Follicular Lymphoma mimicking Metastatic Nodes on the F-18 FDG PET/CT and MRI for Staging of Endometrial Cancer

Abstract

A 53-year-old woman was diagnosed with endometrial carcinoma by vaginal bleeding. F-18 fluorodeoxy glucose positron emission tomography PET/CT (F-18 FDG PET/CT) scan for staging showed intense focal FDG uptake in the endometrium suggesting endometrial malignancy. PET/CT showed multiple node uptakes in the pericaval region, paraaortic region, common iliac, and both internal iliac and external iliac regions suggesting multiple pelvic and retroperitoneal node metastases. MRI showed multiple metastatic lymphadenopathy in the retroperitoneum and pelvic cavity. Pathologic diagnosis performed with dissected pelvic and paraaortic nodes was confirmed as a follicular malignant lymphoma positive for B–cell lymphoma-2(Bcl-2) stain, not the metastatic node of primary endometrioid carcinoma.

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Erratum to: Cutaneous Complications of Targeted Melanoma Therapy

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Follicular Lymphoma mimicking Metastatic Nodes on the F-18 FDG PET/CT and MRI for Staging of Endometrial Cancer

Abstract

A 53-year-old woman was diagnosed with endometrial carcinoma by vaginal bleeding. F-18 fluorodeoxy glucose positron emission tomography PET/CT (F-18 FDG PET/CT) scan for staging showed intense focal FDG uptake in the endometrium suggesting endometrial malignancy. PET/CT showed multiple node uptakes in the pericaval region, paraaortic region, common iliac, and both internal iliac and external iliac regions suggesting multiple pelvic and retroperitoneal node metastases. MRI showed multiple metastatic lymphadenopathy in the retroperitoneum and pelvic cavity. Pathologic diagnosis performed with dissected pelvic and paraaortic nodes was confirmed as a follicular malignant lymphoma positive for B–cell lymphoma-2(Bcl-2) stain, not the metastatic node of primary endometrioid carcinoma.

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Erratum to: Cutaneous Complications of Targeted Melanoma Therapy

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Predictive factors of overall and major postoperative complications after partial nephrectomy: results from a multicenter prospective study (The RECORd 1 project)

Publication date: Available online 5 November 2016
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Andrea Mari, Alessandro Antonelli, Riccardo Bertolo, Giampaolo Bianchi, Marco Borghesi, Vincenzo Ficarra, Cristian Fiori, Maria Furlan, Saverio Giancane, Nicola Longo, Vincenzo Mirone, Giuseppe Morgia, Francesco Porpiglia, Bruno Rovereto, Riccardo Schiavina, Sergio Serni, Claudio Simeone, Alessandro Volpe, Marco Carini, Andrea Minervini




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Impact of diagnosis-to-treatment waiting time on survival in esophageal cancer patients - a population-based study in The Netherlands

Publication date: Available online 5 November 2016
Source:European Journal of Surgical Oncology (EJSO)
Author(s): E. Visser, P.S.N. van Rossum, A.G. Leeftink, S. Siesling, R. van Hillegersberg, J.P. Ruurda
BackgroundThe aim of this study was to determine whether the waiting time from diagnosis to treatment with curative intent for esophageal cancer impacts oncologic outcomes.Patients and methodsAll patients treated by esophagectomy for esophageal carcinoma in 2005-2013 were identified from the Netherlands Cancer Registry. Patients who underwent multimodality treatment and patients treated with surgery only were analyzed separately. Multivariable logistic regression analyses were performed to evaluate the impact of diagnosis-to-treatment waiting time on pT-status, pN-status, and R0 resection rates. Cox regression was applied to estimate the influence of waiting time on overall survival. Analyses were performed with the original scale and in three categorized groups of waiting time (≤5 weeks, 5-8 weeks, and >8 weeks) based on guidelines and previous studies.ResultsOf 3,839 patients, 2,589 underwent multimodality treatment and 1,250 were treated with surgery only. In both groups, pT-status, pN-status, and R0 resection rates were not significantly influenced by waiting time (p-values >0.05). Also, waiting time was not significantly associated with overall survival in the multimodality treatment group (5-8 weeks vs. ≤5 weeks, hazard ratio [HR] 1.12, p=0.171; and >8 weeks vs. ≤5 weeks, HR 1.21, p=0.167), nor in the surgery only group (5-8 weeks vs. ≤5 weeks, HR 0.92, p=0.432; and >8 weeks vs. ≤5 weeks, HR 1.00, p=0. 973).ConclusionThis large population-based cohort study demonstrates that longer waiting time from diagnosis to treatment in patients treated for esophageal cancer with curative intent does not negatively impact pT-status, pN-status, R0 resection rates, and overall survival.



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Complication-related removal of totally implantable venous access port systems: Does the interval between placement and first use and the neutropenia-inducing potential of chemotherapy regimens influence their incidence? A four-year prospective study of 4,045 patients

Publication date: Available online 5 November 2016
Source:European Journal of Surgical Oncology (EJSO)
Author(s): A. Kakkos, L. Bresson, D. Hudry, S. Cousin, C. Lervat, E. Bogart, J.P. Meurant, S. El Bédoui, G. Decanter, K. Hannebicque, C. Regis, A. Hamdani, N. Penel, E. Tresch- Bruneel, F. Narducci
BackgroundTotally implantable venous access port systems are widely used in oncology, with frequent complications that sometimes necessitate device removal. The aim of this study is to investigate the impact of the time interval between port placement and initiation of chemotherapy and the neutropenia-inducing potential of the chemotherapy administered upon complication-related port removal.Patients and MethodsBetween January 2010 and December 2013, 4,045 consecutive patients were included in this observational, single-center prospective study. The chemotherapy regimens were classified as having a low (<10%), intermediate (10-20%), or high (>20%) risk for inducing neutropenia.ResultsThe overall removal rate due to complications was 7.2%. Among them, port-related infection (2.5%) and port expulsion (1%) were the most frequent. The interval between port insertion and its first use was shown to be a predictive factor for complication-related removal rates. A cut-off of 6 days was statistically significant (p = 0.008), as the removal rate for complications was 9.4% when this interval was 0 to 5 days and 5.7% when it was ≥ 6 days. Another factor associated with port complication rate was the neutropenia-inducing potential of the chemotherapy regimens used, with removal for complications involved in 5.5% of low-risk regimens versus 9.4% for the intermediate- and high-risk regimens (p = 0.003).ConclusionAn interval of 6 days between placement and first use of the port reduces the removal rate from complications. The intermediate- and high-risk for neutropenia chemotherapy regimens are related to higher port removal rates from complications than low-risk regimens.



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Letter to the editor – Reply to “Current controversies on sentinel node biopsy in thin and thick cutaneous melanoma”

Publication date: Available online 5 November 2016
Source:European Journal of Surgical Oncology (EJSO)
Author(s): M. Madu, M.W.J.M. Wouters, A.C.J. van Akkooi




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Preoperative Glasgow Prognostic Score as additional independent prognostic parameter for patients with esophageal cancer after curative esophagectomy

Publication date: Available online 5 November 2016
Source:European Journal of Surgical Oncology (EJSO)
Author(s): J. Lindenmann, N. Fink-Neuboeck, A. Avian, M. Pichler, M. Habitzruther, A. Maier, F.M. Smolle-Juettner
BackgroundInflammation accelerates tumor growth followed by reduced survival in patients with cancer. The aim of this study was to evaluate the prognostic relevance of preoperatively increased levels of C-reactive protein (CRP) and the corresponding Glasgow Prognostic Score (GPS) on patients with esophageal carcinoma undergoing curative esophagectomy.MethodsThe data of 174 operated esophageal cancer patients were evaluated retrospectively. Patient´s demographic and clinico-pathological data, tumor specific data, preoperative plasma levels of CRP and albumin, the corresponding GPS, overall survival (OS) and progression free survival (PFS) were assessed.Results103 (59.2%) had adenocarcinoma and 71 (40.8%) had squamous cell carcinoma. 71 patients (43%) had elevated CRP concentrations. 118 patients (71%) had GPS 0, 41 (25%) GPS 1 and 8 (4%) GPS 2. Mean GPS was 0.3 (0-2). 5-year OS was higher in patients with normal CRP than in those with increased CRP (68% vs. 39%; p=0.007). 5-year OS in patients with GPS 0 and GPS 1 and 2 were 65% and 31% (p=0.001). 5-year OS for the whole cohort was 56% (1 year: 83%, 3 years: 64%). Recurrence rate was 16.1% closely associated with GPS (p=0.002). Median follow-up was 23 months (0-118 months). In multivariate analysis GPS, lymph node involvement, T stage and tumor histology were the independent prognostic parameters (p=0.004, <0.001, 0.035, 0.010).ConclusionsPreoperatively increased GPS is significantly associated with reduced postoperative survival and tumor recurrence. The GPS as an independent prognosticator should be interpreted together with the TNM stage when the further postoperative treatment has to be scheduled.



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Benign phyllodes tumours of the breast: (Over) Treatment of margins – a literature review

Publication date: Available online 5 November 2016
Source:European Journal of Surgical Oncology (EJSO)
Author(s): M. Shaaban, L. Barthelmes
BackgroundPhyllodes tumours form a small group of fibroepithelial breast lesions (2-3 %). They are classified as benign, borderline, or malignant. (1). Benign phyllodes tumours are the largest subgroup of phyllodes tumours (50 - 80%), (2) A margin of 1 cm has been suggested as standard of care for all groups of phyllodes tumours (3) (4) (5) (6).MethodsWe performed a literature review from January 2009 to April 2016 including the non-English literature. We compared studies taking a 1 mm margin, 10 mm margin and studies with focal margin involvement.ResultsWe included 12 studies with overall 1702 patients. The range of therapeutic margins differed widely between studies. There is no consensus between studies what constitutes a clear or involved margin. There was a high percentage of margin involvement for benign phyllodes tumours (7.6 – 43.7 %). Despite these inconsistencies, the recurrence rate after excision of benign phyllodes tumours was low in most studies (112 recurrences of 1052 benign phyllodes tumours - 11 %; range 0 – 43 %). There is no difference of the recurrence rate between studies aiming for a 10 mm margin (7.9%) compared to a 1 mm margin (5.7%) (p 0.124). The recurrence rate increases when there are tumour cells at the margin (12.9 %) (p 0.006)ConclusionThere is no difference in recurrence rates between a 1 and a 10 mm margin. 1 mm is an acceptable margin for benign phyllodes tumours. The recurrence rate increases if there is focal margin involvement.



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Developments in targeted therapy in melanoma

Publication date: Available online 5 November 2016
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Valerie C. Amann, Egle Ramelyte, Selina Thurneysen, Rossella Pitocco, Nicoletta Bentele-Jaberg, Simone M. Goldinger, Reinhard Dummer, Joanna Mangana
Melanomas are disease entities driven in part by the mitogen activated protein kinase (MAPK) pathway. The TCGA network recently defined four genetic subtypes based on the most prevalent significantly mutated genes, including mutant BRAF, mutant RAS (N/H/K), mutant NF1, and Triple wild-type melanoma (harboring none of the aforementioned mutations, but instead includes KIT, GNA and GNAQ mutations).The successful development of kinase inhibitors marked a milestone in the treatment of metastatic melanoma. Combination treatment with a BRAF- and MEK-inhibitor is the current standard of care for inoperable stage IIIC/IV BRAF-mutated melanoma. Recent data demonstrate excellent long-term outcome, especially in patients with normal baseline LDH levels, and confirm that there is a subset of BRAF inhibitor-naive patients who experience durable responses without progression on combination treatment. In the future, adding a third compound based on individual genetic alterations might further improve the outcome of targeted therapy.



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Recurrent Merkel cell carcinoma of the testis with unknown primary site: a case report

Merkel cell carcinoma is a rare and aggressive neuroendocrine tumor that commonly arises in the skin. It is rare for it to occur in the testes. There are only seven cases of testicular Merkel cell carcinoma re...

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The prognostic implication of the expression of EGFR, p53, cyclin D1, Bcl-2 and p16 in primary locally advanced oral squamous cell carcinoma cases: a tissue microarray study

Abstract

Oral squamous cell carcinomas comprise a heterogeneous tumor cell population with varied molecular characteristics, which makes prognostication of these tumors a complex and challenging issue. Thus, molecular profiling of these tumors is advantageous for an accurate prognostication and treatment planning. This is a retrospective study on a cohort of primary locally advanced oral squamous cell carcinomas (n = 178) of an Indian rural population. The expression of EGFR, p53, cyclin D1, Bcl-2 and p16 in a cohort of primary locally advanced oral squamous cell carcinomas was evaluated. A potential biomarker that can predict the tumor response to treatment was identified. Formalin-fixed paraffin-embedded tumor blocks of (n = 178) of histopathologically diagnosed cases of locally advanced oral squamous cell carcinomas were selected. Tissue microarray blocks were constructed with 2 cores of 2 mm diameter from each tumor block. Four-micron-thick sections were cut from these tissue microarray blocks. These tissue microarray sections were immunohistochemically stained for EGFR, p53, Bcl-2, cyclin D1 and p16. In this cohort, EGFR was the most frequently expressed 150/178 (84%) biomarker of the cases. Kaplan–Meier analysis showed a significant association (p = 0.038) between expression of p53 and a poor prognosis. A Poisson regression analysis showed that tumors that expressed p53 had a two times greater chance of recurrence (unadjusted IRR—95% CI 2.08 (1.03, 4.5), adjusted IRR—2.29 (1.08, 4.8) compared with the tumors that did not express this biomarker. Molecular profiling of oral squamous cell carcinomas will enable us to categorize our patients into more realistic risk groups. With biologically guided tumor characterization, personalized treatment protocols can be designed for individual patients, which will improve the quality of life of these patients.

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The prognostic implication of the expression of EGFR, p53, cyclin D1, Bcl-2 and p16 in primary locally advanced oral squamous cell carcinoma cases: a tissue microarray study

Abstract

Oral squamous cell carcinomas comprise a heterogeneous tumor cell population with varied molecular characteristics, which makes prognostication of these tumors a complex and challenging issue. Thus, molecular profiling of these tumors is advantageous for an accurate prognostication and treatment planning. This is a retrospective study on a cohort of primary locally advanced oral squamous cell carcinomas (n = 178) of an Indian rural population. The expression of EGFR, p53, cyclin D1, Bcl-2 and p16 in a cohort of primary locally advanced oral squamous cell carcinomas was evaluated. A potential biomarker that can predict the tumor response to treatment was identified. Formalin-fixed paraffin-embedded tumor blocks of (n = 178) of histopathologically diagnosed cases of locally advanced oral squamous cell carcinomas were selected. Tissue microarray blocks were constructed with 2 cores of 2 mm diameter from each tumor block. Four-micron-thick sections were cut from these tissue microarray blocks. These tissue microarray sections were immunohistochemically stained for EGFR, p53, Bcl-2, cyclin D1 and p16. In this cohort, EGFR was the most frequently expressed 150/178 (84%) biomarker of the cases. Kaplan–Meier analysis showed a significant association (p = 0.038) between expression of p53 and a poor prognosis. A Poisson regression analysis showed that tumors that expressed p53 had a two times greater chance of recurrence (unadjusted IRR—95% CI 2.08 (1.03, 4.5), adjusted IRR—2.29 (1.08, 4.8) compared with the tumors that did not express this biomarker. Molecular profiling of oral squamous cell carcinomas will enable us to categorize our patients into more realistic risk groups. With biologically guided tumor characterization, personalized treatment protocols can be designed for individual patients, which will improve the quality of life of these patients.

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Possible association between successful intubation via the right nostril and anatomical variations of the nasopharynx during nasotracheal intubation: a multiplanar imaging study

Abstract

Purpose

Most reported cases of nasopharyngeal laceration following impingement during nasotracheal intubation involved tube insertion via the right nostril. We postulated that recesses on the posterior wall of the nasopharynx might be associated with tube impingement. Using multiplanar imaging and clinical statistics, we evaluated whether anatomical variations in the recesses are related to successful intubation via the right nostril.

Methods

Using multiplanar computed tomography (CT) images of 97 patients, we investigated the locations of recesses relative to the mid-sagittal plane, nasal floor plane and posterior end of the nasal septum, and their shapes. Incidents of impingement of the tube during nasotracheal intubation and the shapes of the fossa of Rosenmüller on CT images were retrospectively evaluated in 170 patients.

Results

Eustachian tube orifices were located approximately 10 mm laterally from the sagittal plane, and approximately 10 mm above the nasal floor plane. The fossa of Rosenmüller was vertically elongated and located 7 mm laterally from the mid-sagittal plane. Pharyngeal bursae were found in 15 % of the subjects. Patients with failed insertion via the right nostril due to impingement frequently had a wide opening of the fossa of Rosenmüller.

Conclusions

Successful intubation via the right nostril is related to the anatomy of structures on the posterior nasopharyngeal wall, particularly recesses located close to the path of nasotracheal tube insertion. Nasopharyngeal anatomical variations should be considered when one notices any resistance to advancement of the tube into the nasopharynx during nasotracheal intubation.

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In reply: Rethinking general anesthesia for cesarean section

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Erratum to: Bridging the etiologic and prognostic outlooks in individualized assessment of absolute risk of an illness: application in lung cancer

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Nonsteroidal anti-inflammatory drugs, statins, and pancreatic cancer risk: a population-based case–control study

Abstract

Purpose

Studies suggest that aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), and statins may reduce risk of some cancers. However, findings have been conflicting as to whether these agents reduce the risk of pancreatic cancer.

Methods

We used data from the Queensland Pancreatic Cancer Study, a population-based case–control study. In total, 704 cases and 711 age- and sex-matched controls were recruited. Participants completed an interview in which they were asked about history of NSAID and statin use. We included 522 cases and 653 controls who had completed the medication section of the interview in this analysis. Unconditional multivariable logistic regression was used to estimate associations between medication use and pancreatic cancer.

Results

We found no consistent evidence of an association between use of NSAIDs or statins and risk of pancreatic cancer. There was some suggestion of a protective effect in infrequent users of selective COX-2 inhibitors, but no association in more frequent users. We did not find evidence of protective effects in analyses stratified by sex, smoking status, time between diagnosis and interview, or presence/absence of metastases.

Conclusions

Overall, our results do support the hypothesis that use of NSAIDs or statins may reduce the odds of developing pancreatic cancer.

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Nonsteroidal anti-inflammatory drugs, statins, and pancreatic cancer risk: a population-based case–control study

Abstract

Purpose

Studies suggest that aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), and statins may reduce risk of some cancers. However, findings have been conflicting as to whether these agents reduce the risk of pancreatic cancer.

Methods

We used data from the Queensland Pancreatic Cancer Study, a population-based case–control study. In total, 704 cases and 711 age- and sex-matched controls were recruited. Participants completed an interview in which they were asked about history of NSAID and statin use. We included 522 cases and 653 controls who had completed the medication section of the interview in this analysis. Unconditional multivariable logistic regression was used to estimate associations between medication use and pancreatic cancer.

Results

We found no consistent evidence of an association between use of NSAIDs or statins and risk of pancreatic cancer. There was some suggestion of a protective effect in infrequent users of selective COX-2 inhibitors, but no association in more frequent users. We did not find evidence of protective effects in analyses stratified by sex, smoking status, time between diagnosis and interview, or presence/absence of metastases.

Conclusions

Overall, our results do support the hypothesis that use of NSAIDs or statins may reduce the odds of developing pancreatic cancer.

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Erratum to: Bridging the etiologic and prognostic outlooks in individualized assessment of absolute risk of an illness: application in lung cancer

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Retraction note to: Prevalence of the C282Y and H63D mutations of the HFE hemochromatosis gene in Azerian major β-thalassemia and iron overload

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Erratum to: Bridging the etiologic and prognostic outlooks in individualized assessment of absolute risk of an illness: application in lung cancer

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Combined antitumor effect of γ-secretase inhibitor and ABT-737 in Notch-expressing non-small cell lung cancer

Abstract

Background

Inhibition of Notch by γ-secretase inhibitor (GSI) has been shown to have an antitumor effect in Notch-expressing non-small cell lung cancer (NSCLC) and to induce apoptosis through modulation of Bcl-2 family proteins. In particular, Bim, a BH3-only member of the Bcl-2 family of proteins, has an important role in the induction of apoptosis in NSCLC when cells are treated with GSI. ABT-737, a BH3-only mimetic, targets the pro-survival Bcl-2 family and also induces apoptosis.

Methods

The Notch-expressing NSCLC cell lines H460, A549, H1793, and HCC2429 were used. The combined antitumor effect of GSI and ABT-737 was evaluated using the MTT proliferation assay in vitro and in xenograft mouse models. The expression of the Notch pathway and Bcl-2 family was analyzed using Western blotting analysis when cells were treated with a single drug treatment or a combination treatment.

Results

GSI XX or ABT-737 alone inhibited cell proliferation in a dose-dependent manner, and combination drug treatment showed a synergistic antitumor effect in vitro. In vivo, this drug combination significantly suppressed tumor proliferation compared to the single drug treatment. Phospho-Bcl-2 was downregulated and Bax was upregulated by both the single and combination drug treatments. Bim was induced by a single drug treatment and was enhanced by combination treatment. Combination treatment-induced apoptosis was decreased by Bim inhibition, suggesting that the antitumor effect of the drug combination was dependent on Bim.

Conclusion

Based on our data, we propose that the combination treatment is a promising strategy for NSCLC therapy.

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Combined antitumor effect of γ-secretase inhibitor and ABT-737 in Notch-expressing non-small cell lung cancer

Abstract

Background

Inhibition of Notch by γ-secretase inhibitor (GSI) has been shown to have an antitumor effect in Notch-expressing non-small cell lung cancer (NSCLC) and to induce apoptosis through modulation of Bcl-2 family proteins. In particular, Bim, a BH3-only member of the Bcl-2 family of proteins, has an important role in the induction of apoptosis in NSCLC when cells are treated with GSI. ABT-737, a BH3-only mimetic, targets the pro-survival Bcl-2 family and also induces apoptosis.

Methods

The Notch-expressing NSCLC cell lines H460, A549, H1793, and HCC2429 were used. The combined antitumor effect of GSI and ABT-737 was evaluated using the MTT proliferation assay in vitro and in xenograft mouse models. The expression of the Notch pathway and Bcl-2 family was analyzed using Western blotting analysis when cells were treated with a single drug treatment or a combination treatment.

Results

GSI XX or ABT-737 alone inhibited cell proliferation in a dose-dependent manner, and combination drug treatment showed a synergistic antitumor effect in vitro. In vivo, this drug combination significantly suppressed tumor proliferation compared to the single drug treatment. Phospho-Bcl-2 was downregulated and Bax was upregulated by both the single and combination drug treatments. Bim was induced by a single drug treatment and was enhanced by combination treatment. Combination treatment-induced apoptosis was decreased by Bim inhibition, suggesting that the antitumor effect of the drug combination was dependent on Bim.

Conclusion

Based on our data, we propose that the combination treatment is a promising strategy for NSCLC therapy.

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The Use of 18F–FDG PET-CT Imaging to Determine Internal Mammary Lymph Node Location for Radiation Therapy Treatment Planning in Breast Cancer Patients

Publication date: Available online 5 November 2016
Source:Practical Radiation Oncology
Author(s): Tima Davidson, Merav Ben-David, Shira Galper, Tess Haskin, Megan Howes, Roland Scaife, Nayroz Kanana, Uri Amit, Noam Weizman, Boris Chikman, Elinor Goshen, Simona Ben-Haim, Zvi Symon, Jeffrey Goldstein
IntroductionAdjuvant Internal mammary lymph node (IMN) radiation is often delivered using 2D techniques that use anatomical landmarks and predetermined depths for field placement and dose specification. In contrast, 3D planning uses the internal mammary vessels (IMV) to localize the IMN for planning. We evaluated if localization of involved-IMN (i-IMN) by ¹⁸F–FDG PET-CT offers opportunities to improve treatment.MethodsBreast cancer patients (n=80) who had i-IMN (n=112) on PET-CT for initial staging (n=40) or recurrence (n=40) were studied. Size, intercostal space (IC), distance from skin, sternum and IMV were recorded. Effects on 2D and 3D planning were evaluated.ResultsMost i-IMN were in the1st-3rd (94.6%) IC. Few were in the 4th (4.5%) or 5th (0.9%) IC. Mean i-IMN depth was 3.4cm (range: 1.1cm–7.3cm). Prescriptive depths of 4cm, 5cm and 6cm would result in under-treatment of 25%, 10.7%, and 5.3% of IMN respectively. Most IMN (86.6%) were lateral or adjacent to the sternal edge. Only13.4% were posterior to the sternum. Use of the ipsilateral or contralateral sternal edge for field placement increases risk of geographic miss or excess normal tissue exposure. Most i-IMN were adjacent to (83%), or ≤0.5cm (14%) from the IMV edge. Three (3%) were >0.5cm beyond the IMV edge. The clinical target volume (CTV) defined by the 1st – 3rd IC encompassed 78% of i-IMN. IMN-CTV coverage of i-IMN increased with inclusion of the 4th IC (82%), 0.5cm medial and lateral margin expansion (93%) or both (96.5%).Conclusion2D treatment techniques risk geographic miss of IMN and exposure of excess normal tissue to radiation. An IMN-CTV defined by the IMV from the 1st-3rd IC with 0.5cm medial and lateral margin expansion encompasses almost all i-IMN identified on PET-CT imaging. Inclusion of the 4th IC offers modest coverage improvement and its inclusion should be weighed against potential increase in cardiac exposure.SummaryThe use of 2D treatment techniques for adjuvant IMN radiation may cause geographic miss of tumor and expose normal tissue to radiation injury. Conformal 3D planning improves coverage and reduces risk of normal tissue damage by using the IMV to define an IMN-CTV. Contouring the IMN-CTV from the 1st -3rd IC space with a 0.5cm expansion medially and laterally encompasses most IMN. PET-CT may have a role in radiation planning by identifying involved-IMN for dose escalation.



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The Use of 18F–FDG PET-CT Imaging to Determine Internal Mammary Lymph Node Location for Radiation Therapy Treatment Planning in Breast Cancer Patients

Publication date: Available online 5 November 2016
Source:Practical Radiation Oncology
Author(s): Tima Davidson, Merav Ben-David, Shira Galper, Tess Haskin, Megan Howes, Roland Scaife, Nayroz Kanana, Uri Amit, Noam Weizman, Boris Chikman, Elinor Goshen, Simona Ben-Haim, Zvi Symon, Jeffrey Goldstein
IntroductionAdjuvant Internal mammary lymph node (IMN) radiation is often delivered using 2D techniques that use anatomical landmarks and predetermined depths for field placement and dose specification. In contrast, 3D planning uses the internal mammary vessels (IMV) to localize the IMN for planning. We evaluated if localization of involved-IMN (i-IMN) by ¹⁸F–FDG PET-CT offers opportunities to improve treatment.MethodsBreast cancer patients (n=80) who had i-IMN (n=112) on PET-CT for initial staging (n=40) or recurrence (n=40) were studied. Size, intercostal space (IC), distance from skin, sternum and IMV were recorded. Effects on 2D and 3D planning were evaluated.ResultsMost i-IMN were in the1st-3rd (94.6%) IC. Few were in the 4th (4.5%) or 5th (0.9%) IC. Mean i-IMN depth was 3.4cm (range: 1.1cm–7.3cm). Prescriptive depths of 4cm, 5cm and 6cm would result in under-treatment of 25%, 10.7%, and 5.3% of IMN respectively. Most IMN (86.6%) were lateral or adjacent to the sternal edge. Only13.4% were posterior to the sternum. Use of the ipsilateral or contralateral sternal edge for field placement increases risk of geographic miss or excess normal tissue exposure. Most i-IMN were adjacent to (83%), or ≤0.5cm (14%) from the IMV edge. Three (3%) were >0.5cm beyond the IMV edge. The clinical target volume (CTV) defined by the 1st – 3rd IC encompassed 78% of i-IMN. IMN-CTV coverage of i-IMN increased with inclusion of the 4th IC (82%), 0.5cm medial and lateral margin expansion (93%) or both (96.5%).Conclusion2D treatment techniques risk geographic miss of IMN and exposure of excess normal tissue to radiation. An IMN-CTV defined by the IMV from the 1st-3rd IC with 0.5cm medial and lateral margin expansion encompasses almost all i-IMN identified on PET-CT imaging. Inclusion of the 4th IC offers modest coverage improvement and its inclusion should be weighed against potential increase in cardiac exposure.SummaryThe use of 2D treatment techniques for adjuvant IMN radiation may cause geographic miss of tumor and expose normal tissue to radiation injury. Conformal 3D planning improves coverage and reduces risk of normal tissue damage by using the IMV to define an IMN-CTV. Contouring the IMN-CTV from the 1st -3rd IC space with a 0.5cm expansion medially and laterally encompasses most IMN. PET-CT may have a role in radiation planning by identifying involved-IMN for dose escalation.



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Presence of encircling granulosa cells protects against oxidative stress-induced apoptosis in rat eggs cultured in vitro

Abstract

Increased oxidative stress (OS) due to in vitro culture conditions can affect the quality of denuded eggs during various assisted reproductive technologies (ARTs). Presence of intact granulosa cells may protect eggs from OS damage under in vitro culture conditions. The present study was aimed to investigate whether encircling granulosa cells could protect against hydrogen peroxide (H₂O₂)-induced egg apoptosis in ovulated cumulus oocyte complexes (COCs) cultured in vitro. The OS was induced by exposing COCs as well as denuded eggs with various concentrations of H₂O₂ for 3 h in vitro. The morphological changes, total reactive oxygen species (ROS) as well as catalase expression, Bax/Bcl-2, cytochrome c levels and DNA fragmentation were analysed in COCs as well as denuded eggs. Our results suggest that H₂O₂ treatment induced morphological apoptotic features in a concentration-dependent manner in denuded eggs cultured in vitro. The 20 µM of H₂O₂ treatment induced OS by elevating total ROS level, reduced catalase and Bcl-2 expression levels with overexpression of Bax and cytochrome c and induced DNA fragmentation in denuded eggs cultured in vitro. The presence of encircling granulosa cells protected H₂O₂-induced morphological apoptotic features by preventing the increase of Bax, cytochrome c expression levels and DNA fragmentation in associated egg. However, 20 µM of H₂O₂ was sufficient to induce peripheral granulosa cell apoptosis in COCs and degeneration in few denuded eggs cultured in vitro. Taken together our data suggest that the presence of encircling granulosa cells could be beneficial to protect ovulated eggs from OS damage under in vitro culture conditions during various ART programs.

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