The value of interventional radiology in clinical trial teams: experience from the BATTLE lung cancer trials.

AIM: To report on the multidisciplinary approach, focusing specifically on the role of the interventional radiologist (IR), used to support the Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) and BATTLE-2 trials. MATERIALS AND METHODS: Patients who underwent percutaneous image-guided biopsy for the BATTLE and BATTLE-2 trials were reviewed. A radiology-based, three-point, lesion-scoring system was developed and used by two IRs. Lesions were given a score of 3 (most likely to yield sufficient material for biomarker analysis) if they met the following criteria: size >2 cm, solid mass, demonstrated imaging evidence of viability, and were technically easy to sample. Lesions not meeting all four criteria were scored 2 with the missing criteria noted as negative factors. Lesions considered to have risks that outweighed potential benefits receive a score of 1 and were not biopsied. Univariate and multivariate analyses were performed to evaluate the score's ability to predict successful yield for biomarker adequacy. RESULTS: A total of 555 biopsies were performed. The overall yield for analysis of the required biomarkers was 86.1% (478/555), and 84% (268/319) and 88.9% (210/236) for BATTLE and BATTLE-2, respectively (p=0.09). Lesions receiving a score of 3 were adequate for biomarker analysis in 89% of cases. Lesions receiving a score of 2 with more than two negative factors were adequate for molecular analysis in 69.2% (IR1, p=0.03) and 74% (IR2, p=0.04) of cases. The two IRs scored 78.4% of the lesions the same indicating moderate agreement (kappa=0.55; 95% confidence interval [CI]: 0.48, 0.61). CONCLUSIONS: IRs add value to clinical trial teams by optimising lesions selected for biopsy and biomarker analysis.

Embryonic origin of primary colon cancer predicts survival in patients undergoing ablation for colorectal liver metastases.

BACKGROUND: In patients with primary colorectal cancer (CRC) or unresectable metastatic CRC, midgut embryonic origin is associated with worse prognosis. The impact of embryonic origin on survival after ablation of colorectal liver metastases (CLM) is unclear. METHODS: We identified 74 patients with CLM who underwent percutaneous ablation during 2004-2015. Survival and recurrence after ablation of CLM from midgut origin (n = 18) and hindgut origin (n = 56) were analyzed. Prognostic value of embryonic origin was evaluated. RESULTS: Recurrence-free survival (RFS) and overall survival (OS) after percutaneous ablation were worse in patients from midgut origin (3-year RFS: 5.6% vs. 24%, P = 0.004; 3-year OS: 25% vs. 70%, P 0.001). In multivariable analysis, factors associated with worse OS were midgut origin (hazard ratio [HR] 4.87, 95% CI 2.14-10.9, P 0.001), multiple CLM (HR 2.35, 95% CI 1.02-5.39, P = 0.044), and RAS mutation (HR 2.78, 95% CI 1.25-6.36, P = 0.013). At a median follow-up of 25 months, 56 patients (76%) had developed recurrence, 16 (89%) with midgut origin and 40 (71%) with hindgut origin (P = 0.133). Recurrent disease was treated with local therapy in 20 patients (36%), 2 (13%) with midgut origin and 18 (45%) with hindgut origin (P = 0.022). CONCLUSION: Compared to CLM from hindgut origin tumors, CLM from midgut origin tumors were associated with worse survival after ablation, which was partly attributable to the fact that patients with hindgut origin were more frequently candidates for local therapy at recurrence.

Local tumour progression after percutaneous ablation of colorectal liver metastases according to RAS mutation status.

BACKGROUND: Percutaneous ablation is a common treatment for colorectal liver metastasis (CLM). However, the effect of rat sarcoma viral oncogene homologue (RAS) mutation on outcome after ablation of CLMs is unclear. METHODS: Patients who underwent image-guided percutaneous ablation of CLMs from 2004 to 2015 and had known RAS mutation status were analysed. Patients were evaluated for local tumour progression as observed on imaging of CLMs treated with ablation. Multivariable Cox regression analysis was performed to determine factors associated with local tumour progression-free survival. RESULTS: The study included 92 patients who underwent ablation of 137 CLMs. Thirty-six patients (39 per cent) had mutant RAS. Rates of local tumour progression were 14 per cent (8 of 56) for patients with wild-type RAS and 39 per cent (14 of 36) for patients with mutant RAS (P = 0·007). The actuarial 3-year local tumour progression-free survival rate after percutaneous ablation was worse in patients with mutant RAS than in those with wild-type RAS (35 versus 71 per cent respectively; P = 0·001). In multivariable analysis, negative predictors of local tumour progression-free survival were a minimum ablation margin of less than 5 mm (hazard ratio (HR) 2·48, 95 per cent c.i. 1·31 to 4·72; P = 0·006) and mutant RAS (HR 3·01, 1·60 to 5·77; P = 0·001). CONCLUSION: Mutant RAS is associated with an earlier and higher rate of local tumour progression in patients undergoing ablation of CLMs.

Differential effects of the novel non-peptidic opioid 4-tyrosylamido-6-benzyl-1,2,3,4 tetrahydroquinoline (CGPM-9) on in vitro rat t lymphocyte and macrophage functions.

Opioid receptors have been reported on immune cells of several species and shown to subserve effector functions of these cell types. Mu-selective opioid agonists such as morphine are immunosuppressive, whereas certain delta-opioid receptor-selective agonists have been associated with immunopotentiation. We have previously shown that intracerebroventricular administration of the non-peptidic delta-opioid receptor agonists did not alter certain parameters of immunocompetence. In this study, we evaluated the in vitro effects of the novel non-peptidic opioid 4-tyrosylamido-6-benzyl-1,2,3,4 tetrahydroquinoline (CGPM-9) on lymphocyte and macrophage functions. We demonstrated that CGPM-9 enhanced rat thymic lymphocyte proliferative response to concanavalin A (2.85- to 5.5-fold increases), and suppressed LPS-induced nitric oxide (67 to 72 percent reduction) and TNF-alpha production (46 percent reduction) by peritoneal macrophages, compared with untreated control. The mu-opioid receptor selective antagonist CTOP used at equimolar doses, significantly suppressed the effect of CGPM-9 on lymphocyte and macrophage functions (CTOP alone did not show any effect on lymphocyte or macrophage functions). In summary, CGPM-9 activated thymic lymphocyte proliferation and suppressed macrophage functions by acting at mu-opioid receptors. This suggests that opioid receptors on immunocytes may be coupled to different signaling pathways depending on the cell type and effector function being analyzed. The mechanism (s) associated with the differential effect of CGPM-9 on these immune cells remains to be elucidated. The pharmacotherapeutic potential for compounds such as CGPM-9 which potentiate T lymphocyte proliferation and suppress production of macrophage-derived inflammatory cytokines is substantial in research and clinical medicine.

Portal vein embolization: rationale, technique and future prospects.

BACKGROUND: Advances in surgery have reduced the mortality rate after major liver resection, but complications resulting from inadequate postresection hepatic size and function remain. Portal vein embolization (PVE) was proposed to induce hypertrophy of the anticipated liver remnant in order to reduce such complications. The techniques, measurement methods and indications for this treatment remain controversial. METHODS: A Medline search was performed to identify papers reporting the use of PVE before hepatic resection. Techniques, complications and results are reviewed. RESULTS: Complications of PVE typically occur in less than 5 per cent of patients. No specific substance (cyanoacrylate, thrombin, coils or absolute alcohol) emerged as superior. The increase in remnant liver volume averages 12 per cent of the total liver. The morbidity rate of resection after treatment is less than 15 per cent and the mortality rate is 6-7 per cent with cirrhosis and 0-6.5 per cent without cirrhosis. Embolization is currently used for patients with a normal liver when the anticipated liver remnant volume is 25 per cent or less of the total liver volume, and for patients with compromised liver function when the liver remnant volume is 40 per cent or less. CONCLUSION: This treatment does not increase the risks associated with major liver resection. It may be indicated in selected patients before major resection. Future prospective studies are needed to define more clearly the indications for this evolving technique.

Recurrent gastrointestinal bleeding: use of thrombolysis with anticoagulation in diagnosis.

PURPOSE: To determine the safety and diagnostic accuracy of a provocative protocol with heparin and urokinase to induce bleeding and determine the source in patients with chronic gastrointestinal hemorrhage. MATERIALS AND METHODS: Nine patients had gastrointestinal bleeding from an indeterminate source and had negative results from esophagogastroduodenoscopy, colonoscopy, small-bowel examination, and angiography. Ten provocative bleeding studies were performed prospectively. Patients had no clinical evidence of bleeding within 2 days before the study. Intravenous administration of heparin and urokinase was performed systemically during a 4-hour period while scintigraphy was performed continuously. Mesenteric angiography was performed immediately in patients in whom substantial gastrointestinal bleeding was detected at scintigraphy. RESULTS: The provocative protocol was successful in inducing scintigraphically detectable hemorrhage in four (40%) studies within 4 hours. In two of these four studies, the source of hemorrhage was determined and treated with embolization or surgery. Three (30%) studies demonstrated scintigraphic evidence of hemorrhage only at delayed imaging (8-24 hours after initiation of the study). The remaining three (30%) studies did not show active bleeding. No complications occurred, including hemodynamic instability or uncontrollable decreases in hematocrit. CONCLUSION: Since this protocol with heparin and urokinase enabled determination of the bleeding source in only two of 10 studies, protocol modifications are necessary before this intervention is used widely.

Long-term results of transrenal ureteral occlusion with use of Gianturco coils and gelatin sponge pledgets.

PURPOSE: To evaluate transrenal ureteral occlusion with Gianturco coils and gelatin sponge pledgets. MATERIALS AND METHODS: The authors reviewed 34 ureteral occlusions in 22 patients during a 4-year period. The indications for this procedure included vesicovaginal fistula in 11 patients and urinary incontinence in three patients. All patients except one had a history of pelvic malignancy and previous radiation therapy. Pre-existing percutaneous nephrostomy tubes were in place in 20 ureters to be embolized. Distal ureteral occlusion was achieved by placement of Gianturco coils alone or in combination with gelatin sponge pledgets. A percutaneous nephrostomy catheter was then placed to provide permanent external diversion. Follow-up ranged from 2 weeks to 29 months (mean, 6.2 months). RESULTS: Occlusion was technically successful in all embolized ureters. All patients experienced prompt resolution of symptoms as indicated by complete or near complete perineal dryness within 72 hours. Complications were limited to coil migration into the renal pelvis in two patients and nephrostomy catheter occlusion requiring replacement in another three patients. CONCLUSION: Ureteral occlusion with Gianturco coils and gelatin sponge is a safe and reliable method of achieving permanent supravesical urinary diversion in the management of chronic lower urinary tract fistulas.

Nonsurgical management of gastric or duodenal perforation from a Wills-Oglesby-type gastrostomy tube.

PURPOSE: To describe the clinical and radiologic appearance of gastrointestinal perforation related to a Wills-Oglesby-type gastrostomy tube, as well as techniques for nonsurgical management. MATERIALS AND METHODS: Five patients with a previously placed 14-F modified Wills-Oglesby-type gastrostomy catheter experienced viscus perforation by the distal limb of the catheter during a 30-month period. RESULTS: The average interval between tube placement and perforation event was 4.3 months. Three patients had migration of the gastrostomy tube into the duodenum and subsequent duodenal perforation. One patient had posterior perforation of the stomach, and one patient developed a gastrocolic fistula. Generalized peritonitis was not present in any patient. All patients were treated successfully without surgery, and tube feedings were re-established in 4-14 days. CONCLUSIONS: Gastrostomy tube-related perforation is an uncommon, delayed complication of percutaneous gastrostomy with the modified Wills-Oglesby-type catheter. Nonsurgical management is feasible in select instances. Because of these gastrointestinal perforations, the gastrostomy tube has been modified (eliminating the distal tip), and no gastrostomy-associated gastrointestinal perforation has been experienced since.

Percutaneous gallstone removal: long-term follow-up.

PURPOSE: To evaluate gallstone and symptom recurrence rates, long-term complications, and life expectancy after percutaneous gallstone removal. PATIENTS AND METHODS: Medical records of 87 patients (mean age, 69 years +/- 14 [standard deviation]) undergoing percutaneous gallstone removal between 1987 and 1992 were reviewed. Physicians and patients (or their families) were contacted for clinical follow-up. Thirty-one patients returned for follow-up ultrasound (US). RESULTS: The final study group consisted of 65 patients. Mean survival from the time of initial gallbladder drainage was 33 months +/- 19. Over a mean clinical follow-up period of 33 months, eight of 65 patients (12%) developed recurrent symptoms; six of these eight had recurrent gallstones shown at US. Of 30 patients with technically adequate US images (mean follow-up, 14 months +/- 12), 12 (40%) had recurrent gallstones. Six of these 12 patients had recurrent symptoms. No long-term complications were identified. CONCLUSION: The risk of gallstone recurrence after percutaneous removal is notable, but the symptom recurrence rate is much lower. Percutaneous gallstone removal is beneficial for patients at prohibitive surgical or general anesthetic risk.

Accuracy of DSA in the evaluation of patency of infrapopliteal vessels.

PURPOSE: To evaluate the accuracy of intraarterial digital subtraction angiography (DSA) in the demonstration of patent infrapopliteal vessels. PATIENTS AND METHODS: One-hundred sixty-five arteriograms were obtained in 153 consecutive patients prospectively enrolled to evaluate lower extremity ischemia. In 86 cases a follow-up angiogram of the infrapopliteal vessels was obtained during surgery or after endovascular intervention (n = 57). Twenty-nine arteriograms were followed by surgical exploration of the infrapopliteal vessels. Standard angiographic technique was performed with intraarterial DSA of the most symptomatic foot. Visualization of distal vessels was compared with intraoperative or postintervention imaging or with the results of surgical exploration. RESULTS: Of the 57 procedures after which either intraoperative or post-endovascular intervention angiography was performed, DSA results were equivalent in 47 (82%) and worse in five (9%). When individual vessels were evaluated, the sensitivity of DSA in the identification of patent named vessels was 95%, and the specificity was 92%. Among 29 cases with a surgical standard of reference, 28 patients underwent bypass to a vessel correctly identified as patent at DSA; one patient was incorrectly identified as having no patent named vessels. CONCLUSION: Intraarterial DSA is accurate and reliable in the assessment of patency in infrapopliteal vessels before surgery or endovascular intervention in patients with infrainguinal atherosclerotic disease.

Subcutaneous urinary diversion utilizing a nephrovesical stent: a superior alternative to long-term external drainage?

OBJECTIVES: The use of external percutaneous nephrostomy drainage in patients with end-stage ureteral obstruction in whom ureteral stenting has failed presents significant compromises in the patient's quality of life. Toward this end, we present the initial experience in the United States with an intracorporeal nephrovesical stent. METHODS: We performed successful subcutaneous urinary diversion in 2 patients with malignant, metastatic periureteral obstruction. Both patients had previously been managed with a chronic percutaneous nephrostomy that was both painful and inconvenient. The nephrovesical stent was inserted utilizing percutaneous access to both the kidney and bladder followed by creation of a subcutaneous tunnel between the two sites. RESULTS: The nephrovesical stents are patent at 6 and 9 weeks postoperatively and both patients have had their nephrostomy tubes removed. Both patients have noted a marked improvement in their overall comfort and quality of life since the stent has been in place. CONCLUSIONS: Subcutaneous urinary diversion with a nephrovesical stent provides effective urinary drainage and may improve the quality of life of patients with malignant metastatic ureteral obstruction. Further long-term studies are needed.

Percutaneous gastrostomy and gastrojejunostomy after gastric surgery.

The authors reviewed their experience with percutaneous gastrostomy and gastrojejunostomy in 30 consecutive patients who had undergone prior gastric surgery consisting of either partial resections (n = 24) or alteration of normal gastric anatomy (n = 6). Parameters evaluated included indications for the procedure, procedural modifications, type of prior gastric surgery, major and minor procedural complications, tube efficacy, and follow-up data. Gastrostomy tubes were placed in 27 patients for enteral feeding and in three for decompression. The success rate (100%), as well as the prevalence of major (0%) and minor (23%) morbidity--transient fever, skin infection, and high gastric residuals--were similar to those reported in patients who had not undergone prior gastric surgery. Thirty-day mortality was 13% (four patients); no deaths were related to the gastrostomy tube placement. Minor procedural modifications such as an extra-long needle, a peel-away sheath, or additional rotational fluoroscopy were necessary in 18 patients (60%). Knowledge of the postsurgical gastric anatomy is crucial in this subset of patients. Prior gastric surgery is no longer a contraindication to percutaneous gastrostomy or gastrojejunostomy tube placement.

Transvenous retrieval of misplaced stainless steel Greenfield filters.

Transvenous retrieval was attempted in five patients following surgical misplacement of stainless steel Greenfield filters. Four filters were located within the right atrium, and one was in the left hepatic vein. All retrievals were attempted within 5 days of placement. Retrieval was successful for the four filters in the right atrium and failed for the filter in the left hepatic vein. One air embolism occurred; this was the only filter- or retrieval-related complication. Transvenous retrieval is a safe and effective minimally invasive method of removing misplaced filters.

Percutaneous cholecystolithotomy: analysis of results and complications in 58 consecutive patients.

Percutaneous cholecystolithotomy was attempted in 58 consecutive patients. Patients were considered for percutaneous cholecystolithotomy only if they had symptomatic gallstones and a strong contraindication to surgical cholecystectomy. The procedure consisted of three parts: (a) initial percutaneous cholecystostomy, (b) tract dilation and stone removal, and (c) tract evaluation and tube removal. Local anaesthesia and intravenously administered analgesia were used in all procedures. Percutaneous cholecystolithotomy was successful in removing all of the stones in 56 patients (97%), including cystic duct calculi in 15 patients and common duct calculi in 10 patients. Major complications occurred in five patients (9%); in four cases, they were related to bile leakage after the cholecystostomy tube was removed. Thirty-day mortality was 3% (two patients). Advantages of percutaneous cholecystolithotomy include avoidance of general anesthesia and the ability to treat patients in any disease setting, including acute cholecystitis. Percutaneous cholecystolithotomy, although technically demanding, is an effective alternative to surgical cholecystectomy in elderly and debilitated patients.

Percutaneous ureteral occlusion with use of Gianturco coils and gelatin sponge. Part II. Clinical experience.

A previous report described the use of coils and gelatin sponge pledgets as a means of producing ureteral occlusion to achieve urinary diversion in patients with urinary fistulas. The authors have performed this procedure in nine ureters of six patients. Five of the patients had urinary leaks with extensive pelvic tumor, and one had severe chronic cystitis. Ureters were occluded with use of Gianturco coils and gelatin sponge pledgets placed via a sheath through a percutaneous nephrostomy tract. The procedure was successful in all patients as judged by means of antegrade nephrostogram or intravenous pyelogram and by marked improvement or complete resolution of symptoms.

Massive upper gastrointestinal hemorrhage with normal findings on arteriography: value of prophylactic embolization of the left gastric artery.

During a 5-year period, 13 patients who presented with massive upper gastrointestinal hemorrhage had normal findings on arteriography. Seven had prophylactic embolization of the left gastric artery, and six had conservative therapy. Normal angiographic findings were associated with clinical cessation of bleeding in 12 of 13 patients. Lesions not treated by embolization or other invasive therapy had a high rate of massive recurrent hemorrhage (four of six). Of lesions subsequently found to be supplied by the left gastric artery, two of four cases not treated by embolization or surgery had clinically significant recurrent hemorrhage, whereas none of six cases treated by embolization had recurrent hemorrhage. Prophylactic embolization of the left gastric artery appears warranted when (1) there is definite prior identification of a lesion in the left gastric artery territory or (2) there is no prior localization of a lesion but the patient is at risk for multiorgan failure if bleeding recurs.

Transcervical salpingoplasty: current techniques and results.

In the last five years angio-interventional techniques have been applied to the recanalization of proximally occluded fallopian tubes in infertile women. The reported technical success of 90% and subsequent pregnancies in up to 54% of patients has led to considerable interest in this technique. This article will discuss current methodologies and review the reported results of this procedure.

Choledochoscopic stone removal through a T-tube tract: experience in 75 consecutive patients.

Retained biliary stones remain a common clinical problem in patients after surgery. Since 1984, the authors have used choledochoscopy in the treatment of suspected retained biliary stones in 75 patients. These procedures were performed in the radiology department with use of local anesthesia supplemented by an intravenously administered sedative and analgesic. A 15-F flexible fiberoptic choledochoscope was used. Fifty-one of the 75 patients were treated as outpatients. Treatment was successful in 74 of 75 patients; in one patient, intrahepatic stones were not completely removed. Electrohydraulic lithotripsy was used to fragment calculi in 11 patients (15%). Biopsies were performed in four patients (5%). Five minor complications occurred; three required overnight admission. Choledochoscopic-assisted removal of retained biliary calculi is a highly effective and safe procedure. Advantages over standard fluoroscopic stone removal include the ability to directly visualize and fragment adherent or impacted stones and visualize noncalculous filling defects, such as air bubbles, mucus, and biliary tumors.

Massive arterial hemorrhage from the stomach and lower esophagus: impact of embolotherapy on survival.

The authors retrospectively reviewed the clinical courses in 36 patients referred for angiographic evaluation of massive arterial hemorrhage from the stomach, gastroesophageal junction, and lower esophagus. Twenty-four patients underwent embolotherapy, and 12 were treated with nontranscatheter therapy such as surgery, Sengstaken-Blakemore tube placement, endoscopic submucosal injection of epinephrine, or supportive medical therapy. Bleeding was controlled completely in 15 (62%) and partially in three (13%) of the patients who underwent embolotherapy. In nine of the patients treated with nontranscatheter therapy (75%), bleeding control was complete. Sixteen patients died, including seven of 28 in whom bleeding was controlled. There was no significant difference in the mortality rates of patients treated with nontranscatheter therapy (46% and 42%, respectively). Survival correlated with the clinical condition at the time of intervention. All patients with multiorgan failure died, while 87% of the other patients, even those with serious cardiovascular compromise, survived. The results imply that massive gastric hemorrhage should be treated aggressively, before it results in multiorgan failure.

Percutaneous cholecystolithotomy: preliminary experience and technical considerations.

Surgical cholecystectomy is associated with a high morbidity and mortality in elderly patients with acute calculous cholecystitis and underlying cardiac or pulmonary disease. Currently there are few alternatives for treating these patients. The authors have used percutaneous cholecystolithotomy in 11 such high-risk patients for definitive treatment of gallbladder calculi. In all 11 patients all stones were successfully removed from the gallbladder and cystic duct. The entire procedure--from initial tube placement to final tube removal--lasted 17-40 days (mean, 21 days). There were two complications: one minor--local wound infection--and one major--bile peritonitis with eventual death. Percutaneous cholecystolithotomy is an effective alternative therapy for acute calculous cholecystitis in elderly, debilitated patients.