Diffusion-weighted magnetic resonance imaging of rectal cancer: tumour volume and perfusion fraction predict chemoradiotherapy response and survival.

BACKGROUND: In locally advanced rectal cancer (LARC), responses to preoperative treatment are highly heterogeneous and more accurate diagnostics are likely to enable more individualised treatment approaches with improved responses. We investigated the potential of diffusion-weighted magnetic resonance imaging (DW MRI), with quantification of the apparent diffusion coefficient (ADC) and perfusion fraction (F), as well as volumetry from T2-weighted (T2W) MRI, for prediction of therapeutic outcome. MATERIAL AND METHODS: In 27 LARC patients receiving neoadjuvant chemotherapy (NACT) before chemoradiotherapy (CRT), T2W- and DW MRI were obtained before and after NACT. Tumour volumes were delineated in T2W MRI and ADCs and Fs were estimated from DW MRI using a simplified approach to the intravoxel incoherent motion (IVIM) model. Mean tumour values and histogram analysis of whole-tumour heterogeneity were correlated with histopathologic tumour regression grade (TRG) and 5-year progression-free survival (PFS). RESULTS: At baseline, high tumour F predicted good tumour response (TRG1-2) (AUC = 0.79, p = 0.01), with a sensitivity of 69% and a specificity of 100%. The combination of F and tumour volume (Fpre/Vpre) gave the highest prediction of poor tumour response (AUC = 0.93, p < 0.001) with a sensitivity of 88% and a specificity of 91%, and also predicted PFS (p < 0.01). Baseline tumour ADC was not significantly related to therapeutic outcome, whereas a positive change in ADC from baseline to after NACT, ΔADC, significantly predicted good tumour response (AUC = 0.83, p < 0.01, 83% sensitivity, 73% specificity), but not PFS. CONCLUSIONS: The MRI parameter F/V at baseline was a remarkably strong predictor of both histopathologic tumour response and 5-year PFS in patients with LARC.

Fibromatosis in vertical rectus abdominis myocutaneous flap imitating tumor recurrence after surgery for locally advanced rectal cancer: case report.

BACKGROUND: Abdominoperineal excision is performed in patients with locally advanced, low rectal carcinoma. Reconstruction of the dorsal vagina and perineum using the vertical rectus abdominis myocutaneous flap following extensive surgery results in favorable surgical outcome and quality of life. However, the rectus abdominis muscle, as part of the anterior abdominal wall, may develop fibrous lesions also as a transplant. CASE PRESENTATION: A 39-year-old female patient with low rectal cancer and extensive colorectal polyposis was treated with neoadjuvant chemoradiotherapy followed by colectomy and abdominoperineal excision with resection of the dorsal vaginal wall and subsequent reconstruction of the perineum using the vertical rectus abdominis myocutaneous flap. At the 6-month follow-up, a suspected 2 × 2 cm tumor recurrence was detected in the transposed tissue and was subsequently surgically removed. Histologic examination concluded with fibromatosis. Genetic testing revealed a known disease-causing mutation in the adenomatous polyposis coli gene, confirming the diagnosis of familial adenomatous polyposis. CONCLUSIONS: Fibromatosis may affect the anterior abdominal wall, that is the rectus abdominis muscle, at the primary site or may develop in the muscle after its transposition into the perineum at pelvic reconstruction. Fibromatosis in the muscle flap after pelvic reconstruction may present a difficult diagnostic challenge for the multidisciplinary team.

The new molecular markers DDIT3, STT3A, ARG2 and FAM129A are not useful in diagnosing thyroid follicular tumors.

Preoperative characterization of thyroid follicular lesions is challenging. Fine-needle aspiration specimens cannot differentiate follicular carcinomas from benign follicular neoplasias. Recently, promising markers have been detected using modern molecular techniques. We conducted a retrospective study to confirm the usefulness of immunohistochemical staining for the protein markers, DDIT3, STT3A (ITM1), ARG2 and FAM129A (C1orf24) in separating benign and malignant thyroid follicular lesions. Formalin-fixed, paraffin-embedded thyroid tissue from 30 in-house cases (15 follicular carcinomas and 15 follicular adenomas), as well as 8 follicular carcinomas and 21 follicular adenomas on tissue microarray slides were stained immunohistochemically for DDIT3, STT3A, ARG2 and FAM129A expression. Control tissue consisted of thyroid parenchyma adjacent to the tumors and 11 separate cases of normal thyroid parenchyma. All in-house cases of follicular adenomas, follicular carcinomas and adjacent normal thyroid tissue showed positive immunostaining with anti-DDIT3 and anti-STT3A. Anti-ARG2 and anti-FAM129A polyclonal antibodies showed positive staining in 20 and 60% of in-house follicular adenomas, and 40 and 87% of in-house follicular carcinomas, respectively. Monoclonal anti-FAM129A demonstrated positive staining in 13 and 33% of in-house follicular adenomas and follicular carcinomas, respectively. Polyclonal anti-DDIT3, -STT3A and -FAM129A antibodies showed positive staining in all tissue microarray slides of follicular carcinoma and in 76, 85 and 81% of the follicular adenomas, respectively. Monoclonal anti-STT3A stained 81% of the follicular adenoma cores. Anti-ARG2 stained positive in 13% of follicular carcinomas and 10% of follicular adenomas on the tissue microarray slides. In conclusion, DDIT3, STT3A, ARG2 and FAM129A immunohistochemistry does not appear to be useful in the diagnosis of thyroid follicular neoplasias, as they do not reliably distinguish follicular thyroid carcinoma from follicular thyroid adenoma.

Preoperative radiotherapy in rectal signet-ring cell carcinoma - magnetic resonance imaging and treatment outcome: Report of six cases.

BACKGROUND: Signet-ring cell carcinoma (SRCC) is an uncommon tumor entity in rectal cancer, often considered to be resistant to non-surgical therapy. In locally advanced primary or recurrent rectal cancer, diagnostic information from magnetic resonance imaging (MRI) is considered superior in planning the optimal treatment strategy, which usually includes preoperative radiotherapy. The recognition of MRI features that correlate with the radiation response might ultimately be used to select patients for tailored treatment and, in addition, avoid potentially toxic therapy in non-responding patients. MATERIAL AND METHODS: In a cohort of 120 rectal cancer patients who had received preoperative radiotherapy (50 Gy in 2 Gy fractions), six patients were noted to have SRCC tumor differentiation. Initial diagnostic MRI examination included assessment of local T- and N-stage and tumor morphology. Histological tumor response was subsequently assessed in the resected specimens, and postoperative follow-up data was compiled until disease recurrence. RESULTS: Following the preoperative radiotherapy, two distinctly different histological responses - complete response (ypT0N0) or no response - were observed. Extensive mesorectal lymph node metastasis (N2 disease) at the pretreatment MRI examination was unambiguously associated with lack of response and rapid development of disseminated disease. Importantly, patients with complete response have been observed for 23-52 months postoperatively without evidence of recurrent disease. DISCUSSION: Our review may suggest that patients with locally advanced growth of rectal SRCC, despite poorer outcome when compared to patients with conventional-type rectal adenocarcinoma, when presenting limited lymph node disease should be offered preoperative radiotherapy in a tentatively curative setting.

NUT expression in primary lung tumours.

BACKGROUND: Nuclear protein in testis (NUT) midline carcinomas (NMC) are rare, highly aggressive epithelial neoplasms, characterised by protein expression of NUT-fusion proteins which reflects the genetic translocation between chromosome 15 and 19. NMC occurs mainly in midline structures, but there are reports regarding occurrence in structures outside the midline. We investigated specimens from 519 surgically resected lung carcinomas and carcinoid tumours for the presence of NUT protein using immunohistochemistry. Normal testis and two previously confirmed NMCs served as positive controls. FINDINGS: All 483 evaluable cases (278 adenocarcinomas, 140 squamous cell carcinomas, 30 large cell carcinomas, 7 small cell carcinomas, 10 undifferentiated carcinomas and 18 carcinoids) were completely negative for expression of NUT protein. CONCLUSION: NUT gene rearrangement does not seem to be relevant in primary pulmonary carcinomas or carcinoid tumours of the lung.

[Fine needle cytology of the thyroid gland]. / Finnålscytologiske undersøkelser av thyreoidea.

BACKGROUND: Application of fine needle cytology (FNC) is important in the preoperative assessment of thyroid lesions. The method is rapid, minimally invasive and cost effective. The aim of this study was to evaluate the role of fine needle cytology at The Norwegian Radium Hospital in the management of thyroid nodules. MATERIAL AND METHODS: Data on FNC and comparable histology results were retrieved from the pathology database during the 5-year-period 1998 through 2003. 1770 FNC samples and corresponding histology results from 443 lesions were compared. Reviews of cytological slides were done in 39 discrepant cases and quality assessment parameters calculated. RESULTS: High complete sensitivity (77.5%) and specificity (90.1%) were found. The false positive rate was 1.2% and the false negative rate 23.7%. Inadequate FNCs were particularly seen in submitted specimens. A review of the discrepant cases showed that the main cause of false negative samples was sampling error. Micropapillary carcinoma was the predominant tumour type with false negative FNC. Eleven malignancies were diagnosed in repeat FNC specimens. INTERPRETATION: FNC is a highly reliable test to assess whether a thyroid nodule is benign or malignant. Diagnostic pitfalls are mainly due to inability to procure the diagnostic material.

Magnetic resonance-guided histopathology for improved accuracy of tumor response evaluation of neoadjuvant treatment in organ-infiltrating rectal cancer.

BACKGROUND AND PURPOSE: The novel procedure of magnetic resonance-(MR) guided histopathology was applied to determine the false-negative rate of conventional histopathologic tumor response evaluation of neoadjuvant radiation/chemoradiation therapy (RT/CRT) in organ-infiltrating rectal cancer. MATERIALS AND METHODS: Ninety-two consecutive patients that had received RT/CRT and proceeded to extended total mesorectal excision for organ-infiltrating rectal cancer were identified from the institutional database. For each patient, the study radiologist and pathologist separately interpreted preoperative MR images and histologic preparations from the surgical specimen, to determine whether tumor down-staging had resulted. In cases of discrepancy (52 patients), histologic sections were jointly reassessed for residual tumor in areas outside the mesorectal fascial compartment, using MR images as guidance for where to inspect. RESULTS: Following RT/CRT, 67.5% of cases were found to remain ypT4, even though half of the study population had complete (ypT0; 7.6%) or near-complete (sparsely remaining tumor; 43.5%) histomorphologic tumor regression. After MR-guided histologic reassessment of surgical specimens, the false-negative rate of conventional histopathology for detection of ypT4 was determined to be 41.1%. Five-year estimate for locally recurrent disease was 12.7%. CONCLUSION: This response data to neoadjuvant RT/CRT in organ-infiltrating rectal cancer indicate that tumor down-staging is over-estimated by conventional evaluation.

Efficacy of ultrasound-guided percutaneous ethanol injection treatment in patients with a limited number of metastatic cervical lymph nodes from papillary thyroid carcinoma.

CONTEXT: Repeated neck explorations can be a difficult task in patients with recurrent metastatic cervical lymph nodes from papillary thyroid carcinoma (PTC). OBJECTIVE: The aim of this retrospective study has been to assess the efficacy of ultrasound (US)-guided percutaneous ethanol injection (PEI) as treatment of metastatic cervical lymph nodes from PTC. MATERIALS AND METHODS: Sixty-nine patients who previously had undergone thyroidectomy for PTC were selected for inclusion. However, three patients were later excluded due to lack of follow-up. Lymph node status was determined by US-guided fine-needle aspiration biopsy and/or by raised levels of thyroglobulin in washouts from the cytological needle. Guided by US, 0.1-1.0 ml of 99.5% ethanol was injected into the metastatic lymph nodes. RESULTS: Three patients (eight metastatic lymph nodes in total) were reassigned to surgery due to progression (multiple new metastases), leaving 63 patients and 109 neck lymph nodes to be included. Mean observation time was 38.4 months (range, 3-72). A total of 101 of the 109 (93%) metastatic lymph nodes responded to PEI treatment, 92 (84%) completely and nine incompletely. Two did not respond, and four progressed. Two lymph nodes previously considered successfully treated showed evidence of malignancy during follow-up. No significant side effects were reported. CONCLUSION: US-guided PEI treatment of metastatic lymph nodes seems to be an excellent alternative to surgery in patients with a limited number of neck metastases from PTC. This procedure should replace "berry picking" surgery.

Prediction of response to preoperative chemoradiotherapy in rectal cancer by multiplex kinase activity profiling.

PURPOSE: Tumor response of rectal cancer to preoperative chemoradiotherapy (CRT) varies considerably. In experimental tumor models and clinical radiotherapy, activity of particular subsets of kinase signaling pathways seems to predict radiation response. This study aimed to determine whether tumor kinase activity profiles might predict tumor response to preoperative CRT in locally advanced rectal cancer (LARC). METHODS AND MATERIALS: Sixty-seven LARC patients were treated with a CRT regimen consisting of radiotherapy, fluorouracil, and, where possible, oxaliplatin. Pretreatment tumor biopsy specimens were analyzed using microarrays with kinase substrates, and the resulting substrate phosphorylation patterns were correlated with tumor response to preoperative treatment as assessed by histomorphologic tumor regression grade (TRG). A predictive model for TRG scores from phosphosubstrate signatures was obtained by partial-least-squares discriminant analysis. Prediction performance was evaluated by leave-one-out cross-validation and use of an independent test set. RESULTS: In the patient population, 73% and 15% were scored as good responders (TRG 1-2) or intermediate responders (TRG 3), whereas 12% were assessed as poor responders (TRG 4-5). In a subset of 7 poor responders and 12 good responders, treatment outcome was correctly predicted for 95%. Application of the prediction model on the remaining patient samples resulted in correct prediction for 85%. Phosphosubstrate signatures generated by poor-responding tumors indicated high kinase activity, which was inhibited by the kinase inhibitor sunitinib, and several discriminating phosphosubstrates represented proteins derived from signaling pathways implicated in radioresistance. CONCLUSIONS: Multiplex kinase activity profiling may identify functional biomarkers predictive of tumor response to preoperative CRT in LARC.