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Biomedical subjects

P J Hewett

Publications and source records attributed to P J Hewett.

At least 19 recordsLinked to original sources
PubMed2004

Dipeptidase 1: a candidate tumor-specific molecular marker in colorectal carcinoma.

The aim of this study was to identify tumor-specific markers for the detection of rare disseminated colorectal tumor cells in peripheral venous blood and in intra-peritoneal saline lavage samples collected before and after resection of colorectal tumors. Using cDNA micro-array screening, we found dipeptidase 1 (DPEP1) to be highly expressed in colon tumors compared to matched normal mucosa. Relative reverse transcriptase (RT)-PCR showed that DPEP1 was over-expressed by >/=2 fold in colon tumor compared to normal colonic mucosal tissue in 56/68 (82%) patients. Using immunobead RT-PCR, a technique that first enriches for epithelial cells, we found DPEP1 positive cells in intra-peritoneal lavage and venous blood samples from 15/38 (39%) colorectal cancer cases. This is the first report of DPEP1 as a marker for disseminated colon tumor cells.

Adult↗
PubMed2002

Variables in the spread of tumor cells to trocars and port sites during operative laparoscopy.

BACKGROUND: Port-site recurrences have delayed the uptake of laparoscopic colectomy, but the etiology of these is incompletely understood. These studies were designed to investigate variables such as the size of the tumor inoculum and the volume and pressure of the insufflated gas during operative laparoscopy that might affect the deposition of these cells in relation to trocars and port sites. METHODS: Radiolabeled human colon cancer cells were injected into the peritoneal cavity of pigs. Three trocars were inserted, and the abdomen was insufflated with carbon dioxide. The movement of cells within the abdomen was traced on a gamma camera. After 2 h, the trocars were removed and the port sites excised. Two studies were performed. In the first study, tumor inocula were varied from 1.5 x 10(5) to 120 x 10(5). In the second study, insufflation pressure was varied, with pressures 0, 4, 8 and 12 mmHg were studied. RESULTS: When larger tumor inocula were injected, the contamination of both trocars (p = 0.005, Kendall's rank correlation) and trocar sites (p = 0.04, Kendall's rank correlation) increased. The deposition of cells on a trocar site was linked to contamination of its trocar (p = 0.03, chi-square), but the contamination of trocars did not always result in trocar-site contamination (p = 0.5, chi-square). Increased volumes of gas insufflation caused increased intraabdominal movement of tumour cells (p = 0.01, Kendall's rank correlation), although this did not lead to greater contamination of trocars or port sites (p = 0.82, Kendall's rank correlation). Decreased insufflation pressures resulted in increased contamination of trocars and port sites (p = 0.01, Kendall's rank correlation). CONCLUSIONS: If clinical situations parallel this study, strategies such as increasing insufflation pressure, reducing episodes of desufflation and gas leaks, and using frequent intraabdominal lavage may help to reduce the numbers of viable tumor cells displaced to port sites during laparoscopic surgery for intraabdominal malignancy. This may reduce the rate of port-site metastases.

Abdominal Wall↗
PubMed2002

The effect of lavage on intraabdominal cell burden.

BACKGROUND: Abdominal lavage is a common surgical practice, but few studies have been conducted to assess its efficacy at removing cells from the abdominal cavity, particularly during laparoscopic surgery. METHODS: After three 12-mm trocars were inserted into six female 30-kg pigs at the umbilicus left and right iliac fossae, the abdomen was insufflated with carbon dioxide. The pelvis of each pigs was injected with 6 million radiolabeled LIM 1215 cells. Then the abdominal cavity was irrigated with either 500 ml 0.9% saline, 500 ml 10% betadine solution, or 1 L 0.9% saline. A maximum of 5 L of solution was used for each animal. The lavage fluid was suctioned into separate containers after each aliquot, and each container was measured for radioactivity. RESULTS: Significantly greater numbers of cells were removed by lavage by the first to third lavage cycle; however, after four lavage cycles, relatively few cells were removed by each further cycle. No difference was observed between 500-ml and 1-L aliquots. Additionally, the mechanical efficacy of 0.9% saline and 10% betadine solution appeared similar. CONCLUSION: These findings suggest that optimal lavage consists of four irrigation/suction cycles utilizing 500-ml aliquots.

Abdomen↗
PubMed2002

Experimental study of peritoneal blood flow and insufflation pressure during laparoscopy.

BACKGROUND: Port-site metastases after laparoscopic surgery may occur with greater frequency than would be expected following open resection of intra-abdominal malignancies, but the causal mechanism for this is incompletely understood. The possibility that insufflation may increase peritoneal blood flow producing a wound environment conducive to the formation of metastases was investigated. METHODS: The effects of insufflation gas type and pressure were studied in 30-kg female pigs. Pigs were divided into five groups, which were subjected to insufflation at 12 mmHg pressure with helium, insufflation at 12, 8 or 4 mmHg pressure with carbon dioxide, or laparotomy. A microsphere technique utilizing two distinct radiotracers, 99mTc-labelled macroaggregated albumin (MAA) and 51Cr-labelled MAA, was used to study blood flow to the peritoneum, liver and kidneys. RESULTS: Insufflation with carbon dioxide or helium gases had no effect on renal (P < 0.09) or hepatic blood flow (P = 0.54). However, insufflation significantly increased peritoneal blood flow when carbon dioxide (P < 0.05), but not when helium (P = 0.99), was used as the insufflating gas. CONCLUSION: These data suggest that blood flow within the peritoneum is influenced by insufflation with carbon dioxide. It is conceivable that such hyperaemia could increase the propensity for implanted tumour cells to metastasize in these sites following laparoscopy.

Animals↗
PubMed2002

Experimental study of the material composition of laparoscopic ports on tumour cell adherence.

BACKGROUND: Laparoscopic resection of intra-abdominal malignancies has yet to be widely adopted, partly because of concerns over the possible increase in the rate of port-site metastasis. The aetiology of these is unclear, but the laparoscopic instrumentation used may influence the deposition of tumour cells at the port sites during operation. An in vitro model to examine tumour cell adherence to laparoscopic ports and to port sites was developed to examine this hypothesis. METHODS: A pilot study (study 1) was performed in which six smooth plastic, six ribbed plastic and six metal ports were introduced through the shaved abdominal wall of a cadaveric sheep and suspended in a water-bath containing radiolabelled LIM 1215 human colonic cancer cells for 30 min. Radioactivity on both ports and port sites was measured and the number of cells adherent to each structure was calculated. The study was expanded to include a further 36 smooth plastic ports and 36 metal ports (study 2). RESULTS: In study 1 metal ports were found to have significantly more adherent cells than plastic ports (P = 0.004), as did ribbed ports when compared with smooth ports (P < 0.05). In study 2 increased numbers of cells were again detected on metal ports (P < 0.001) when compared with plastic ports. Significantly greater numbers of cells were also detected on the sites through which metal ports had passed than on sites through which plastic ports had passed (P = 0.03). CONCLUSION: In this model, the use of metal ports as opposed to plastic ports resulted in increased deposition of tumour cells on both ports and port sites.

Animals↗
PubMed2001

Receptor protein tyrosine kinase EphB4 is up-regulated in colon cancer.

BACKGROUND: We have used commercially available cDNA arrays to identify EphB4 as a gene that is up-regulated in colon cancer tissue when compared with matched normal tissue from the same patient. RESULTS: Quantitative RT-PCR analysis of the expression of the EphB4 gene has shown that its expression is increased in 82% of tumour samples when compared with the matched normal tissue from the same patient. Using immunohistochemistry and Western analysis techniques with an EphB4-specific antibody, we also show that this receptor is expressed in the epithelial cells of the tumour tissue and either not at all, or in only low levels, in the normal tissue. CONCLUSION: The results presented here supports the emerging idea that Eph receptors play a role in tumour formation and suggests that further elucidation of this signalling pathway may identify useful targets for cancer treatment therapies.

Journal Article↗
PubMed2001

Hematogenous spread as a mechanism for the generation of abdominal wound metastases following laparoscopy.

BACKGROUND: We designed this study to determine whether hematogenous spread has a role in the etiology of port site metastases following laparoscopic surgery. METHODS: The study design had two parts. In experiment 1, two groups (n = 30) of male Dark Agouti rats were studied. Under general anesthesia, the first group (20 rats) underwent 15 mins of laparoscopic insufflation, followed by an injection of a suspension of 105 Dark Agouti mammary adenocarcinoma (DAMA) cells into the internal jugular vein and a further 15-mins period of insufflation. The laparoscopic ports were then removed, and the wounds were closed and marked. In the second group (n = 10), the procedure was identical except that a 2.5-cm midline laparotomy was performed 15 mins after the commencement of anesthesia and insufflation was not used. The laparotomy was closed in two layers. In experiment 2, one group (n = 4) was studied. The study protocol was identical to the first laparoscopic group except that a larger number of 106 DAMA cells were injected. All rats in both experiments were killed 15 days later, and the injection site, laparoscopy wounds, and laparotomy wound were examined histologically by a blinded histopathologist. RESULTS: In experiment 1, one port site tumor was detected in the laparoscopic group and no wound metastases were found in the laparotomy group. Postoperative weight loss was significantly less in the laparoscopic group (p < 0.001). In experiment 2, no port site metastases were detected. CONCLUSION: Although hematogenous spread is a possible mechanism in the development of port site metastases, judging from the low number of port site metastases in this study as compared to previous reports using this tumor model, this mechanism is unlikely to be a major contributor to the problem of wound metastasis following laparoscopy.

Abdomen↗
PubMed2000

Molecular detection of blood-borne epithelial cells in colorectal cancer patients and in patients with benign bowel disease.

In colorectal cancer (CRC), a proportion of patients with early stage disease still die of metastatic or recurrent disease within 5 years of "curative" resection. Detection of carcinoma cells in the peripheral circulation at presentation may identify a subgroup of patients with micro-metastatic disease who may benefit from adjuvant chemotherapy or radiotherapy. Our aim was to determine the presence and clinical significance of colon carcinoma cells in peripheral blood at the time of surgery. Preoperative peripheral blood samples were collected from 94 patients with CRC and 64 patients undergoing bowel resection for benign conditions (adenoma, diverticular disease or Crohn's colitis). Blood was also obtained from 20 normal donors not undergoing bowel surgery. Immunomagnetic beads were used to isolate epithelial cells followed by reverse transcription-polymerase chain reaction (RT-PCR) analysis of expression of cytokeratin (CK) 19, CK 20, mucin (MUC) 1 and MUC 2. Nineteen of 94 (20%) CRC patients were positive for epithelial cells in preoperative blood, including 6 with early stage disease. Kaplan-Meier survival analysis showed that detection of epithelial cells in preoperative blood was associated with reduced disease-free and overall survival (log-rank test, p = 0.0001). Surprisingly, circulating epithelial cells were detected in 3/30 (10%) patients resected for adenoma, and in 4/34 (12%) patients resected for benign inflammatory conditions, suggesting that cells from nonmalignant colonic epithelium may also gain entry into the bloodstream in the presence of bowel pathology. All 20 normal control bloods were negative for epithelial cells.

Adenoma↗
PubMed2000

Ischiorectal fossa block decreases posthemorrhoidectomy pain: randomized, prospective, double-blind clinical trial.

PURPOSE: Hemorrhoidectomy can be associated with severe pain in the immediate postoperative period. The aim of this study was to assess the efficacy of a preemptive local anesthetic, ischiorectal fossa block, in the reduction of pain and analgesic requirements after hemorrhoidectomy. METHODS: All patients were suitable for an established day surgery hemorrhoidectomy protocol. Immediately before surgery patients were randomly assigned either to receive (Group 1) or not receive (Group 2) the local anesthetic block. All other aspects of surgery and anesthesia were standardized. Nursing staff assessed pain at 30 minutes and 2, 4, and 24 hours postoperatively using a visual analog scale (1-10, where 1 represented no pain and 10 represented the worst pain imaginable). Analgesic requirements also were recorded at these times. Both the patients and the nursing staff were blinded to which local anesthetic protocol had been used. RESULTS: Twenty patients were enrolled in the trial. Ten patients were randomly assigned to Group I and ten to Group 2. Mean pain scores for Group 1 (anal block) at 0.5, 2, 4, and 24 hours were 1.5, 1.8, 2.1, and 2.5, respectively, compared with Group 2, with mean pain scores of 3.4, 3.4, 3.9, and 5.1. These differences were statistically significant. Patients in Group 1 used less analgesia in the first 24 hours postoperatively than those in Group 2. CONCLUSION: The use of a preemptive local anesthetic, ischiorectal fossa block, is associated with a significant decrease in pain and analgesia requirements after hemorrhoidectomy.

Adult↗
PubMed1999

The activity of caspase-3-like proteases is elevated during the development of colorectal carcinoma.

Activated caspase-3-like proteases promote apoptotic cell death by cleaving cellular substrates. Caspase-3-like activity was measured in colonic carcinomas and in matched normal colonic mucosa from 31 patients and was significantly elevated in 25/ 31 colonic carcinomas and adenomas when compared to normal mucosa (P < 0.0001). Caspase-3-like activity was much higher in normal mucosa and tumours of female subjects than of males (P < 0.0001). No correlation was obtained between caspase-3-like activity and location of the tumour, tumour grade, stage, or patient age. The marked increase in caspase-3-like activity in colorectal carcinomas may reflect an increase in the proportion of cells undergoing spontaneous apoptosis.

Adenoma↗
PubMed1999

In vivo real-time analysis of intraperitoneal radiolabeled tumor cell movement during laparoscopy.

PURPOSE: A porcine model has been developed to allow the real-time imaging of radiolabeled tumor cell movement throughout the peritoneal cavity, both at rest and during carbon dioxide insufflation. METHODS: Fifteen 30-kg domestic white female pigs were used. Under anesthesia, 15 to 20 million radiolabeled human colorectal tumor cells (LIM1215) were introduced into the peritoneal cavity under laparoscopic vision into the pelvis. Radiolabeled tumor cell movement was examined by using a 25-cm-diameter, low-energy mobile gamma camera with high resolution collimator. Tumor cell movement and distribution during two hours without insufflation was examined in four pigs. Then tumor cell movement and distribution during two hours with CO2 insufflation was examined in four pigs. In a further four pigs, tumor cells were then mixed with blood and injected into the peritoneal cavity and the effect of no insufflation vs. insufflation was noted. A further three pigs were examined with manipulation of the intra-abdominal contents after injection of LIM1215 cells into the peritoneal cavity. Venting insufflating CO2 was filtered for tumor cells. RESULTS: Widespread intraperitoneal distribution of tumor cells from the pelvis was identified both with CO2 insufflation of the peritoneal cavity and without insufflation. Tumor cells dispersed throughout the peritoneal cavity at a slower rate without carbon dioxide insufflation. There was a differential rate of tumor cell movement to the left upper quadrant and right upper quadrant with insufflation and without insufflation. Blood within the peritoneal cavity and an extended contact of the laparoscopic trocars with the peritoneal cavity in this setting increased contamination of the trocars and trocar sites with tumor cells. Tumor cells were identified on laparoscopic instruments in all experiments. No evidence of aerosolization of tumor cells was found. CONCLUSION: Tumor cells move throughout the peritoneal cavity both at rest and during CO2 insufflation. The pattern of tumor cell dispersion differs with CO2 insufflation. The presence of blood and extended contact of trocars with peritoneal contents are a major factor in trocar and trocar site tumor cell contamination.

Animals↗
PubMed1999

Laparoscopic-assisted colonoscopic polypectomy: technique and preliminary experience.

BACKGROUND: The majority of colonic polyps found at endoscopy are suitable for diathermy snare excision via colonoscope. Due to location or size, some are deemed unsafe to treat in this manner and therefore require colectomy. This study describes the technique and early results of a laparoscopic-assisted colonoscopic polypectomy technique that can be used to manage such polyps and thereby avoid laparotomy and colectomy. METHODS: Colonoscopy with simultaneous laparoscopy was utilized to locate the site of the polyp. The colon was mobilized, if required, and the polyp resected by electrosurgical snare via the colonoscope while the serosal aspect of the colon was monitored laparoscopically. RESULTS: The technique has been tried successfully in six patients. Three polyps were in the cecum and three were within the left colon. The size of the polyps ranged from 3 to 7 cm. All polyps were benign on histological examination. The patients were discharged on the day following the procedure. There were no complications. CONCLUSIONS: The combination of laparoscopy with colonoscopic resection of a select group of large polyps represents a safe alternative to colonic resection.

Adult↗
PubMed1999

Core temperature changes during open and laparoscopic colorectal surgery.

BACKGROUND: Perioperative hypothermia increases the morbidity of surgery. However, the true incidence of hypothermia during prolonged laparoscopic surgery is still unknown. To investigate this issue, we compared the temperature change between patients undergoing open and laparoscopic colorectal surgery. METHODS: Sixty consecutive patients who were undergoing laparoscopic (33) or open (27) colorectal surgery had a transesophageal temperature probe placed after induction of anesthesia. Core temperature values were measured at 15-min intervals. RESULTS: The groups were not statistically different with respect to age, sex, body surface area, or initial transesophageal temperature. The type of surgical access (open or laparoscopic) caused no difference in the incidence of hypothermia. The use of a forced-air warming device produced significantly less hypothermia during laparoscopic surgery. Men showed significantly less variability in temperature change than women. CONCLUSIONS: The incidence of hypothermia in open and laparoscopic colorectal surgery is similar. Forced-air warming devices are of value in prolonged laparoscopic surgery. A gender difference in the response to a hypothermic situation has not been previously reported. This finding warrants further investigation.

Adult↗
PubMed1999

Localization of the nonpalpable colonic lesion with intraoperative ultrasound.

Localization of an nonpalpable colonic lesion at the time of colectomy usually requires intraoperative colonoscopy. The use of ultrasound to locate the lesion has not been described. A soft bowel clamp is placed above the expected location of the lesion and a catheter placed in the anus. Saline is then instilled into the colon and rectum. The lesion is located by ultrasound scan of the fluid filled colon with the probe placed on the serosal surface. Refinement of the technique was performed on resected colonic specimens. An in vivo trial was then performed with rapid and accurate localization of the lesion for resection. Intraoperative ultrasound of the colon can accurately localize nonpalpable colonic lesions and is an alternative to currently available techniques of localization.

Adenoma↗
PubMed1999

Day-case haemorrhoidectomy.

BACKGROUND: Ligation excision haemorrhoidectomy is usually performed on an inpatient basis. This study was designed to assess the feasibility of day-case haemorrhoidectomy. METHODS: Patients fulfilling criteria for day surgery underwent ligation excision haemorrhoidectomy with the intention of a same-day discharge from hospital. A standardized protocol for anaesthesia, perioperative analgesia and antiemesis was followed. Patients received daily home nursing visits until they felt both comfortable and confident. Staff recorded pain and nausea scores on a visual analogue scale (range 1-10) until the first bowel action. Patient satisfaction was assessed independently after operation. RESULTS: Fifty-one patients underwent planned day-case haemorrhoidectomy. Forty-two (82 per cent) were discharged on the day of surgery. All patients were discharged within 26 h of surgery. Four patients required readmission, two with reactive bleeding, one with urinary retention and one for pain control. Pain and nausea were well controlled. Forty-four patients (86 per cent) were totally or very satisfied with their overall care. CONCLUSION: Ligation excision haemorrhoidectomy can be performed successfully as a day-case procedure.

Adult↗
PubMed1999

Deregulation of apoptosis in colorectal carcinoma: theoretical and therapeutic implications.

Apoptosis, or programmed cell death, maintains the structure of the colonic crypts by providing a balance to the rate of cell proliferation. Colorectal carcinoma arises partly from a disruption in this balance in the favour of uncontrolled growth. Until recently, most research into colon cancer has focused on the molecular regulators of cell-cycle progression and proliferation, but it is now evident that apoptosis is also defective. A failure of cells to die in response to premalignant damage may allow the progression of the disease and maintain the resistance of cancer cells to cytotoxic therapy. This review outlines the importance of apoptosis in the normal colon and presents recent studies that demonstrate that induction of apoptosis is defective in colonic tumours. When the molecular regulation of apoptosis is better understood, this knowledge may lead to the earlier detection of patients at greater risk of developing colorectal carcinoma, and also to the development of more effective therapies.

Apoptosis↗
PubMed1998

From inside out. Microperforation of the gallbladder during laparoscopic surgery may liberate mucosal cells.

BACKGROUND: Port-side recurrence after laparoscopic surgery on known and unsuspected gastrointestinal malignancies has been reported. The mechanisms of this type of metastatic spread are poorly understood. For in situ malignancies, microperforation of the viscus by laparoscopic instruments may liberate cells to facilitate malignant cell movement. METHODS: Twenty-three patients undergoing laparoscopic cholecystectomy for benign disease were prospectively studied. The laparoscopic fundal grasper was washed with sterile saline at the start and conclusion of surgery. These washings were examined for the presence of mucosal cells as evidence that gallbladder perforation occurred during the operation. RESULTS: No mucosal cells were seen from washings at the start of surgery. Thirteen cases (56%) of perforation or attempted choledochogram were recorded during surgery. Four of these 13 washings contained mucosal cells. One washing was positive for mucosal cells in the absence of perforation or attempted choledochogram. CONCLUSIONS: Microperforation of the gallbladder by laparoscopic instruments occurs during laparoscopic cholecystectomy.

Cholecystectomy, Laparoscopic↗