Myoepithelioma of the cerebellopontine angle: a previously not documented benign salivary gland-type neoplasm within the cranium

Myoepithelioma is a dimorphic neoplasm with contractile-epithelial phenotype, originally interpreted as deriving from, but not actually restricted to the salivary glands. As a novel addition to the list of exquisitely rare intracranial salivary gland-type tumors and tumor-like lesions, we report on an example of myoepithelioma encountered in the left cerebellopontine angle of a 32-year-old male. Clinically presenting with ataxia and dizziness, this extraaxial mass of 4 × 3.5 × 3 cm was surgically resected, and the patient is alive 6 years postoperatively. Histologically, the tumor exhibited a continuum ranging from compact fascicles of spindle cells to epithelial nests and trabeculae partitioned by hyalinized septa, while lacking tubular differentiation. Regardless of architectural variations, there was robust immunoexpression of S100 protein, smooth muscle actin, GFAP, cytokeratin, and vimentin. Cytologic atypia tended to be modest throughout, and the MIB1 labeling index averaged less than 1%. Fluorescent in situ hybridization indicated no rearrangement of the EWSR1 locus. We interpret these results to suggest that myoepithelioma of the posterior fossa - along with related salivary epithelial tumors in this ostensibly incongruous locale - may possibly represent analogous neoplasms to their orthotopic counterparts, ones arising within aberrant salivary anlagen. The presence of the latter lends itself to being mechanistically accounted for by either postulating placodal remnants in the wake of branchial arch development, or linking them to exocrine glandular nests within endodermal cysts. Alternatively, myoepithelioma at this site could be regarded as a non tissue-specific lesion similar to its relatives ubiquitously occurring in the soft parts.

Intratumoral budding (ITB) in preoperative biopsies predicts the presence of lymph node and distant metastasis in colon and rectal cancer patients

Schnüriger2, D. Inderbitzin2, I. Zlobec1, A. Lugli1,3

Relative survival is an adequate estimate of cancer-specific survival: baseline mortality-adjusted 10-year survival of 771 rectal cancer patients.

BACKGROUND The objective of the present investigation is to assess the baseline mortality-adjusted 10-year survival of rectal cancer patients. METHODS Ten-year survival was analyzed in 771 consecutive American Joint Committee on Cancer (AJCC) stage I-IV rectal cancer patients undergoing open resection between 1991 and 2008 using risk-adjusted Cox proportional hazard regression models adjusting for population-based baseline mortality. RESULTS The median follow-up of patients alive was 8.8 years. The 10-year relative, overall, and cancer-specific survival were 66.5% [95% confidence interval (CI) 61.3-72.1], 48.7% (95% CI 44.9-52.8), and 66.4% (95% CI 62.5-70.5), respectively. In the entire patient sample (stage I-IV) 47.3% and in patients with stage I-III 33.6 % of all deaths were related to rectal cancer during the 10-year period. For patients with AJCC stage I rectal cancer, the 10-year overall survival was 96% and did not significantly differ from an average population after matching for gender, age, and calendar year (p = 0.151). For the more advanced tumor stages, however, survival was significantly impaired (p < 0.001). CONCLUSIONS Retrospective investigations of survival after rectal cancer resection should adjust for baseline mortality because a large fraction of deaths is not cancer related. Stage I rectal cancer patients, compared to patients with more advanced disease stages, have a relative survival close to 100% and can thus be considered cured. Using this relative-survival approach, the real public health burden caused by rectal cancer can reliably be analyzed and reported.

The search for the primary tumor in metastasized gastroenteropancreatic neuroendocrine neoplasm.

Gastroenteropancreatic neuroendocrine tumors (NETs) often present as liver metastasis from a carcinoma of unknown primary. We recently showed that primary NETs from the pancreas, small intestine and stomach as well as their respective liver metastases differ from each other by the expression profile of the three genes CD302, PPWD1 and ABHB14B. The gene and protein expression of CD302, PPWD1, and ABHB14B was studied in abdominal NET metastases to identify the site of the respective primary tumors. Cryopreserved tissue from NET metastases collected in different institutions (group A: 29, group B: 50, group C: 132 specimens) were examined by comparative genomic hybridization (Agilent 105 K), gene expression analysis (Agilent 44 K) (groups A and B) and immunohistochemistry (group C). The data were blindly evaluated, i.e. without knowing the site of the primary. Gene expression analysis correctly revealed the primary in the ileum in 94 % of the cases of group A and in 58 % of group B. A pancreatic primary was predicted in 83 % (group A) and 20 % (group B), respectively. The combined sensitivity of group A and B was 75 % for ileal NETs and 38 % for pancreatic NETs. Immunohistochemical analysis of group C revealed an overall sensitivity of 80 %. Gene and protein expression analysis of CD302 and PPWD1 in NET metastases correctly identifies the primary in the pancreas or the ileum in 80 % of the cases, provided that the tissue is well preserved. Immunohistochemical profiling revealed CD302 as the best marker for ileal and PPWD1 for pancreatic detection.

Suprasellar chordoid neoplasm with expression of thyroid transcription factor 1: evidence that chordoid glioma of the third ventricle and pituicytoma may form part of a spectrum of lineage-related tumors of the basal forebrain.

Chordoid glioma of the third ventricle is a rare neuroepithelial tumor characterized by a unique histomorphology and exclusive association with the suprasellar/third ventricular compartment. Variously interpreted as either astrocytic- or ependymal-like, and speculatively ascribed to the lamina terminalis/subcommissural organ, its histogenesis remains, nevertheless, unsettled. Here, we report on a suprasellar chordoid glioma occurring in a 52-year-old man. Although displaying otherwise typical morphological features, the tumor was notable for expression of thyroid transcription factor 1, a marker of tumors of pituicytic origin in the context of the sellar region. We furthermore found overlapping immunoprofiles of this example of chordoid glioma and pituicytic tumors (pituicytoma and spindle cell oncocytoma), respectively. Specifically, phosphorylated ribosomal protein S6, a marker of mTOR pathway activation, was expressed in both groups. Based on these findings, we suggest that chordoid glioma and pituicytic tumors may form part of a spectrum of lineage-related neoplasms of the basal forebrain.

Second St. Gallen European Organisation for Research and Treatment of Cancer Gastrointestinal Cancer Conference: consensus recommendations on controversial issues in the primary treatment of rectal cancer

Primary treatment of rectal cancer was the focus of the second St. Gallen European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Cancer Conference. In the context of the conference, a multidisciplinary international expert panel discussed and voted on controversial issues which could not be easily answered using published evidence. Main topics included optimal pretherapeutic imaging, indication and type of neoadjuvant treatment, and the treatment strategies in advanced tumours. Here we report the key recommendations and summarise the related evidence. The treatment strategy for localised rectal cancer varies from local excision in early tumours to neoadjuvant radiochemotherapy (RCT) in combination with extended surgery in locally advanced disease. Optimal pretherapeutic staging is a key to any treatment decision. The panel recommended magnetic resonance imaging (MRI) or MRI + endoscopic ultrasonography (EUS) as mandatory staging modalities, except for early T1 cancers with an option for local excision, where EUS in addition to MRI was considered to be most important because of its superior near-field resolution. Primary surgery with total mesorectal excision was recommended by most panellists for some early tumours with limited risk of recurrence (i.e. cT1-2 or cT3a N0 with clear mesorectal fascia on MRI and clearly above the levator muscles), whereas all other stages were considered for multimodal treatment. The consensus panel recommended long-course RCT over short-course radiotherapy for most clinical situations where neoadjuvant treatment is indicated, with the exception of T3a/b N0 tumours where short-course radiotherapy or even no neoadjuvant therapy were regarded to be an option. In patients with potentially resectable tumours and synchronous liver metastases, most panel members did not see an indication to start with classical fluoropyrimidine-based RCT but rather favoured preoperative short-course radiotherapy with systemic combination chemotherapy or alternatively a liver-first resection approach in resectable metastases, which both allow optimal systemic therapy for the metastatic disease. In general, proper patient selection and discussion in an experienced multidisciplinary team was considered as crucial component of care.

Malignant neoplasm deaths, Illinois residents : statistical summary.

Chiefly tables.

Scaling of rectal gland mass in the European lesser-spotted dogfish

In the European lesser-spotted dogfish Scyliorhinus canicula, rectal gland mass in mg (M-Rg) followed the allometric relationship: M-Rg = 1.15 M-0.68, where M is body mass (g). The concept of allometric scaling is an important consideration in studies investigating the function Of osmoregulatory organs. (C) 2003 the Fisheries Society of the British Isles.

Plasma osmolyte concentrations and rectal gland mass of bull sharks Carcharhinus leucas, captured along a salinity gradient

Bull sharks (Carcharhinus leucas) were captured across a salinity gradient from freshwater (FW) to seawater (SW). Across all salinities, C leucas were hyperosmotic to the environment. Plasma osmolarity in FW-captured animals (642 +/- 7 mosM) was significantly reduced compared to SW-captured animals (1067 +/- 21 mosM). In FW animals, sodium, chloride and urea were 208 +/- 3, 203 +/- 3 and 192 +/- 2 mmol l(-1), respectively. Plasma sodium, chloride and urea in SW-captured C leucas were 289 +/- 3, 296 +/- 6 and 370 +/- 10 mmol l(-1), respectively. The increase in plasma osmolarity between FW and SW was not linear. Between FW (3 mosM) and 24%o SW (676 mosM), plasma osmolarity increased by 22% or 0.92% per 1parts per thousand rise in salinity. Between 24%o and 33parts per thousand, plasma osmolarity increased by 33% or 4.7% per 1 parts per thousand rise in salinity, largely due to a sharp increase in plasma urea between 28parts per thousand and 33parts per thousand. C. leucas moving between FW and SW appear to be faced with three major osmoregulatory challenges, these occur between 0-10parts per thousand, 11-20parts per thousand and 21-33parts per thousand. A comparison between C leucas captured in FW and estuarine environments (20-28%o) in the Brisbane River revealed no difference in the mass of rectal glands between these animals. However, a comparison of rectal gland mass between FW animals captured in the Brisbane River and Rio San Juan/Lake Nicaragua showed that animals in the latter system had a significantly smaller rectal gland mass at a given length than animals in the Brisbane River. The physiological challenges and mechanisms required for C leucas moving between FW and SW, as well as the ecological implications of these data are discussed. (C) 2004 Elsevier Inc. All rights reserved.

Papillary urothelial neoplasm of low malignant potential: reliability of diagnosis and outcome

OBJECTIVE To determine the ability of pathologists to reproducibly diagnose a newly defined lesion, i.e. the papillary urothelial neoplasm of low malignant potential (PUNLMP) using the published criteria, defined by the 1998 World Health Organisation/International Society of Urological Pathology (WHO/ISUP) classification system; in addition, debate remains about the clinical behaviour of these lesions, thus the rates of recurrence and progression of PUNLMP lesions were assessed and compared with low-grade papillary urothelial carcinomas (LG-PUC) and high-grade (HG-PUC) over a 10-year follow-up. PATIENTS AND METHODS Forty-nine cases of superficial bladder cancer (G1-3 pTa) representing an initial diagnosis of transitional cell carcinoma made in 1990 were identified and re-graded using the 1998 WHO/ISUP classification by two pathologists. Inter-observer agreement was assessed using Cohen weighted kappa statistics. After reclassification the clinical follow-up was reviewed retrospectively, and episodes of recurrence and progression recorded. RESULTS The inter-observer agreement was moderate, regardless of whether one (kappa 0.45) or two (kappa 0.60) pathologists were used to grade these lesions. Re-classification identified 12 PUNLMP, 28 LG-PUC and nine HG-PUC. PUNLMP lesions recurred in 25% (3/12) of cases; no progression was documented. Recurrence rates were 75% (21/28) and 67% (6/9) for LG- and HG-PUC, respectively, and progression rates were 4% (1/28) and 22% (2/9). CONCLUSION The 1998 WHO/ISUP classification of urothelial neoplasms can be reproducibly applied by pathologists, with a moderate level of agreement. There is evidence that PUNLMP lesions have a more indolent clinical behaviour than urothelial carcinomas. However, the risk of recurrence and progression remains, and clinical monitoring of these patients is important.

Freshwater to seawater acclimation of juvenile bull sharks ( Carcharhinus leucas): plasma osmolytes and Na +/K +-ATPase activity in gill, rectal gland, kidney and intestine

This study examined the osmoregulatory status of the euryhaline elasmobranch Carcharhinus leucas acclimated to freshwater (FW) and seawater ( SW). Juvenile C. leucas captured in FW ( 3 mOsm l(-1) kg(-1)) were acclimated to SW ( 980 - 1,000 mOsm l(-1) kg(-1)) over 16 days. A FW group was maintained in captivity over a similar time period. In FW, bull sharks were hyper-osmotic regulators, having a plasma osmolarity of 595 mOsm l(-1) kg(-1). In SW, bull sharks had significantly higher plasma osmolarities ( 940 mOsm l(-1) kg(-1)) than FW-acclimated animals and were slightly hypoosmotic to the environment. Plasma Na+, Cl-, K+, Mg2+, Ca2+, urea and trimethylamine oxide (TMAO) concentrations were all significantly higher in bull sharks acclimated to SW, with urea and TMAO showing the greatest increase. Gill, rectal gland, kidney and intestinal tissue were taken from animals acclimated to FW and SW and analysed for maximal Na+/ K+-ATPase activity. Na+/ K+-ATPase activity in the gills and intestine was less than 1 mmol Pi mg(-1) protein h(-1) and there was no difference in activity between FW- and SW-acclimated animals. In contrast Na+/ K+-ATPase activity in the rectal gland and kidney were significantly higher than gill and intestine and showed significant differences between the FW- and SW-acclimated groups. In FW and SW, rectal gland Na+/ K+-ATPase activity was 5.6 +/- 0.8 and 9.2 +/- 0.6 mmol Pi mg(-1) protein h(-1), respectively. Na+/ K+-ATPase activity in the kidney of FW and SW acclimated animals was 8.4 +/- 1.1 and 3.3 +/- 1.1 Pi mg(-1) protein h(-1), respectively. Thus juvenile bull sharks have the osmoregulatory plasticity to acclimate to SW; their preference for the upper reaches of rivers where salinity is low is therefore likely to be for predator avoidance and/or increased food abundance rather than because of a physiological constraint.

Promising results of a cooperative group phase II trial of preoperative chemoradiation for locally advanced rectal cancer (TROG 9801)

PURPOSE: This article reports the overall survival, failure-free survival, local failure, and late radiation toxicity of a phase II trial of preoperative radiotherapy with continuous infusion 5-fluorouracil for rectal cancer after a minimum 3.5 years of follow-up. METHODS: Eligible patients were those with newly diagnosed localized adenocarcinoma of the rectum, within 12 cm of the anal verge, staged T3-T4 and deemed suitable for curative resection. Radiotherapy (50.4 Gy in 28 fractions in five weeks and three days) was given with continuous infusion 5-fluorouracil throughout the course of radiotherapy. RESULTS: A total of 82 patients were accrued in 13 months. The median follow-up time was 4.1 (range, 2.3-4.5) years. There were 55 males (67 percent) and the median age was 59 (range, 27-87) years. Patients were staged pretreatment as T3 (89 percent) and resectable T4 (11 percent). Endorectal ultrasound was performed in 70 percent and magnetic resonance imaging in another 5 percent. The four-year overall and failure-free survival rates were 82 percent (95 percent Cl: 72-89) and 69 percent (95 percent Cl: 58-78), respectively. The cumulative incidence of local failure at four years was 3.9 percent (95 percent CI: 1.3-11). Risk of failures, local and distant, has not reached a plateau phase. CONCLUSION: This regimen can be delivered safely and without leading to a significant increase in late toxicity. It provides excellent local control and favorable overall survival. There is a need for longer follow-up than has commonly been used for the proper evaluation of failures after an effective regimen of preoperative chemoradiation.

Laparoscopically-assisted resection rectopexy for rectal prolapse: Ten years' experience

PURPOSE: This study has been undertaken to audit a single-center experience with laparoscopically-assisted resection rectopexy for full-thickness rectal prolapse. The clinical Outcomes and long-term results were evaluated. METHODS: The data were prospectively collected for the duration of the operation, time to passage of flatus postoperatively, hospital stay, morbidity, and mortality. For follow-up, patients received a questionnaire or were contacted. The data were divided into quartiles over the study period, and the differences in operating time and length of hospital stay were tested using the Kruskal-Wallis test. RESULTS: Between March 1992 and October 2003, a total of 117 patients underwent laparoscopic resection rectopexy for rectal prolapse. The median operating time during the first quartile (representing the early experience) was 180 minutes compared with 110 minutes for the fourth quartile (Kruskal-Wallis test for operating time = 35.523, 3 df, P < 0.0001). Overall morbidity was 9 percent (ten patients), with one death (< 1 percent). One patient had a ureteric injury requiring conversion. One minor anastomotic leak Occurred, necessitating laparoscopic evacuation of a pelvic abscess. Altogether, 77 patients were available for follow-up. The median follow-up was 62 months. Eighty percent of the patients reported alleviation of their symptoms after the operation. Sixty-nine percent of the constipated patients experienced an improvement in bowel frequency. No patient had new or worsening symptoms of constipation after Surgery. Two (2.5 percent) patients had full-thickness rectal prolapse recurrence. Mucosal prolapse recurred in 14 (18 percent) patients. Anastomotic dilation was performed for stricture in five (4 percent) patients. CONCLUSIONS: Laparoscopically-assisted resection rectopexy for rectal prolapse provides a favorable functional outcome and low recurrence rate. Shorter operating time is achieved with experience. The minimally invasive technique benefits should be considered when offering rectal prolapse patients a transabdominal approach for repair, and emphasis should now be on advanced training in the laparoscopic approach.