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Biomedical subjects

J L McCall

Publications and source records attributed to J L McCall.

At least 19 recordsLinked to original sources

Skip metastases in colon cancer: assessment by lymph node mapping using molecular detection.

BACKGROUND: Colon cancer has been assumed to spread sequentially through the regional lymphatic bed, with skip metastases occurring in only 1% to 3% of cases. Molecular techniques allow the detection of occult metastases, but to date have not been applied to assess the pattern of regional lymphatic spread of colon cancer. METHODS: Fifty-five tumors from 54 patients with colonic adenocarcinoma were studied. Lymph node mapping was performed on fresh colonic specimens recording the position of each node on an anatomical diagram. Half of each lymph node was submitted for routine histology examination and half assayed for keratin 20 gene expression by reverse transcription-polymerase chain reaction. Logistic regression was used to analyze the distribution of histologic and occult metastases. RESULTS: A total of 1084 lymph nodes were dissected (median, 19 nodes; range, 4-52). Sixty-four lymph nodes from 20 tumors had histologically evident metastases and 76 lymph nodes from 13 tumors had occult metastases. There was no difference in the distribution of either histologic or occult metastases among paracolic, intermediate, and apical node groups. Ten patients had evidence of anatomical skip lesions after lymph node mapping and molecular analysis, only 1 of which was histologically detectable. CONCLUSIONS: This study demonstrates a higher incidence of skip metastases in colon cancer assessed by molecular techniques than has previously been reported, challenging the concept of sequential development of early lymph node metastases.

Actins↗

Sequential changes in the metabolic response to orthotopic liver transplantation during the first year after surgery.

OBJECTIVE: To quantify the sequential changes in the metabolic response occurring in patients with end-stage liver disease after orthotopic liver transplantation (OLT). SUMMARY BACKGROUND DATA: Detailed quantification of the changes in energy expenditure, body composition, and physiologic function that occur in patients after OLT has not been performed. Understanding these changes is essential for the optimal management of these patients. METHODS: Fourteen patients who underwent OLT for end-stage liver disease had measurements of resting energy expenditure, body composition, and physiologic function immediately before surgery and 5, 10, 15, 30, 90, 180, and 360 days later. RESULTS: Resting energy expenditure was significantly elevated after surgery (24% above predicted), peaking around day 10 after OLT, when it averaged 42% above predicted. A significant degree of hypermetabolism was still present at 6 months, but at 12 months measured resting energy expenditure was close to predicted values. Before surgery, measured total body protein was 82% of estimated preillness total body protein. During the first 10 days after OLT, a further 1.0 kg (10%) of total body protein was lost, mostly from skeletal muscle. Only 54% of this loss was restored by 12 months. Significant overhydration of the fat-free body was seen before OLT, and it was still present 12 months later. Although significant losses of body fat and bone mineral occurred during the early postoperative period, only body fat stores were restored at 12 months. Both subjective fatigue score and voluntary hand grip strength improved rapidly after OLT to exceed preoperative levels at 3 months. At 12 months grip strength was close to values predicted for these patients when well. Respiratory muscle strength improved less markedly and was significantly lower than predicted normal levels at 12 months. CONCLUSIONS: Before surgery, these patients were significantly protein-depleted, overhydrated, and hypermetabolic. After surgery, the period of hypermetabolism was prolonged, restoration of body protein stores was gradual and incomplete, and respiratory muscle strength failed to reach expected normal values. Our measurements indicate that OLT does not normalize body composition and function and imply that a continuing metabolic stress persists for at least 12 months after surgery.

Adolescent↗

Keratin 20 is a specific marker of submicroscopic lymph node metastases in colorectal cancer: validation by K-RAS mutations.

Lymph node status has major prognostic importance in colorectal cancer and greater precision in the diagnosis of lymph node metastases should provide better prognostic and therapeutic guidance. Keratin 20 (K20) gene expression has been used as a marker of lymph node metastases, but the evidence for this remains circumstantial. This study has therefore sought to determine K20 specificity and to correlate K20 expression with mutant K-RAS expression, in order to provide direct evidence that K20 expression in lymph nodes of colorectal cancer patients genuinely reflects metastatic disease. Specificity of K20 expression was established against a range of tissue types and 289 lymph nodes from 41 non-cancer control patients. K20 expression was restricted to gastrointestinal epithelia and was only present in one of the 289 control lymph nodes, giving a calculated specificity of 97.6% (95% confidence limits: 87.1-99.9%). Forty-two tumour samples were analysed for the presence of K-RAS codon 12 gene mutations using a RT-PCR mutant allele-specific amplification (MASA) technique. Thirteen tumours (31%) had codon 12 mutations detected by MASA and these were further analysed to determine the exact nature of the mutation. MASA was then used to screen the lymph nodes from these patients for the presence of the tumour-specific K-RAS transcript and the results were compared with K20 RT-PCR and histopathology from the same samples. Whilst K-RAS MASA was not as sensitive as K20 RT-PCR, there was substantial agreement between the assays. There were no K20-negative lymph nodes which were found to be K-RAS MASA-positive, whereas seven nodes in four patients were K20-positive and K-RAS-negative, in keeping with the differences in assay sensitivity. These results further validate K20 as a marker by providing greater certainty that what is being detected represents occult metastatic disease.

Biomarkers, Tumor↗

Surgery for colorectal liver metastases with hepatic lymph node involvement: a systematic review.

BACKGROUND: Liver resection for colorectal metastases is the only known treatment associated with long-term survival; extrahepatic disease is usually considered a contraindication to such treatment. However, some surgeons do not regard spread to the hepatic lymph nodes as a contraindication provided that these nodes can be excised adequately. A systematic review of the literature was undertaken to address this issue. METHODS: An electronic search using Medline, Cancerlit and Embase databases was performed for studies reporting liver resection for colorectal metastases from 1964 to 1999. Data were extracted from papers reporting outcome for patients with positive hepatic nodes and analysed according to predetermined criteria. RESULTS: Fifteen studies were identified that gave survival data on 145 node-positive patients. Five patients were reported to have survived 5 years after liver resection; one was disease free, two had recurrent disease and the disease status was not described in the remaining two. Five studies containing 83 patients specified a formal lymph node dissection as part of the surgical procedure and four of the five node-positive 5-year survivors were from these studies. CONCLUSION: There are few 5-year survivors after liver resection, with or without lymph node dissection, for colorectal hepatic metastases involving the hepatic lymph nodes.

Colorectal Neoplasms↗

Recurrence and survival after potentially curative surgery for colorectal cancer.

AIMS: To measure long-term outcomes in an unselected consecutive series of patients undergoing potentially curative surgery for colorectal cancer at Dunedin Hospital and identify risk factors for disease recurrence and mortality. METHOD: A retrospective study of 241 patients operated on between January 1990 and December 1992, and followed up to January 1996. RESULTS: Overall five-year actuarial survival was 55 percent, and 66, 56 and 43 percent respectively for Dukes' stage A, B and C disease. Factors associated with increased overall mortality were advanced Dukes' stage, perioperative blood transfusion and smoking, whereas factors associated with disease recurrence were advanced Dukes' stage, large tumour size and presentation with obstruction. CONCLUSIONS: Mortality following potentially curative surgery for colorectal cancer in Dunedin has not changed significantly since the previous study 15 years earlier and is similar to more recently published data from other New Zealand centres.

Aged↗

Analysis of IGF2 gene imprinting in breast and colorectal cancer by allele specific-PCR.

The insulin-like growth factor II (IGF2) gene is imprinted with the paternal allele expressed and the maternal one silent. Loss of imprinting (LOI) of IGF2 has been suggested to play a role in the development of tumours, but the reported incidence of IGF2 LOI in tumours shows considerable variation, which may stem from different methodologies employed. In particular, partial digestion of reverse transcriptase-polymerase chain reaction (RT-PCR) products by restriction enzymes can lead to inaccurate measurements. To overcome the problem of partial enzymatic digestion, a novel method termed allele specific-polymerase chain reaction (AS-PCR) has recently been reported, which provides a significant advance over enzymatic digestion. A second problem with measurements of biallelic IGF2 transcription is that the co-amplification of contaminating genomic DNA during the RT-PCR step can lead to an overestimation of the frequency of biallelic IGF2 expression. To investigate the extent of this problem, total RNA from breast and colorectal cancer was analysed using two methods. The first method involved a first-round PCR using cDNA generated with primers spanning exons 8 and 9 (exon connection), followed by a second round of AS-PCR using primers from within exon 9. The second method used only AS-PCR with primers from within exon 9. The result was that the exon-connection approach was more accurate, thereby highlighting a significant problem in imprinting analyses where genomic DNA contamination cannot be completely ruled out.

Alleles↗

Liver transplantation for hepatocellular carcinoma in patients without underlying liver disease: a systematic review.

Liver resection is the treatment of choice for hepatocellular carcinoma (HCC) occurring in the absence of underlying chronic liver disease. Orthotopic liver transplantation (OLT) is reserved for patients with unresectable disease but remains controversial. The aim of this study was to review the published literature on OLT for HCC in patients without coexisting chronic liver disease. A Medline-based search identified 126 patients reported in 16 papers over the last 32 years. One third had fibrolamellar HCC (FL-HCC), and two thirds had non-FL-HCC. Recurrence data were given in 55 patients of whom 27 had tumor recurrence. Seventy-five percent of the recurrences occurred within the first 2 years after OLT, although recurrences were reported up to 72 months after OLT for FL-HCC. The 5-year survival rate was greater in patients who underwent transplantation for FL-HCC than for non-FL-HCC (39.4% and 11.2%, respectively). There was insufficient information available to determine the influence of tumor size, distribution, stage, and vascular invasion on survival, although most patients in whom tumor characteristics were specified had advanced disease. This study indicates that FL-HCC carcinoma is a more favorable indication for OLT than non-FL-HCC in patients without underlying liver disease, although more detailed prognostic information is required to improve patient selection.

Carcinoma, Hepatocellular↗

Analysis of potential markers for detection of submicroscopic lymph node metastases in breast cancer.

We have developed sensitive assays for cytokeratin (K) 8, 16, 19, stromelysin 3 (ST3), MUC1 and maspin mRNAs using reverse transcription polymerase chain reaction (RT-PCR) and used these to assess lymph node status in patients undergoing surgery for breast cancer. In addition the RT-PCR assays were tested against lymph nodes from non-cancer patients to determine their specificity. Despite high sensitivity RT-PCR assays for K8, K16, K19, ST3 and maspin were not found to be useful as markers of submicroscopic disease as transcripts of these genes were detected in the great majority of control lymph nodes tested. Expression of MUC1 was also not found to be useful as it was both insensitive and non-specific. The importance of assessing potential markers against an adequately sized control population is demonstrated, as failure to do so can lead to erroneous conclusions.

Biomarkers, Tumor↗

Cholecystostomy: a review of recent experience.

BACKGROUND: Operative (OC) and percutaneous cholecystostomy (PC) are rarely undertaken for severe acute cholecystitis in patients in whom cholecystectomy is technically difficult or those with significant comorbidity. METHODS: A retrospective review was undertaken of the clinical, radiological and audit records of patients who were treated by cholecystostomy between 1988 and 1997 at Auckland Hospital. RESULTS: During the 10-year period 19 patients (eight male, 11 female; median age: 70 years, range: 35-90 years) had a cholecystostomy (OC: n = 8; PC: n = 11). The main indication for PC was high anaesthetic risk (10 cases). The main indication for OC was failed cholecystectomy (six cases). The patients undergoing PC tended to have a higher American Society of Anesthesiologists (ASA) grade than patients undergoing OC. The median delay from presentation to cholecystostomy was 3 days. More than half (11/19) were done during the 3 years (1992-94) after the introduction of laparoscopic cholecystectomy. The number of tube-related complications was significantly higher in PC patients (10/11 vs 3/8; P = 0.04), and the number of systemic complications was higher in the OC patients (4/8 vs 0/11; P = 0.018). The median duration of tube drainage was 17 days (range: 0-82 days) for OC and 24 days (range: 5-93 days) for PC. Four patients had stone extraction at the time of OC, including two who also had a partial cholecystectomy. One OC patient had stone extraction via the cholecystostomy tract. A cholecystectomy was performed in four patients. CONCLUSION: The data indicate that PC is a safe approach for high-risk patients. Operative cholecystostomy had a role following failed cholecystectomy. But PC might be safer in these patients if they could be identified pre-operatively.

Acute Disease↗

Detection and significance of minimal residual disease in colorectal cancer.

Colorectal cancer (CRC) is one of the most common causes of cancer death in the developed world. Although the primary treatment for CRC is surgical, disease relapse due to minimal residual disease (MRD) following apparently curative surgery occurs in up to fifty percent of patients. Most patients who develop overt metastases beyond the regional lymph nodes eventually die of the disease. At present adjuvant chemotherapy is used to improve survival in patients with metastases to regional lymph nodes demonstrated by routine histopathology with no other evidence of spread. The ability to identify metastatic disease at an earlier stage could be of considerable benefit in directing adjuvant therapy to patients at high risk of relapse who are not identified by current methods. Several techniques have been developed for the detection of MRD, including immunohistochemical and molecular methods, however their role in clinical practise is not yet established. The purpose of this paper is to review these techniques and their potential clinical use in the management of CRC.

Colorectal Neoplasms↗

Accessory right hepatic artery arising from the left: implications for split liver transplantation.

BACKGROUND: Variant arterial anatomy must be recognized and appropriately managed during split liver transplantation to ensure complete vascular supply to both grafts. We describe an accessory posterior right hepatic artery, arising from the left and passing behind the portal vein bifurcation. METHODS: Thirty-seven consecutive livers were examined during ex vivo liver-splitting procedures. An abnormal right accessory artery arising from the left hepatic artery was identified high in the porta hepatis. The anatomical variant is described and illustrated by methylene blue injection and arteriography. RESULTS: The anomaly was encountered in 2 of 37 split liver procedures. The two right lobes with the abnormal artery were discarded. CONCLUSION: Care should be taken during dissection behind the portal vein bifurcation to exclude an accessory segmental right hepatic artery. If present, the liver may not be suitable for splitting without compromising the right lobe, unless the left hepatic artery can be divided distal to the origin of the accessory vessel.

Hepatic Artery↗

Hepatic resection with cryotherapy to involved or inadequate resection margin (edge freeze) for metastases from colorectal cancer.

BACKGROUND: In patients undergoing liver resection for colorectal liver metastases, a resection edge either involved by tumour or with the tumour extending to within 1 cm is associated with a high risk of liver recurrence and survival is reduced markedly. METHODS: Twenty-six patients underwent cryotherapy of the resection edge following liver resection for metastases from colorectal carcinoma with an involved or inadequate (less than 1 cm) resection margin. RESULTS: At a median follow-up of 23 (range 1-47) months four patients were alive and disease free, and 21 had developed recurrence, of whom 13 had died. One patient died following surgery. Sixteen patients developed recurrences involving the liver, only five of which were at the resection margin. CONCLUSION: Cryotherapy to involved or inadequate resection margins improves local disease control considerably. The use of resection edge cryotherapy might allow a greater proportion of patients with liver metastases to be usefully treated and help to avoid high-risk resections.

Adult↗

A method to track surgical site infections.

We present an approach to assessing the impact of surveillance for surgical site infections and providing feedback to surgeons on their progress, as part of continuous quality improvement. Adjusting for patient risk factors using the Standardized Mortality Ratio, there was a marked decrease over time in both SMR (1.3 to 0.27) and crude infection rates (32 to 10 per thousand operations per year). These declines cannot be explained by decreased length of hospital stay.

Benchmarking↗