BRAF Inhibitors for BRAF V600E Mutant Colorectal Cancers: Literature Survey and Case Report.

The main method of fighting against colon cancer is targeted treatment. BRAF inhibitors, which are accepted as standard treatment for V600E mutant malign melanomas, are the newest approach for targeted treatment of V600E mutant colorectal cancers. In this case report, we share our experience about the use of BRAF inhibitor vemurafenib on a V600E mutant metastatic right colon adenocarcinoma patient. A 59-year-old male with only lung multiple metastatic V600E mutant right colon cancer presented to our clinic. The patient was evaluated and FOLFOX + bevacizumab treatment was initiated, which was then continued with vemurafenib. A remarkable response was achieved with vemurafenib treatment in which the drug resistance occurred approximately in the sixth month. Even though the patient benefited majorly from vemurafenib, he died on the 20th month of the diagnosis. The expected overall survival for metastatic V600E mutant colon adenocarcinoma patients is 4.7 months. BRAF inhibitors provide new treatment alternatives for V600E mutant colorectal cancers, with prolonged overall survival. BRAF inhibitors in combination with MEK inhibitors are reported as feasible treatment to overcome BRAF inhibitor drug resistance on which phase studies are still in progress. To conclude, BRAF inhibitors alone or in combination with other drugs provide a chance for curing BRAF V600E mutant colorectal cancer patients.

Effects and Results of Omentopexy During Laparoscopic Sleeve Gastrectomy.

PURPOSE: The aim of this study was to demonstrate that gastric volvulus can be prevented by omentopexy and sleeve gastrectomy without increasing other complication rates. MATERIALS AND METHODS: A total of 1385 patients who underwent omentopexy and sleeve gastrectomy between April 2013 and September 2017 were included this study. Body mass index, age, sex, comorbidities, and postoperative complications of the patients were recorded as data. RESULTS: A total of 1385 patients underwent sleeve gastrectomy and omentopexy. There were 999 female and 386 male patients. The mean age of the patients was 36 years (14 to 71 y). The mean body mass index was 42.74 kg/m (35 to 73 kg/m). Twenty-one patients had previously undergone gastric banding and the other 80 patients had previous abdominal operation. The number of patients undergoing simultaneous cholecystectomy was 98. Three patients had hemorrhage due to hypertension and anticoagulant treatment in the postoperative period and the patients were treated medically. One staple-line leakage was observed. Twist, and stricture were not observed and no mortalities were noted. CONCLUSIONS: Sleeve gastrectomy and omentopexy can prevent the gastric twist, which is a functional cause of gastric stenosis, by stabilizing the posterior stomach wall.

Prevention of Intraabdominal Adhesions: An Experimental Study Using Mitomycin-C and 4% Icodextrin.

BACKGROUND: Intraabdominal adhesions remain a significant cause of morbidity and mortality. Moreover, intraabdominal adhesions can develop in more than 50% of abdominal operations. AIMS: We compared the anti-adhesive effects of two different agents on postoperative adhesion formation in a cecal abrasion model. STUDY DESIGN: Experimental animal study. METHODS: Forty Wistar albino type female rats were anesthetized and underwent laparotomy. Study groups comprised Sham, Control, Mitomycin-C, 4% Icodextrin, and Mitomycin-C +4% Icodextrin groups. Macroscopic and histopathological evaluations of adhesions were performed. RESULTS: The frequencies of moderate and severe adhesions were significantly higher in the control group than the other groups. The mitomycin-C and Mitomycin-C +4% Icodextrin groups were associated with significantly lower adhesion scores compared to the control group and 4% Icodextrin group scores (p=0.002 and p=0.008, respectively). The adhesion scores of the Mitomycin-C group were also significantly lower than those of the 4% Icodextrin group (p=0.008). CONCLUSION: Despite its potential for bone marrow toxicity, Mitomycin-C seems to effectively prevent adhesions. Further studies that prove an acceptable safety profile relating to this promising anti-adhesive agent are required before moving into clinical trials.

Comparison of the effects of Mitomycin-C and sodium hyaluronate/carboxymethylcellulose [NH/CMC] (Seprafilm) on abdominal adhesions.

INTRODUCTION: Intra-abdominal adhesions (IA) may occur after abdominal surgery and also may lead to complications such as infertility, intestinal obstruction and chronic pain. The aim of this study was to compare the effects of Mitomycin-C (MM-C) and sodium hyaluronate/carboxymethylcellulose [NH/CMC] on abdominal adhesions in a cecal abrasion model and to investigate the toxicity of MM-C on complete blood count (CBC) and bone marrow analyses. METHODS: The study comprised forty rats in four groups (Control, Sham, Cecal abrasion + MM-C, and Cecal abrasion + NH/CMC). On postoperative day 21, all rats except for the control (CBC + femur resection) group, were sacrificed. Macroscopical and histopathological evaluations of abdominal adhesions were performed. In order to elucidate the side effects of MM-C; CBC analyses and femur resections were performed to examine bone marrow cellularity. RESULTS: CBC analyses and bone marrow cellularity assessment revealed no statistically significant differences between MM-C, NH/CMC and control groups. No significant differences in inflammation scores were observed between the groups. The MM-C group had significantly lower fibrosis scores compared to the NH/CMC and sham groups. Although the adhesion scores were lower in the MM-C group, the differences were not statistically significant. CONCLUSION: Despite its potential for systemic toxicity, MM-C may show some anti-fibrosis and anti-adhesive effects. MM-C is a promising agent for the prevention of IAs, and as such, further trials are warranted to study efficacy.

Prevention and acute management of biliary injuries during laparoscopic cholecystectomy: Expert consensus statement.

Gallstone disease is very common and laparoscopic cholecystectomy is one of the most common surgical procedures all over the world. Parallel to the increase in the number of laparoscopic cholecystectomies, bile duct injuries also increased. The reported incidence of bile duct injuries ranges from 0.3% to 1.4%. Many of the bile duct injuries during laparoscopic cholecystectomy are not due to inexperience, but are the result of basic technical failures and misinterpretations. A working group of expert hepatopancreatobiliary surgeons, an endoscopist, and a specialist of forensic medicine study searched and analyzed the publications on safe cholecystectomy and biliary injuries complicating laparoscopic cholecystectomy under the organization of Turkish Hepatopancreatobiliary Surgery Association. After a series of e-mail communications and two conferences, the expert panel developed consensus statements for safe cholecystectomy, management of biliary injuries and medicolegal issues. The panel concluded that iatrogenic biliary injury is an overwhelming complication of laparoscopic cholecystectomy and an important issue in malpractice claims. Misidentification of the biliary system is the major cause of biliary injuries. To avoid this, the "critical view of safety" technique should be employed in all the cases. If biliary injury is identified intraoperatively, reconstruction should only be performed by experienced hepatobiliary surgeons. In the postoperative period, any deviation from the expected clinical course of recovery should alert the surgeon about the possibility of biliary injury.

Systematic review of studies investigating sentinel node navigation surgery and lymphatic mapping for gastric cancer.

Evolutions in minimally invasive surgical techniques and advances in sentinel node navigation surgery (SNNS) have had considerable impact on current insights into surgical treatment of gastric cancer. Extensive data on this method of surgical application have accumulated but have been principally derived from single-institute studies. Isosulfan blue and patent blue violet have been the most frequently used dye tracers in the past; however, indocyanine green has now is increasingly popular. The double-tracer method, where dye and radioisotope tracers are used together, seems to be more effective than any single tracer. Among newly emerging adjunct techniques and promising alternative in particular are infrared ray electronic endoscopy, florescence imaging, nanoparticles, and near-infrared technology. Hematoxylin and eosin (H&E) staining is still the method of choice for the detection of sentinel lymph node (SLN) metastases. Immunohistochemical staining can be used to support H&E findings, but the equipment costs of ultrarapid processing systems are currently slowing down their worldwide spread. We believe minimally invasive function-preserving resection of the stomach, together with lymphatic basin dissection navigated by SLNs, can represent the ideal approach for SNNS to detect clinically node-negative early gastric cancer, although this remains to be elucidated. Patients with cT3 or more advanced disease should still be treated by means of standard D2 dissection.

The effects of hyperbaric oxygen therapy on experimental colon anastomosis after preoperative chemoradiotherapy.

The aim of the present study was to investigate the effect of hyperbaric oxygen therapy (HBOT) on colon anastomosis after chemoradiotherapy (CRT). Sixty female Wistar-Albino rats were divided into 5 groups and underwent left colon resection and end-to-end anastomosis. CRT simulation was performed on 2 sham groups before the anastomosis, and 1 of these groups was administered additional postoperative HBOT. Two groups were administered CRT before the anastomosis, and 1 of them received additional postoperative HBOT. On postoperative day 5, all groups underwent relaparotomy; burst pressure was measured and samples were obtained for histopathologic and biochemical analysis. There was a significant weight loss in the CRT groups and postoperative HBOT had an improving effect. Significantly decreased burst pressure values increased up to the levels of the controls after HBOT. Hydroxyproline levels were elevated in all groups compared to the control group. Hydroxyproline levels decreased with HBOT after CRT. No significant difference was observed between the groups regarding fibrosis formation at the anastomosis site. However, regression was observed in fibrosis in the group receiving HBOT after CRT. Preoperative CRT affected anastomosis and wound healing unfavorably. These unfavorable effects were alleviated by postoperative HBOT. HBOT improved the mechanical and biochemical parameters of colon anastomosis in rats.

The role of 2-[f-18] fluoro 2-deoxy d-glucose positron emission tomography in the preoperative staging of gastric cancer.

OBJECTIVE: FDG-PET can contribute significantly to the preoperative period of patients with planned curative resections or with isolated liver or lung metastasis. In this study, we analyze the importance and diagnostic value of FDG-PET in the preoperative evaluation of gastric cancers by correlating its value with computerized tomography (CT). MATERIALS AND METHODS: A prospective study was conducted. Abdominal and pelvic CTs were obtained for preoperative staging in each patient. Separate stagings were performed according to the findings of conventional methods and PET scans, and the results were compared with the operative and histological findings. RESULTS: When the patients were evaluated according to the pathological stage, eight patients were Stage 1 (26.7%), five were Stage 2 (16.7%), eight were Stage 3 (26.7%), and nine were Stage 4 (30%). FDG-PET and CT down-staged the disease in eight (26.7%) and twelve (40%) patients, respectively. FDG-PET and CT up-staged the disease in two (6.7%) and five patients (16.7%), respectively. FDG-PET accurately staged the disease in eighteen patients (60%) (p= 0.182). CONCLUSION: To develop highly sensitive radioactive tests that show invasive local lymph node and peritoneal metastases, more studies in the preoperative staging of gastric cancer are needed. FDG-PET indicates a high specificity in the staging of gastric cancer. In patients who are planned for curative surgery, FDG-PET provides better staging when used with CT.

A rare pathology that caused high-level intestinal obstruction: Left paraduodenal hernia.

The aim of this report is to assess clinical findings and surgical treatment of left paraduodenal hernia, which is an unusual type of internal herniation, in light of the literature. The diagnosis and treatment course of a 42-year-old male patient with findings of intestinal obstruction was assessed and presented together with literature search. The patient underwent surgery with a preliminary diagnosis of intestinal obstruction and the definitive diagnosis of internal herniation was made intraoperatively. Nearly two-thirds of the small intestine was found to be herniated into the retroperitoneal space from the left paraduodenal region. Small bowel loops were pulled out of the hernia sac and anatomically positioned in the intraperitoneal area. The hernia sac was repaired primarily. The patient was discharged on the fourth postoperative day, uneventfully. Left paraduodenal hernia should be considered as a part of differential diagnosis in patients who have recurring abdominal pain episodes accompanied by symptoms suggestive of intestinal obstruction. Timely diagnosis is important to prevent complications. Reduction of hernia content followed by primary repair of the defect appears to be a safe and effective treatment.

Abdominal aortic injury due to lumbar disc surgery: A case report.

Complications arising from lumbar intervertebral disc surgery are rare but fatal. Major vascular injury is one complication that may end in death unless it is diagnosed and treated immediately. Herein we report an abdominal aortic injury due to L3-L4 intervertebral disc surgery that was treated successfully and discuss it in light of current literature. Diagnosis and treatment of an abdominal aortic injury in a 31-year-old male patient operated on for L3-L4 intervertebral disc degeneration is discussed. Interestingly, in spite of abdominal aortic injury this particular patient was hemodynamically stable. The diagnosis was made 12 hours after disc surgery and laparotomy was performed immediately. As the injury in the aorta was large and had irregular margins, it could not be repaired with primary repair but an end-to-end anastomosis with partial resection was performed. In lumbar intervertebral disc hernia surgery, peroperative hemodynamic instability should raise suspicion of major vascular injury with high mortality and appropriate surgical treatment should be done as soon as possible. If there is any finding suggesting an intraoperative vascular injury, the patient should be kept under close monitoring in order not to delay diagnosis and treatment. It should not be forgotten that hemodynamic stability does not rule out major vascular injury.

Acute ischemic cholecystitis after transarterial chemoembolization with drug-eluting beads.

Transarterial chemoembolization (TACE) is a widely used treatment choice for hepatocellular cancer. DC Bead microspheres are a new embolic material for TACE that doxorubicin can be loaded to. The tumor response rate of this well-tolerated treatment was changed between 60% and 81.8%. We report a case of ischemic cholecystitis after TACE with drug-eluting beads (DEB) that required cholecystectomy. The possibility of cholecystitis is always remembered during TACE-DEB for tumors in segment IV and/or V. Although selective catheterization is related with a lower risk for ischemic cholecystitis, the anatomic and vascular variability in patients with malignancy may lead to some unexpected conditions.

Sentinel lymph node biopsy for gastric cancer: Where do we stand?

Development of sentinel node navigation surgery (SNNS) and advances in minimally invasive surgical techniques have greatly shaped the modern day approach to gastric cancer surgery. An extensive body of knowledge now exists on this type of clinical application but is principally composed of single institute studies. Certain dye tracers, such as isosulfan blue or patent blue violet, have been widely utilized with a notable amount of success; however, indocyanine green is gaining popularity. The double tracer method, a synchronized use of dye and radio-isotope tracers, appears to be superior to any of the dyes alone. In the meantime, the concepts of infrared ray electronic endoscopy, florescence imaging, nanoparticles and near-infrared technology are emerging as particularly promising alternative techniques. Hematoxylin and eosin staining remains the main method for the detection of sentinel lymph node (SLN) metastases. Several specialized centers have begun to employ immunohistochemical staining for this type of clinical analysis but the equipment costs involving the associated ultra-rapid processing systems is limiting its widespread application. Laparoscopic function-preserving resection of primary tumor from the stomach in conjunction with lymphatic basin dissection navigated by SLN identification represents the current paramount of SNNS for early gastric cancer. Patients with cT3 stage or higher still require standard D(2) dissection.

Mycophenolic acid may delay allograft fibrosis by inhibiting transforming growth factor-beta1-induced activation of Nox-2 through the nuclear factor-kappaB pathway.

BACKGROUND: We evaluated the role of renal tubular Nox-2 in the pathogenesis of epithelial-to-mesenchymal transition (EMT) in kidney allografts. METHODS: We examined this question in the human kidney allografts with interstitial fibrosis and tubular atrophy not otherwise specified (IFTANOS), in the Fisher to Lewis rat transplant model, and in the in vitro model of transforming growth factor-beta1-induced EMT in normal rat kidney epithelial cells (NRK52E). RESULTS: We first demonstrated that Nox-2 and alpha-smooth muscle actin (SMA) were increased in renal tubules from kidney transplant recipients on calcineurin inhibitors, mycophenolic acid (MPA), and prednisone with IFTANOS, suggestive of EMT (n=6). Next, we examined Nox-2 expression and fibrogenesis in syngeneic transplants, allogeneic transplants treated with MPA 40 mg/kg per 24 hr, and untreated allogeneic transplants for 6 months (n=14 in each group). Immunofluorescent and immunohistochemical studies for Nox-2, alpha-SMA, and E-cadherin showed that similar to patients with IFTANOS, rat allografts had greater tubulointerstitial staining for Nox-2 and alpha-SMA. MPA therapy prevented these changes. Immunoblot analyses examining Nox-2 signaling (phospho-nuclear factor [NF]-kappaB), redox signaling (phospho-smad2), and fibrosis (alpha-SMA and fibronectin) demonstrated that MPA treatment prevented the up-regulation of Nox-2, inhibited p-NF-kappaB and p-smad2, and down-regulated alpha-SMA and fibronectin levels. Finally, we examined Nox-2 signaling in vitro and confirmed that MPA inhibited phospho-NF-kappaB, Nox-2, phospho-smad2, and alpha-SMA during transforming growth factor-beta1-induced EMT of NRK52E cells while reducing Nox-2, vimentin, and fibronectin mRNA levels. CONCLUSIONS: MPA may down-regulate Nox-2 activation and EMT through the NF-kappaB pathway in the tubular epithelial cells, suggesting a novel role for this drug independent of its immunosuppressive properties.

Multicenter prospective randomized trial comparing modified Limberg flap transposition and Karydakis flap reconstruction in patients with sacrococcygeal pilonidal disease.

BACKGROUND: There is still no consensus as to the optimal treatment for sacrococcygeal pilonidal disease (SPD). Many recommend off-midline closure, if any excisional procedure is to be selected. METHODS: The authors prospectively studied 145 patients with SPD who presented at 3 hospitals. Patients were randomly assigned to undergo either modified Limberg flap (MLF) transposition (n = 72) or Karydakis flap reconstruction (n = 73). Surgical findings, complications, recurrence rates, and degree of patient satisfaction, evaluated via a standardized telephone interview, were compared. RESULTS: Operation time was longer in the MLF group. There were no significant differences between the two groups in terms of complication rate, length of stay, or recurrence rate. Patients in the Karydakis group reported feeling completely healed more quickly postoperatively. The two groups reported similar rates of satisfaction. Mandatory patient withdrawal from a given study arm because of the orifice straying from the midline occurred more frequently in the Karydakis group. CONCLUSIONS: The MLF technique and the Karydakis procedure appear to generate comparable outcomes. With laterally situated orifices, however, the applicability of the Karydakis method may be limited.

Does the type of resuscitative fluid affect healing of colonic anastomosis in experimentally induced hemorrhagic shock in rats?

OBJECTIVE: The aim of the study was to investigate the effects of different resuscitative fluids on the healing of intestinal anastomosis in a hemorrhagic-shock rat model. MATERIALS AND METHODS: Closed-colony Wistar male rats (n = 40; 8 rats per group) were subjected to volume-controlled hemorrhagic shock, followed by a 30-min shock phase. The animals were then resuscitated with one of the following fluids (which also corresponds to their respective groups): lactated Ringer's solution (LR), hydroxyethyl starch (HES), 7.5% hypertonic saline (HS) and autologous blood (AB). There was also a control group (CL), which did not experience hemorrhagic shock or receive any resuscitative fluids. All rats underwent laparotomy, segmental resection and anastomosis of the left colon. Five days later, a 2nd laparotomy was performed and the anastomotic bursting pressure was measured in vivo. Thereafter, the anastomosed segment was resected to measure the tissue hydroxyproline level and the grade of anastomotic fibrosis. RESULTS: All experimental groups (LR, HES, HS and AB) exhibited lower anastomotic bursting pressures than the CL group; however, no intergroup differences achieved statistical significance. The mean tissue hydroxyproline level and fibrosis grade also were similar across all 5 groups. CONCLUSION: In traumatic hemorrhagic shock, anastomosis safety does not appear to be affected by the type of fluid used for resuscitation. Moreover, LR, HES and HS all seemed to reinforce healing as effectively as transfused blood.

Management and mid- to long-term results of early referred bile duct injuries during laparoscopic cholecystectomy.

BACKGROUND/AIMS: Bile duct injuries (BDI) usually need operative repair and remain as a challenge even for surgeons who specialize in hepatobiliary surgery. The objective of this study was to define the presentation, in-hospital management, and mid- to long-term outcome of BDIs during laparoscopic cholecystectomy (LC) referred to a tertiary center in their early period. METHODOLOGY: From January 1996 to January 2006, 31 patients with BDI sustained during or after LC were treated at our institution. Patients were referred to our center from 18 community hospitals in their first 15 postoperative days. Patients' charts were retrospectively reviewed; presentation, management, and follow-up details recorded at the primary hospitals and at our institution were documented. RESULTS: There were 5 patients with type-A and one with type-C injury, according to Strasberg classification. The remainders had a major BDI. The mean time to referral was 3.45 (median 2) days. Treatment methods chosen after referral were as follows: drainage-observation in 2 patients (6.5%), nasobiliary drainage in 4 (12.9%), endoscopic sphincterotomy plus biliary stenting in 1 (3.2%), and surgical intervention (duct-to-duct anastomosis or biliary-enteric reconstruction) in 24 patients (77.4%). Although a success rate of 83.3% was achieved in the early period, 10 patients (32.3%) had late postoperative complications (stricture and cholangitis), and of these, 3 required endoscopic stent placement, and 7 patients underwent a biliary diversion with Roux-en-Y Hepaticojejunostomy. One out of 24 patients with long-term follow-up developed biliary cirrhosis, and one patient with malignancy expired. CONCLUSIONS: Minor BDIs can be satisfactorily treated with endoscopic interventions. Extended lateral injuries, complete CBD transsections, and long segment stenosis usually require surgical therapy. Duct-to-duct anastomosis may be an option as the first-line therapy in selected patients after early referral, though many patients eventually require a Roux-en-Y hepaticojejunostomy.

Idiopathic granulomatous mastitis.

OBJECTIVE: To discuss the clinical and radiological features and treatment approaches in 14 patients diagnosed with idiopathic granulomatous mastitis (GM). METHODS: We retrospectively evaluated the clinical features, radiological findings, and treatment approaches in 14 patients with idiopathic GM in the General Surgery Department, Gulhane School of Medicine, Ankara, Turkey between April 2000 and June 2006. RESULTS: The mean age of the patients was 34.5 years (range 27-41 years). The complaints at admission were a mass in the breast in 7 (50%) patients, an abscess and a mass in 6 (42.8%), and a skin fistula in one (7.2%). Granulomatous mastitis was unilateral in all subjects (on the right in 5 patients and on the left in 9). All of the patients underwent ultrasonographic evaluation. Mammography was performed in 8 and magnetic resonance imaging in 5 patients. Seven patients (50%) were suspected to have breast carcinoma according to radiological findings. We performed large excision in 11, incisional biopsy plus abscess drainage in one, and incisional biopsy plus abscess drainage plus medical treatment (prednisolone, methotrexate) in 2 patients. Due to the development of abscess after 9 months, drainage and large excision were also performed in one patient who received medical treatment. CONCLUSION: Idiopathic GM is a disease that generally affects young women of reproductive age and may be mistaken for breast carcinoma in clinical and radiological evaluations. The gold standard for the diagnosis is histopathologic evaluation.

Preoperative administration of oral carbohydrate-rich solutions: Comparison of glucometabolic responses and tolerability between patients with and without insulin resistance.

OBJECTIVE: Preoperative carbohydrate loading with clear fluids is thought to reduce surgery-related insulin resistance (IR). However, IR per se is already present in some patients scheduled for elective surgery. Data on the safety of preoperative oral carbohydrate loading in patients with IR undergoing surgery is lacking. We aimed to evaluate the effects of preoperative carbohydrate loading on the glucometabolic state and gastric content of patients with and without IR. METHODS: Thirty-four non-diabetics received 800 mL of a special carbohydrate-containing drink on the evening before the operation and then 400 mL 2 h before surgery. Blood samples for glucose, insulin, and cortisol levels were taken immediately before the second dose, at 40 and 90 min after intake of the drink, and at the onset of surgery. Patients with a homeostasis model assessment IR score >2.5 were considered to have IR. The differences between patients with and without IR were then evaluated. RESULTS: Eight of the 34 patients had IR and the remaining 26 did not. Glucose levels in the IR group were higher than those in the non-IR group, but the differences did not reach significance. The initially elevated insulin concentrations then tended to decrease to the corresponding levels detected in the non-IR group. The cortisol concentrations were similar in both groups. CONCLUSION: Patients with IR receiving a carbohydrate-rich drink before surgery appear not to be affected adversely by the beverage. Furthermore, they also obtain the probable beneficial effects related to these drinks and, like patients without IR, can undergo surgery safely.

Invasive pulmonary aspergillosis after liver transplantation: rapid and complete response to combined and sequential antifungal therapy.

BACKGROUND: Invasive pulmonary aspergillosis is a rare, but severe and potentially fatal, complication after liver transplantation. There is no therapeutic regimen accepted worldwide for both initial and continuation therapy; nevertheless, several options have been proposed. METHODS: Case report and review of the pertinent English-language literature. RESULTS: In a patient with pulmonary aspergillosis after a liver transplant, combined and sequential therapy with caspofungin and voriconazole with termination of the immunosuppressive regimen and careful management were helpful to control the infection rapidly, possibly because of a positive drug interaction. CONCLUSION: In cases of invasive aspergillosis that are refractory to monotherapy, this regimen may be used in an attempt to overcome the infection.