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Purpose: To review the outcomes of rectal cancer patients treated with a nonsurgical approach using contact x-ray brachytherapy (CXB) when suspicious residual disease (≤3 cm) was present after external beam chemoradiation therapy/radiation therapy (EBCRT/EBRT)., Methods and Materials: Outcome data for rectal cancer patients referred to our institution from 2003 to 2012 were retrieved from an institutional database. These patients were referred after initial local multidisciplinary team discussion because they were not suitable for, or had refused, surgery. All selected patients received a CXB boost after EBCRT/EBRT. Most patients received a total of 90 Gy of CXB delivered in 3 fractions over 4 weeks., Results: The median follow-up period was 2.5 years (range 1.2-8.3). Of 345 consecutive patients with rectal cancer referred to us, 83 with suspicious residual disease (≤3 cm) after EBCRT/EBRT were identified for a CXB boost. Their median age was 72 years (range 36-87), and 58 (69.9%) were men. The initial tumor stages were cT2 (n = 28) and cT3 (n = 55), and 54.2% were node positive. A clinical complete response (cCR) was achieved in 53 patients (63.8%) after the CXB boost that followed EBCRT/EBRT. Of these 53 patients, 7 (13.2%) developed a relapse after achieving a cCR, and the 6 patients (11.6%) with nonmetastatic regrowth underwent salvage surgery (100%). At the end of the study period, 69 of 83 patients (83.1%) were cancer free., Conclusions: Our data suggest that a CXB boost for selected patients with suspicious residual disease (≤3 cm) after EBCRT/EBRT can be offered as an alternative to radical surgery. In our series, patients with a sustained cCR had a low rate of local regrowth, and those with nonmetastatic regrowth could be salvaged successfully. This approach could provide an alternative treatment option for elderly or comorbid patients who are not suitable for surgery and those with rectal cancer who wish to avoid surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: A watch and wait policy for patients with a clinical complete response (cCR) after external beam chemoradiotherapy (EBCRT) for rectal cancer is an attractive option. However, approximately one-third of tumours will regrow, which requires surgical salvage for cure. We assessed whether contact X-ray brachytherapy (CXB) can improve organ preservation by avoiding surgery for local regrowth., Methods: From our institutional database, we identified 200 of 573 patients treated by CXB from 2003 to 2012. Median age was 74 years (range 32-94), and 134 (67%) patients were males. Histology was confirmed in all patients and was staged using CT scan, MRI or endorectal ultrasound. All patients received combined CXB and EBCRT, except 17 (8.5%) who had CXB alone., Results: Initial cCR was achieved in 144/200 (72%) patients. 38/56 (68%) patients who had residual tumour received immediate salvage surgery. 16/144 (11%) patients developed local relapse after cCR, and 124/144 (86%) maintained cCR. At median follow up of 2.7 years, 161 (80.5%) patients were free of cancer. The main late toxicity was bleeding (28%). Organ preservation was achieved in 124/200 (62%) patients., Conclusion: Our data suggest that CXB can reduce local regrowth to 11% compared with around 30% after EBCRT alone. Organ preservation of 62% achieved was higher than reported in most published watch and wait studies. Advances in knowledge: CXB is a promising treatment option to avoid salvage surgery for local regrowth, which can improve the chance of organ preservation in patients who are not suitable for or refuse surgery.

Background: Recent evidence shows that the majority of rectal cancers demonstrate occult tumor scatter after neoadjuvant chemoradiotherapy that can extend for several centimeters under adjacent normal-appearing mucosa beside the residual mucosal abnormality or scar., Objective: This systematic review aimed to determine all of the published selection criteria and technical descriptions for local excision to date with regard to this phenomenon., Data Sources: PubMed, MEDLINE, and Embase were searched using the following key words: rectal cancer, local excision, radiotherapy, and neoadjuvant., Study Selection: Studies that assessed local excision of rectal cancer after neoadjuvant chemoradiotherapy were included. Duplicate series were excluded from final analysis., Intervention: All of the data points were tabulated and analyzed using Microsoft Excel., Main Outcome Measures: Criteria for patient selection, surgical technique, clinical restaging, pathologic assessment, and indications for completion surgery were analyzed., Results: After exclusions, data from 25 studies that in total evaluated local excision in 1001 patients were included. Compared with the single accepted technique of total mesorectal excision, described techniques for local excision after neoadjuvant therapy demonstrate significant variability in many critical technical issues, such as marking/tattooing original tumor margins before neoadjuvant therapy, using pretreatment tumor size/stage as exclusion criteria, and specifically stating lateral excision margins. Where detailed, the majority of local recurrences occurred in patients with clear pathological margins, yet significant variation existed for pathological assessment and reporting, with few studies detailing R status and some not reporting margin status at all. Significant variability also existed for adverse tumor features that mandated completion surgery, and, importantly, many series describe patients refusing completion surgery where indicated., Limitations: We were unable to perform meta-analysis because studies lacked sufficient methodologic homogeneity to synthesize., Conclusions: The observations from this study prompt additional study, standardization of technique, and cautious use of local excision of rectal cancer in the setting of neoadjuvant chemoradiotherapy.

Background: Radical surgery is associated with significant perioperative mortality in elderly and comorbid populations. Emerging data suggest for patients with a clinical complete response after neoadjuvant chemoradiotherapy that a watch-and-wait approach may provide equivalent survival and oncological outcomes., Objective: The purpose of this study was to compare the cost-effectiveness of watch and wait and radical surgery for patients with rectal cancer after a clinical complete response following chemoradiotherapy., Design: Decision analytical modeling and a Markov simulation were used to model long-term costs, quality-adjusted life-years, and cost-effectiveness after watch and wait and radical surgery. Sensitivity analysis was used to investigate the effect of uncertainty in model parameters., Settings: A third-party payer perspective was adopted., Patients: Patients included in the study were a 60-year-old male cohort with no comorbidities, 80-year-old male cohorts with no comorbidities, and 80-year-old male cohorts with significant comorbidities., Interventions: Radical surgery and watch-and-wait approaches were studied., Main Outcome Measures: Incremental cost, effectiveness, and cost-effectiveness ratio over the entire lifetime of the hypothetical patient cohorts were measured., Results: Watch and wait was more effective (60-year-old male cohort with no comorbidities = 0.63 quality-adjusted life-years (95% CI, 2.48-3.65 quality-adjusted life-years); 80-year-old male cohort with no comorbidities = 0.56 quality-adjusted life-years (95% CI, 0.52-1.59 quality-adjusted life-years); 80-year-old male cohort with significant comorbidities = 0.72 quality-adjusted life-years (95% CI, 0.34-1.76 quality-adjusted life-years)) and less costly (60-year-old male cohort with no comorbidities = $11,332.35 (95% CI, $668.50-$23,970.20); 80-year-old male cohort with no comorbidities = $8783.93 (95% CI, $2504.26-$21,900.66); 80-year-old male cohort with significant comorbidities = $10,206.01 (95% CI, $2762.014-$24,135.31)) independent of patient cohort age and comorbidity. Consequently, watch and wait was more cost-effective with a high degree of certainty (range, 69.6%-89.2%) at a threshold of $50,000/quality-adjusted life-year., Limitations: Long-term outcomes were derived from modeled cohorts. Analysis was performed for a United Kingdom third-party payer perspective, limiting generalizability to other healthcare contexts., Conclusions: Watch and wait is likely to be cost-effective compared with radical surgery. These findings strongly support the discussion of organ-preserving strategies with suitable patients.

Background: In elderly and comorbid patients with rectal cancer, radical surgery is associated with significant perioperative mortality. Data suggest that a watch-and-wait approach where a complete clinical response is obtained after neoadjuvant chemoradiotherapy might be oncologically safe., Objective: This study aimed to determine whether patient age and comorbidity should influence surgeon and patient decision making where a complete clinical response is obtained., Design: Decision-analytic modeling consisting of a decision tree and Markov chain simulation was used. Modeled outcome parameters were elicited both from comprehensive literature review and from a national patient outcomes database., Settings: Outcomes for 3 patient cohorts treated with neoadjuvant therapy were modeled after either surgery or watch and wait., Patients: Patients included 60-year-old and 80-year-old men with mild comorbidities (Charlson score <3) and 80-year-old men with significant comorbidities (Charlson score >3)., Main Outcome Measures: Absolute survival, disease-free survival, and quality-adjusted life years were measured., Results: The model found that absolute survival was similar in 60-year-old patients but was significantly improved in fit and comorbid 80-year-old patients at 1 year after treatment where watch and wait was implemented instead of radical surgery, with a survival advantage of 10.1% (95% CI, 7.9-12.6) and 13.5% (95% CI, 10.2-16.9). At all of the other time points, absolute survival was equivalent for both techniques. There were no short- or long-term differences among any patient groups managed either by radical surgery or watch and wait in terms of either disease-free survival or quality-adjusted life years., Limitations: Oncologic data for the watch-and-wait approach used for this study is derived from only a small number of studies pertaining to a highly selected group of patients. The 90-day postoperative mortality rate derived from the United Kingdom population-based study might be lower in other countries or individual institutions., Conclusions: This study suggests competing effects of oncologic and surgical risk when using watch-and-wait management and that elderly and comorbid patients have the most to gain from this approach.

Background: In recent years, the technique of sentinel lymph node (SLN) mapping has been applied to colorectal cancer. One aim was to ultrastage patients who were deemed node negative by routine pathologic processing but who went on to develop systemic disease. Such a group may benefit from adjuvant chemotherapy., Methods: With fully informed consent and ethical approval, 37 patients with primary colorectal cancer and 3 patients with large adenomas were prospectively mapped. Isosulfan blue dye (1 to 2 mL) was injected around tumors within 5 to 10 minutes of resection. After gentle massage to recreate in vivo lymph flow, specimens were placed directly into formalin. During routine pathologic analysis, all nodes were bivalved, and blue-staining nodes were noted. These later underwent multilevel step sectioning with hematoxylin and eosin and cytokeratin staining., Results: SLNs were found in 39 of 40 patients (98% sensitivity), with an average of 4.1 SLNs per patient (range, 1-8). In 14 of 16 (88% specificity) patients with nodal metastases on routine reporting, SLN status was in accordance. Focused examination of SLNs identified occult tumor deposits in 6 (29%) of 21 node-negative patients. No metastatic cells were found in SLNs draining the three adenomas., Conclusions: The ability to identify SLNs after formalin fixation increases the ease and applicability of SLN mapping in colorectal cancer. Furthermore, the sensitivity and specificity of this simple ex vivo method for establishing regional lymph node status were directly comparable to those in previously published reports.

Cranial MR imaging was performed in three patients in whom herpes simplex encephalitis was subsequently proved. In all cases, the postcontrast T1 weighted MR images obtained with magnetization transfer saturation showed greater central nervous system involvement than was apparent on the conventional MR images. Specifically, the postcontrast magnetization transfer images were superior at delineating generalized meningeal enhancement as well as focal areas of brain involvement not seen on noncontrast T2-weighted images orconventionalpostcontrast T1-weightedimages.

An unusual pathway of local spread of rhinocerebral mucormycosis is presented with MR and pathologic correlation. Perineural extension, proved with pathology, followed the trigeminal nerve to the pons. Enhancement of the nerve was seen on MR.

Radiologists in hospital practice often encounter radiographs that either bear no patient identification or are incorrectly labeled as those of a different patient. To avoid repeating these improperly labeled radiographs, and to establish correct patient identity, most radiologists compare these radiographs with previous radiographs of several patients. This happens most often with portable chest radiographs. To study the reliability of various surgical, pathologic, and anatomic features and to help establish a fast and accurate method of establishing the correct patient identity, we performed a retrospective study of 50 patients in the intensive care unit. The characteristic location and configuration of surgical material, fractures, and dense parenchymal/pleural scars with or without calcifications are extremely helpful in establishing patient identity. In the vast majority of patients who lack such characteristic surgical and pathologic features, the anatomic structures that are most reliable for identification purposes are, in order of decreasing reliability, the transverse processes of the first thoracic vertebrae and the adjoining tubercles of the first ribs, the spinous processes, and the scapular wings. We believe that this information will help radiologists to identify the right patient when radiographs are incorrectly labeled.

Studies were made on the disposition of mineral ions in matrix vesicles (MV) and their relationship to alkaline phosphatase by treatment of MV-enriched microsomes (MVEM) with graded levels of Ca2+-chelating agents to complex accessible ions, fractionation of MVEM on hypertonic sucrose gradients at two different pH values (7.5 and 8.0) to evaluate for the presence of calcium phosphate mineral, and passage of MVEM through cation-exchange columns to determine the accessibility of the Ca2+. The effect of removal of Ca2+ and Pi on subsequent ability of MVEM to induce mineral formation from synthetic cartilage lymph was also determined. Passage through cation-exchange columns revealed that MV Ca2+ was not freely exchangeable, but coeluted in the void volume with alkaline phosphatase. However, upon incubation in synthetic cartilage lymph, progressively more Ca2+ was retained by the column. These findings indicate that, initially, the majority of Ca2+ in MVEM is internal and not readily exchangeable, but as Ca2+ accumulates, progressively more becomes external. The mineral in MV is labile and readily susceptible to loss; treatment with graded levels of EGTA removed major portions of the original Ca2+ and Pi. 45Ca uptake by these mineral-depleted MV was markedly reduced, even in the presence of alkaline phosphatase substrates. Sucrose gradient fractionation of MVEM caused extensive loss of Pi, but not Ca2+, from the low-density alkaline phosphatase-rich fractions. This reveals that Ca2+ and Pi are not initially coupled together: Pi is largely soluble, whereas Ca2+ must be tightly bound. In the high-density vesicles, large amounts of both Ca2+ and Pi are present. The slightly enhanced recovery at higher pH suggests the presence of a solid mineral phase. During mineralization by MV, Ca2+ became externalized, and concomitantly alkaline phosphatase activity declined. This suggests that a direct association exists between the enzyme and the developing mineral.

Activity of the bone/liver/kidney isozyme of alkaline phosphatase (AP) is known to be critical for mineralization in developing bone, although its role is unclear. The work now reported explores changes in the activity of this Zn2+-containing enzyme that occur during Ca2+ accumulation by matrix vesicles (MV). A marked loss (up to 65-70%) in AP activity was found to accompany Ca2+ accumulation by MV. These two events were highly correlated, both temporally and quantitatively. Investigation into possible causes revealed that the decline in AP activity during Ca2+ uptake was not due to action of proteases but rather resulted from interaction with the developing mineral phase, loss of metal ions (Zn2+ and Mg2+) from the active site of the enzyme, and concomitant irreversible denaturation of the enzyme. Protease inhibitors did not protect AP from loss of activity during mineralization; in contrast, protease treatments, which progressively destroyed the ability of MV to accumulate Ca2+ actually reduced loss of AP activity. These findings clearly demonstrate that AP is present at the site of MV mineralization and that its catalytic activity is profoundly reduced by the mineralization process.

The roles of alkaline phosphatase and labile internal mineral in matrix vesicle-mediated mineralization have been studied by selectively releasing the enzyme from a wide variety of matrix vesicle preparations using treatment with a bacterial phosphatidylinositol-specific phospholipase C and by demineralization of the vesicles using isosmotic pH 6 buffer. Following depletion of 50-90% of the alkaline phosphatase activity or treatment with citrate buffer, the vesicles were tested for their ability to accumulate 45Ca2+ and 32Pi from a synthetic cartilage lymph. Removal of alkaline phosphatase by phospholipase C treatment caused two principal effects, depending on the matrix vesicle preparation. In rapidly mineralizing vesicle fractions which did not require organic phosphate esters (Po) to accumulate mineral ions, release of alkaline phosphatase had only a minor effect. In slowly mineralizing vesicles preparations or those dependent on Po substrates for mineral ion uptake, release of alkaline phosphatase caused significant loss of mineralizing activity. The activity of rapidly calcifying vesicles was shown to be dependent on the presence of labile internal mineral, as demonstrated by major loss in activity when the vesicles were decalcified by various treatments. Ion uptake by demineralized vesicles or those fractionated on sucrose step gradients required Po and was significantly decreased by alkaline phosphatase depletion. Uptake of Pi, however, was not coupled with hydrolysis of the Po substrate. These findings argue against a direct role for alkaline phosphatase as a porter in matrix vesicle Pi uptake, contrary to previous postulates. The results emphasize the importance of internal labile mineral in rapid uptake of mineral ions by matrix vesicles.