Ophelimus mediterraneus sp. n. (Hymenoptera, Eulophidae): a new Eucalyptus gall wasp in the Mediterranean region.

We report here for the first time the presence of Ophelimus mediterraneus sp. n. in Mediterranean Europe. This species appears to be closely related to Ophelimus maskelli, a well-known invasive pest of Eucalyptus. Based on molecular (cytochrome oxidase I, 28S), morphological (multivariate ratio analysis) and bio-ecological investigations, our study gives unambiguous relevant criteria that allow the discrimination between these two species. A full description of O. mediterraneus sp. n. is also provided. The geographic distribution of O. mediterraneus sp. n. as well as its impact on Eucalyptus species needs to be more widely assessed since its presence may have been confused with O. maskelli in their sympatric introduced areas. Further investigations of potential parasitoids in the native area may thus be welcomed to evaluate classical biological control achievability.

Incidence and epidemiology of spinal cord injury within a closed American population: the United States military (2000-2009).

STUDY DESIGN: Cohort study. OBJECTIVES: The objective of this study was to characterize the incidence of spinal cord injury (SCI) within the population of the United States military from 2000-2009. This investigation also sought to define potential risk factors for the development of SCI. SETTING: The population of the United States military from 2000-2009. METHODS: The Defense Medical Epidemiology Database was queried for the years 2000-2009 using the International Classification of Diseases, Ninth Revision, Clinical Modification codes for SCI (806.0, 806.1, 806.2, 806.3, 806.4, 806.5, 806.8, 806.9, 952.0, 952.1, 952.2, 952.8, 952.9). The raw incidence of SCI was calculated and unadjusted incidence rates were generated for the risk factors of age, sex, race, military rank and branch of service. Adjusted incidence rate ratios were subsequently determined via multivariate Poisson regression analysis that controlled for other factors in the model and identified significant independent risk factors for SCI. RESULTS: Between 2000 and 2009, there were 5928 cases of SCI among a population at-risk of 13,813,333. The raw incidence of SCI within the population was 429 per million person-years. Male sex, white race, enlisted personnel and service in the Army, Navy or Marine Corps were found to be significant independent risk factors for SCI. The age groups 20-24, 25-29 and >40 were also found to be at significantly greater risk of developing the condition. CONCLUSIONS: This study is one of the few investigations to characterize the incidence, epidemiology and risk factors for SCI within the United States. Results presented here may represent the best-available evidence for risk factors of SCI in a large and diverse American cohort.

Genomic analysis of response to bacillus Calmette-Guérin (BCG) treatment in high-grade stage 1 bladder cancer patients.

BACKGROUND: Intravesical bacillus Calmette-Guérin (BCG) therapy is standard treatment for high-risk non-muscle invasive bladder cancer (NMIBC) but overall efficacy is low, and no reliable predictive biomarkers currently exist to refine patient selection. We performed genomic analysis on high-grade (HG) T1 NMIBCs to determine if response to therapy is predicted by certain mutational and/or expressional changes. METHODS: Patients with HG T1 NMIBC treated with induction BCG were stratified by response into durable and non-durable responders. Baseline tumor samples were subjected to targeted DNA sequencing and whole-exome RNAseq. Genomic variants differing significantly between response groups were analyzed using Ingenuity Pathway Analysis (IPA) software. Variant selection was refined to target potential biomarker candidates for responsiveness to BCG. RESULTS: Among 42 patients, the median follow-up was 51.7 months and 40.5% (n=17) were durable BCG responders. Deleterious mutations in the RNA sequence of JCHAIN, S100A7, CLEC2B, and ANXA10 were more common in non-durable responders. Mutations in MCL1 and MSH6 detected on targeted sequencing were more commonly found in durable responders. Of all deleterious DNA and RNA mutations identified, only MCL1 was significantly associated with longer recurrence free survival (RFS) (P=0.031). CONCLUSIONS: Differences in the genomic profiles of HG T1 NMIBC tumors exist between those who show durable response to BCG and those who do not. Using pathway analysis, those differences imply upregulation of several interconnected inflammatory pathways among responders. Specific variants identified here, namely MCL1, are candidates for further study and, if clinically validated, may serve as useful biomarkers in the future.

Effects of serial anesthesia using ketamine or ketamine/medetomidine on hematology and serum biochemistry values in rhesus macaques (Macaca mulatta).

BACKGROUND: This study aimed at determining the cumulative effect of daily anesthesia, using two drug regimens, over hematological and biochemical parameters. METHODS: Blood samples were obtained from rhesus monkeys 20 minutes after intramuscular administration of ketamine or ketamine/medetomidine combination for three consecutive days and results were evaluated to determine their effect on hematological and serum biochemistry values. Statistical significance of drug, day, and interaction of these two variables were evaluated. RESULTS: Drug effect resulted in a dramatic increase of aspartate aminotransferase and creatine kinase values. Day effect resulted in decreases of RBC, HCT, Hgb, and alkaline phosphatase but an increase of other biochemical parameters evaluated. The drug/day interaction effect was found to be -significant for RBC, platelets, aspartate aminotransferase, alanine aminotransferase, and creatine kinase values. CONCLUSION: The results of our study suggest a cumulative effect of serial anesthesia and should be an important consideration when interpreting hematology and serum biochemistry in rhesus macaques.

Strategies in the management of renal tumors amenable to partial nephrectomy.

PURPOSE: The laparoscopic approach to radical and partial nephrectomy is becoming the standard of care for treating patients with renal tumors. Hand-assisted laparoscopic partial nephrectomy (HALPN) provides some advantages over the pure laparoscopic approach which include manual manipulation of the kidney, tactile feedback, and timely specimen removal. MATERIALS AND METHODS: We describe our technique for HALPN and emphasize the implementation of an in-room pathologist to examine gross margins during the period of renal arterial occlusion. Between 2004 and 2007, 46 patients underwent HALPN performed by the same surgeons. Mean patient age was 59.5 years and mean tumor size was 2.55 cm. Twelve of these patients underwent significant concomitant procedures. RESULTS: Our mean operating time was 173.26 min (range 90-306 min) and our mean warm ischemic time was 28.32 min (range 14-54 min). Average estimated blood loss was 116.82 ml (range 10-1000 ml) with no transfusions. Thirty-six (78%) tumors were renal cell carcinoma, seven (15%) were oncocytomas, and three (7%) were angiomyolipomas. The average length of stay was 5.17 days (range 3-9 days) and there were no positive margins. There was one postoperative bleed (2%) and two postoperative urine leaks (4.3%). DISCUSSION: In our institution, the hand-assist approach to laparoscopic partial nephrectomy has resulted in favorable perioperative outcomes. The use of an in-room pathologist to provide real-time assessment of gross tumor margins has allowed us to achieve a 0% positive final margin rate. We believe that the use of an in-room pathologist during the timely extraction of the specimen made possible by the hand-assisted approach provides a great advantage over pure laparoscopic partial nephrectomy. This low positive margin rate is also the result of maintaining a bloodless field of resection with temporary renal arterial occlusion as well as the avoidance of visual tissue distortion with cold, sharp scissor dissection.

A Rare Presentation of Stage IV Large Cell Neuroendocrine Carcinoma of the Cervix with Metastasis to the Cranium.

Neuroendocrine tumors (NETs) are aggressive diseases developing from neuroendocrine cells that most frequently involve the gastro-entero-pancreatic tract and the lung, but more rarely are found in almost all body tissues. Limited biological and clinical data are currently available for NETs in uncommon sites, such as female genital tract. NETs represent 0.9% to 1.5% of the tumors of the uterine cervix. This case is reported on a 75-year-old Caucasian woman, presenting with dental and generalized pain for two weeks. Later during her admission, facial droop and diplopia were noticed. Radiological findings ruled out cerebrovascular accident but revealed multiple bone marrow lesions involving the left and the right clivus, right Meckel's cave, and posterior margin of the right cavernous sinus. Findings also included pulmonary nodules and adenopathy supporting diagnosis of likely stage IV metastatic carcinoma. Further imaging revealed homogeneous enhancement of the uterus suggestive of diffusely infiltrative carcinoma; pathology results confirmed large cell neuroendocrine carcinoma of the uterine cervix (LCNEC) giving her a 1.5-month median survival range.

Microsatellite instability in endometrial carcinoma.

Microsatellite instability (MI), detected as electrophoretic shifts in allele sizes of microsatellite DNA sequences, has been identified in some colorectal carcinomas. Investigators have previously attributed such microsatellite instability to replication errors (RER). The colorectal carcinomas with RER have been found to arise either sporadically or in association with the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Because endometrial carcinoma is also commonly associated with HNPCC, we studied 30 cases of endometrial carcinoma to characterize the presence of MI in these neoplasms. Seven cases (23%) showed MI. Four cases showed both Type I (large shifts) and Type II (small shifts) mutation patterns and the remaining three cases showed Type I mutations only. We conclude that MI frequently occurs in endometrial cancers and that this type of genetic alteration may be an important pathogenetic feature of this tumor type.

Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study.

PURPOSE: To determine whether the addition of paclitaxel to doxorubicin plus cisplatin improves overall survival (OS) in women with advanced or recurrent endometrial carcinoma. Secondary comparisons included progression-free survival (PFS), response rate (RR), and toxicities. PATIENTS AND METHODS: Eligible, consenting patients received doxorubicin 60 mg/m(2) and cisplatin 50 mg/m(2) (AP), or doxorubicin 45 mg/m(2) and cisplatin 50 mg/m(2) (day 1), followed by paclitaxel 160 mg/m(2) (day 2) with filgrastim support (TAP). The initial doxorubicin dose in the AP arm was reduced to 45 mg/m(2) in patients with prior pelvic radiotherapy and those older than 65 years. Both regimens were repeated every 3 weeks to a maximum of seven cycles. Patients completed a neurotoxicity questionnaire before each cycle. RESULTS: Two hundred seventy-three women (10 ineligible) were registered. Objective response (57% v 34%; P <.01), PFS (median, 8.3 v 5.3 months; P <.01), and OS (median, 15.3 v 12.3 months; P =.037) were improved with TAP. Treatment was hematologically well tolerated, with only 2% of patients receiving AP, and 3% of patients receiving TAP experiencing neutropenic fever. Neurologic toxicity was worse for those receiving TAP, with 12% grade 3, and 27% grade 2 peripheral neuropathy, compared with 1% and 4%, respectively, in those receiving AP. Patient-reported neurotoxicity was significantly higher in the TAP arm following two cycles of therapy. CONCLUSION: TAP significantly improves RR, PFS, and OS compared with AP. Evaluation of this regimen in the high-risk adjuvant setting is warranted, but close attention should be paid to the increased risk of peripheral neuropathy.

Subforaminal bridges in Hymenoptera (Insecta), with a focus on Chalcidoidea.

Variation in structures of the posterior surface of the head in Hymenoptera is compared and interpreted according to theories of head capsule evolution, with focus on understanding previously baffling conditions in the superfamily Chalcidoidea. Features are investigated separately without first classifying subforaminal bridges into subcategories. In Proctotrupomorpha (including Chalcidoidea), Ceraphronoidea and some Ichneumonoidea, there are multiple posterior pits associated with the tentorium. In most examined Hymenoptera with a subforaminal bridge, there was a differentiated median area, typically with highly variable microtrichia. This area is elevated in Cephoidea and Pamphilioidea, but is not elevated in other Hymenoptera. Subforaminal bridges in Apocrita previously classified as hypostomal bridges are discussed in the context of A.P. Rasnitsyn's hypothesis that relative importance of adult feeding drives subforaminal bridge evolution.

Micropapillary serous carcinoma of the ovary. A distinctive low-grade carcinoma related to serous borderline tumors.

According to the International Federation of Gynecology and Obstetrics (FIGO) and the World Health Organization (WHO), stromal invasion, defined as destructive infiltrative growth, is the sole criterion used to distinguish serous borderline tumors from invasive serous carcinomas of the ovary. Although this criterion effectively identifies most malignant tumors, it does not permit the identification of a small subset of well-differentiated ovarian carcinomas that do not display destructive infiltrative growth but that may be associated with malignant behavior. In this study, we describe a group of such serous neoplasms that have distinctive morphologic features and that are often associated with progressive, invasive disease. We have designated these tumors micropapillary serous carcinomas (MPSC). They are characterized by a filigree pattern of highly complex micropapillae arising directly from large, bulbous papillary structures. The micropapillae are covered by round to cuboidal cells with a high nuclear-to-cytoplasmic ratio. Typical serous borderline tumors tend to display a hierarchical pattern of branching terminating in small papillae or tufts, and the cells covering the papillae tend to be more columnar and often ciliated compared with cells of MPSC. We reviewed more than 400 cases of serous ovarian borderline tumors and well-differentiated serous carcinomas and identified 26 cases of MPSC. Seventeen tumors lacked destructive infiltrative growth (noninvasive), and nine contained areas of invasion ranging from minimal to extensive. Eight of the 26 tumors were stage I, and none of the patients developed recurrence whether or not their tumors had demonstrable invasion. In contrast, of the 16 women presenting with stage II disease or higher and who had more than 1 year of follow-up, eight (50%) have either died of intra-abdominal carcinomatosis or are alive with carcinoma. Twenty-four (92%) of MPSCs contained areas of serous borderline tumor. The frequent association of MPSCs with serous borderline tumors suggests that MPSCs arise from the latter and may account for the few cases of serous borderline tumors that have been associated with progression to invasive carcinoma.

Pathology residents' use of a Web-based tutorial to improve Gleason grading of prostate carcinoma on needle biopsies.

Little is known about pathology residents' ability to Gleason grade or their ability to learn surgical pathology using Internet-based technology. A free Web-based program (available at www.pathology. jhu.edu/prostate) was developed that consisted of 20 pretutorial images for grading, 24 tutorial images, and the same 20 posttutorial images for Gleason grading. The grading images were selected from cases that had a consensus Gleason grade from 10 uropathology experts. In 2.5 months, 255 residents visited the website, and 151 (59%) completed it. Of those who completed the website, their year in training was known in 85 (56%): 1st year, 25.8%; 2nd year, 20%; 3rd year, 22.3%; 4th year, 14.1%; 5th year, 15.3%; and 6th year, 2.4%. Eighty percent learned Gleason grading in residency versus being self-taught, and 66% were male. In a multivariate analysis, higher pretutorial scores were associated with both their year in training (P = .001) and their hospital size (P = .003). Improvements in grading posttutorial were not related to the residents' year in training. Overall, the website significantly improved grading in 11 of 20 images and had no effect in 9 of 20 images. Improvements were noted in 1 of 1 Gleason score 4; 2 of 7 Gleason score 5 to 6; 2 of 6 Gleason score 7; and 6 of 6 Gleason score above 7 tumors. In summary, a Web-based tutorial improved Gleason grading accuracy by pathology residents to an equal extent regardless of their year in training. It is more difficult to teach residents to grade Gleason scores 5 to 7 tumors, and additional training should be concentrated in this area.

Late recurrence of clear-cell adenocarcinoma of the cervix: case report.

In the last 10 years, new observations have been made of the biologic behavior of clear-cell adenocarcinoma of the cervix and vagina arising in young women exposed to diethylstilbestrol in utero. Of particular note is the tumor's capacity to recur after an extended disease-free interval following initial therapy. We report the case of a woman who had her first recurrence 17 years after initial therapy, presenting with metastatic disease to the lungs and cerebellum. This case represents the longest reported interval between primary therapy and recurrence and supports the conclusion made by others that women who have been treated for clear-cell adenocarcinoma of the cervix and vagina may remain at risk of disease progression for many years after initial therapy. Therefore, these women should continue to be monitored. We also recommend periodic chest x-rays for two reasons: 1) The lungs are the most common site of distant spread of disease; and 2) metastatic nodules may be amenable to curative surgical intervention.

Detection of occult tumor using indium 111-labeled anticarcinoembryonic antigen antibodies.

Even with the advancement of radiologic techniques, metastatic cancers can still be difficult to detect. In this study, 48 patients suspected of having occult metastases were studied by radioimmunodetection following the administration of 92.5 to 181.3 MBq of indium 111-labeled monoclonal anticarcinoembryonic antigen antibody. All but seven patients were thought to have metastatic colorectal carcinoma. In the majority of cases, physical examinations and computed tomographic scans had failed to detect a lesion. At least one lesion that was later proved to exist was detected in 34 of the 50 studies performed on these patients. Seven of eight patients with normal radioimmunodetection scans remain free of disease. One hundred one sites were detected overall; 60 were considered true-positive sites and 27 false-positive sites. Fourteen sites remained in question. Nineteen false-negative sites occurred. Radioimmunoimaging appears valuable for the detection of occult cancer where standard, noninterventional techniques have failed to detect the suspected disease.

Dermis-fat graft for orbital reconstruction after subtotal exenteration.

A surgical technique for reconstruction after subtotal orbital exenteration uses an autogenous dermis-fat graft. A musculocutaneous flap is advanced over the graft to provide the anterior vascular supply for the free dermis-fat graft. The periorbita and remaining orbital tissue provide the vascular supply posteriorly. This technique eliminates extensive skin grafting and delayed spontaneous healing. Wound healing is rapid and surgical morbidity is minimized. We have used this procedure in three patients with sebaceous gland adenocarcinoma, two patients with severe posttraumatic contracted sockets, and as a palliative procedure in one patient with a fungating choroidal melanoma and widespread metastasis.

Subtle injuries of the Lisfranc joint.

In fifteen patients, a subtle injury of the Lisfranc joint (tarsometatarsal articulation) was found. The lesion was defined as a diastasis of two to five millimeters between the bases of the first and second metatarsals, as seen on anteroposterior radiographs. There often was a long delay between injury and diagnosis. Eight patients were treated with a below-the-knee cast only, three had treatment with a cast and then tarsometatarsal arthrodesis, two had no initial treatment but later had arthrodesis, and two had open reduction and internal fixation. The duration of follow-up ranged from two to thirteen years after the diagnosis. There was no correlation between the severity of the diastasis and the patient's functional result. Marked disability and pain persisted in seven patients, and six of them had flattening of the longitudinal arch. Maintenance of the longitudinal arch usually was associated with a better functional outcome. When a patient has a subtle injury of the Lisfranc joint, weight-bearing lateral radiographs of both feet are needed to identify flattening of the longitudinal arch. Such radiographs should be made routinely in the evaluation of all injuries of the foot that may involve the Lisfranc joint.

Instrumented measurement of anterior laxity of the knee.

We performed instrumented measurement of anterior-posterior laxity of the knee in thirty-three cadaver specimens, 338 normal subjects, and eighty-nine patients with unilateral disruption of the anterior cruciate ligament. The test instrument was the Medmetric knee arthrometer, model KT-2000. We measured total anterior-posterior laxity, produced by anterior and posterior loads of eighty-nine newtons (twenty pounds), and the anterior compliance index. The total anterior-posterior laxity is composed of an anterior displacement and a posterior displacement; these are measured from a testing reference position, defined as the resting position of the knee after applying and then releasing a posterior load of eighty-nine newtons. The anterior compliance index is defined as the anterior displacement between an anterior load of sixty-seven newtons and one of eighty-nine newtons. All tests were performed with the knee held on a thigh support that placed the knee in 20 +/- 5 degrees of flexion. The mean anterior displacement at eighty-nine newtons was 5.7 millimeters in a group of normal subjects and 13.0 millimeters in a group of patients with a disrupted anterior cruciate ligament. Ninety-two per cent of the normal subjects had a left knee-right knee difference in anterior displacement of no more than two millimeters, while 96 per cent of the patients with a unilateral disruption of the anterior cruciate ligament had an injured knee-normal knee difference in anterior displacement of more than two millimeters. Ninety-three per cent of the normal subjects had a difference in the left-right compliance index of no more than 0.5 millimeter, and 85 per cent of the patients with unilateral disruption of the anterior cruciate ligament had a difference in the compliance index of the injured and normal sides of more than 0.5 millimeter.

The effect of continuous passive motion on anterior cruciate ligament reconstruction stability.

This study was undertaken to examine the immediate effect of continuous passive motion (CPM) on anterior cruciate ligament (ACL) reconstruction stability. Cadaver knees were tested with a knee arthrometer with the anterior cruciate intact and then with the anterior cruciate sectioned. One of three anterior cruciate reconstructions was then performed and stability was restored to the knee and it was again tested with the knee arthrometer. Stability was defined as being within 2 mm of the intact measurement. The three operations selected were the Marshall-MacIntosh "over-the-top," (OTT) a patellar bone-patellar tendon-tubercle bone (BTB) graft, and a semitendinosis reconstruction. The specimens were placed on a CPM device in a cooler at 38 degrees F and put through a range of motion of 20 to 70 degrees at 10 cycles per minute for 3 days. A success was less than a 2 mm increase in the post-CPM measurement compared to pre-CPM. All three bone-tendon-bone operations failed. The semitendinosis operation was successful in only three out of eight specimens. The OTT operation was successful in eight out of nine specimens. The possible reasons for success and failure are discussed. Because of the potential problems with failure of an ACL with CPM it is suggested that the particular technique being used for an anterior cruciate reconstruction be tested prior to it being used with CPM clinically.

Anatomy of the lateral ankle ligaments.

The anatomy of the lateral ankle ligaments that is frequently described in articles and book chapters often lacks the precision of orientation and attachment points. We believe a knowledge of this precise anatomy is important to better reconstruct or repair lateral ligaments. We dissected cadaveric ankles free of skin and soft tissue and made the following measurements: areas of attachments of the anterior talofibular ligament, length and width of the anterior talofibular ligament, and locations of the attachments on the fibula and talus. The same measurements were made of the calcaneofibular and posterior talofibular ligaments. The distance of the calcaneofibular calcaneal attachments from the subtalar joint as well as the angle in the sagittal plane with the fibula was determined. We then used these anatomic attachments of the ligaments to make comparisons with the Watson-Jones and modified Elmslie reconstructions. Our results enable us to suggest a more anatomic placement for ligaments in a reconstruction.

Short-term effects of knee washout for osteoarthritis.

Twenty-nine knees in 23 patients with symptomatic osteoarthritis underwent washout with lactated Ringer's solution. Two arthroscopic cannulas were placed into the knee under local anesthetic. Three liters of fluid were run through the knee using varying inflow and outflow to alternately inflate and deflate the knee. We obtained Hospital for Special Surgery knee scores, Knee Society pain and function ratings, and visual analog pain scales before washout and up to 2 years after washout. At 1 year, the mean Hospital for Special Surgery score increased from 72 to 87, the Knee Society pain rating from 64 to 89, and the Knee Society function rating from 62 to 82. Twenty-five knees had a good or excellent result at 1 year. Twenty-one of these were observed at 2 years; 17 had good or excellent results. This study confirms the value of a fluid washout in an arthritic knee for some patients. This may explain some of the symptom relief seen with arthroscopic procedures in this condition.