Effects of bone marrow or mesenchymal stem cell transplantation on oral mucositis (mouse) induced by fractionated irradiation

Background and purpose

Oral mucositis is a severe and dose limiting early side effect of radiotherapy for head-and-neck tumors. This study was initiated to determine the effect of bone marrow- and mesenchymal stem cell transplantation on oral mucositis (mouse tongue model) induced by fractionated irradiation.

Material and methods

Daily fractionated irradiation (5?×?3 Gy/week) was given over 1 (days 0–4) or 3 weeks (days 0–4, 7–11, 14–18). Each protocol was terminated (day 7 or 21) by graded test doses (5 dose groups, 10 animals each) in order to generate complete dose–effect curves. The incidence of mucosal ulceration, corresponding to confluent mucositis grade 3 (RTOG/EORTC), was analyzed as the primary, clinically relevant endpoint. Bone marrow or mesenchymal stem cells were transplanted intravenously at various time points within these fractionation protocols.

Results

Transplantation of 6?×?10⁶, but not of 3?×?10⁶ bone marrow stem cells on day ??1, +?4, +?8, +?11 or +?15 significantly increased the ED₅₀ values (dose, at which an ulcer is expected in 50?% of the mice); transplantation on day +?2, in contrast, was ineffective. Mesenchymal stem cell transplantation on day ??1, 2 or +?8 significantly, and on day +?4 marginally increased the ED₅₀ values.

Conclusion

Transplantation of bone marrow or mesenchymal stem cells has the potential to modulate radiation-induced oral mucositis during fractionated radiotherapy. The effect is dependent on the timing of the transplantation. The mechanisms require further investigation.     

The effects of antimuscarinic treatments in overactive bladder: a systematic review and meta-analysis

OBJECTIVES: To evaluate the tolerability, safety and efficacy of antimuscarinic drugs used to treat overactive bladder and to identify any differences between individual antimuscarinics. METHODS: Medline, Embase, CCTR and Cinahl databases were searched for published RCTs including an antimuscarinic agent from 1966 to August 2004. Data from included trials were extracted and meta-analysed where possible. RESULTS: Fifty-six trials were included. The antimuscarinics were found to be safe and efficacious. All antimuscarinics apart from oxybutynin IR were found to be well tolerated. Dry mouth was the most commonly reported adverse event and no drug was associated with an increase in any serious adverse event. There were significant differences between the antimuscarinics in rates of withdrawal and rates and range of adverse events and efficacy outcomes. CONCLUSIONS: The antimuscarinics have different tolerability and safety profiles, which are clinically significant.     

Safety of Gastric Resections During Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis

Background  Cytoreductive surgery (CRS) including gastric resection combined with hyperthermic intraperitoneal chemotherapy (HIPEC) can improve the prognosis of selected patients with peritoneal surface malignancies. Perioperative morbidity of this aggressive treatment strategy is high; however, overall mortality can be low in specialized centers. The aim of this study was to assess the safety of gastric resections with anastomosis during CRS and HIPEC. Methods  Between 2005 and 2008, 204 patients underwent CRS and HIPEC at our tertiary referral centre. Of these, 37 procedures (male/female 24/13, median age 55 years) included gastric resections. The clinical data of all patients were introduced into a database and analyzed with respect to the morbidity associated with the gastric resections. Results  Of all patients included, 16 had pseudomyxoma peritonei, 11 gastric carcinoma, 4 ovarian carcinoma, 3 malignant peritoneal mesothelioma, and 3 colon carcinoma. Twenty-seven patients had previous surgery (n = 22) and/or systemic chemotherapy (n = 18). Fifteen total gastrectomies, 3 subtotal gastrectomies, 12 distal gastrectomies, and 7 gastric wedge resections were performed during CRS. The overall postoperative morbidity was 45%; main surgical complications were pancreatitis (n = 6), abdominal abscess (n = 4), bile leakage (n = 2), and digestive fistula (leakage of ileorectostomy and small bowel perforation) (n = 2). However, no complications occurred at the site of the esophageal anastomosis (n = 15), gastric anastomosis (n = 15) or gastric suture (n = 7). No patient died postoperatively during the hospitalization period. Conclusions  CRS in combination with HIPEC is associated with high postoperative morbidity; however, anastomosis following total or subtotal gastrectomy is safe in experienced centers. No leakages related to gastric resections occurred in this high-risk patient group. Pompiliu Piso and Przemyslaw Slowik have contributed equally to this study.     

Seudoquiste adrenal grande que simula feocromocitoma quístico: exéresis minimizando el acceso laparoscópico

IntroductionAdrenal cysts and pseudocysts are rare and usually benign and asymptomatic; they are discovered either accidentally or during examination for non-specific abdominal discomfort. Less frequently, they may cause gastrointestinal symptoms or abdominal or lumbar pain, particularly when they are quite large. Histologically, they are classified as epithelial, endothelial, parasitic and pseudocysts (with a fibrous wall but no epithelium). The differential diagnosis for adrenal cysts must consider cystic adrenal carcinoma and cystic pheochromocytoma, which are both extremely rare, but more severe and difficult to treat.Patients and resultsA 55 year-old woman reported right-side flank pain; imaging studies discovered a 10cm cystic adrenal tumour, with radiological indications of cystic pheochromocytoma. Total transperitoneal laparoscopic excision was performed through three access ports. The cyst was drained by intra-abdominal bagging and aspiration before excision, in order to minimise surgical incisions. Pathological study showed benign pseudocyst.ConclusionsAs less invasive laparoscopic procedures become widespread, an increasing number of case reports and series of cases regarding adrenal cyst operations have recently been reported. A review of the literature shows that the cysts are generally benign, but it is not always possible to identify cystic adrenal carcinoma or cystic pheochromocytoma from the radiology image. Draining the cyst using an aseptic and oncologically safe procedure is useful for minimising surgical wounds and increases the benefits of laparoscopic access.     

The association between killer‐cell immunoglobulin‐like receptor (KIR) and KIR ligand genotypes and the likelihood of BK virus replication after kidney transplantation

BK virus is a common opportunistic post‐transplantation viral infection. Although some risk factors have been studied in this context, the contribution of NK cells has not been assessed in detail. In a group of kidney transplant recipients, we studied the association between (i) the likelihood of BK virus replication during the two‐year period after kidney transplantation and (ii) the genotypes of the killer cell immunoglobulin‐like receptor (KIR) repertoire and their human leukocyte antigen (HLA) ligands. Other clinical factors (such as defective organ recovery and immunosuppressive treatment) were also assessed. BK virus replication was observed in 43 of the 103 recipients (41%). Patients with BK virus replication in the plasma were more likely to display defective organ recovery in the first seven days post‐transplantation. BK virus replication was not associated with Missing KIR ligands. However, BK virus replication was more frequent in patients with responsive NK cells (i.e. when a ligand for activating KIRs was not homozygous in the recipient and present in the donor). Our results suggest that defective organ recovery and the recipient's activating KIR repertoire may be related (depending on HLA ligands present in the couple recipient / donor) to the reactivation of BK virus replication after kidney transplantation.     

Isolated Duodenal Rupture due to Go-Karting Accidents – Braking News

INTRODUCTION

Isolated duodenal injury due to blunt abdominal trauma is extremely rare. We present a series of three such injuries due to go-karting accidents, which presented to our hospital over 5 months.

CASE REPORTS

Between October 2007 and February 2008, three cases of D3/D4 duodenal rupture presented to our hospital after go-karting accidents. Trauma occurred as a result of the steering wheel impacting on the abdomen. All patients presented similarly with symptoms of epigastric and right upper quadrant pain. In all cases, computed tomography scanning was highly suggestive of duodenal injury and, in particular, demonstrated presence of retroperitoneal air centred around the duodenum. Treatment required laparotomy and operative repair in all cases.

CONCLUSIONS

Duodenal injury presents insidiously due to its retroperitoneal position. A low threshold for investigating patients presenting with epigastric and right upper quadrant pain should be adopted along with active clinical vigilance to exclude serious and life-threatening trauma after go-karting accidents.     

Early and frequent histological recurrence of Crohn's disease in small intestinal allografts

BACKGROUND: Recurrence of Crohn's disease in small intestinal allografts, although rarely described, can cause serious morbidity and jeopardize graft survival among transplant recipients with Crohn's disease. However, systematic studies to determine the frequency, predictors, and clinical implications of recurrent Crohn's disease have not been reported METHODS: We analyzed our transplant program's experience with small intestinal allografts in patients with Crohn's disease based on retrospective review of clinical and pathological records and corresponding pathology slides. RESULTS: Of 67 patients undergoing 70 transplantations between 1998 and 2004, six adults (three males, three females; mean age 48.1 years) had Crohn's disease complicated by short gut syndrome and total parenteral nutrition failure. Four survivors surveyed endoscopically for a mean 29 (range, 20-40) months and underwent a mean 37 endoscopic examinations with biopsies (range, 31-44) while on maintenance immunosuppression. Despite absence of any endoscopic or clinical manifestations of Crohn's disease throughout this period, two patients had granulomatous enteritis characteristic of Crohn's disease in multiple biopsies, one patient in 8/44 examinations (18%) ranging from 34 days to 20 months postoperatively and the other in 6/32 examinations (19%) ranging from 20 days to 22 months postoperatively. No comparable changes occurred in 57 other patients without Crohn's disease followed endoscopically under the same protocol CONCLUSIONS: Histological recurrence of Crohn's disease may occur in small intestinal allografts despite the absence of endoscopic and clinical disease manifestations. Such recurrences are probably not rare, may occur as early as 3 weeks after transplantation, and do not necessarily portend early clinical recurrence or mandate aggressive therapy to prevent allograft loss.     

Clinical value of a high-fat and low-carbohydrate diet before FDG-PET/CT for evaluation of patients with suspected cardiac sarcoidosis

Background

We hypothesized that a high-fat and low-carbohydrate (HFLC) diet before FDG-PET/CT could identify patients with active cardiac sarcoidosis (CS).

Methods

Fifty-eight sarcoidosis patients with a suspicion of CS consumed a HFLC diet before FDG-PET/CT. Clinical, electrical, and other imaging investigations were compared to PET results.

Results

Using Japanese Ministry of Health and Welfare (JMHW) criteria as a gold standard, 21% (12/58) of patients had a CS. Sensitivity and specificity of PET (visual analysis) were 83% (10/12) and 78% (36/46), respectively, with a very good interobserver agreement (k = 0.86). 70% (7/10) of the patients with a positive PET and negative JMHW criteria exhibited abnormalities suggestive of CS either on MR (n = 3) or SPECT (n = 4). Comparison with the presence of delayed enhancement on magnetic resonance imaging helped to classify patients with active (PET positive) or non-active CS (PET negative). In addition, when MR and PET were both negative, none of the patients met the JMHW criteria. PET response under treatment was concordant with clinical evolution in 11/13 patients.

Conclusions

FDG-PET/CT after HFLC diet is a sensitive tool for the diagnosis of active CS. Combined use of PET and MR is promising for the detection and characterization of CS lesions.     

Functional outcome in a contemporary series of major lower extremity amputations

PURPOSE: We undertook this study to document the functional natural history of patients undergoing major amputation in an academic vascular surgery and rehabilitation medicine practice. METHODS: A retrospective review was conducted of consecutive patients undergoing major lower extremity amputation and rehabilitation in a university and Department of Veterans Affairs hospital. Main outcome variables included operative mortality, follow-up, survival, median time to incision healing, secondary operative procedures for wound management, and conversion from below-knee amputation (BKA) to above-knee amputation (AKA). For surviving patients, quality of life was determined by degree of ambulation, eg, outdoors, indoors only, or no ambulation; use of a prosthesis; and independence, eg, community housing or nursing facility. RESULTS: From August 1997 through March 2002, 154 patients (130 men; median age, 62 years) underwent 172 major amputations, 78 AKA and 94 BKA, because of either critical limb ischemia (87%) or diabetic neuropathy (13%). Thirty-day operative mortality was 10%. Mean follow-up was 14 months. Healing at 100 and 200 days, as determined with the Kaplan-Meier method, was 55% and 83%, respectively, for BKA, and 76% and 85%, respectively, for AKA. Twenty-three BKA and 16 AKA required additional operative revision, and 18 BKA ultimately were converted to AKA. Survival was 78% at 1 year and 55% at 3 years. Function in surviving patients at 10 and 17 months, respectively, was as follows: 21% and 29% of patients ambulated outdoors, 28% and 25% ambulated indoors only, and 51% and 46% of patients were nonambulatory; 32% and 42% of patients used prosthetic limbs; and 17% and 8% of patients who lived in the community before amputation required care in a nursing facility. CONCLUSIONS: We were surprised to find that vascular patients in a contemporary setting who require major lower extremity amputation and rehabilitation often remain independent despite infrequent prosthesis use and outdoor ambulation. Although any hope for postoperative ambulation in this population requires salvaging the knee joint, because of the morbidity incurred in both wound healing and rehabilitation efforts, aggressive effort should be reserved for selected patients at good risk. Ability to predict ambulation after BKA in the vascular population is poor.