Tailored radiation dose according to margin width for patients with ductal carcinoma in situ after breast-conserving surgery.

A 2 mm resection margin is considered adequate for ductal carcinoma in situ (DCIS). We assessed the effectiveness of a tailored radiation dose for margins < 2 mm and the appropriate margin width for high-risk DCIS. We retrospectively evaluated 137 patients who received adjuvant radiotherapy after breast-conserving surgery for DCIS between 2013 and 2019. The patients were divided into three- positive, close (< 2 mm), and negative (≥ 2 mm) margin groups. Radiation dose to the tumor bed in equivalent dose in 2 Gy fractions were a median of 66.25 Gy, 61.81 Gy, and 59.75 Gy for positive, close, and negative margin groups, respectively. During a median follow-up of 58 months, the crude rates of local recurrence were 15.0%, 6.7%, and 4.6% in the positive, close, and negative margin groups, respectively. The positive margin group had a significantly lower 5-year local recurrence-free survival (LRFS) rate compared to the close and negative margin groups in propensity-weighted log-rank analysis (84.82%, 93.27%, and 93.20%, respectively; p = 0.008). The difference in 5-year LRFS between patients with the high- and non-high-grade tumors decreased as the margin width increased (80.4% vs. 100.0% for margin ≥ 2 mm, p < 0.001; 92.3% vs. 100.0% for margin ≥ 6 mm, p = 0.123). With the radiation dose tailored for margin widths, positive margins were associated with poorer local control than negative margins, whereas close margins were not. Widely clear margins (≥ 2 mm) were related to favorable local control for high-grade DCIS.

Dosimetric comparison between RapidArc and HyperArc in hippocampal-sparing whole-brain radiotherapy with a simultaneous integrated boost.

The HyperArc technique is known for generating high-quality radiosurgical treatment plans for intracranial lesions or hippocampal-sparing whole-brain radiotherapy (WBRT). However, there is no reported feasibility of using the HyperArc technique in hippocampal-sparing WBRT with a simultaneous integrated boost (SIB). This study aimed to compare dosimetric parameters of 2 commercially-available volumetric-modulated arc radiotherapy techniques, HyperArc and RapidArc, when using hippocampal-sparing WBRT with a SIB to treat brain metastases. Treatment plans using HyperArc and RapidArc techniques were generated retrospectively for 19 previously treated patients (1 to 3 brain metastases). The planning target volumes for the whole brain (excluding the hippocampal avoidance region; PTVWB) and metastases (PTVmet) were prescribed 25 and 45 Gy, respectively, in 10 fractions. Each plan included homogeneous and inhomogeneous delivery to the PTVmet. Dosimetric parameters for the target (conformity index [CI], homogeneity index [HI], target coverage [D95%]), and nontarget organs at risk were compared for the HyperArc and RapidArc plans. For homogeneous delivery, dosimetric parameters, including mean CI, HI, and target coverage in PTVWB and PTVmet, were superior for HyperArc than RapidArc plans (all p < 0.01). The PTVWB and PTVmet target coverage for HyperArc plans was significantly greater than for RapidArc plans (96.17% vs 93.38%, p < 0.01; 94.02% vs 92.21%, p < 0.01, respectively). HyperArc plans had significantly lower mean hippocampal Dmax and Dmin values than RapidArc plans (Dmax: 15.53 Gy vs, 16.71 Gy, p < 0.01; Dmin: 8.33 Gy vs 8.93 Gy, p < 0.01, respectively). Similarly, inhomogeneous delivery of hyperArc produced a superior target and lower hippocampal dosimetric parameters than RapidArc, except for the HI of PTVmet (all p < 0.01). HyperArc generated superior conformity and target coverage with lower hippocampal doses than RapidArc. HyperArc could be an attractive technique for hippocampal-sparing WBRT with an SIB.

Effect of high-dose radiation therapy on positive margins after breast-conserving surgery for invasive breast cancer.

PURPOSE: Positive margins after breast-conserving surgery are associated with poor oncological outcomes and warrant additional surgery. This study aimed to evaluate the effectiveness of high-dose radiation therapy for positive margins by comparing local recurrence between patients with positive and negative margins. METHODS: We retrospectively evaluated 550 patients treated with adjuvant radiation therapy after breast-conserving surgery for invasive breast cancer between 2013 and 2019. The total equivalent dose in 2 Gy fractions (EQD2) to the tumor bed ranged from 65.81 to 66.25 Gy for positive margins and 59.31-61.81 Gy for negative margins. The differences in local recurrence between the positive and negative margin groups were analyzed. RESULTS: After a median follow-up of 58 months, the crude local recurrence rate was 7.3% in the positive margin group (n = 55) and 2.4% in the negative margin group (n = 495). Positive margins were associated with higher local recurrence without statistical significance in the entire cohort (p = 0.062). Among patients aged <60 years, those with positive margins had a significantly lower 5-year local recurrence-free survival rate than those with negative margins (89.16% vs. 97.57%, respectively; p = 0.005). In contrast, there was no significant difference in the 5-year local recurrence-free survival rate between patients with positive and negative margins among those aged ≥60 years (100.00% vs. 94.38%, respectively; p = 0.426). CONCLUSION: In this study, positive margins were not associated with poor local control in older patients after a high-dose boosts. Further prospective studies are needed to verify our findings.

Mutant pattern of p53 predicts local recurrence and poor survival rate in gastric cancer.

BACKGROUND: TP53 mutation is a poor prognostic factor for various organ malignancies such as colorectal cancer, breast cancer, ovarian cancer, hepatocellular carcinoma, lung adenocarcinoma and clinical pathologists previously evaluated it using immunohistochemistry for p53. The clinicopathologic significance of p53 expression in gastric cancer remains unclear due to inconsistent classification methods. METHODS: Immunohistochemistry for p53 protein was performed using tissue microarray blocks generated from 725 cases of gastric cancer, and p53 expression was divided into three staining patterns using a semi-quantitative ternary classifier: heterogeneous (wild type), overexpression, and absence (mutant pattern). RESULTS: Mutant pattern of p53 expression had a male predominance, greater frequency in cardia/fundus, higher pT stage, frequent lymph node metastasis, local recurrence clinically, and more differentiated histology microscopically compared with wild type. In survival analysis, p53 mutant pattern was associated with worse recurrent-free survival and overall survival rates, and significance was maintained in subgroup analysis of early versus advanced gastric cancers. In Cox regression analysis, p53 mutant pattern was a significant predicting factor for local recurrence (relative risk (RR=4.882, p<0.001)) and overall survival (RR=2.040, p=0.007). The p53 mutant pattern remained significant for local recurrence (RR=2.934, p=0.018) in multivariate analyses. CONCLUSIONS: Mutant p53 pattern on immunohistochemistry was a significant prognostic factor for local recurrence and poor overall survival in gastric cancer.

A High-Fat Diet in the Absence of Obesity Increases Lymphangiogenesis by Inducing VEGF-C in a Murine Lymphedema Model.

BACKGROUND: Many researchers have attempted to induce lymphangiogenesis for the treatment of lymphedema. However, most previous studies had limited clinical usefulness. A high-fat diet (HFD) increases serum ß-hydroxybutyrate (ß-OHB) levels, which can stimulate lymphangiogenesis. The authors hypothesized that an HFD will ameliorate lymphedema through enhanced lymphangiogenesis. METHODS: The effects of ß-OHB on the lymphangiogenic process in human dermal lymphatic endothelial cells were analyzed. A mouse tail lymphedema model was used to evaluate the effects of an HFD on lymphedema. Experimental mice were fed an HFD (45% kcal as fat, 20% as protein, and 35% as carbohydrates) for 4 weeks. Tail volume was measured using the truncated cone formula. Biopsy specimens were taken 6 weeks after surgical induction of lymphedema. RESULTS: In human dermal lymphatic endothelial cells, treatment with 20 mM of ß-OHB increased cell viability ( P = 0.008), cell migration ( P = 0.011), tube formation ( P = 0.005), and VEGF-C mRNA and protein expression ( P < 0.001) compared with controls. HFD feeding decreased tail volume by 14.3% and fibrosis by 15.8% ( P = 0.027), and increased the lymphatic vessel density ( P = 0.022) and VEGF-C protein expression ( P = 0.005) compared with those of operated, standard chow diet-fed mice. CONCLUSIONS: The authors' findings demonstrated that ß-OHB promoted lymphatic endothelial cell function and increased VEGF-C mRNA and protein expression. When mice with tail lymphedema were fed an HFD, volume and fibrosis of the tail decreased. Therefore, the authors' findings suggest that an HFD can be a successful novel dietary approach to treating lymphedema. CLINICAL RELEVANCE STATEMENT: Lymphatic regeneration after vascularized lymph node transfer can be augmented when a high-fat diet is used in conjunction with vascularized lymph node transfer.

Peripheral Microneedle Patch for First-Aid Hemostasis.

Despite the minimized puncture sizes and high efficiency, microneedle (MN) patches have not been used to inject hemostatic drugs into bleeding wounds because they easily destroy capillaries when a tissue is pierced. In this study, a shelf-stable dissolving MN patch is developed to prevent rebleeding during an emergency treatment. A minimally and site-selectively invasive hemostatic drug delivery system is established by using a peripheral MN (p-MN) patch that does not directly intrude the wound site but enables topical drug absorption in the damaged capillaries. The invasiveness of MNs is histologically examined by using a bleeding liver of a Sprague-Dawley (SD) rat as an extreme wound model in vivo. The skin penetration force is quantified to demonstrate that the administration of the p-MN patch is milder than that of the conventional MN patch. Hemostatic performance is systematically studied by analyzing bleeding weight and time and comparing them with that of conventional hemostasis methods. The superior performance of a p-MN for the heparin-pretreated SD rat model is demonstrated by intravenous injection in vivo.

Colorectal cancers with a residual adenoma component: Clinicopathologic features and KRAS mutation.

BACKGROUND/AIM: Colorectal cancer is well known for its "adenoma-carcinoma" sequential carcinogenesis. Some colorectal cancers demonstrate a residual adenoma component during progression from adenoma to invasive carcinoma. However, the clinicopathological significance of residual adenoma component remains unclear. In this study, we aimed to investigate the clinicopathologic and molecular characteristics including the KRAS mutation in colorectal cancers containing a residual adenoma component. MATERIALS AND METHODS: In this study, 498 surgically resected colorectal cancer patients were enrolled. Their detailed clinicopathologic features and results of molecular study including KRAS mutation test and microsatellite instability were analyzed. RESULTS: A residual adenoma component was identified in 42 (8.4%) patients with colorectal cancer. The presence of a residual adenoma component was associated with a high frequency of the KRAS mutation (65%, p = 0.031) as well as indolent clinicopathological features, including polypoid gross type (p < 0.001), well-differentiated histology (p < 0.001), low pT (p < 0.001) and pN stage (p = 0.003), absence of vascular invasion (p = 0.005), and a better progression-free prognosis (p = 0.029). The cases with an adenoma component had a 35.7% discordance rate on the KRAS mutation tests in their adenoma and carcinoma regions. CONCLUSION: In conclusion, colorectal cancer with a residual adenoma component showed indolent clinicopathologic features and frequent KRAS mutations. Due to the discordance in the incidence of the KRAS mutation between the adenoma and carcinoma components, the adenoma component should be documented in the pathology report, and care should be taken not to include the adenoma component when collecting samples for molecular testing.

High expression of the phosphoinositide 3-kinase p11γ isoform can predict poor prognosis of non-small cell lung cancer.

The protein p110γ is an isoform of the catalytic subunit of class I phosphoinositide 3-kinases (PI3Ks). PI3Ks are involved in the regulation of cell survival, growth, proliferation, and migration and have been implicated in the oncogenesis of various cancers. In this study, p110γ expression in non-small cell lung cancer (NSCLC) and its association with clinicopathological factors and patient survival were evaluated. A total of 230 NSCLC tumors were immunohistochemically stained for p110γ. Of these, 174 (75.7%) and 56 (24.3%) were placed in the low and high expression groups, respectively. The positive rate of p110γ was significantly higher in adenocarcinoma than in squamous cell carcinoma (p⟨0.001). Advanced stage NSCLCs showed higher p110γ expression than those at an early stage (p=0.002). Irrespective of the histological tumor type, the patients with high p110γ expression had significantly worse overall survival than those with low p110γ expression (p=0.004). p110γ expression was an independent poor prognostic factor in the multivariate analysis. Our results suggest that p110γ may be involved in the development and progression of NSCLC, and that p110γ has promising potential as a prognostic factor or novel therapeutic target for NSCLC.

ACE2 and TMPRSS2 Immunolocalization and COVID-19-Related Thyroid Disorder.

Thyroid dysfunction has been reported to be an extrapulmonary symptom of COVID-19. It is important to identify the tissue subset that expresses angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), which are essential for host infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in order to understand the viral pathogenesis of COVID-19-related thyroid dysfunction. We investigated the expression and distribution of ACE2- and TMPRSS2-expressing cells in the thyroid gland. RT-PCR and Western blotting were performed on human thyroid follicular cells (Nthy-ori3-1) and rat thyroid tissues to detect the expression levels of ACE and TMPRSS2 mRNA and proteins. We also analyzed the expression patterns of ACE2 and TMPRSS2 in 9 Sprague-Dawley rats and 15 human thyroid tissues, including 5 normal, 5 with Hashimoto's thyroiditis, and 5 with Graves' disease, by immunohistochemistry (IHC) and immunofluorescence. Both ACE2 and TMPRSS2 mRNAs and proteins were detected in the thyroid tissue. However, ACE2 and TMPRSS2 proteins were not expressed in thyroid follicular cells. In IHC, ACE2 and TMPRSS2 were not stained in the follicular cells. No cells co-expressed ACE2 and TMPRSS2. ACE2 was expressed in pericytes between follicles, and TMPRSS2 was mainly stained in the colloid inside the follicle. There was no difference in expression between the normal thyroid, Hashimoto's thyroiditis, and Graves' disease. SARS-CoV-2 does not directly invade the thyroid follicular cells. Whether SARS-CoV-2 infection of pericytes can affect COVID-19-related thyroid dysfunction warrants further study.

Thyroid Hormone Ameliorates Lymphedema by Suppressing Adipogenesis in a Murine Lymphedema Model.

Background: Exogenous supplementation of thyroid hormone could inhibit excessive fat deposition in lymphedema tissue by suppressing adipogenesis. Methods and Results: Cell viability, adipogenic differentiation, and mRNA expression were measured in 3T3-L1 preadipocytes treated with L-thyroxine. Twelve mice were divided into control and L-thyroxine groups. Two weeks after lymphedema was surgically induced, the experimental mice were fed L-thyroxine for 4 weeks. Tail volume and body weight were measured, and 6 weeks after the surgery, tail skin and subcutaneous tissue were harvested for histopathologic examination and protein isolation. In 3T3-L1 cells, treatment with 10-500 µM L-thyroxine did not affect cell viability. Eight days after induction of adipogenic differentiation, lipid accumulation decreased significantly in the 50 and 100 µM L-thyroxine groups (p < 0.001). mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), and fatty acid-binding protein 4 (FABP4) decreased significantly in the 100 µM L-thyroxine group compared with the control group (p = 0.017). Lymphedema tails treated with L-thyroxine exhibited decreased volume (p = 0.028) and thickness of dermal and subcutaneous tissue (p = 0.01) and increased vascular endothelial growth factor-C protein expression (p = 0.017) compared with the control. Conclusion: Thyroid hormone therapy inhibits the adipogenesis of 3T3-L1 cells in vitro and decreases the volume of murine lymphedema tail in vivo. These findings suggest that thyroid hormone therapy could be used to treat lymphedema.

Promotion of dermal tissue engineering in a rat model using a composite 3D-printed scaffold with electrospun nanofibers and recipient-site preconditioning with an external volume expansion device.

We hypothesized that use of a composite three-dimensionally (3D) printed scaffold with electrospun nanofibers in conjunction with recipient-site preconditioning with an external volume expansion (EVE) device would enable successful dermal tissue regeneration of a synthetic polymer scaffold. Cell viability, cell infiltration, extracellular matrix deposition, scaffold contraction, and mRNA expression by dermal fibroblasts cultured on three different scaffolds, namely, 3D-printed scaffold with a collagen coating, 3D-printed scaffold with an electrospun polycaprolactone nanofiber and collagen coating, and 3D-printed scaffold with an electrospun polycaprolactone/collagen nanofiber, were measured. Before scaffold implantation, rats were treated for 2 h with an EVE device to evaluate the effect of this device on the recipient site. Cell proliferation rates were significantly higher on the 3D-printed scaffold with electrospun polycaprolactone nanofiber and collagen coating than on the other scaffolds. In cell invasion studies, the 3D-printed scaffold with electrospun polycaprolactone nanofiber and collagen coating showed better cell integration than the other scaffolds. Under stereomicroscopy, fibroblasts adhered tightly to the electrospun area, and the fibroblasts effectively produced both collagen and elastin. Rat skin treated with an EVE device exhibited increased HIF-1α protein expression and capillary neoformation compared with control skin. Invasion of CD8+ cytotoxic lymphocytes surrounding the scaffold decreased when the recipient site was preconditioned with the EVE device. The composite 3D printed scaffold with electrospun nanofibers provided a favorable environment for proliferation, migration, and extracellular matrix synthesis by fibroblasts. Recipient-site preconditioning with an EVE device allowed for scaffold incorporation with less inflammation due to improved angiogenesis.

Patient-related risk factors for late rectal bleeding after hypofractionated radiotherapy for localized prostate cancer: a single-center retrospective study.

BACKGROUND: Several studies have reported patient-related risk factors for late rectal bleeding following conventionally fractionated radiotherapy for prostate cancer. We investigated patient-related risk factors for late rectal bleeding after hypofractionated radiotherapy. METHODS: A total of 231 patients with local or locally advanced prostate cancer treated with hypofractionated radiotherapy (70 or 67.2 Gy in 28 fractions) were evaluated retrospectively. All patients received intensity-modulated radiotherapy with daily image guidance. The relationships between late rectal bleeding and risk factors like diabetes, hypertension, cirrhosis, and anticoagulant use were analyzed. RESULTS: During a median follow-up of 23 months, the crude rates of grade ≥ 1, grade ≥ 2, and grade ≥ 3 late rectal bleeding were 23.8%, 16.9%, and 9.5%, respectively. Cirrhosis and anticoagulant use predicted an increased risk of grade ≥ 3 rectal bleeding in multivariable analyses (hazard ratio [HR] 14.37, 95% confidence interval [CI] 3.09-66.87, P = 0.001, and HR 2.93, 95% CI 1.14-7.55, P = 0.026, respectively). The non-anticoagulant group had a significantly superior 5-year freedom from grade ≥ 3 bleeding compared to the anticoagulant group in a propensity-weighted log-rank analysis (88.0% vs. 76.7%, P = 0.041). A receiver operating characteristic curve analysis revealed that rectal bleeding was minimized in the anticoagulant group if the equivalent dose at fractionation of 2 Gy (EQD2) V77 Gy of the rectum was < 4.5% or if the EQD2 V8.2 Gy was < 71.0%. CONCLUSIONS: Patients taking anticoagulants or those with cirrhosis had a significantly higher risk of severe late rectal bleeding than other patients after hypofractionated radiotherapy for prostate cancer in the present study. The bleeding risk could be lowered by minimizing hotspots in patients taking anticoagulants.

ACE2 and TMPRSS2 immunolocalization and oral manifestations of COVID-19.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into the host cells depends on the expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). We investigated the distribution of ACE2- and TMPRSS2-expressing cells in various oral tissues to identify the underlying mechanism of oral manifestations in patients with coronavirus disease 2019. SUBJECTS: We analyzed the expression patterns of ACE2 and TMPRSS2 in the oral mucosa (tongue, palate, and buccal mucosa), trigeminal ganglion, vessels, and salivary glands of 9 Sprague-Dawley rats using immunohistochemistry and immunofluorescence. RESULTS: ACE2 and TMPRSS2 were strongly expressed in the intermediate layer of the squamous epithelia of tongue papillae and buccal mucosa. ACE2- and TMPRSS2-positive cells were observed in the taste buds of the tongue. Additionally, ACE2 and TMPRSS2 were co-expressed in the ductal epithelium and acinar cells of salivary glands. Furthermore, both ACE2 and TMPRSS2 were stained in the neuronal cell body of trigeminal ganglia, but not in Schwann cells. Moreover, ACE2 and TMPRSS2 were expressed in capillaries, but not in venules/arterioles. CONCLUSIONS: SARS-CoV-2 can spread the suprabasal area of squamous epithelia of the oral mucosa, invades taste bud, trigeminal nerve, parotid gland, and microvessel, resulting in oral manifestations.

Clinical Outcomes of RTOG 9310 Protocol for Primary Central Nervous System Lymphoma: Single-Center Experience with 87 Patients.

The Radiation Therapy Oncology Group (RTOG) 9310 protocol clinical trial established high-dose methotrexate (HDMTX) as the standard for primary central nervous system lymphoma (PCNSL). We aimed to investigate the RTOG 9310 protocol's PCNSL outcomes by examining progression-free survival (PFS) and overall survival (OS) rates and determining the influential factors. Between 2007 and 2020, 87 patients were histopathologically diagnosed with PCNSL and treated with the RTOG 9310 protocol. All received HDMTX 2.5 g/m2 and vincristine 1.4 mg/m2/day for 1 day during weeks 1, 3, 5, 7, and 9, and procarbazine 100 mg/m2/day for 1 day during weeks 1, 5, and 9. Dexamethasone was administered on a standard tapering schedule from the first week to the sixth week. Whole brain radiotherapy (WBRT), consisting of 45 Gy for patients with less than a complete response to the chemotherapy or 36 Gy for complete responders, was started 1 week after the last dose of chemotherapy was administered. Within three weeks of the completion of WBRT, patients received two courses of cytarabine, which were separated by 3-4 weeks. Clinical, radiological, and histopathological characteristics were retrospectively reviewed. All patients completed five HDMTX cycles and a mean follow-up of 60.2 (range, 6-150) months. Twenty-eight (32.2%) patients experienced recurrence during follow-up. The mean time to recurrence was 21.8 months, while the mean PFS was 104.3 (95% confidence interval (CI), 90.6-118.0) months. Eleven (12.6%) patients died; the mean OS was 132.1 (95% CI, 122.2-141.9) months. The 3- and 5-year survival rates were 92.0% and 87.4%, respectively. One patient experienced acute renal failure, while the remainder tolerated any cytotoxic side effects. On multivariate analysis, the Eastern Cooperative Oncology Group performance score ≤ 2; the International Extranodal Lymphoma Study Group low-risk status; XBP-1, p53, and c-Myc negativity; homogenous enhancement; gross total resection, independently correlated with long PFS and OS. The RTOG 9310 protocol is effective for PCNSL and features good outcomes.

Venous Invasion and Perineural Invasion as Upstaging and Poor Prognostic Factors in N0 Gastric Cancers.

BACKGROUND/AIM: Lymph node metastasis is an important prognostic factor in gastric cancer patients. In node-negative (N0) gastric cancer patients, additional prognostic factors are needed to reinforce TNM staging. PATIENTS AND METHODS: We semi-quantitatively recorded the presence of lymphatic, venous, and perineural invasion and evaluated the possibility that they could be used as upstaging factors in N0 gastric cancer by comparing N0 gastric cancer cases with N1 cases. RESULTS: Venous (p<0.001) and perineural (p<0.001) invasion were important factors in the relapse-free survival of N0 patients, but lymphatic invasion was not. N0 cases with venous or perineural invasion had survival curves similar to those of N1 patients. In addition, the number of invasive features (lymphatic, venous, or perineural) was an important factor in predicting poor patient survival. CONCLUSION: Venous and perineural invasion were significant prognostic factors in N0 gastric cancer cases. It is necessary to record lymphatic, venous, and perineural invasion separately in the pathology report, especially in cases of N0 gastric cancer.

Interfractional diaphragmatic position variation according to stomach volume change during respiratory-gated radiotherapy for hepatocellular carcinoma.

PURPOSE: We evaluated the correlation between stomach volume change and interfractional baseline shifts of the diaphragm in image-guided radiotherapy (IGRT) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Twenty-four patients with HCC underwent ten fractions of IGRT, and a total of 240 cone beam computed tomography (CBCT) and on-board imager (OBI) kV image sets were acquired. These image sets were retrospectively analyzed. Baseline shifts of the diaphragm relative to bone and stomach volume change ratios were evaluated using four-dimensional simulation CT, kV image, and CBCT images. Associations between baseline shifts and patient physiologic factors were investigated. RESULTS: The average baseline shift of the diaphragm in the superior-inferior (SI) direction was 1.5 mm (standard deviation 4.6 mm), which was higher than the shift in other directions (0.7, 2.0 mm and 0.9, 2.6 mm in right-left (RL) and anterior-posterior (AP) directions, respectively). Interfractional baseline shifts of the diaphragm in the SI and AP directions were positively correlated with the stomach volume change ratio (Pearson's r: 0.416 and 0.302, p-value: <0.001 and <0.001, respectively). CONCLUSIONS: The interfractional baseline shifts of the diaphragm in the SI and AP directions correlated well with stomach volume changes. Efforts to maintain a constant stomach volume before the simulation and each treatment, such as fasting, may reduce interfractional baseline shifts of liver tumors.

Non-Small Cell Carcinoma-Not Otherwise Specified on Cytology Specimens in Patients with Solitary Pulmonary Lesion: Primary Lung Cancer or Metastatic Cancer?

CONTEXT: Subtyping of solitary pulmonary lesion (SPL) in small amount of cytology specimen using a limited panel of immunohistochemistry (IHC) markers is very important to the correct choice of treatment. This study was performed to categorize non-small cell carcinoma-not otherwise specified (NSCC-NOS) on cytology in patients with SPL, especially with regard to the incidence of metastatic cancer. MATERIALS AND METHODS: We reviewed 91 cases, in which a precise morphology-based, lineage-specific IHC-aided subtyping was not possible, that qualified as NSCC-NOS on cytology. A stepwise clinical approach and IHC of organ-specific markers was performed on each cell block (CB) to exclude metastasis from extrapulmonary malignancies. RESULTS: Of the 91 evaluated cases, 65 (71.4%) were diagnosed as non-small cell lung carcinoma (NSCLC)-NOS, 24 (26.4%) were metastatic cancer, and the remaining 2 (2.2%) had undetermined diagnoses. The most frequent primary tumor site was the colorectum (41.7%), followed by breast (20.8%), kidney (8.3%), and then stomach, duodenum, liver, pancreas, gallbladder, prostate, and skin (4.2% each, 1 of 24). Moreover, we found that 7 of the 24 patients with metastatic cancer had a history of extrapulmonary malignancy that was unknown at the time of cytology-based diagnosis. CONCLUSIONS: These results underscored the need for accurate and stepwise clinical correlation to rule out the possibility of pulmonary metastasis from other sites and appropriate but judicious IHC (i.e., CDX2) on CB for SPL to increase refinement of the cytology diagnosis of NSCC-NOS.

Relationship between 18F-FDG uptake and heat shock protein 90α expression in colorectal cancer.

OBJECTIVE: We investigated whether heat shock protein 90α (HSP90α) expression is associated with fluorine-18-labeled fluoro-2-deoxy-D-glucose (18F-FDG) uptake and whether 18F-FDG positron emission tomography/computed tomography (PET/CT) can be used to predict the status of HSP90α expression in colorectal cancer (CRC). SUBJECTS AND METHODS: The medical records and preoperative 18F-FDG PET/CT studies of 51 patients with newly diagnosed CRC who underwent surgical treatment were retrospectively reviewed. The maximum standardized uptake value (SUVmax) of the primary tumor was calculated from the level of 18F-FDG uptake. HSP90α expression was determined by immunohistochemistry. The relationship between SUVmax and HSP90α expression was analyzed. RESULTS: Colorectal cancer with high HSP90α expression had significantly higher SUVmax than CRC with low HSP90α expression (18.88±10.06 vs. 12.38±5.04, P=0.003). There was a significant correlation between HSP90α expression and 18F-FDG uptake (r=0.354, P=0.011). The highest accuracy for determining HSP90α status (68.6%) was obtained with a SUVmax cut-off of 15.4. Maximum SUV was the only predictor of HSP90α expression on multivariate logistic regression analysis (Odds Ratio=5.384, P=0.016). CONCLUSION: The expression status of HSP90α was significantly related to 18F-FDG uptake in CRC.

Randomized controlled trial comparing a conventional needle and a novel needle for endoscopic ultrasound (EUS)-guided histology of peripancreatic masses.

INTRODUCTION: Cytological study of samples obtained by Endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNA) allows for recognition of clear signs of malignant transformation. However, certain neoplasms can be difficult to diagnose without histological analysis. Recently, a novel EUS-guided fine needle biopsy (EUS-FNB) needle was developed to increase tissue acquisition. This study set out to investigate the usefulness of this novel EUS-FNB needle (NEFN) in terms of obtaining a proper histology compared with a conventional EUS-FNA needle (CEFN). METHODS: This investigation was a prospective, single-blind, randomized study in a single academic hospital. Primary outcome was the acquisition rate of an appropriate and sufficient specimen for histologic assessment. Secondary outcomes were diagnostic yield of peripancreatic masses using a CEFN and a NEFN. Furthermore, we assessed the feasibility of determining K-ras mutation status according to needle type. RESULTS: The study enrolled 56 consecutive patients. Technical success rates were 96.6% (28/29) for the CEFN and 100% (27/27) for the NEFN (P = 1.000). No complications occurred during or after the procedure in either needle group. An adequate sample for cytologic diagnosis was obtained in 89.7% (26/29) of patients in the CEFN group vs 96.3% (26/27) of patients in the NEFN group (P = .612). For histologic diagnosis, a sample with a biopsy adequacy score of 2 or more was obtained in 41.4% (12/29) of CEFN-acquired samples vs 88.9% (24/27) of NEFN-acquired samples (P < .001). K-ras mutation analysis using histologic specimens was possible in 13 (44.8%) CEFN-acquired samples and 25 (92.6%) of NEFN-acquired samples. This difference was significant (P < .001). CONCLUSIONS: The present study suggests that the NEFN is an effective and reliable alternative compared to a CEFN in terms of tissue acquisition rate and quality of histologic sampling.

Prognostic significance of glucose-related protein 94 in colorectal cancer.

AIMS: The expression of glucose-related protein 94 (GRP94), a member of the heat shock protein 90 family, was correlated with a variety of clinicopathological factors and patient survival in a large colorectal cancer (CRC) cohort. We aimed to elucidate the role of GRP94 in the prognosis of CRC patients. METHODS: Tissue microarray blocks were generated from 709 CRC samples and immunohistochemically stained for GRP94. RESULTS: Of the 709 tumours, 164 (23.1%) and 545 (76.9%) were classified in the low and high expression groups, respectively. GRP94 expression was high in CRC cases with larger tumours (p =  0.005) and advanced pT stage (p =  0.021). GRP94 expression was higher in females than males (p =  0.024). In univariate and multivariate survival analyses, high GRP94 expression was unexpectedly associated with better overall survival in CRC patients younger than 65 years of age (p =  0.001) CONCLUSION: Our conflicting results indicate that GRP94 has the ability to switch between oncogenic and tumour-suppressive roles depending on the conditions and microenvironment of the tumour cells. Furthermore, GRP94 could be a candidate biomarker to predict better prognosis in CRC patients.