of the HCC and the postulated promoting role of the inflammation.