The First International Conference on Sentinel Node Biopsy in Mucosal Head and Neck Cancer and adoption of a multicenter trial protocol.

BACKGROUND: Sentinel node biopsy (SNB) is a new technique in staging the clinically N0 neck. On June 25 and 26, 2001, the First International Conference on Sentinel Node Biopsy in Mucosal Head and Neck Cancer took place in Glasgow, United Kingdom. METHODS: Twenty-two centers contributed results on the use of SNB as a staging tool in head and neck squamous cell carcinoma. The pathology of the sentinel node was compared with that of the pathologic neck specimen. RESULTS: Three hundred sixteen clinically N0 necks were included. Sentinel nodes were identified in 301 necks (95%). Of these 301 necks, 76 necks were staged positive with SNB, and 225 were staged negative. The overall sensitivity of the procedure was 90%. Centers who had performed < or = 10 cases had a lower sensitivity (57%), discovering only 4 of 7 metastatic nodes, in comparison with 72 of 77 metastatic nodes discovered for centers that had performed >10 cases (sensitivity, 94%). CONCLUSIONS: The cumulative results of all those who contributed to the first international conference confirm that there is a role for SNB for staging the clinically N0 neck, and it has a similar sensitivity to that of a staging neck dissection.

The ability of lymphoscintigraphy to direct sentinel node biopsy in the clinically N0 neck for patients with head and neck squamous cell carcinoma.

This study aimed to evaluate the ability of lymphoscintigraphy (LSG) to direct sentinel node biopsy (SNB) in the identification of occult metastases in the clinically N0 neck for patients with head and neck squamous cell carcinoma (HNSCC). 57 clinically N0 neck sides in 48 patients were assessed using the triple diagnostic approach of pre-operative LSG, intra-operative use of a gamma probe and blue dye. SNB was performed after radiocolloid and blue dye injection. Pre-operative LSG and the intra-operative use of a gamma probe identified radioactive sentinel nodes, and visualization of blue stained lymphatics identified blue sentinel nodes. 104 sentinel nodes were harvested from 43 patients. The identification rate was 90% (43 of 48). Of the 104 nodes harvested, 17 of 62 (27%) nodes identified as both radioactive and blue were positive for occult metastases compared with 5 of 42 (12%) nodes identified as hot or blue only (p<0.05). Sentinel nodes were identified in 39 of 48 (81%) patients using LSG. Of 39 patients in whom sentinel nodes were identified using LSG, 37 of 39 (95%) had radioactive sentinel nodes harvested intra-operatively. In patients who had no sentinel nodes identified on LSG, 4 of 9 (44%) had radioactive sentinel nodes harvested intra-operatively. This difference was statistically significant using the t-test (p<0.05). LSG directs SNB and is essential in the identification of occult metastases within the clinically N0 neck for patients with HNSCC.

The accuracy of head and neck carcinoma sentinel lymph node biopsy in the clinically N0 neck.

BACKGROUND: Sentinel lymph node (SLN) biopsy originally was described as a means of identifying lymph node metastases in malignant melanoma and breast carcinoma. The use of SLN biopsy in patients with oral and oropharyngeal squamous cell carcinoma and clinically N0 necks was investigated to determine whether the pathology of the SLN reflected that of the neck. METHODS: Patients undergoing elective neck dissections for head and neck squamous cell carcinoma accessible to injection were enrolled into our study. Sentinel lymph node biopsy was performed after blue dye and radiocolloid injection. Preoperative lymphoscintigraphy and the perioperative use of a gamma probe identified radioactive SLNs; visualization of blue stained lymphatics identified blue SLNs. A neck dissection completed the surgical procedure, and the pathology of the SLN was compared with that of the remaining neck dissection. RESULTS: Sentinel lymph node biopsy was performed on 40 cases with clinically N0 necks. Twenty were pathologically clear of tumor and 20 contained subclinical metastases. SLNs were found in 17 necks with pathologic disease and contained metastases in 16. The sentinel lymph node was the only lymph node containing tumor in 12 of 16. CONCLUSIONS: The SLN, in head and neck carcinomas accessible to injection without anesthesia, is an accurate reflector of the status of the regional lymph nodes, when found in patients with early tumors. Sentinel lymph nodes may be found in clinically unpredictable sites, and SLN biopsy may aid in identifying the clinically N0 patient with early lymph node disease. If SLNs cannot be located in the neck, an elective lymph node dissection should be considered.

Pethidine-augmented white cell scintigraphy in inflammatory bowel disease.

Technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) white cell scintigraphy is invaluable for assessing the presence and extent of disease activity in patients with inflammatory bowel disease. Interpretation of images can be compromised by physiological excretion of tracer into the bowel via the biliary tree. This study assesses the effect of intravenous pethidine administered with the labelled white cells in an attempt to reduce the enterohepatic circulation of the tracer. Ninety-one subjects with proven or suspected inflammatory bowel disease were included in this study, all of whom underwent 99mTc-HMPAO white cell scintigraphy. The control group of 50 subjects underwent the standard protocol for this study performed in our department. The other 41 subjects received an intravenous injection of 0.3 mg/kg of pethidine at the same time as re-injection of the labelled white cells. Images were graded using a five-point scale at both 1 and 2.5 h and categorised as positive, negative or non-diagnostic. Each scan was also assessed for the presence of a visible gall-bladder. The pethidine group had significantly fewer non-diagnostic scans than the control group (P=0.003), and significantly (P=0.001) more studies in which the gall-bladder was visualised. It is concluded that the use of pethidine appears to reduce biliary excretion of tracer during 99mTc-HMPAO white cell scintigraphy. This may allow the delayed images, and early images with low-grade tracer uptake in the bowel, to be interpreted with greater confidence and thereby reduce the number of scans classified as non-diagnostic.

A suggested method for sentinel node biopsy in squamous cell carcinoma of the head and neck.

BACKGROUND: Debate continues over the management of the N0 neck in head and neck malignancy. Therefore, the possibility of performing sentinel node biopsy in these patients was investigated to formulate a method for the procedure. METHODS: Patients undergoing prophylactic or therapeutic neck dissections were injected with either Patent Blue V dye alone or with blue dye and 99m-Tc labeled Albures. The latter group underwent preoperative lymphoscintigraphy. During surgery, blue stained lymphatics were followed to blue nodes, and a neoprobe was used to identify radioactive nodes. RESULTS: In 5 of 13 patients receiving blue dye, a blue node was identified, but none contained tumor. Metastases were identified in other neck nodes in 3 of 5. Sentinel nodes were identified in 15 of 16 patients receiving dye, and Albures. Sentinel node biopsy was accurate in 7 of 7 necks containing impalpable metastases when all nodes had been evaluated after dissection. DISCUSSION: Sentinel node biopsy using blue dye and radiocolloid may prove to be a reliable technique in the N0 neck and warrants further investigation.

Pulmonary embolism exclusion: a practical approach to low probability using the PIOPED data. Prospective Investigation of Pulmonary Embolism Diagnosis.

A recent trend among physicians is the categorisation of lung scans as normal [excludes pulmonary embolism (PE)], high probability (confirms PE) and non-diagnostic (no judgement on PE risk). The low probability scan is therefore being eliminated as a functional category. This occasional survey contends that such an approach is misguided. Correction of the original PIOPED data with certain assumptions provides a more reproducible, albeit restricted, low probability scan category which excludes PE in 97% of cases in the low pre-test clinical category. Patients with a low probability scan with risk factors for PE (i.e. medium clinical risk) will require further investigation. More important, the very low probability scan category excludes PE in 98% of patients with low and more than 92% of patients with medium pre-test clinical likelihood. The demise of "low probability" is premature.

A preliminary evaluation of diagnostic odds in lung scan reporting.

Reporting of lung scans for pulmonary embolism (PE) using a descriptive probability notation is tried and tested. Subjectivity in interpretation of this jargon can be a problem for internists. Parallel descriptive and numerical probability reporting has been recommended, but the numerical probability scale is less precise than likelihood ratios expressed as odds. We therefore assessed internists' intuitive understanding of lung scan reports in the odds format compared to the descriptive probability notation. A questionnaire was sent to Scotland's 217 internists to assess their intuitive understanding of odds reporting and to compare their management strategies when confronted by lung scan reports in both an odds and a descriptive probability notation. There was a broad understanding of numerical odds. Internists used 'normal' and '100:1 against PE' identically; similarly, 'low probability' and '10:1 against PE'. There was a statistically significant preference for the diagnosis of PE when internists were given the '1:1 evens' report compared with the 'indeterminate' report. There does appear to be a greater awareness of the risk of PE when non-diagnostic lung scans are reported in numerical odds as compared with the descriptive probability format.

Prospective assessment of the hepatic perfusion index in patients with colorectal cancer.

BACKGROUND: This prospective study was designed to test the hypothesis that abnormal liver blood flow is related to poor prognosis in patients with colorectal cancer. METHODS: The hepatic perfusion index (HPI), measured by dynamic hepatic scintigraphy, was assessed in 202 patients with colorectal cancer. Assessment for overt hepatic metastasis included liver palpation at laparotomy and perioperative computed tomography (CT). Follow-up at a dedicated clinic included regular abdominal ultrasonography and CT. RESULTS: The HPI was abnormal (greater than 0.37) in 92 (88 per cent) of 105 patients with overt liver metastases. Of 89 patients with no evidence of overt metastases or residual tumour after primary resection, 52 had an abnormal and 37 a normal HPI. At a median follow-up of 39 (range 13-76) months, 25 of 38 patients with recurrence had an abnormal HPI. Some 31 of 45 patients who died had an abnormal HPI. The HPI predicted overall recurrence (P=0.04, log rank test). Multivariate analysis showed the HPI was independent of Dukes stage for predicting disease-free survival (P=0.04, relative risk 1.94 (95 per cent confidence interval (c.i.) 1.03-3.67)) but this just failed to attain significance for overall survival (P=0.055, relative hazard 1.88 (95 per cent c.i. 1.00-3.58)). CONCLUSION: The HPI predicts a poor outcome in patients with colorectal cancer and may be useful in patient selection for adjuvant chemotherapy.

Gastric emptying in patients with constipation following childbirth and due to idiopathic slow transit.

BACKGROUND: Idiopathic slow transit constipation (ISTC) is considered to be a heterogeneous condition in which patients have varying sites and degrees of delayed gastrointestinal transit. The majority of patients have pancolonic disease, and colectomy with ileocolorectal anastomosis has been the mainstay of surgical treatment. Severe constipation following traumatic childbirth is now being recognized and this subgroup of patients may have delayed transit confined to the rectosigmoid colon. In theory, proximal transit in these patients should be normal. METHODS: Gastric emptying was studied in patients with constipation following childbirth or ISTC and in controls. After an overnight fast, both patients and controls received breakfast, which consisted of cornflakes, sugar and milk. The liquid marker 111In-labelled di-ethylene tri-amine penta-acetic acid (DTPA) was added to the milk. A solid marker, 99mTc-labelled colloid, was impregnated on to paper and sealed with cellulose. The t1/2 for gastric emptying was calculated. RESULTS: Liquid phase emptying was normal in both constipation following childbirth and ISTC. Solid phase emptying was delayed significantly in ISTC compared with that in patients with constipation following childbirth and controls. In addition, half the patients with ISTC had delayed transit through the small bowel and proximal colon. Small bowel and colonic transit were normal in patients with constipation following childbirth. CONCLUSION: Patients with constipation following childbirth represent a distinct subgroup with normal proximal gastrointestinal function. Gastric emptying studies may be helpful in selecting patients for surgical management of severe constipation.

Dynamic hepatic scintigraphy in colorectal cancer.

The clinical usefulness of the hepatic perfusion index (HPI) at the time of presentation has been evaluated in patients with colorectal cancer. In 83 consecutive patients, the HPI was abnormally elevated in 34 of 37 (93%) patients with overt metastases. This study confirms that the HPI is elevated in most patients with overt hepatic metastases. Long-term follow-up of patients with abnormal HPI and no obvious liver metastases is continuing.

Lung scan reporting language: what does it mean?

The aim of this study was to analyse the understanding of the verbal probability language used for communicating lung scan findings. A questionnaire providing a series of expressions of probability in lung scan reporting was sent to 211 consultant nuclear medicine providers in the UK. Respondents were asked to estimate the probability of pulmonary embolism (PE) communicated by each reporting expression on a visual linear probability scale. Analysis of 135 replies revealed a wide variation in the interpretation of the probability language. We suggest that different training, the nature of the probability scale itself and the difficulties of expressing a verbal report on a numerical scale are major reasons for this finding. We conclude that use of verbal probability language complicates the communication of PE risk and that likelihood ratios provide a logical alternative.

Radionuclide migration through the genital tract in infertile women with endometriosis.

The migration of radionuclide through the genital tract was observed, comparing 20 patients with endometriosis and infertility with a control group of 23 infertile patients who had a normal pelvis. All patients had patent tubes at laparoscopy and chromopertubation, performed in both groups for the investigation of infertility and to diagnose the presence and extent of endometriosis. A radionuclide tubal test, using human albumin microspheres labelled with 99m-technetium (99mTc) was subsequently undertaken to observe the extent of genital tract migration of radionuclide to uterus, Fallopian tube and peritoneal cavity. The results show that radionuclide migration to the peritoneal cavity was impaired in patients with endometriosis, compared with the control group (30 versus 83%, respectively; P < 0.001). There was no relationship between migration and the severity of endometriosis. We conclude that impaired tubal function may be a cause of infertility in some patients with endometriosis.

Lung scan reports: interpretation by clinicians.

A questionnaire was sent to 217 consultant physicians in Scotland who were likely to encounter pulmonary embolism (PE) in their daily practice. Replies were received from 194 (89%). Only 34% of physicians understood that a normal lung scan made PE highly unlikely, while 65% considered a low probability scan equivalent to an uncertain diagnosis. This pattern of interpretation of lung scan reports was confirmed by a question on post-test management. After a normal lung scan report, 31% of physicians were uncertain about the diagnosis and this uncertainty increased to 37% for a low probability scan report. This survey has shown misunderstanding by a significant number of physicians of the risk of PE indicated by normal and low probability lung scan reports. It underlines the need for individuals reporting the test to provide informed guidance for clinical staff following ventilation/perfusion (V/Q) imaging. It may point in addition to a need for a more easily understood style of reporting of lung scans.

Glass yttrium-90 microspheres for patients with colorectal liver metastases.

Total calculated uniform liver doses of up to 150 Gy were achieved using glass yttrium-90 microspheres administered via the hepatic artery and targeted to tumour using angiotensin II in seven patients with colorectal liver metastases. No toxicity was observed. Hepatic metastatic progression was delayed in six patients. Median survival was 11 months (range 5-25 + months).

Clinical correlation of high activity dynamic hepatic scintigraphy in patients with colorectal cancer.

The hepatic perfusion index, the ratio of hepatic arterial to total liver blood flow, was measured in 50 consecutive patients with colorectal cancer using radiolabelled colloid with high administered activity. In patients with proven liver metastases the diagnostic sensitivity of the HPI was 96% and the predictive value of a negative test was 92%. Dynamic hepatic scintigraphy is of value in the management of patients with colorectal cancer.

Dynamic hepatic scintigraphy: the effect of using high administered activity on reproducibility of hepatic perfusion index value.

The hepatic perfusion index (HPI) may be of value in the detection of both overt and occult hepatic metastases in patients with colorectal carcinoma. Using the standard technique, the low counts obtained in each region of interest can produce statistical unreliability in the curve generation and render many studies unsuitable for analysis. In this study the effects of a high administered activity (400 MBq) on the inter- and intra-observer reproducibility of dynamic hepatic scintigraphy was investigated in 18 consecutive patients with colorectal cancer. All 18 patient studies were suitable for analysis by two observers. The correlation coefficient of measurements between observers was 0.98 (P less than 0.000 01 linear regression analysis), with a root mean square difference of replicate HPI measurements between observers of 0.045. The median range of HPI for four reprocessings by one observer was 0.035, with a maximum range of 0.11. Although high administered activity improves count statistics, for the individual patient study the activity used is not the major source of uncertainty in the derived HPI value.

Angiotensin II as a potential method of targeting cytotoxic-loaded microspheres in patients with colorectal liver metastases.

Regional chemotherapy is commonly used to treat patients with colorectal liver metastases. However, improvement in survival has still not been demonstrated. Cytotoxic loaded albumin microspheres for arterial administration have been described as a means of improving the the therapeutic index, but their distribution depends upon the prevailing pattern of arterial blood-flow at the time of injection. In this study, the ability of the vasoactive drug angiotensin II to target arterially injected microspheres to colorectal liver metastases is assessed in nine patients using scintigraphic planar and tomographic imaging. The median tumour: normal ratio in nine patients with colorectal liver metastases was 3.4:1 before the administration of angiotensin II. The corresponding ratio after administration of angiotensin II was 7.3:1. The median improvement factor was 1.8 (P less than 0.05). The data suggest that worthwhile tumour targeting can be achieved with angiotensin II in patients with colorectal liver metastases.

Investigation of tubal infertility by radionuclide migration.

Investigation of the tubal factor in infertility is limited to an assessment of anatomical structure and tubal patency. No test of ascendant tubal function is currently available. The migration of radionuclide (99mTc-labelled human albumin microspheres) through the genital tract in 96 infertile women was compared with pelvic findings at laparoscopy and chromopertubation. The radionuclide test correlated with laparoscopy in the diagnosis of patency or blockage in 83 cases (86%). In nine patients, where 'blockage' was diagnosed on the radionuclide test but patency found at laparoscopy, a higher prevalence of pelvic abnormality was found, compared to the 78 patients where both tests demonstrated patency (P less than 0.02). The radionuclide test may facilitate detection of diseased but patent tubes and, as an adjunct to laparoscopy and chromopertubation, may provide useful information about tubal function.

Arteriovenous shunting in patients with colorectal liver metastases.

The outlook for patients with colorectal liver metastases is poor. Microspheres have been combined with cytotoxics and administered via the hepatic artery in an attempt to improve tumour drug exposure within the liver. However, it has been suggested that arteriovenous connections might occur in association with intrahepatic tumours causing loss of regional advantage, and that the administration of microspheres further exacerbates arteriovenous shunting. In seven patients with colorectal liver metastases, base-line shunting was measured using a tracer quantity of radio-labelled albumin microspheres. The shunted fraction of a 'therapeutic quantity' of microspheres was subsequently measured in the same group of patients using albumin microspheres carrying a different radio-label. Base-line shunt for 0.5 x 10(6) microspheres was found to be 2.2 +/- 1.8% (mean +/- s.d.); the percentage shunt of a therapeutic quantity (40-80 x 10(6)) of microspheres was 3.0 +/- 0.8%. We conclude that arteriovenous shunting in patients with colorectal liver metastases is minimal, and is not significantly increased by the administration of therapeutic quantity of microspheres during regional chemotherapy.

The use of angiotensin II as a potential method of targeting cytotoxic microspheres in patients with intrahepatic tumour.

Cytotoxic microspheres have been developed for intra-arterial use in patients with liver metastases. Following injection, the distribution of microspheres reflects the pattern of hepatic arterial blood-flow. Vasoactive agents, such as angiotensin II, by producing vasoconstriction in normal liver, might divert arterial blood toward tumour and thereby enhance the delivery of drug-loaded particles. Using a double isotope technique, the distribution of radiolabelled microspheres to tumour and normal liver tissue was measured before and after angiotensin II infusion in nine patients with multiple liver metastases. The median increase in tumour: normal ratio following angiotensin II infusion was by a factor of 2.8 (range 0.8-11.7, P less than 0.05). This novel approach to regional chemotherapy, using a combination of angiotensin II infusion and cytotoxic microspheres, increases the exposure of tumour to cytotoxic agents and may, therefore, enhance tumour response rates.