Securin identifies a subgroup of patients with poor outcome in rectal cancer treated with long-course (chemo)radiotherapy.

BACKGROUND: Securin is an oncogene with functions in cell proliferation, tumour initiation and progression. Its prognostic value in rectal cancer is somewhat unknown. Accordingly, we studied securin expression together with Ki-67 in rectal cancer in relation to preoperative (chemo)radiotherapy (RT) and disease outcome. MATERIAL AND METHODS: Biopsies (n = 65 for securin; n = 57 for Ki-67) and operative specimens (n = 207) from 211 patients treated with short-course RT (n = 87), long-course RT (n = 54) or surgery only (n = 70) were studied with immunohistochemistry (IHC) for securin and Ki-67 expression. In the long-course RT group, 45 patients received chemotherapy (5-fluorouracil or capecitabine) concomitantly with RT. The results of IHC were related to clinicopathological variables, disease outcome and tumour regression grade (TRG) after long-course RT. RESULTS: Both markers showed significant reduction after RT (p < 0.001). No differences in expression was seen in the long-course RT group between the patients with or without concomitant chemotherapy (p = 0.23 for securin; p = 0.31 for Ki-67). Low Ki-67 expression, but not that of securin, in operative specimens was significantly related to excellent TRG (p = 0.02 for Ki-67; p = 0.21 for securin). In univariate survival analysis, excellent TRG predicted longer disease-specific survival (DSS; p = 0.03). In multivariate Cox analysis, high securin expression after long-course (chemo)RT was an independent predictor of shorter DSS (p = 0.036) together with patient age (p = 0.043) and disease recurrence (local or distant; p = 0.009), whereas no similar appearance was seen in other treatment groups. CONCLUSION: Securin expression in rectal cancer is significantly reduced after RT. High securin expression and poor TRG after long-course (chemo)RT are indicators of unfavourable disease outcome.

Monitoring microvascular free flaps with tissue oxygen measurement and PET.

Tissue oxygen measurement and positron emission tomography (PET) were evaluated as methods for predicting ischemia in microvascular free flaps of the head and neck. Ten patients with head and neck squamous cell cancer underwent resection of the tumour followed by microvascular reconstruction with a free flap. Tissue oxygenation of the flap (P(ti)O(2)) was continuously monitored for three postoperative (POP) days and the blood flow of the flap was assessed using oxygen-15 labelled water and PET. In three free flaps a perfusion problem was suspected due to a remarkable drop in P(ti)O(2)-values, due to two anastomosis problems and due to POP turgor. No flap losses occurred. During the blood flow measurements with PET [mean 8.5 mL 100 g(-1) min(-1 )(SD 2.5)], the mean P(ti)O(2) of the flaps [46.8 mmHg (SD 17.0)] appeared to correlate with each other in each patient (p<0.05, n=10). Tissue oxygenation measurement is a feasible monitoring system of free flaps. The perfusion-study with PET correlates with P(ti)O(2)-measurement.

Whole body positron emission tomography in follow-up of high risk melanoma.

The aim of this study was to determine the clinical impact of whole body positron emission tomography (FDG PET) to detect clinically silent metastases in the follow-up of patients with high risk melanoma. FDG PET was performed to 30 asymptomatic melanoma patients (AJCC stage IIB-IIIC) 7-24 months after the primary surgery and sentinel node biopsy. FDG PET was able to detect six of seven recurrences, constituting 20% of all study patients. One patient presented with a negative FDG PET finding at the very first scanning, but was positive later in a repeated scan after manifestation of palpable mass in the axilla. The positive PET finding had an impact on treatment decisions in every case: three patients underwent surgical resection and four patients received chemotherapy or interferon. The mean follow-up time was 27 months (range, 12-48 months) and during that time the other 23 patients with true negative FDG PET were disease-free. One of the seven recurrences was in remission after surgical metastasectomy. In conclusion, whole body FDG PET is a valuable follow-up tool in high risk melanoma to diagnose recurrences and to select the patients, who are suitable for surgical metastasectomy.

Functional evaluation of microvascular free flaps with positron emission tomography.

BACKGROUND: The aim of this study was to assess blood flow (BF) of microvascular free flaps studied with positron emission tomography (PET) in patients with head and neck squamous cell cancer (HNSCC) undergoing major radical surgery 3-4 weeks after high-dose radiotherapy. METHODS: Five patients underwent resection of the HNSCC of the oral cavity followed by microvascular reconstruction with a radial forearm flap. Regional BF in oral and neck tissues was measured with PET using radiolabelled water ([15O]H2O) twice (1-2 and 12-14 days, respectively) following radical surgery. RESULTS: In the first postoperative PET study, the median BF in the cutaneous flap area was 5.1 mL/100 g/min, and in the muscle contra-lateral to the recipient site 19.9 mL/100 g/min. A low flap-to-muscle BF ratio appeared to correlate with circulatory incongruity, and thus with poorer flap success. The follow-up study on the second postoperative week supported the results of the primary PET scan. CONCLUSIONS: This pilot study suggests that PET using [15O]H2O is a feasible method to quantitatively evaluate BF of the whole free flap in patients operated on for oral

Adenocarcinoma of the esophagus and the esophagogastric junction: positron emission tomography improves staging and prediction of survival in distant but not in locoregional disease.

In adenocarcinoma of the esophagus and esophagogastric junction for prognostication and treatment allocation, one prerequisite is accurate pretreatment staging. This staging, we hypothesized, would be improved by the use of positron emission tomography (PET). After 55 patients suitable for radical esophageal resection were staged with PET, spiral computed tomography (CT), and endoscopic ultrasonography (EUS), results were compared with histopathology and with survival. Accuracy in detecting locoregional lymph node metastasis did not differ significantly between EUS (72%), PET (60%), and CT (58%). Adding PET to standard staging failed to improve the accuracy of N staging (P=0.250). In M staging, accuracy between CT (75%) and PET (76%) did not differ. The accuracy of combined studies of CT and PET and of EUS, CT, and PET were 87% (P=0.016 versus CT) and 91% (P=0.031 versus EUS and CT), respectively. Of the 55 patients, 19 (35%) had metastatic lesions. By combined use of CT and EUS and by combined use of CT, EUS, and PET, 8 and 14 (P=0.031), respectively, could be detected. In nodal disease without distant metastases, PET did not improve the prediction of survival. However, positive PET for distant metastasis by either positive EUS or CT predicts well the poor survival of these patients. The staging value of PET by itself in adenocarcinoma of the esophagus is limited because of low accuracy for nodal and the lack of specificity for distant disease prognosis. Adding PET to standard staging does, however, improve detection of stage IV disease and its associated poor survival.

Prospective analysis of accuracy of positron emission tomography, computed tomography, and endoscopic ultrasonography in staging of adenocarcinoma of the esophagus and the esophagogastric junction.

BACKGROUND: Exact preoperative staging of esophageal cancer is essential for accurate prognosis and selection of appropriate treatment modalities. METHODS: Forty-two patients with adenocarcinoma of the esophagus or the esophagogastric junction suitable for radical esophageal resection were staged with positron emission tomography (PET), spiral computed tomography (CT), and endoscopic ultrasonography (EUS). RESULTS: Diagnostic sensitivity for the primary tumor was 83% for PET and 67% for CT; for local peritumoral lymph node metastasis, it was 37% for PET and 89% for EUS; and for distant metastasis, it was 47% for PET and 33% for CT. Diagnostic specificity for local lymph node metastasis was 100% with PET and 54% with EUS, and for distant metastasis, it was 89% for PET and 96% for CT. Accuracy for locoregional lymph node metastasis was 63% for PET, 66% for CT, and 75% for EUS, and for distant metastasis, it was 74% with PET and 74% with CT. Of the 10 patients who were considered inoperable during surgery, PET identified 7 and CT 4. The false-negative diagnoses of stage IV disease in PET were peritoneal carcinomatosis in two patients, abdominal para-aortic cancer growth in one, metastatic lymph nodes by the celiac artery in four, and metastases in the pancreas in one. PET showed false-positive lymph nodes at the jugulum in three patients. CONCLUSIONS: The diagnostic value of PET in the staging of adenocarcinoma of the esophagus and the esophagogastric junction is limited because of low accuracy in staging of paratumoral and distant lymph nodes. PET does, however, seem to detect organ metastases better than CT.