Positron Emission Tomography (PET) is a functional imaging modality widely used in clinical oncol... more Positron Emission Tomography (PET) is a functional imaging modality widely used in clinical oncology. Over the years the sensitivity and specificity of PET has improved with the advent of specific radiotracers, increased technical accuracy of PET scanners and incremental experience of Radiologists. However, significant limitations exist-most notably false positives and false negatives. Additionally, the accuracy of PET varies between cancer types and in some cancers, is no longer considered a standard imaging modality. This review considers the relative influence of macroscopic tumour features such as size and morphology on 2-Deoxy-2-[ 18 F]fluoroglucose ([ 18 F]FDG) uptake by tumours which, though well described in the literature, lacks a comprehensive assessment of biomolecular features which may influence [ 18 F]FDG uptake. The review aims to discuss the potential influence of individual molecular markers of glucose transport, glycolysis, hypoxia and angiogenesis in addition to the relationships between these key cellular processes and their influence on [ 18 F]FDG uptake. Finally, the potential role for biomolecular profiling of individual tumours to predict positivity on PET imaging is discussed to enhance accuracy and clinical utility.
This study evaluated the role of 18 F-FDG PET as an early predictor of histopathologic response t... more This study evaluated the role of 18 F-FDG PET as an early predictor of histopathologic response to neoadjuvant chemoradiotherapy and overall survival in patients with adenocarcinoma of the esophagus undergoing multimodal therapy. Methods: Thirty-seven patients with locally advanced adenocarcinoma of the esophagus underwent pretreatment and an intratreatment 18 F-FDG PET scan in the second week of a 6-wk regimen of neoadjuvant chemoradiotherapy. Histopathologic response and overall survival were correlated with percentage change in 18 F-FDG uptake (%Dmaximum standardized uptake value [%DSUVmax]). Results: In 16 patients (43%), treatment induced a histopathologic response (,10% viable tumor cells), which was associated with a significant (P , 0.05) survival benefit. The optimal reduction in 18 F-FDG uptake, which separated histopathologic responders and nonresponders, was a 226.4% DSUVmax (receiver-operating-characteristic curve analysis). At this separation, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy (area under the receiver operating characteristic curve) were 62.5%, 71.4%, 62.5%, 71.4%, and 67.4%, respectively, for intratreatment 18 F-FDG PET scans. Kaplan-Meier survival analysis of 18 F-FDG PET responders (.26.4% reduction in SUVmax), compared with 18 F-FDG PET nonresponders (,26.4% reduction in SUVmax), revealed no survival benefit for responders (P 5 0.6812). Conclusion: The %DSUVmax during the second week of induction chemoradiation did not correlate either with histopathologic response or with survival. Our results show that, in contrast to published reports on neoadjuvant chemotherapy, combined chemoradiotherapy in patients with adenocarcinoma of the esophagus lowers the predictive accuracy of early repeated 18 F-FDG PET in identifying histopathologic responders and those with chances for increased survival below clinically applicable levels.
data of cases were collected, characteristics of the carcinomas were described, and available FFP... more data of cases were collected, characteristics of the carcinomas were described, and available FFPE tissue slides were immunostained for β-catenin, P53 and phospho-S6 (a downstream target of mTOR). Furthermore, we performed DNA mutation analyses for BRAF, KRAS, and P53, and LOH analyses for LKB1 and P53. Results: Twenty-eight of the 144 patients (19%, 64% males) from 20 families developed 30 GI malignancies at a median age of 44 years (IQR 35-57) at diagnosis of first cancer (Table). Two patients were diagnosed with two primary GI carcinomas. Three (10%) malignancies were discovered during surveillance; all carcinomas in situ (one colorectal and two gastric lesions). Twenty-three patients (82%) deceased at a median age of 54 years (IQR 36-61); 19 (68%) of whom had died as a direct cause of GI cancer. Of these 23 patients, median survival after GI cancer diagnosis was 6 months (IQR 1-18). Of 16 carcinomas FFPE tissue was available for molecular analysis. Nuclear β-catenin was detected in 3/5 (60%) primary intestinal carcinomas. Overexpression of P53 was observed in 7/16 (44%) carcinomas, and a total absence of P53 was observed in one (6%) sample. All available samples showed heterogeneous expression of pS6, in which epithelial expression was more pronounced compared to the stromal component in 9/14 (64%) cases. Mutation and LOH analyses are currently being performed. Conclusion: Gastrointestinal cancer often affects PJS patients already at a young age. Alterations in Wnt/ β-catenin signaling and in P53 are observed in a subset of PJS carcinomas, while activation of mTOR signaling seems to be altered in the majority of these carcinomas, predominantly in the epithelial compartment. These results suggest that treatment with mTOR inhibitors may be beneficial in the anti-cancer treatment of PJS patients. Location of gastrointestinal carcinomas in Peutz-Jeghers syndrome patients
Series from high volume oesophageal centres highlight an increasing prevalence of early malignant... more Series from high volume oesophageal centres highlight an increasing prevalence of early malignant (EM) lesions. The advent of endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) offer alternatives to traditional surgery. The evolution of this pattern of care in a high volume centre is analysed. Data were collected from a prospectively maintained database. 96 patients were treated with an EM lesion from 2000 to 2011. Surgery was the standard approach during the initial period (2000-2006). In 2007, with the introduction of EMR±RFA to our Centre, a rising trend toward definitive endoscopic treatment was seen. This study details the selection of cases into treatment groups and their outcomes. From 2000 to 2006, 23 patients were treated with EM lesions, 96% by surgery. Seventy-three were treated from 2007 to 2011, 55% surgically and 45% by EMR±RFA. In the entire experience, there was one death from surgery and morbidity was higher in the surgery group compared with EMR±RFA (p<0.001). Three surgical patients (4.8%) relapsed with HGD or cancer, and one patient with T1N1 disease died of disease recurrence. At a median of 13 months, EMR±RFA offered 100% disease control, 72% had no endoscopic or histological evidence of Barrett's oesophagus and one patient represented with low grade dysplasia. This study highlights the changing pattern of care in the management of early oesophageal cancer. EMR±RFA appears an acceptable alternative to surgery in carefully selected cases. However, long-term outcome analysis using these methods is required and close interdisciplinary collaboration of specialists in gastroenterology, surgery, pathology and radiology is mandatory to achieve optimum outcomes.
The aim was to evaluate the impact of FDG-PET scan on tumour staging and management decisions in ... more The aim was to evaluate the impact of FDG-PET scan on tumour staging and management decisions in oesophageal cancer. One-hundred consecutive patients referred for consideration of surgery underwent a whole body FDG-PET scan in addition to CT imaging. Based on CT scan, a curative approach could be considered in 62 patients. The PET scan altered regional nodal (N) staging in 16 patients overall, but did not alter management decisions. Metastatic status (M) was increased in 14 patients, with altered management in 10/62 (16%). Nine were downstaged, with management changed in 3/38 (8%). Seventeen patients underwent 19 additional tests to clarify findings on PET, in 15 patients (88%) the tests revealed no pathology. FDG-PET alters M stage in 23% of patients and may impact on surgical decision-making. The spurious investigations and cost of the high false-positive rate of further tests is of concern.
To determine the correlation between 18 F-fluorodeoxyglucose positron emission tomographycomputed... more To determine the correlation between 18 F-fluorodeoxyglucose positron emission tomographycomputed tomography (PET-CT) derived esophageal tumor parameters [maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV)] and endoscopic ultrasound (EUS) derived tumor parameters (T stage, N stage) and their prognostic implications. 150 consecutive patients with cancer of the esophagus or esophagogastric junction underwent staging PET-CT and staging EUS. PET-CT derived SUVmax and MTV of the primary tumor was recorded. EUS evaluated T and N stage. Relationships between parameters were investigated using the Mann-Whitney U tests, survival analysis performed using Kaplan-Meier and independent prognostic factors determined using Cox regression multivariate analysis. A significant difference in MTV was noted between EUS T1/T2 tumors (median 6.7 cm 3) and EUS T3/T4 tumors (median 35.7 cm 3 ; P < 0.0001). An MTV of <23.4 cm 3 (P 5 0.0001), SUVmax < 4.1 (P 5 0014), EUS T stage (P < 0.0001), EUS N stage (P < 0.0001), and clinical stage (P < 0.0001) were all significantly associated with survival, with MTV <23.4 cm 3 (P 5 0.004), EUS T stage (P 5 0.01), and EUS N stage (P 5 0.01) significant in multivariate analysis. MTV, a volumetric parameter of PET-CT, has more prognostic importance than SUVmax and provides valuable prognostic information in esophageal and junctional cancer, along with EUS T and N stage. MTV provides complementary information to EUS and should be included in the staging of esophageal and junctional cancer.
Purpose: 18 F-Fluorodeoxyglucose positron emission tomography (18 F-FDG PET) imaging is increasin... more Purpose: 18 F-Fluorodeoxyglucose positron emission tomography (18 F-FDG PET) imaging is increasingly the standard of care in the staging of esophageal cancer. Synchronous neoplasms may be identified, and this study evaluated the prevalence of such tumors and their impact on management. Methods: Five hundred ninety-one (73.6%) of 803 consecutive patients with biopsy-proven esophageal cancer underwent staging 18 F-FDG PET or PET/CT scans. 18 FYFDG-avid lesions were considered synchronous primary neoplasms if occurring at locations atypical for metastases from the known primary, a marked discordance in the 18 F-FDG avidity from that of the primary tumor, and if there was no prior detection on conventional imaging. Additional investigations as appropriate were undertaken, and histopathological verification was obtained where possible to validate the suspected synchronous neoplasm. Results: A synchronous neoplasm was suspected in 55 (9.3%) of 591 patients, predominantly at sites in the colon (26) and head and neck (21). Additional investigations in 43 cases revealed malignant neoplasms in 8 (18.6%), premalignant in 9 (20.9%), and benign lesions in 26 (60.5%) cases. The management plan was altered in 8 patients, 1.4% overall. The total cost of added tests was $27,482.57 (€21,024) with the decision to treat the esophageal cancer deferred by a mean of 10.7 days. Conclusion: 18 F-FDG uptake concerning for synchronous neoplasms is evident in approximately 1 in 10 cases, and of these a minority will represent a malignant neoplasm that significantly impacts on treatment. The overall added costs per patient are relatively modest and the treatment delay within acceptable limits of clinical practice.
This study evaluated the role of 18 F-FDG PET as an early predictor of histopathologic response t... more This study evaluated the role of 18 F-FDG PET as an early predictor of histopathologic response to neoadjuvant chemoradiotherapy and overall survival in patients with adenocarcinoma of the esophagus undergoing multimodal therapy. Methods: Thirty-seven patients with locally advanced adenocarcinoma of the esophagus underwent pretreatment and an intratreatment 18 F-FDG PET scan in the second week of a 6-wk regimen of neoadjuvant chemoradiotherapy. Histopathologic response and overall survival were correlated with percentage change in 18 F-FDG uptake (%Dmaximum standardized uptake value [%DSUVmax]). Results: In 16 patients (43%), treatment induced a histopathologic response (,10% viable tumor cells), which was associated with a significant (P , 0.05) survival benefit. The optimal reduction in 18 F-FDG uptake, which separated histopathologic responders and nonresponders, was a 226.4% DSUVmax (receiver-operating-characteristic curve analysis). At this separation, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy (area under the receiver operating characteristic curve) were 62.5%, 71.4%, 62.5%, 71.4%, and 67.4%, respectively, for intratreatment 18 F-FDG PET scans. Kaplan-Meier survival analysis of 18 F-FDG PET responders (.26.4% reduction in SUVmax), compared with 18 F-FDG PET nonresponders (,26.4% reduction in SUVmax), revealed no survival benefit for responders (P 5 0.6812). Conclusion: The %DSUVmax during the second week of induction chemoradiation did not correlate either with histopathologic response or with survival. Our results show that, in contrast to published reports on neoadjuvant chemotherapy, combined chemoradiotherapy in patients with adenocarcinoma of the esophagus lowers the predictive accuracy of early repeated 18 F-FDG PET in identifying histopathologic responders and those with chances for increased survival below clinically applicable levels.
Positron Emission Tomography (PET) is a functional imaging modality widely used in clinical oncol... more Positron Emission Tomography (PET) is a functional imaging modality widely used in clinical oncology. Over the years the sensitivity and specificity of PET has improved with the advent of specific radiotracers, increased technical accuracy of PET scanners and incremental experience of Radiologists. However, significant limitations exist—most notably false positives and false negatives. Additionally, the accuracy of PET varies between cancer types and in some cancers, is no longer considered a standard imaging modality. This review considers the relative influence of macroscopic tumour features such as size and morphology on 2-Deoxy-2-[18F]fluoroglucose ([18F]FDG) uptake by tumours which, though well described in the literature, lacks a comprehensive assessment of biomolecular features which may influence [18F]FDG uptake. The review aims to discuss the potential influence of individual molecular markers of glucose transport, glycolysis, hypoxia and angiogenesis in addition to the rel...
Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus, Jan 15, 2016
To determine the correlation between (18) F-fluorodeoxyglucose positron emission tomography-compu... more To determine the correlation between (18) F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) derived esophageal tumor parameters [maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV)] and endoscopic ultrasound (EUS) derived tumor parameters (T stage, N stage) and their prognostic implications. 150 consecutive patients with cancer of the esophagus or esophagogastric junction underwent staging PET-CT and staging EUS. PET-CT derived SUVmax and MTV of the primary tumor was recorded. EUS evaluated T and N stage. Relationships between parameters were investigated using the Mann-Whitney U tests, survival analysis performed using Kaplan-Meier and independent prognostic factors determined using Cox regression multivariate analysis. A significant difference in MTV was noted between EUS T1/T2 tumors (median 6.7 cm(3) ) and EUS T3/T4 tumors (median 35.7 cm(3) ; P < 0.0001). An MTV of <23.4 cm(3) (P = 0.0001), SUVmax < 4.1 (P = 0014), EUS ...
The aim of this study is to assess CT-PET and endoscopic assessment postneoadjuvant chemoradiothe... more The aim of this study is to assess CT-PET and endoscopic assessment postneoadjuvant chemoradiotherapy (nCRT) in predicting complete pathologic response (pCR) in locally advanced esophageal cancer (LAEC). A prospective cohort study. nCRT is increasingly standard of care in LAEC, with pCR a surrogate for excellent outcome. Predicting pCR before surgery, with metabolic imaging and endoscopy, may spare patients' operative intervention. One hundred thirty-eight consecutive patients [mean age 61 ± 8, 99 male (72%), 103 (75%) adenocarcinoma] underwent nCRT with CT-PET and endoscopy 4 to 6 weeks later, and surgery subsequently. A complete metabolic response (cMR) was defined as SUVmax of <4. A complete endoscopic response (cER) was no residual mucosal abnormality. The association of pCR with cMR and cER was analyzed. pCR was achieved in 30 patients (22%); 37% SCC and 17% adenocarcinoma. A cMR was evident in 63 (46%), of whom 17 (27%) had a pCR and 17(27%) were ypN+. A cER was observe...
Journal of Plastic Reconstructive Aesthetic Surgery, Jan 12, 2010
Background: Basal cell carcinomas are the most prevalent of all skin cancers worldwide and form t... more Background: Basal cell carcinomas are the most prevalent of all skin cancers worldwide and form the majority of the surgical workload for most modern cutaneous malignancy centres. Primary surgical removal of basal cell carcinomas remains the gold standard of treatment but, despite almost two centuries of surgical experience, rates of incomplete surgical excision of up to 50% are still reported.
Positron emission tomography and computed tomography (PET-CT) is established in the staging of es... more Positron emission tomography and computed tomography (PET-CT) is established in the staging of esophageal cancer. In this study, an MRI protocol was designed to emulate the anatomical (T1-weighed (T1W) and T2W imaging) and functional information (diffusion-weighted imaging) provided by PET-CT. In all, 49 patients with carcinoma of the esophagus underwent PET-CT and whole-body MRI (WBMRI). WBMRI was carried out using dedicated sequences tailored to detect metastatic disease at each area corresponding to the anatomical coverage of PET-CT. Nodal status was determined from histopathology and endoscopic ultrasound biopsy (EUS). PET-CT and WBMRI identified the primary tumor in 46/49 (94%) and 48/49 (98%) patients, respectively. Nodal analysis in patients undergoing surgery (n = 18) yielded sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 27, 100, 100, 47 and 56% for PET-CT, compared with 30, 100, 100, 53 and 61% for WBMRI. When nodal analysis included both surgical specimens and EUS criteria (n = 39), sensitivity, specificity, PPV, NPV and accuracy were 46, 91, 93, 40 and 59% for PET-CT compared with 59, 92, 94, 50 and 67% for WBMRI. Both imaging modalities identified distant metastases in 2 patients. WBMRI has similar accuracy to PET-CT in detecting the primary tumor, nodal deposits and for exclusion of systemic metastatic disease.
To determine whether [(18)F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) could pred... more To determine whether [(18)F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) could predict the pathological response in oesophageal cancer after only the first week of neoadjuvant chemoradiation. Thirty-two patients with localised oesophageal cancer had a pretreatment PET scan and a repeat after the first week of chemoradiation. The change in mean maximum standardised uptake value (SUV) and volume of metabolically active tissue (MTV) was compared with the tumour regression grade (TRG) in the final histology. Those who achieved a TRG of 1 and 2 were deemed responders and 3-5 nonresponders. In the responders (28%), the SUV fell from 12.6 (+/-6.3) to 8.1 (+/-2.9) after 1 week of chemoradiation (P=0.070). In nonresponders (72%), the results were 9.7 (+/-5.4) and 7.1 (+/-3.8), respectively (P=0.003). The MTV in responders fell from 36.6 (+/-22.7) to 22.3 (+/-10.4) cm(3) (P=0.180), while in nonresponders, this fell from 35.9 (+/-36.7) to 31.9 (+/-52.7) cm(3) (P=0.405). There wer...
Positron Emission Tomography (PET) is a functional imaging modality widely used in clinical oncol... more Positron Emission Tomography (PET) is a functional imaging modality widely used in clinical oncology. Over the years the sensitivity and specificity of PET has improved with the advent of specific radiotracers, increased technical accuracy of PET scanners and incremental experience of Radiologists. However, significant limitations exist-most notably false positives and false negatives. Additionally, the accuracy of PET varies between cancer types and in some cancers, is no longer considered a standard imaging modality. This review considers the relative influence of macroscopic tumour features such as size and morphology on 2-Deoxy-2-[ 18 F]fluoroglucose ([ 18 F]FDG) uptake by tumours which, though well described in the literature, lacks a comprehensive assessment of biomolecular features which may influence [ 18 F]FDG uptake. The review aims to discuss the potential influence of individual molecular markers of glucose transport, glycolysis, hypoxia and angiogenesis in addition to the relationships between these key cellular processes and their influence on [ 18 F]FDG uptake. Finally, the potential role for biomolecular profiling of individual tumours to predict positivity on PET imaging is discussed to enhance accuracy and clinical utility.
This study evaluated the role of 18 F-FDG PET as an early predictor of histopathologic response t... more This study evaluated the role of 18 F-FDG PET as an early predictor of histopathologic response to neoadjuvant chemoradiotherapy and overall survival in patients with adenocarcinoma of the esophagus undergoing multimodal therapy. Methods: Thirty-seven patients with locally advanced adenocarcinoma of the esophagus underwent pretreatment and an intratreatment 18 F-FDG PET scan in the second week of a 6-wk regimen of neoadjuvant chemoradiotherapy. Histopathologic response and overall survival were correlated with percentage change in 18 F-FDG uptake (%Dmaximum standardized uptake value [%DSUVmax]). Results: In 16 patients (43%), treatment induced a histopathologic response (,10% viable tumor cells), which was associated with a significant (P , 0.05) survival benefit. The optimal reduction in 18 F-FDG uptake, which separated histopathologic responders and nonresponders, was a 226.4% DSUVmax (receiver-operating-characteristic curve analysis). At this separation, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy (area under the receiver operating characteristic curve) were 62.5%, 71.4%, 62.5%, 71.4%, and 67.4%, respectively, for intratreatment 18 F-FDG PET scans. Kaplan-Meier survival analysis of 18 F-FDG PET responders (.26.4% reduction in SUVmax), compared with 18 F-FDG PET nonresponders (,26.4% reduction in SUVmax), revealed no survival benefit for responders (P 5 0.6812). Conclusion: The %DSUVmax during the second week of induction chemoradiation did not correlate either with histopathologic response or with survival. Our results show that, in contrast to published reports on neoadjuvant chemotherapy, combined chemoradiotherapy in patients with adenocarcinoma of the esophagus lowers the predictive accuracy of early repeated 18 F-FDG PET in identifying histopathologic responders and those with chances for increased survival below clinically applicable levels.
data of cases were collected, characteristics of the carcinomas were described, and available FFP... more data of cases were collected, characteristics of the carcinomas were described, and available FFPE tissue slides were immunostained for β-catenin, P53 and phospho-S6 (a downstream target of mTOR). Furthermore, we performed DNA mutation analyses for BRAF, KRAS, and P53, and LOH analyses for LKB1 and P53. Results: Twenty-eight of the 144 patients (19%, 64% males) from 20 families developed 30 GI malignancies at a median age of 44 years (IQR 35-57) at diagnosis of first cancer (Table). Two patients were diagnosed with two primary GI carcinomas. Three (10%) malignancies were discovered during surveillance; all carcinomas in situ (one colorectal and two gastric lesions). Twenty-three patients (82%) deceased at a median age of 54 years (IQR 36-61); 19 (68%) of whom had died as a direct cause of GI cancer. Of these 23 patients, median survival after GI cancer diagnosis was 6 months (IQR 1-18). Of 16 carcinomas FFPE tissue was available for molecular analysis. Nuclear β-catenin was detected in 3/5 (60%) primary intestinal carcinomas. Overexpression of P53 was observed in 7/16 (44%) carcinomas, and a total absence of P53 was observed in one (6%) sample. All available samples showed heterogeneous expression of pS6, in which epithelial expression was more pronounced compared to the stromal component in 9/14 (64%) cases. Mutation and LOH analyses are currently being performed. Conclusion: Gastrointestinal cancer often affects PJS patients already at a young age. Alterations in Wnt/ β-catenin signaling and in P53 are observed in a subset of PJS carcinomas, while activation of mTOR signaling seems to be altered in the majority of these carcinomas, predominantly in the epithelial compartment. These results suggest that treatment with mTOR inhibitors may be beneficial in the anti-cancer treatment of PJS patients. Location of gastrointestinal carcinomas in Peutz-Jeghers syndrome patients
Series from high volume oesophageal centres highlight an increasing prevalence of early malignant... more Series from high volume oesophageal centres highlight an increasing prevalence of early malignant (EM) lesions. The advent of endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) offer alternatives to traditional surgery. The evolution of this pattern of care in a high volume centre is analysed. Data were collected from a prospectively maintained database. 96 patients were treated with an EM lesion from 2000 to 2011. Surgery was the standard approach during the initial period (2000-2006). In 2007, with the introduction of EMR±RFA to our Centre, a rising trend toward definitive endoscopic treatment was seen. This study details the selection of cases into treatment groups and their outcomes. From 2000 to 2006, 23 patients were treated with EM lesions, 96% by surgery. Seventy-three were treated from 2007 to 2011, 55% surgically and 45% by EMR±RFA. In the entire experience, there was one death from surgery and morbidity was higher in the surgery group compared with EMR±RFA (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). Three surgical patients (4.8%) relapsed with HGD or cancer, and one patient with T1N1 disease died of disease recurrence. At a median of 13 months, EMR±RFA offered 100% disease control, 72% had no endoscopic or histological evidence of Barrett&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s oesophagus and one patient represented with low grade dysplasia. This study highlights the changing pattern of care in the management of early oesophageal cancer. EMR±RFA appears an acceptable alternative to surgery in carefully selected cases. However, long-term outcome analysis using these methods is required and close interdisciplinary collaboration of specialists in gastroenterology, surgery, pathology and radiology is mandatory to achieve optimum outcomes.
The aim was to evaluate the impact of FDG-PET scan on tumour staging and management decisions in ... more The aim was to evaluate the impact of FDG-PET scan on tumour staging and management decisions in oesophageal cancer. One-hundred consecutive patients referred for consideration of surgery underwent a whole body FDG-PET scan in addition to CT imaging. Based on CT scan, a curative approach could be considered in 62 patients. The PET scan altered regional nodal (N) staging in 16 patients overall, but did not alter management decisions. Metastatic status (M) was increased in 14 patients, with altered management in 10/62 (16%). Nine were downstaged, with management changed in 3/38 (8%). Seventeen patients underwent 19 additional tests to clarify findings on PET, in 15 patients (88%) the tests revealed no pathology. FDG-PET alters M stage in 23% of patients and may impact on surgical decision-making. The spurious investigations and cost of the high false-positive rate of further tests is of concern.
To determine the correlation between 18 F-fluorodeoxyglucose positron emission tomographycomputed... more To determine the correlation between 18 F-fluorodeoxyglucose positron emission tomographycomputed tomography (PET-CT) derived esophageal tumor parameters [maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV)] and endoscopic ultrasound (EUS) derived tumor parameters (T stage, N stage) and their prognostic implications. 150 consecutive patients with cancer of the esophagus or esophagogastric junction underwent staging PET-CT and staging EUS. PET-CT derived SUVmax and MTV of the primary tumor was recorded. EUS evaluated T and N stage. Relationships between parameters were investigated using the Mann-Whitney U tests, survival analysis performed using Kaplan-Meier and independent prognostic factors determined using Cox regression multivariate analysis. A significant difference in MTV was noted between EUS T1/T2 tumors (median 6.7 cm 3) and EUS T3/T4 tumors (median 35.7 cm 3 ; P < 0.0001). An MTV of <23.4 cm 3 (P 5 0.0001), SUVmax < 4.1 (P 5 0014), EUS T stage (P < 0.0001), EUS N stage (P < 0.0001), and clinical stage (P < 0.0001) were all significantly associated with survival, with MTV <23.4 cm 3 (P 5 0.004), EUS T stage (P 5 0.01), and EUS N stage (P 5 0.01) significant in multivariate analysis. MTV, a volumetric parameter of PET-CT, has more prognostic importance than SUVmax and provides valuable prognostic information in esophageal and junctional cancer, along with EUS T and N stage. MTV provides complementary information to EUS and should be included in the staging of esophageal and junctional cancer.
Purpose: 18 F-Fluorodeoxyglucose positron emission tomography (18 F-FDG PET) imaging is increasin... more Purpose: 18 F-Fluorodeoxyglucose positron emission tomography (18 F-FDG PET) imaging is increasingly the standard of care in the staging of esophageal cancer. Synchronous neoplasms may be identified, and this study evaluated the prevalence of such tumors and their impact on management. Methods: Five hundred ninety-one (73.6%) of 803 consecutive patients with biopsy-proven esophageal cancer underwent staging 18 F-FDG PET or PET/CT scans. 18 FYFDG-avid lesions were considered synchronous primary neoplasms if occurring at locations atypical for metastases from the known primary, a marked discordance in the 18 F-FDG avidity from that of the primary tumor, and if there was no prior detection on conventional imaging. Additional investigations as appropriate were undertaken, and histopathological verification was obtained where possible to validate the suspected synchronous neoplasm. Results: A synchronous neoplasm was suspected in 55 (9.3%) of 591 patients, predominantly at sites in the colon (26) and head and neck (21). Additional investigations in 43 cases revealed malignant neoplasms in 8 (18.6%), premalignant in 9 (20.9%), and benign lesions in 26 (60.5%) cases. The management plan was altered in 8 patients, 1.4% overall. The total cost of added tests was $27,482.57 (€21,024) with the decision to treat the esophageal cancer deferred by a mean of 10.7 days. Conclusion: 18 F-FDG uptake concerning for synchronous neoplasms is evident in approximately 1 in 10 cases, and of these a minority will represent a malignant neoplasm that significantly impacts on treatment. The overall added costs per patient are relatively modest and the treatment delay within acceptable limits of clinical practice.
This study evaluated the role of 18 F-FDG PET as an early predictor of histopathologic response t... more This study evaluated the role of 18 F-FDG PET as an early predictor of histopathologic response to neoadjuvant chemoradiotherapy and overall survival in patients with adenocarcinoma of the esophagus undergoing multimodal therapy. Methods: Thirty-seven patients with locally advanced adenocarcinoma of the esophagus underwent pretreatment and an intratreatment 18 F-FDG PET scan in the second week of a 6-wk regimen of neoadjuvant chemoradiotherapy. Histopathologic response and overall survival were correlated with percentage change in 18 F-FDG uptake (%Dmaximum standardized uptake value [%DSUVmax]). Results: In 16 patients (43%), treatment induced a histopathologic response (,10% viable tumor cells), which was associated with a significant (P , 0.05) survival benefit. The optimal reduction in 18 F-FDG uptake, which separated histopathologic responders and nonresponders, was a 226.4% DSUVmax (receiver-operating-characteristic curve analysis). At this separation, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy (area under the receiver operating characteristic curve) were 62.5%, 71.4%, 62.5%, 71.4%, and 67.4%, respectively, for intratreatment 18 F-FDG PET scans. Kaplan-Meier survival analysis of 18 F-FDG PET responders (.26.4% reduction in SUVmax), compared with 18 F-FDG PET nonresponders (,26.4% reduction in SUVmax), revealed no survival benefit for responders (P 5 0.6812). Conclusion: The %DSUVmax during the second week of induction chemoradiation did not correlate either with histopathologic response or with survival. Our results show that, in contrast to published reports on neoadjuvant chemotherapy, combined chemoradiotherapy in patients with adenocarcinoma of the esophagus lowers the predictive accuracy of early repeated 18 F-FDG PET in identifying histopathologic responders and those with chances for increased survival below clinically applicable levels.
Positron Emission Tomography (PET) is a functional imaging modality widely used in clinical oncol... more Positron Emission Tomography (PET) is a functional imaging modality widely used in clinical oncology. Over the years the sensitivity and specificity of PET has improved with the advent of specific radiotracers, increased technical accuracy of PET scanners and incremental experience of Radiologists. However, significant limitations exist—most notably false positives and false negatives. Additionally, the accuracy of PET varies between cancer types and in some cancers, is no longer considered a standard imaging modality. This review considers the relative influence of macroscopic tumour features such as size and morphology on 2-Deoxy-2-[18F]fluoroglucose ([18F]FDG) uptake by tumours which, though well described in the literature, lacks a comprehensive assessment of biomolecular features which may influence [18F]FDG uptake. The review aims to discuss the potential influence of individual molecular markers of glucose transport, glycolysis, hypoxia and angiogenesis in addition to the rel...
Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus, Jan 15, 2016
To determine the correlation between (18) F-fluorodeoxyglucose positron emission tomography-compu... more To determine the correlation between (18) F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) derived esophageal tumor parameters [maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV)] and endoscopic ultrasound (EUS) derived tumor parameters (T stage, N stage) and their prognostic implications. 150 consecutive patients with cancer of the esophagus or esophagogastric junction underwent staging PET-CT and staging EUS. PET-CT derived SUVmax and MTV of the primary tumor was recorded. EUS evaluated T and N stage. Relationships between parameters were investigated using the Mann-Whitney U tests, survival analysis performed using Kaplan-Meier and independent prognostic factors determined using Cox regression multivariate analysis. A significant difference in MTV was noted between EUS T1/T2 tumors (median 6.7 cm(3) ) and EUS T3/T4 tumors (median 35.7 cm(3) ; P < 0.0001). An MTV of <23.4 cm(3) (P = 0.0001), SUVmax < 4.1 (P = 0014), EUS ...
The aim of this study is to assess CT-PET and endoscopic assessment postneoadjuvant chemoradiothe... more The aim of this study is to assess CT-PET and endoscopic assessment postneoadjuvant chemoradiotherapy (nCRT) in predicting complete pathologic response (pCR) in locally advanced esophageal cancer (LAEC). A prospective cohort study. nCRT is increasingly standard of care in LAEC, with pCR a surrogate for excellent outcome. Predicting pCR before surgery, with metabolic imaging and endoscopy, may spare patients' operative intervention. One hundred thirty-eight consecutive patients [mean age 61 ± 8, 99 male (72%), 103 (75%) adenocarcinoma] underwent nCRT with CT-PET and endoscopy 4 to 6 weeks later, and surgery subsequently. A complete metabolic response (cMR) was defined as SUVmax of <4. A complete endoscopic response (cER) was no residual mucosal abnormality. The association of pCR with cMR and cER was analyzed. pCR was achieved in 30 patients (22%); 37% SCC and 17% adenocarcinoma. A cMR was evident in 63 (46%), of whom 17 (27%) had a pCR and 17(27%) were ypN+. A cER was observe...
Journal of Plastic Reconstructive Aesthetic Surgery, Jan 12, 2010
Background: Basal cell carcinomas are the most prevalent of all skin cancers worldwide and form t... more Background: Basal cell carcinomas are the most prevalent of all skin cancers worldwide and form the majority of the surgical workload for most modern cutaneous malignancy centres. Primary surgical removal of basal cell carcinomas remains the gold standard of treatment but, despite almost two centuries of surgical experience, rates of incomplete surgical excision of up to 50% are still reported.
Positron emission tomography and computed tomography (PET-CT) is established in the staging of es... more Positron emission tomography and computed tomography (PET-CT) is established in the staging of esophageal cancer. In this study, an MRI protocol was designed to emulate the anatomical (T1-weighed (T1W) and T2W imaging) and functional information (diffusion-weighted imaging) provided by PET-CT. In all, 49 patients with carcinoma of the esophagus underwent PET-CT and whole-body MRI (WBMRI). WBMRI was carried out using dedicated sequences tailored to detect metastatic disease at each area corresponding to the anatomical coverage of PET-CT. Nodal status was determined from histopathology and endoscopic ultrasound biopsy (EUS). PET-CT and WBMRI identified the primary tumor in 46/49 (94%) and 48/49 (98%) patients, respectively. Nodal analysis in patients undergoing surgery (n = 18) yielded sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 27, 100, 100, 47 and 56% for PET-CT, compared with 30, 100, 100, 53 and 61% for WBMRI. When nodal analysis included both surgical specimens and EUS criteria (n = 39), sensitivity, specificity, PPV, NPV and accuracy were 46, 91, 93, 40 and 59% for PET-CT compared with 59, 92, 94, 50 and 67% for WBMRI. Both imaging modalities identified distant metastases in 2 patients. WBMRI has similar accuracy to PET-CT in detecting the primary tumor, nodal deposits and for exclusion of systemic metastatic disease.
To determine whether [(18)F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) could pred... more To determine whether [(18)F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) could predict the pathological response in oesophageal cancer after only the first week of neoadjuvant chemoradiation. Thirty-two patients with localised oesophageal cancer had a pretreatment PET scan and a repeat after the first week of chemoradiation. The change in mean maximum standardised uptake value (SUV) and volume of metabolically active tissue (MTV) was compared with the tumour regression grade (TRG) in the final histology. Those who achieved a TRG of 1 and 2 were deemed responders and 3-5 nonresponders. In the responders (28%), the SUV fell from 12.6 (+/-6.3) to 8.1 (+/-2.9) after 1 week of chemoradiation (P=0.070). In nonresponders (72%), the results were 9.7 (+/-5.4) and 7.1 (+/-3.8), respectively (P=0.003). The MTV in responders fell from 36.6 (+/-22.7) to 22.3 (+/-10.4) cm(3) (P=0.180), while in nonresponders, this fell from 35.9 (+/-36.7) to 31.9 (+/-52.7) cm(3) (P=0.405). There wer...
Uploads
Papers by Vinod Malik