Implant Therapy in the Rehabilitation of Treated Mandibular Arteriovenous Malformations.

Mandibular arteriovenous malformations are rare congenital malformations that require multidisciplinary care. Implant-supported rehabilitation of significant bone defect after embolization and resection is poorly described in the literature. We present the case of a 24-year-old patient with a right-sided mandibular arteriovenous malformation diagnosed after massive hemorrhage and treated by embolization and resection surgery. Implant rehabilitation was carried out 9 years later with a prior bone graft through iliac extraction and 3 short implants. Implant survival rate and patient satisfaction were evaluated at 3 years postplacement. Arteriovenous malformations treatments frequently result in bone defects that are difficult to reconstruct because of probable unstable vascularization due to embolization. The presence of osteosynthesis material and artifacts at the radiological level complicates implant planning due to the lack of visualization of the inferior alveolar nerve or artery and necessitates the placement of low-height implants. Osteointegration in contact with embolization products should be monitored. The creation of a case series could be of interest in order to better understand implant treatment for patients with a history of arteriovenous malformations.

Hepatectomy for recurrent colorectal liver metastases after radiofrequency ablation.

BACKGROUND: The results of surgery for recurrent colorectal liver metastases (CLM) after radiofrequency ablation (RFA) have not been evaluated. METHODS: From 1993 to 2009, data on patients who underwent resection or RFA for recurrent CLM were collected prospectively. Inclusion criteria for this study were RFA as initial treatment for CLM and resection of recurrent CLM after RFA. Postoperative results and oncological outcomes were analysed. RESULTS: Twenty-eight patients (median number of tumours 1 (1-3), median size 2·8 (2·0-4·0) cm) met the inclusion criteria. Of these, 22 had recurrence at the site of RFA only, two developed new lesions, whereas four had both recurrent and de novo metastases. At the time of resection, patients had a median of 1 (1-13) CLM with a median maximum tumour diameter of 5·0 (1·8-11·0) cm, significantly larger than at the time of RFA (P = 0·021). Ninety-day postoperative morbidity and mortality rates were 46 per cent (13 of 28) and 7 per cent (2 of 28) respectively. After a median follow-up of 35 (0-70) months, 3-year overall and disease-free survival rates calculated by Kaplan-Meier analysis were 60 and 29 per cent respectively. Plasma carcinoembryonic antigen level over 5 ng/ml at the time of resection and a rectal primary tumour were associated with worse survival (P = 0·041 and P = 0·021 respectively). CONCLUSION: Resection for recurrence after RFA is associated with significant morbidity and modest long-term benefit.

Optimal modeling for phase I design of a two drug combination-results of a phase I study of cisplatin with 9-nitrocamptothecin.

Combination of platinum with topoisomerase-I inhibitors are synergistic. The objectives of this study were to determine MTD range and toxicity profile of combinations of oral 9-nitrocamptothecin (9NC) and intravenous cisplatin in patients with refractory solid tumors. Each course was 28 days starting on day 1 with cisplatin, and then 9NC daily for 5 days/week for three weeks. A new two arm crossing design was created: patients in arm 1 were treated with at the single agent recommended dose of cisplatin (50 mg/m(2)), and increasing doses of 9NC and in arm 2 with the single agent recommended dose of 9NC (1.5 mg/day) and increasing dose of cisplatin. Once a dose limiting toxicity was observed, the dose of the escalated drug was decreased by one level, and the fixed-dose drug was then escalated. A 3 + 3 design was used. Eligibility criteria were standard for a phase I trial. Pharmacokinetics was performed. Eighteen patients were treated on Arm 1, 3 at the crossing level, and 33 on Arm 2. Dose limiting toxicities were gastrointestinal at the crossing dose level. After crossing, prolonged grade 3 thrombocytopenia was the DLT in arm 1, and grade 4 neutropenia in Arm 2. Only one patient with ovarian cancer had a partial remission, and 12 patients had disease stabilization (24% of clinical benefit). A Bayesian optimal dose finding was tested post-facto. The recommended doses for phase II studies by the 3 + 3 design are cisplatin 60 mg/m(2) and 9NC 1.25 mg/day and cisplatin 40 mg/m(2) and 9NC 2.0 mg/day. The Bayesian optimal dose finding suggested a different solution, closest to that of the latter dosing which may be less toxic.

Portal vein embolization before major hepatectomy and its effects on regeneration, resectability and outcome.

BACKGROUND: This study evaluated the safety of portal vein embolization (PVE), its impact on future liver remnant (FLR) volume and regeneration, and subsequent effects on outcome after liver resection. METHODS: Records of 112 patients were reviewed. Standardized FLR (sFLR) and degree of hypertrophy (DH; difference between the sFLR before and after PVE), complications and outcomes were analysed to determine cut-offs that predict postoperative hepatic dysfunction. RESULTS: Ten (8.9 per cent) of 112 patients had PVE-related complications. Postoperative complications occurred in 34 (44 per cent) of 78 patients who underwent hepatic resection and the 90-day mortality rate was 3 per cent. A sFLR of 20 per cent or less after PVE or DH of not more than 5 per cent (versus sFLR greater than 20 per cent and DH above 5 per cent) had a sensitivity of 80 per cent and a specificity of 94 per cent in predicting hepatic dysfunction. Overall, major and liver-related complications, hepatic dysfunction or insufficiency, hospital stay and 90-day mortality rate were significantly greater in patients with a sFLR of 20 per cent or less or DH of not more than 5 per cent compared with patients with higher values. CONCLUSION: DH contributes prognostic information additional to that gained by volumetric evaluation in patients undergoing PVE.

Staging of pancreatic cancer with multidetector CT in the setting of preoperative chemoradiation therapy.

BACKGROUND: Preoperative chemoradiation can potentially improve outcomes in patients with pancreatic cancer. This study addresses its effect on staging pancreatic cancer with multidetector computed tomography (MDCT). METHODS: Fifty-five patients underwent a dual-phase MDCT pancreas protocol for proved pancreatic cancer. Of these, 16 patients underwent preoperative chemoradiation. Three radiologists independently reviewed images to assess for locally advanced disease, liver and peritoneal metastases on baseline studies of all 55 patients, and on follow-up preoperative studies for the 16 patients receiving preoperative therapy. Overall score for resectability was graded on a scale from 1 to 5 (1, definitely resectable; 5. definitely unresectable). Receiver operating characteristic curves and weighted (kappa statistics were determined. RESULTS: The areas under the receiver operating characteristic curves for readers 1, 2, and 3 were 0.98, 0.96, and 0.90, respectively. Weighted kappa values for reader 1 versus reader 2, reader 1 versus reader 3, and reader 2 versus reader 3 were 0.90, 0.57, and 0.54, respectively. Interpreting scores of 1 to 3 for resectability as resectable disease, the mean values for sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were 0.92, 0.91, 0.74, 0.98, and 0.92 respectively. CONCLUSION: The negative predictive value for MDCT for identifying unresectable pancreatic cancer in the setting of preoperative therapy is comparable to that reported in the absence of neoadjuvant therapy.

Use of thin-section, multidetector row helical CT images for coronal oblique reformations for optimal visualization of structures in the hepatoduodenal ligament.

Multidetector row computed tomography (CT) can acquire abdominal images of unprecedented thinness in a single breath-hold. This study investigated whether acquiring source axial images at 1.25 mm as opposed to 2.5 mm would result in a perceptible difference in image quality for coronal oblique reformations. Similarly, the hypothesis that a slice pitch of 3:1 would be superior to 6:1 was evaluated. Twenty-nine CT studies were retrospectively evaluated. The images were divided into four groups: 1.25-mm axial images, pitch 3:1; 2.5-mm axial images, pitch 3:1; 1.25-mm axial images, pitch 6:1; and 2.5-mm axial images, pitch 6:1. Three radiologists evaluated by consensus the coronal oblique reformations for overall image quality and image quality of structures in the hepatoduodenal ligament and of nodal groups. Use of 1.25-mm rather than of 2.5-mm source axial images resulted in statistically significant better scores for overall image quality and visualization of the hepatic artery, portal vein, pancreatic duct, and nodal groups. However, a pitch of 3:1 rather than of 6:1 did not result in significant differences in ratings of image quality. Use of 1.25-mm rather than of 2.5-mm source axial images improves image quality when creating coronal oblique reformations for abdominal anatomy.

Phase II study of carboplatin and liposomal doxorubicin in patients with recurrent squamous cell carcinoma of the cervix.

BACKGROUND: The activity of the combination of carboplatin and liposomal doxorubicin was tested in a Phase II study of patients with recurrent cervical carcinoma. METHODS: The combination of carboplatin (area under the concentration curve [AUC], 5) and liposomal doxorubicin (Doxil; starting dose, 40 mg/m(2)) was administered intravenously every 28 days to 37 patients with recurrent squamous cell cervical carcinoma to determine antitumor activity and toxicity profile. RESULTS: Twenty-nine patients were assessable for response, and 35 patients were assessable for toxicity. The overall response rate was 38%, the median time to response was 10 weeks, the median duration of response was 26 weeks, and the median survival was 37 weeks. The main toxic effect was myelosuppression, with Grade 3 and 4 neutropenia in 16 patients, anemia in 12 patients, thrombocytopenia in 11 patients, and neutropenic fever in 3 patients. Four patients had five infusion-related reactions during the infusion of liposomal doxorubicin, leading to treatment discontinuation in three patients. Grade > or = 2 nonhematologic toxicity included nausea in 17 patients, emesis in 14 patients, fatigue in 9 patients, mucositis and/or stomatitis in 8 patients, constipation in 6 patients, weight loss in 5 patients, hand-foot syndrome in 2 patients, and skin reactions in 3 patients. CONCLUSIONS: The combination of carboplatin and liposomal doxorubicin has modest activity in patients with recurrent cervical carcinoma.

Radio-frequency ablation of liver tumors: assessment of therapeutic response and complications.

An alternative to surgical resection of liver tumors, radio-frequency ablation induces in situ thermal coagulation necrosis through the delivery of high-frequency alternating current to the tissues. Imaging helps to detect treatable lesions, guide the placement of the probe, and assess the effect of therapy. Computed tomography (CT) is used most frequently to determine whether the ablation is complete and to screen for early recurrences that may benefit from reablation. Complete ablation creates an area of necrosis that, at CT, is of low attenuation compared with the surrounding liver tissue, is often homogeneous, and has smooth margins. The most important features are the size of the necrotic defect, which, immediately after treatment, should be larger than that of the pretreatment tumor, and the sharpness of the margins, which indicates an abrupt change in attenuation between the necrotic tissue and surrounding liver tissue. Enhancement, when present, is due to perfusion abnormality or granulation tissue and forms a regular rim or a homogeneous zone at the margin of the defect. It is seen immediately after ablation but may be prolonged. Enhancement is affected by the scanning technique. Over time, the size of the defect remains stable or decreases. Any variation from this general pattern is suggestive of incomplete ablation or recurrence.

Radiographic appearance of the chest following therapy for Hodgkin disease.

This study was carried out to define the post-treatment appearance of the chest radiographs in 44 consecutive patients with Hodgkin disease who received mantle irradiation with or without chemotherapy and to determine how the incidence and severity of post-treatment abnormalities relate to the radiation parameters and chemotherapeutic regimens. Radiographs of the chest in 44 patients, computed tomograms of the chest in 31 patients and of the abdomen of 35 patients were reviewed, prior to and following treatment, for mediastinal contours, pericardial status, cardiac size and pulmonary fibrosis. All patients were followed for a minimum of 1 year and 27 were followed for more than 5 years. Stable post-treatment imaging studies were correlated with the initial extent of disease, radiation parameters, and chemotherapeutic regimens. Stable post-treatment findings were categorised as follows: the chest radiograph was normal or showed subtle vascular reorientation; moderate paramediastinal fibrosis was present; severe pulmonary fibrosis had occurred with narrowing of the cardiomediastinal silhouette in some patients. In general, the severity of the fibrosis was dependent on (1) the size of the radiation fields and on whether or not the coverage of the hila included a 1- to 2-cm margin; (2) the amounts of chemotherapy and particularly bleomycin containing regimens and (3) individual susceptibility of normal tissue irradiation. Therapy for Hodgkin disease is not necessarily associated with radiographic sequelae regardless of the initial status of the mediastinum or the treatment. However, the post-treatment appearance of the chest radiographs in this study was related strongly to (1) the initial extent of disease and particularly the status of the hila, both of which influenced the amounts of lung parenchyma that were included in the treatment fields; (2) the use of bleomycin in chemotherapy regimens and (3) individual normal tissue radiosensitivity.

Hepatocellular carcinoma and intrahepatic peripheral cholangiocarcinoma: enhancement patterns with quadruple phase helical CT--a comparative study.

PURPOSE: To define the hemodynamic features of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma by using quadruple phase helical computed tomography (CT) and determine the value of this information in characterizing tumors. MATERIALS AND METHODS: Helical CT of the liver was performed in 45 patients with newly diagnosed HCC or peripheral cholangiocarcinoma. Scans were obtained before and 25 seconds, 70 seconds, and 2-6 minutes after the start of the contrast material injection. The intensity and spatial distribution of contrast material uptake were evaluated during all phases. Time-attenuation curves were established for each lesion. Relative attenuation and lesion conspicuity were assessed. A diagnostic confidence level was assigned to each lesion. RESULTS: In the majority of HCC lesions, a single, early peak of enhancement followed by a continuous decrease in tumor attenuation over time was seen. The greatest tumor conspicuity occurred during the delayed phase. In cholangiocarcinoma, tumor attenuation increased during the delayed phase. In the majority of lesions, the greatest tumor conspicuity was seen during the portal venous phase. In both tumor types, the diagnostic confidence level improved when the delayed phase was used. CONCLUSION: The variation over time in the intensity of contrast enhancement in HCC and cholangiocarcinoma differs sufficiently to make this a useful diagnostic criterion. The delayed phase is particularly important because it amplifies this difference.

Metastases to the pancreas from renal cell carcinoma: findings on three-phase contrast-enhanced helical CT.

OBJECTIVE: Our goal was to define the lesion enhancement characteristics of renal cell carcinoma metastases to the pancreas using three-phase helical CT. MATERIALS AND METHODS: Thin-section three-phase contrast-enhanced CT scans of nine patients with renal cell carcinoma metastases to the pancreas were evaluated. The helical CT protocol included 3-mm collimation and a 2:1 pitch. Scans through the pancreas were obtained in three series beginning 25, 60, and 120 sec after the start of administration of i.v. contrast material delivered at 3 ml/sec. The Hounsfield densities of the pancreatic lesions and normal pancreatic parenchyma during each of the enhancement phases were recorded and compared. RESULTS: The enhancement patterns of the metastatic deposits and the normal pancreas differed. Thirty-four lesions ranging in size from 6 to 110 mm were identified. All metastases showed rapid enhancement during the early (arterial and portal) phases, resulting in differential attenuations (compared with normal pancreatic parenchyma) of approximately 50-100 H. The differential attenuations were approximately 5-45 H on delayed-phase scans, resulting in poorer conspicuity of the lesions. Multifocal metastases were clearly identified on the early-phase scans in seven patients. CONCLUSION: Renal cell carcinoma metastases to the pancreas enhance most conspicuously during the early phases of helical CT. Such metastases may fail to be appreciated in the delayed phase. In patients with suspected renal cell carcinoma metastases to the pancreas, early-phase scanning after i.v. contrast administration should be performed.

A phase II clinical and pharmacological study of oral 9-nitrocamptothecin in patients with refractory epithelial ovarian, tubal or peritoneal cancer.

9-Nitrocamptothecin (9-NC) is a water-insoluble topoisomerase I inhibitor with a broad antitumor activity in animal models. A phase II study was performed in patients with heavily refractory ovarian, tubal or peritoneal cancer (median number of previous chemotherapy regimens > 3) to determine the activity of a daily oral dose of 9-NC. 9-NC dose was 1.5 mg/m2/day for four consecutive days every week. Increments of 0.25 mg/day were authorized in patients without significant side effects. Of 29 evaluable patients, a 7% remission rate was observed. Thirty-four percent of patients had stable disease. The median survival was 8 months. Toxicity was evaluated in 31 patients. Grade 3 or 4 hematologic toxicity consisted of anemia in 10 patients (32%), neutropenia in eight (26%) and thrombocytopenia in three (10%). Grade > or = 2 non-hematologic toxic effects were nausea and vomiting in 26 (84%), diarrhea in 12 (39%), weight loss in seven (22%), chemical cystitis in six (19%) and neutropenic sepsis in six (19%). 9-NC was tolerated for sustained periods of time in some patients (up to 47 weeks). The observed 8-month survival in such a refractory patient population is noteworthy. Further clinical research of prolonged exposure to less toxic analogs of 9-NC is warranted.

Octreotide induced remission of a refractory small cell carcinoma of the endometrium.

This is the first report of remission obtained with octreotide in a woman diagnosed with recurrent small cell carcinoma of the endometrium with neuroendocrine features, refractory to a combination of etoposide, cisplatin, and radiation therapy. Stabilization of disease was obtained with a combination of tamoxifen and leuprolide depot. Regression of disease was then achieved by the addition of octreotide. The use of octreotide as an antitumor agent is reviewed.

Dissociation between bone resorption and bone formation in osteopenic transgenic mice.

Bone mass is maintained constant in vertebrates through bone remodeling (BR). BR is characterized by osteoclastic resorption of preexisting bone followed by de novo bone formation by osteoblasts. This sequence of events and the fact that bone mass remains constant in physiological situation lead to the assumption that resorption and formation are regulated by each other during BR. Recent evidence shows that cells of the osteoblastic lineage are involved in osteoclast differentiation. However, the existence of a functional link between the two activities, formation and resorption, has never been shown in vivo. To define the role of bone formation in the control of bone resorption, we generated an inducible osteoblast ablation mouse model. These mice developed a reversible osteopenia. Functional analyses showed that in the absence of bone formation, bone resorption continued to occur normally, leading to an osteoporosis of controllable severity, whose appearance could be prevented by an antiresorptive agent. This study establishes that bone formation and/or bone mass do not control the extent of bone resorption in vivo.