Kinetics of porphyrin fluorescence accumulation in pediatric brain tumor cells incubated in 5-aminolevulinic acid

Background

Fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) enables more complete resections of tumors in adults. 5-ALA elicits accumulation of fluorescent porphyrins in various cancerous tissues, which can be visualized using a modified neurosurgical microscope with blue light. Although this technique is well established in adults, it has not been investigated systematically in pediatric brain tumors. Specifically, it is unknown how quickly, how long, and to what extent various pediatric tumors accumulate fluorescence. The purpose of this study was to determine utility and time course of 5-ALA–induced fluorescence in typical pediatric brain tumors in vitro.

Methods

Cell cultures of medulloblastoma [DAOY and UW228], cPNET [PFSK] atypical teratoid rhabdoid tumor [BT16] and ependymoma [RES196] were incubated with 5-ALA for either 60 minutes or continuously. Porphyrin fluorescence intensities were determined using a fluorescence-activated cell sorter (FACS) after 1, 3, 6, 9, 12 and 24 hours. C6 and U87 cells served as controls.

Results

All pediatric brain tumor cell lines displayed fluorescence compared to their respective controls without 5-ALA (p?<?0.05). Sixty minutes of incubation resulted in peaks between 3 and 6 hours, whereas continuous incubation resulted in peaks at 12 hours or beyond. 60 minute incubation peak levels were between 52 and 91 % of maxima achieved with continuous incubation. Accumulation and clearance varied between cell types.

Conclusions

We demonstrate that 5-ALA exposure of cell lines derived from typical pediatric central nervous system (CNS) tumors induces accumulation of fluorescent porphyrins. Differences in uptake and clearance indicate that different application modes may be necessary for fluorescence-guided resection, depending on tumor type.     

Fluorescence-guided surgery with 5-aminolevulinic acid for resection of brain tumors in children—a technical report

Background

5-aminolevulinic acid (5-ALA) can be used as an adjunct for the surgery of adult malignant glioma and improves the rate of gross total resection and patient survival. So far, only three casuistic reports of fluorescence-guided surgery used in children have been published. We report our pilot series of 16 pediatric brain tumors treated with 5-ALA.

Methods

Sixteen patients (mean age 9 years, range 1–16 years) received a standardized 5-ALA dose according to the published protocol after informed parental consent. The fluorescence status (positive versus negative) in correlation with histology as well as blood samples and adverse clinical symptoms were recorded.

Results

Histology revealed pilocytic astrocytoma (n?=?7), classical medulloblastoma (n?=?4), anaplastic astrocytoma (n?=?1), glioblastoma (n?=?3) and anaplastic ependymoma (n?=?1). Positive fluorescence was observed in cases of anaplastic astrocytoma, glioblastoma, and medulloblastoma, respectively. Significant increases were registered for alanine aminotransferase (14.92?±?1.106 U/l vs. 37.70?±?3.795 U/l, P?=?0.0020) and gamma glutamyl transpeptidase (12.69?±?1.638 U/l vs. 39.29?±?6.342 U/l, P?=?0.0156), correlated with young age. No further adverse reactions were evident.

Conclusion

Positive fluorescence was observed in two high-grade gliomas and one medulloblastoma after oral administration of 5-ALA. Thus, 5-ALA appears capable of inducing fluorescence in pediatric high-grade tumors. Adverse reactions observed in children were similar to those reported for adults, although very young children might be at increased risk. Further studies are required to elucidate pharmacokinetic and pharmacodynamic properties of 5-ALA in children and to assess its prognostic role in the resection of pediatric brain tumors.     

5-ALA complete resections go beyond MR contrast enhancement: shift corrected volumetric analysis of the extent of resection in surgery for glioblastoma

Background

The technique of 5-aminolevulinic acid (5-ALA) tumor fluorescence is increasingly used to improve visualization of tumor tissue and thereby to increase the rate of patients with gross total resections. In this study, we measured the resection volumes in patients who underwent 5-ALA-guided surgery for non-eloquent glioblastoma and compared them with the preoperative tumor volume.

Methods

We selected 13 patients who had received a complete resection according to intraoperative 5-ALA induced fluorescence and CRET according to post-operative T1 contrast-enhanced MRI. The volumes of pre-operative contrast enhancing tissue, post-operative resection cavity and resected tissue were determined through shift-corrected volumetric analysis.

Results

The mean resection cavity (29 cm³) was marginally smaller than the pre-operative contrast-enhancing tumor (39 cm³, p?=?0.32). However, the mean overall resection volume (84 cm³) was significantly larger than the pre-operative contrast-enhancing tumor (39 cm³, p?=?0.0087). This yields a mean volume of resected 5-ALA positive, but radiological non-enhancing tissue of 45 cm³. The mean calculated rim of resected tissue surpassed pre-operative tumor diameter by 6 mm (range 0–10 mm).

Conclusions

Results of the current study imply that (i) the resection cavity underestimates the volume of resected tissue and (ii) 5-ALA complete resections go significantly beyond the volume of pre-operative contrast-enhancing tumor bulk on MRI, indicating that 5-ALA also stains MRI non-enhancing tumor tissue. Use of 5-ALA may thus enable extension of coalescent tumor resection beyond radiologically evident tumor. The impact of this more extended resection method on time to progression and overall survival has not been determined, and potentially puts adjacent and functionally intact tissue at risk.     

The impact of fluorescence guidance on spinal intradural tumour surgery

Purpose

5-Aminolevulinic acid (5-ALA)-based fluorescence-guided surgery was shown to be beneficial for cerebral malignant gliomas. Extension of this technique for resection of meningiomas and cerebral metastasis has been recently evaluated. Aim of the present study is to evaluate the impact of fluorescence-guided surgery in spinal tumor surgery.

Methods

Twenty-six patients with intradural spinal tumors were included in the study. 5-ALA was administered orally prior to the induction of anesthesia. Intraoperative, 440 nm fluorescence was applied after exploration of the tumor and, if positive, periodically during and at the end of resection to detect tumor-infiltrated sites.

Results

Tumors of WHO grade III and IV were found in five patients. In detail intra- or perimedullary metastasis of malignant cerebral gliomas was found including glioblastoma WHO grade IV (n = 2), anaplastic astrocytoma WHO grade III (n = 1), anaplastic oligoastrocytoma WHO grade III (n = 1). In addition, one patient suffered from a spinal drop metastasis of a cerebellar medulloblastoma WHO grade IV. Tumors of WHO grade I were diagnosed in 18 patients: Eight cases of meningioma (two recurrences), six cases of neurinoma, one neurofibroma, two ependymoma and one plexus papilloma. At least, benign pathologies were histologically proven in three patients. All four spinal metastasis of malignant glioma (100 %), seven of eight meningiomas (87.5 %) and one of two ependymoma (50 %) were found to be ALA-positive.

Conclusion

The present study demonstrates that spinal intramedullary gliomas and the majority of spinal intradural meningiomas are 5-ALA positive. As a surgical consequence, especially in intramedullary gliomas, the use of 5-ALA fluorescence seems to be beneficial.     

Sodium fluorescein–guided resection under the YELLOW 560 nm surgical microscope filter in malignant brain tumor surgery—a feasibility study

Objective

In glioma surgery, the extent of resection (EOR) is one important predictor of progression-free survival. In 2006, fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) was shown to improve the EOR in malignant gliomas. However, the use of 5-ALA is complex and causes certain side effects. Sodium fluorescein (FL) is a fluorescent dye that is used for angiography in ophthalmic surgery. FL accumulates in areas of the disturbed blood-brain barrier and can be visualized under a 560-nm wavelength fluorescent light source (YELLOW 560 nm, Carl Zeiss Meditec, Oberkochen, Germany). Here, we present the first experiences with low-dose FL and YELLOW 560 nm in 35 patients with malignant brain tumors.

Patients and method

A total of 200 mg of FL (3–4 mg/kg bodyweight) was administered in 35 patients during craniotomy as an off-label use between May and August 2012. We retrospectively analyzed the histology, pre-treatment, clinical parameters pre- and postoperatively and occurrence of any adverse effects. The feasibility and efficacy (‘helpful,’ ‘not helpful’) of FL under YELLOW 560 nm (demarcation of the tumor margin) was assessed by the responsible neurosurgeon (n?=?5) for each surgical procedure.

Results

Twenty-six patients had gliomas (1 WHO grade I, 3 WHO grade II, 5 WHO grade III, 17 WHO grade IV), 5 patients had cerebral metastases, 2 had non-malignant astrogliosis and 2 had post-radiation necrosis. The fluorescence signal was detected in all patients immediately after the FL administration. FL application was classified as ‘helpful’ in 28 patients, implying improved visualization of the tumor margins. The intensity of the fluorescence signal seemed to be correlated to the histology and was strongly dependent on the pre-treatment status. We did not record any allergic reactions or any other adverse effects.

Conclusion

The use of FL for the resection of brain tumors is safe and feasible. Presumably, the visualization of the tumor margin depends on the histopathology and on the pre-treatment status. A randomized evaluation of FL under the YELLOW 560 nm filter is planned to prospectively analyze the extent of resection in patients with malignant brain tumors.     

Resection of Colorectal Liver Metastases: Is a Resection Margin of 3 mm Enough?

Background

A safety margin of ≥10 mm is generally accepted in surgery for colorectal metastases. It is reasonable that modern methods of liver parenchyma dissection may allow for a reduction in this distance.

Methods

A total of 333 patients were included in a multicenter trial after resection of colorectal liver metastases. Dissection of the liver had been performed with a CUSA^®, UltraCision^®, or water-jet dissector. The size of the resection margin was correlated with recurrence risk and survival.

Results

The median hepatic recurrence-free survival reached 35 months for all patients; median recurrence-free survival was 24 months and overall survival was 41 months. Univariate analysis of different groups denoting the extent of resection margin (≥10 mm, 6–9 mm, 3–5 mm, 1–2 mm, 0 mm (R1)) indicated that a margin of 1–2 mm leads to a significantly reduced median hepatic recurrence-free survival of 20 months (p = 0.004) and recurrence-free survival of 19 months (p = 0.011). Patients with R1 resection had the worst prognosis. Overall survival was not influenced by the size of the resection margin. Surgical margins were significantly reduced in simultaneous resections of four or more liver metastases and in cases in which metastatic infiltration of central liver segments was present. At multivariate analysis, resection margins of 1–2 mm and 0 mm were independent predictors of hepatic recurrence and overall recurrence.

Conclusion

The indication for resection of metastases can be safely extended to cases in which tumors sit closer than 1 cm to nonresectable structures.     

Good Candidates for a Third Liver Resection of Colorectal Metastasis

Background

Having three liver resections for colorectal metastases has long been considered to be associated with a high risk of postoperative complications. The present study was designed to assess the feasibility and survival benefits of three liver resections.

Methods

Between 2004 and 2011, data for 273 consecutive patients with colorectal metastases were analyzed. The patient characteristics, tumor status, operation-related variables, degree of liver steatosis, and short- and long-term outcomes were compared according to the number of liver resections.

Results

The history of preoperative chemotherapy was higher for patients who had had three liver resections as compared with other resections: i.e., one resection 41.0 %, versus two resections 56.8 %, versus three resections 81.8 %; p = 0.04. Patients receiving three liver resections had a high rate of liver steatosis (17.9 vs. 32.4 vs. 59.1 %; p = 0.03). The median operative time for three resections was significantly longer than for the other resections (359 min [range: 115–579 min] vs. 395 min [range: 178–740 min], vs. 482 min [range: 195–616 min]; p = 0.04). However, the complication rate and the postoperative hospital stay did not differ among the three groups. The 1-, 3- and 5-year survival rates did not differ significantly among the three groups (83.3, 57.5, and 44.6 % for one resection vs. 92.3, 52.1, and 35.7 % for two resections vs. 93.3, 49.0, and 34.1 % for three resections). Patients who had <5 tumors at a third liver resection and a recurrence interval of ≥500 days from the second resection were good candidates for three resections.

Conclusions

Undergoing three resections of colorectal metastasis is feasible and provides a similar survival benefit as one or two resections, without increasing morbidity or mortality.     

Fluorescence-guided surgery in high grade gliomas using an exoscope system

Background

Fluorescence-guided microsurgical resections of high-grade gliomas using 5-aminolevulinic acid (5-ALA) is superior to conventional microsurgery. An optical device, usually a modified microscope, is needed for these procedures. However, an exoscope may be implemented for fluorescence techniques. We present the use of an exoscope to perform tumor resection guided by 5-ALA fluorescence in 21 consecutive patients with high-grade glioma and two neuronavigation-guided biopsies.

Methods

Twenty-three patients underwent operations. Tumor volume and localization were quantified with pre- and postoperative volumetric MRI in non-biopsy cases.

Results

In non-biopsy cases, the age range was 20 to 79 years, with a median of 56 (interquartile range?=?45-66). Histological analysis indicated that 14 had glioblastoma multiforme, 2 grade-III oligodendrogliomas and 1 anaplastic astrocytoma, 3 metastases and 1 low-grade astrocytoma. Total resection was achieved in 15 cases; subtotal resection was performed in 5 patients. The result was partial resection in one case. There was no perioperative mortality. The median fluorescence intensity, on a scale of 1–5, was 4.5 in the GBM group (IQR?=?4-5), 3 (IQR?=?2.5-3.5) in anaplastic glioma, and 2.5 (IQR?=?2.25-2.75) for oligodendrogliomas. Of the three metastases, one showed fluorescence level 4. As for the two biopsy cases, one was anaplastic astrocytoma and one glioblastoma multiforme. The samples obtained were fluorescent in both cases.

Conclusions

An exoscope can be also used for fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) and neuronavigation-guided biopsy. With an important advantage of low cost, this allows the surgeon to perform collaborative surgeries and adds agility to the procedure.     

Role of intraoperative neurophysiological monitoring during fluorescence-guided resection surgery

Background

Fluorescence-guided resection (FGR) using 5-aminolevulinic acid (5-ALA) exhibits a potential risk of permanent neurological deficits that can be minimized using intraoperative neurophysiological monitoring (IONM). We assessed the role of IONM in FGR surgery in patients harboring tumors in or near eloquent areas.

Methods

IONM and FGR surgeries were performed on 34 patients (49.8?±?2.4 years) harbored malignant primary gliomas near eloquent cortical areas or semioval center. Different combinations of neurophysiological techniques were used depending on each patient.

Results

Gross total resection (GTR) was achieved in 66.7 % of the patients, mean 90.4?±?3.7 % without neurological deficits. Resection in four patients was stopped by the occurrence of severe warning criteria despite the presence of fluorescence. Hemispheric transcranial electrical stimulation was safe and confident even in cortical surgery. Notably, a significant percentage of patients exhibited clinical improvement after the surgery. One week after surgery, only one patient worsened, and seven patients improved. At 3 months, 27.8 % of the patients improved, and the other patients maintained a similar status to their pre-surgery condition. Warning common criteria (amplitude reduction and/or latency increase) appeared in 68.2 and 50.0 % of patients during cortical or semioval surgery, respectively, with neither a false-negative nor a false-positive clinical outcome. Although 5-ALA exhibits phototoxicity, VEP did not induce any secondary effects in the visual system, including eyelids.

Conclusions

IONM can be helpful during surgery to maximize the tumor resection, meanwhile help to avoid neurological deficits and, therefore, to improve the quality of life of these patients.     

Photodynamic Diagnosis (5-Aminolevulinic Acid) of Transitional Cell Carcinoma After Bacillus Calmette-Guérin Immunotherapy and Mitomycin C Intravesical Therapy

Background

Photodynamic diagnosis (PDD) is a technique that enhances the detection of occult bladder tumors during cystoscopy using a fluorescent dye.

Objective

To study the differential effects of bacillus Calmette-Guérin (BCG) and mitomycin C (MMC) intravesical therapy on the false-positive rate of PDD of bladder cancer.

Design, setting, and participants

This study included 552 procedures and 1874 biopsies.

Intervention

Tumors were resected and biopsies were taken from suspicious areas, under guidance of white-light endoscopy and 5-ALA (5-aminolevulinic acid)–induced fluorescence cystoscopy.

Measurements

The influence of intravesical BCG immunotherapy and intravesical MMC chemotherapy on pyuria, inflammation, and PDD specificity was examined in univariate analyses.

Results and limitations

BCG significantly results in inflammation (odds ratio [OR]: 1.53, p = 0.002), leukocyturia (OR: 1.84, p = 0.034), and false positives in PDD (OR: 1.49, p = 0.001). However, a single BCG instillation within 3 mo before PDD is most likely not associated with increased false-positive rates (OR: 0.35, p = 0.26). Leukocyturia normalizes within 6 wk after the last BCG instillation, but PDD specificity is reduced up to 3 mo.

Conclusions

BCG is an important predictor for false positives in PDD (5-ALA). More than one BCG instillation within 3 mo before fluorescence cystoscopy decreases the specificity of PDD.     

Visualization of subcapsular hepatic malignancy by indocyanine-green fluorescence imaging during laparoscopic hepatectomy

Background

Although laparoscopic hepatectomy has increasingly been used to treat cancers in the liver, the accuracy of intraoperative diagnosis may be inferior to that of open surgery because the ability to visualize and palpate the liver surface during laparoscopy is relatively limited. Fluorescence imaging has the potential to provide a simple compensatory diagnostic tool for identification of cancers in the liver during laparoscopic hepatectomy.

Methods

In 17 patients who were to undergo laparoscopic hepatectomy, 0.5 mg/kg body weight of indocyanine green (ICG) was administered intravenously within the 2 weeks prior to surgery. Intraoperatively, a laparoscopic fluorescence imaging system obtained fluorescence images of its surfaces during mobilization of the liver.

Results

In all, 16 hepatocellular carcinomas (HCCs) and 16 liver metastases (LMs) were resected. Of these, laparoscopic ICG fluorescence imaging identified 12 HCCs (75 %) and 11 LMs (69 %) on the liver surfaces distributed over Couinaud’s segments 1–8, including the 17 tumors that had not been identified by visual inspections of normal color images. The 23 tumors that were identified by fluorescence imaging were located closer to the liver surfaces than another nine tumors that were not identified by fluorescence imaging (median [range] depth 1 [0–5] vs. 11 [8–30] mm; p < 0.001).

Conclusions

Like palpation during open hepatectomy, laparoscopic ICG fluorescence imaging enables real-time identification of subcapsular liver cancers, thus facilitating estimation of the required extent of hepatic mobilization and determination of the location of an appropriate hepatic transection line.     

Detection of Metastatic Lymph Nodes Using 5-Aminolevulinic Acid in Patients with Gastric Cancer

Background

Precise diagnosis of lymph node metastases is essential to select therapeutic strategy for patients with gastric cancer, and rapid intraoperative diagnosis is useful for performing less invasive surgery. In this study, we focused on a known photosensitizer, 5-aminolevulinic acid (5-ALA), and examined the feasibility of 5-ALA-induced protoporphyrin IX (PpIX) fluorescence to detect metastatic foci in excised lymph nodes of patients with gastric cancer.

Methods

A total of 144 lymph nodes obtained from 14 gastric cancer patients were examined. The patients were administered 5-ALA orally before surgery. Excised lymph nodes were cut in half and observed by fluorescence microscopy. The diagnostic results were compared to those of the routine histopathological examination.

Results

Observed red fluorescence of PpIX was identical to the metastatic focus, with 84 % accuracy. Twelve non-metastatic lymph nodes showed unexpected PpIX accumulation to lymphoid follicles, but these could be discriminated based on their characteristic fluorescence patterns. With incorporation of this morphological consideration, this method demonstrated good diagnostic power with 92.4 % accuracy. On the quantitative analysis using the signal intensity ratio of red to the sum of red, green, and blue (R/(R + G + B) ratio) as an index corresponding to red fluorescence of PpIX, metastatic lymph nodes showed significantly higher value than non-metastatic lymph nodes (p < 0.0001). The area under the curve was calculated as 0.832 throughout Receiver operating characteristic analysis.

Conclusions

Our results demonstrated that 5-ALA-induced fluorescence diagnosis is a simple and safe method and is a potential candidate for a novel rapid intraoperative diagnostic method applicable to clinical practice.     

A novel liver retractor for reduced or single-port laparoscopic surgery

Background

Retraction of either lobe of liver is required for surgical access to the respective organ. A novel liver retractor device and technique is described, which applies a vacuum between the liver and diaphragm to lift the liver, and which does not require additional incisions.

Methods

A novel liver retractor was tested in two anesthetized sheep at incrementally higher levels of suction from ?100 to ?700 mmHg (?13 to ?93 kPa), and any signs of trauma were recorded. The animals recovered for 5 days, then were humanely killed and postmortem examination of the liver and diaphragms performed.

Results

Successful liver retraction was achieved from ?200 to ?600 mmHg (?27 to ?80 kPa) suction. An imprint of the retractor was observed on the liver surface, but there was no breach of the liver serosa. Negligible ecchymoses were observed on the corresponding surface of the diaphragms. Both sheep recovered well after surgery. There was no macroscopic evidence of injury to the liver and diaphragm 5 days postoperatively. Histological examination revealed normal liver parenchyma deep to the site where the devices had been placed, and hemorrhagic changes within the serosa only varied between a few microns to a maximum of 1.4-mm depth.

Conclusions

The novel liver retractor described achieved an effective liver retraction without trauma. It has potential application in reduced or single-port laparoscopic upper abdominal surgery.     

Bleeding and hemostasis in laparoscopic liver surgery

Background

Minimally invasive liver resection is gaining acceptance worldwide. However, the laparoscopic approach often is reserved for small segmental resections due to the fear of significant blood loss. The expansion of laparoscopic liver surgery will depend on the ability of expert surgeons and technological advances to address the management of bleeding and hemostasis with any new approach. The 4½- year experience of a single center performing totally laparoscopic liver resections is presented, with special reference to the techniques the authors have developed to limit blood loss.

Methods

Between 2003 and 2007, 80 patients underwent laparoscopic liver surgery for benign and malignant conditions including colorectal cancer metastases (n = 31), hepatocellular carcinoma (n = 6), neuroendocrine tumor (n = 3), cystic lesion (n = 10), adenoma (n = 8), and focal nodular hyperplasia (n = 7). Totally laparoscopic resections included sectionectomy (n = 27), hemihepatectomy (n = 10), and single/multiple segmentectomies (n = 21). Data for all resections were recorded and analyzed retrospectively to assess blood loss, hospital stay, and morbidity.

Results

The median operative time was 150 min, and the median blood loss was 120 ml, with significantly more blood loss for right-sided transections than for the left liver surgery (821 vs 147 ml; p = 0.012). Four (57%) of seven resections converted to open procedures because of bleeding. No deaths occurred, and only two patients required intraoperative blood transfusions. There were eight complications and one bile leak. The median length of hospital stay was 3 days.

Conclusions

The authors’ experience with 80 totally laparoscopic liver resections over a 4½-year period demonstrates that laparoscopic liver surgery is safe and effective in experienced hands for major resections. An intimate knowledge of the technology and techniques available for preventing and managing significant hemorrhage during laparoscopic liver resection is required for all surgeons performing laparoscopic liver surgery.     

Photodynamic diagnosis in patients with T1G3 bladder cancer: influence on recurrence rate

Introduction

Therapeutic strategies on treatment of T1G3 urothelial cancer of the urinary bladder are controversial. The objective of this study was to investigate the impact of photodynamic diagnosis (PDD) on the recurrence-free survival rate of patients with the initial diagnosis of T1G3 bladder cancer.

Patients and methods

Between 1995 and 2007, 153 patients were treated for T1G3 bladder cancer at our institution. In 77 patients, initial TUR-BT was performed under PDD condition at our hospital, and 76 patients underwent TUR-BT in a standard white light setting at other institutions. PDD was performed either using 5-aminolevulinate or hexaminolevulinate for induction of fluorescence. Average follow-up was 53.9 months. Fisher’s exact test and Kaplan–Meier method were used to test data for significance.

Results

Of the 77 patients who were treated using PDD at initial TUR-BT, recurrence was observed in 23 (29.9%) cases, whereas 43 of 76 (56.6%) patients treated without PDD showed recurrence (P < 0.001). The detection rate of additional carcinoma in situ was 35.4% in the PDD group versus 21.8% in the white light group (P = 0.077). A limitation of the present study is the retrospective, monocentre setting, which is more likely to be biased.

Conclusion

PDD during initial TUR-BT in T1G3 bladder cancer seems to reduce significantly the rate of recurrence in our study population. Therefore, PDD seems to be associated with superior initial tumour control and more effective tumour treatment even in patients with highly aggressive tumours like T1G3 bladder cancer.     

5-aminolevulinic acid (5-ALA) fluorescence guided surgery of high-grade gliomas in eloquent areas assisted by functional mapping. Our experience and review of the literature

Background

Only few data are available on the specific topic of 5-aminolevulinic acid (5-ALA) guided surgery of high-grade gliomas (HGG) located in eloquent areas. Studies focusing specifically on the post-operative clinical outcome of such patients are yet not available, and it has not been so far explored whether such approach could be more suitable for some particular subgroups of patients.

Methods

Patients affected by HGG in eloquent areas who underwent surgery assisted by 5-ALA fluorescence and intra-operative monitoring were prospectively recruited in our Department between June 2011 and August 2012. Resection rate was reported as complete resection of enhancing tumor (CRET), gross total resection (GTR) >98 % and GTR?>?90 %. Clinical outcome was evaluated at 7, 30, and 90 days after surgery.

Results

Thirty-one patients were enrolled. Resection was complete (CRET) in 74 % of patients. Tumor removal was stopped to avoid neurological impairment in 26 % of cases. GTR?>?98 % and GTR?>?90 % was achieved in 93 % and 100 % of cases, respectively. First surgery and awake surgery had a CRET rate of 80 % and 83 %, respectively. Even though at the first-week assessment 64 % of patients presented neurological impairment, there was a 3 % rate of severe morbidity at the 90th day assessment. Newly diagnosed patients had a significantly lower morbidity (0 %) and post-operative higher median KPS. Both pre-operative neurological condition and improvement after corticosteroids resulted significantly predictive of post-operative functional outcome.

Conclusions

5-ALA surgery assisted by functional mapping makes high HGG resection in eloquent areas feasible , through a reasonable rate of late morbidity. This emerges even more remarkably for selected patients.     

Surgical Treatment of Pediatric Desmoid Tumors. A 12-Year, Single-Center Experience

Background

Pediatric desmoid tumors (PDTs) represent a group of rare, distinct lesions. While sparse, available literature suggests that PDT are particularly aggressive and difficult to control when compared with their adult counterpart.

Methods

A retrospective review identified 39 patients who underwent treatment of PDT at St. Jude Children’s Research Hospital over a 12-year period. Clinicopathologic and treatment characteristics were analyzed to identify predictors of outcome.

Result

A total of 39 patients were treated during the study period, with a total number of 67 resections. Median age was 12.2 years; 49 % of patients were male, and 51 % were female. Median tumor size was 9.8 cm. PDT most commonly arose in the extremities (40 %), thorax (23 %), head and neck (21 %), and trunk (16 %). Also, 18 % of resections had negative margins (R0), 48 % were microscopic positive (R1), and 30 % were macroscopic positive (R2). The 1- and 5-year recurrence-free survival (RFS) was 97.1 and 73.1 %, respectively. Factors associated with worse RFS were patient age >12 years (HR = 5.08, p = 0.038) and tumor size >5 cm (HR = 1.22, p = 0.0597). Margin status did not affect RFS. Selective use of radiation therapy appeared to improve RFS.

Conclusions

Our study suggests that margin status alone at the time of extirpation is not a predictor of ultimate cure or likelihood of recurrence. Many patients received adjuvant therapy, with benefits suggested after analysis. For patients with PDT, surgical extirpation should not come at the expense of functional preservation, as overall survival is excellent.     

Poor prognosis and complications are common in limb salvage surgery for malignant tumors of the proximal tibia invading the fibula

Background

Malignant tumors in proximal tibia invading fibula usually have a large tumor volume and are adjacent to the neurovascular bundles. The prognoses and functional outcomes of limb salvage for these patients are uncertain. We, therefore, asked whether patients with limb salvage surgery for malignant tumors in proximal tibia invading fibula had poorer oncological prognosis, higher complication rate, and lower postoperative functional score compared with patients without fibula invasion.

Methods

We retrospectively reviewed 129 patients with primary malignant tumors in proximal tibia. The patients were divided into two groups, i.e., with and without proximal fibula invasion. A total of 35 and 94 patients were in the group with and without fibula invasion, respectively. Data on demography, operation time, blood loss volume, complications, survival time, and postoperative function were compared between two groups.

Results

The patients with fibula invasion had a longer mean operative time (p = 0.011), less percentage of obtaining wide surgical margin (p = 0.027), lower estimated 5-year survival rate (p = 0.05), higher tumor local recurrence rate (p = 0.042), and earlier postoperative complications (p = 0.01) than the patients without fibula invasion. The difference in postoperative functions as evaluated by the Musculoskeletal Tumor Society functional scoring system was not significant (p = 0.233).

Conclusion

Patients with limb salvage surgery for malignant tumors in proximal tibia invading fibula had poorer oncological prognosis, higher complication rate, and acceptable postoperative functions compared with patients without fibula invasion.     

Laparoscopic resection for hepatocellular carcinoma: a matched-pair comparative study

Background

Only a few series have demonstrated the safety of laparoscopic resection for hepatocellular carcinoma (HCC) and the benefits of this approach. Moreover, these studies reported mostly minor and nonanatomic hepatic resections. This report describes the results of a pair-matched comparative study between open and laparoscopic liver resections for HCC in a series of essentially anatomic resections.

Methods

Patients were retrospectively matched in pairs for the following criteria: sex, age, American Society of Anesthesiology (ASA) score, severity of liver disease, tumor size, and type of resection. A total of 42 patients undergoing laparoscopy were compared with patients undergoing laparotomy during the same period. Surgeons from the authors’ department not trained in laparoscopy performed open resections. Operative, postoperative, and oncologic outcomes were compared.

Results

The mean duration of surgery was similar in the two groups. Significantly less bleeding was observed in the laparoscopic group (364.3 vs. 723.7 ml; p < 0.0001). Transfusion was required for four patients (9.5%) in the laparoscopic group and seven patients (16.7%) in the open surgery group (p = 0.51). Postoperative ascites was less frequent after laparoscopic resections (7.1 vs. 26.1%; p = 0.03). General morbidity was similar in the two groups (9.5 vs. 11.9%; p = 1.00). The mean hospital stay was significantly shorter for the patients undergoing laparoscopy (6.7 vs. 9.6 days; p < 0.0001). The surgical margin and local recurrence adjacent to the liver stump were not affected by laparoscopy. The overall postoperative survival rates in the laparoscopic group were 93.1% at 1 year, 74.4% at 3 years, and 59.5% at 5 years and, respectively, 81.8, 73, and 47.4% in the open surgery group (p = 0.25). The postoperative disease-free survival rates in the laparoscopic group were at 81.6% at 1 year, 60.9% at 3 years, and 45.6% at 5 years, respectively, 70.2, 54.3, and 37.2% in the open surgery group (p = 0.29).

Conclusions

Laparoscopic resection of HCC for selected patients gave a better postoperative outcome without oncologic consequences. Prospective trials are required to confirm these results.     

Randomized controlled multicenter trial on the effectiveness of the collagen hemostat Sangustop® compared with a carrier-bound fibrin sealant during liver resection (ESSCALIVER study,NCT00918619)

Background

Despite improvements in liver surgery over the past decades, hemostasis during hepatic resections remains challenging. This multicenter randomized study compares the hemostatic effect of a collagen hemostat vs. a carrier-bound fibrin sealant after hepatic resection.

Methods

Patients scheduled for elective liver resection were randomized intraoperatively to receive either the collagen hemostat (COLL) or the carrier-bound fibrin sealant (CBFS) for secondary hemostasis. The primary endpoint was the proportion of patients with hemostasis after 3 min. Secondary parameters were the proportions of patients with hemostasis after 5 and 10 min, the total time to hemostasis, and the complication rates during a 3 months follow-up period.

Results

A total of 128 patients were included. In the COLL group, 53 out of 61 patients (86.9 %) achieved complete hemostasis within 3 min after application of the hemostat compared to 52 out of 65 patients (80.0 %) in the CBFS group. The 95 % confidence interval for this difference [?6.0 %, 19.8 %] does not include the lower noninferiority margin (?10 %). Thus, the COLL treatment can be regarded as noninferior to the comparator. The proportions of patients with hemostasis after 3, 5, and 10 min were not significantly different between the two study arms. Postoperative mortality and morbidity were similar in both treatment groups.

Conclusion

The collagen hemostat is as effective as the carrier-bound fibrin sealant in obtaining secondary hemostasis during liver resection with a comparable complication rate.