Outcome After Resection of Craniopharyngiomas and the Important Role of Stereotactic Radiosurgery in Their Management.

OBJECTIVE: Experience with management of craniopharyngiomas (CPH) was evaluated retrospectively. METHODS: Between 1981 and 2012, 100 patients underwent removal of a CPH (the main surgical group), and an original tumor grading system was applied to these cases. The mean length of follow-up was 121 months. Additionally, 17 patients underwent removal of a CPH between 2012 and 2017 (the supplementary surgical group), and in 6 of them, CyberKnife radiosurgery was performed on a residual tumor (in 5 cases) or at the time of recurrence (in 1 case). RESULTS: In the main surgical group, the gross total resection (GTR) rate was 81%. The early and late disease-specific postoperative mortality rates were 0% and 2%, respectively. Tumor recurrence was never noted after GTR. There was a statistically significant increase in the Karnofsky Performance Scale (KPS) score after surgery. The tumor surgical grade was inversely associated with both the pre- and postoperative KPS scores, and was lower in cases operated on via the transnasal transsphenoidal approach, but was unrelated to the GTR rate. In the supplementary surgical group, the GTR rate was 65%. CyberKnife radiosurgery consistently resulted in tumor shrinkage. CONCLUSION: GTR is the preferred management option for CPH. The original surgical grading system developed at Tokyo Women's Medical University may be helpful for clinical decision-making. CyberKnife radiosurgery for residual and recurrent CPH is associated with high tumor response rates.

[Postoperative Adjuvant Chemotherapy for Descending Colon Cancer Treated with Imatinib for Chronic Myeloid Leukemia].

A66 -year-old man was diagnosed with chronic myeloid leukemia(CML). Imatinib treatment had been initiated, and a major molecular response(MMR)was achieved. The patient had anemia and was diagnosed with descending colon cancer. The patient was surgically treated, and then received postoperative adjuvant chemotherapy with UFT/LV. However, imatinib was not administered during that period. The patient could undergo postoperative adjuvant chemotherapy for 6 months without acute exacerbation of the CML.

Overexpression of Lysophosphatidylcholine Acyltransferase 1 and Concomitant Lipid Alterations in Gastric Cancer.

BACKGROUND: The involvement of lipids in carcinogenic and developmental processes has been reported in some malignancies, but their roles in gastric cancer remain to be analyzed. In this study, we compared the lipid content of gastric cancer tissue and adjacent nonneoplastic mucosa using imaging mass spectrometry. METHODS: Mass spectra were acquired from 12 sections of human gastric cancer tissue and adjacent nonneoplastic mucosa using a matrix-assisted laser desorption-ionization time-of-flight tandem mass spectrometry type mass spectrometer equipped with a 355 nm Nd:YAG laser. Protein expression of lysophosphatidylcholine acyltransferase 1 (LPCAT1), which converts lysophosphatidylcholine (LPC) to phosphatidylcholine (PC) in the presence of acyl-CoA in Lands' cycle, was immunohistochemically analyzed in 182 gastric cancer specimens. RESULTS: The averaged mass spectra from the cancer tissue and nonneoplastic mucosa were identical. Most of the signals that differed between cancer tissue and nonneoplastic mucosa corresponded to phospholipids, the majority of which were PC and LPC. Two signals, m/z 798.5 and 496.3, were higher and lower, respectively, in cancer tissues, predominantly in differentiated adenocarcinoma. A database search enabled identification of the ions at m/z 798.5 and m/z 496.3 as potassium-adducted PC (16:0/18:1) and proton-adducted LPC (16:0), respectively. Immunohistochemical analysis revealed that LPCAT1 was highly expressed in cancer lesions compared to nonneoplastic mucosa, predominantly in differentiated adenocarcinoma. LPCAT1 expression levels correlated positively with tumor differentiation and negatively with tumor depth, lymph node metastasis, and tumor stage. CONCLUSIONS: Overexpressed LPCAT1 protein in gastric mucosa appears to play important roles in the tumorigenic process of gastric cancer by converting LPC to PC.

Quantitative assessment of the free jejunal graft perfusion.

BACKGROUND: Reconstruction with free jejunal graft (FJG) is often performed for patients with hypopharyngeal or cervical esophageal cancer. During reconstruction with an FJG after pharyngoesophagectomy, it is critical to intraoperatively detect venous anastomotic failure and subsequent venous malperfusion to avoid postoperative FJG necrosis. This study introduces a novel method for assessing blood perfusion in FJGs by using indocyanine green (ICG) fluorescence angiography. METHODS: We used ICG fluorescence angiography to quantitatively assess FJG blood perfusion in archived fluorescence video files from 26 patients who had undergone FJG transfer. A software program "ROIs", was used to create a time-fluorescence intensity curve. We retrospectively measured the maximum fluorescence intensity at the terminal ileum and the duration (T1/2max) between when the intensity began rising and when it reached half of the maximum. RESULTS: Among the 26 patients, 5 patients suffered venous anastomotic failure. In three of these cases, anastomosis was corrected intraoperatively; the other two patients underwent a second FJG transfer. Retrospective assessment showed that the mean T1/2max at the FJG serosae was significantly longer in these five patients than that in FJGs with good blood perfusion. Our analysis revealed that a T1/2max >9.6 s may be a good indicator of FJG venous malperfusion. CONCLUSIONS: Quantitative analysis of ICG fluorescence angiography proved useful for detecting venous anastomotic failure of FJG, and may help to reduce vascular problems in FJG reconstruction.

Shifts in endotracheal tube position due to chest compressions: a simulation comparison by fixation method.

BACKGROUND: Endotracheal tube placement during resuscitation is important for definite tracheal protection. Accidental extubation due to endotracheal tube displacement is a rare event that can result in severe complications. OBJECTIVE: This study evaluated how endotracheal tube displacement is affected by tape vs. tube holder fixation using a manikin and auto-chest compression machine simulation. METHODS: The endotracheal tube was placed in either a shallow or a deep position, with the tube cuff at the center of the glottis or 26 cm from the incisors in an advanced lifesaving simulator. Trials were performed five times in each setting with: no fixation; Durapore® tape fixation; Multipore® tape fixation; and Thomas tube holder® fixation. After 10 min of automated chest compressions, endotracheal tube shift was measured. Statistical analysis was performed with one-way repeated analysis of variance or χ(2) test, with p < 0.05 considered significant. RESULTS: In the shallow setting, endotracheal tube extubation occurred in all trials with no fixation, Durapore, and Multipore. In contrast, no extubation occurred in the Tube holder trials (p < 0.05). In the deep setting, no extubation was confirmed in any trial. Relative to no fixation (0.56 ± 0.11 cm), endotracheal tube shift was significantly less in the Durapore tape, Multipore tape, and Tube holder groups (p < 0.05). Of the three fixation methods, Tube holder (0.04 ± 0.05 cm) showed significantly less shift (p < 0.05) relative to Durapore (0.28 ± 0.04 cm) and Multipore (0.32 ± 0.08 cm). CONCLUSION: Endotracheal tube displacement occurs less with Tube holder fixation than with Durapore tape or Multipore tape during simulation of continuous chest compressions.

Muscle relaxant effects on insertion efficacy of the laryngeal mask ProSeal(®) in anesthetized patients: a prospective randomized controlled trial.

BACKGROUND: Anesthesiologists often encounter LMA-ProSeal(®) (ProSeal) insertion difficulty due to its large cuff size. We performed a randomized clinical trial to examine how insertion efficacy and sealing pressure of ProSeal are affected by muscle relaxant administration in anesthetized patients. METHODS: Our adult patients were either administered rocuronium (0.9 mg kg(-1)) as a muscle relaxant (R group; 40 patients) or not (C group; 40 patients). Anesthesia was induced with propofol and fentanyl. We compared the two groups with regard to the number of attempts required for successful insertion, sealing pressure, and subjective difficulty for insertion. RESULTS: Total insertion attempts required for successful ventilation in the two groups were one (R group, 38 patients; C group, 28 patients), two (R group, one patient; C group, seven patients), and three (R group, one patient; C group, five patients), revealing a significant difference between groups (p < 0.001). Sealing pressure was significantly higher in the R group than in the C group (R group, 27.4 ± 5.4 cmH2O; C group, 21.2 ± 5.2 cmH2O; p < 0.001). Leakage volume by mechanical ventilation was significantly smaller in the R group than in the C group (R group, 17.4 ± 29.1 ml; C group, 46.8 ± 45.5 ml; p < 0.001). Subjective difficulty of insertion was significantly lower in the R group than in the C group (R group, 12.3 ± 23.1 mm; C group, 39.4 ± 31.9 mm; p < 0.001). CONCLUSIONS: Muscle relaxation appears to facilitate ProSeal insertion efficacy by enabling higher successful insertion rates, higher sealing pressure, lower leakage volume, and lower subjective difficulty of insertion in anesthetized patients.

[Laryngeal Tube Position Shift after Chest Compression: Comparison of Fixation Methods Using Durapore Tape, Multipore Tape, or a Neck Tape].

BACKGROUND: The laryngeal tube (LT ; Smiths Medical, Minnesota, U. S. A) is an inflatable supraglottic device for emergency airway management such as during chest compression, the instability after insertion remains a problem. METHODS: We investigated the effectiveness of three fixation methods of LT using a manikin and automated chest compressor. RESULTS: After 10-minute chest compression, LT without fixation was shifted by 0.4 ± 0.1 cm, which was greater than with Durapore tape (0.2 ± 0.1 cm), Multipore tape (0.2 ± 0.1 cm), or a neck tape (0.1 ± 0.1 cm). The shift of the position was smaller with neck tape fixation compared to Durapore or Multipore tape fixation. CONCLUSIONS: A fixation neck tape may be useful in stabilizing the inserted position of LT during cardiopulmonary resuscitation.

Anti-VEGF antibody therapy induces tumor hypoxia and stanniocalcin 2 expression and potentiates growth of human colon cancer xenografts.

Tumor angiogenesis plays a critical role in colorectal cancer progression. Recent randomized clinical trials have revealed the additive effect of bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF)-A, to conventional chemotherapy in the improved survival of patients with metastatic colorectal cancer. However, a number of preclinical reports indicate the development of resistance to anti-angiogenic therapy. In this study, we addressed the effects of anti-VEGF antibodies on the growth and malignant behavior of colorectal cancer cells. TK-4, a solid tumor strain derived from a colon cancer patient, was subcutaneously or orthotopically implanted into nude mice. Short-term administration of anti-VEGF antibodies inhibited the growth of cecal tumors at day 14 by suppressing mitosis, but prolonged treatment resulted in the recovery of cellular proliferation and suppression of apoptosis at day 35. Intratumoral hypoxia induced by anti-VEGF antibody treatment resulted in activation of hypoxia inducible factor-1α protein and an increased number of aldehyde dehydrogenase 1-positive tumor cells. In microarray analysis, stanniocalcin 2 (STC2) was the most highly upregulated gene in anti-VEGF antibody-treated tumors. In vitro analyses showed that the growth and migration of SW480 colon cancer cells under hypoxic conditions were significantly inhibited by knockdown of STC2. In vivo serial transplantation of TK-4 revealed that long-term administration of anti-VEGF antibodies increased the tumorigenicity of colon cancers and accelerated tumor growth when transplanted into secondary recipient mice. Our data provide a potential molecular explanation for the limited clinical effectiveness of anti-VEGF antibodies.

Laparoscopic narrow-band imaging for the diagnosis of peritoneal metastasis in gastric cancer.

BACKGROUND: Staging laparoscopy (SL) is often used to diagnose peritoneal metastasis in patients with advanced gastric cancer, but accurate detection of metastasis can be difficult. We evaluated the usefulness of laparoscopic narrow-band imaging (NBI) versus conventional laparoscopic white-light imaging (WLI) for the diagnosis of peritoneal metastasis. METHODS: We excised 37 white nodules from the parietal peritoneum of 26 patients with gastric cancer and suspected peritoneal metastasis. The WLI and NBI findings were compared with the pathological findings. All the peritoneal lesions examined were observed as white nodules on WLI. Intranodular vessels were evaluated by WLI and NBI for (1) vessel dilatation, (2) vessel tortuousness, (3) vessel heterogeneity, and (4) brown spots. RESULTS: Each individual abnormal finding had a diagnostic accuracy of less than 79 % with or without NBI. Detection of any one abnormal finding had a sensitivity, specificity, and accuracy of 47.8, 85.7, and 62.2 %, respectively, on WLI and 91.3, 71.4, and 83.8 %, respectively, on NBI, for detection of peritoneal metastasis. Detection of any one abnormal finding on NBI plus clear demarcation of the nodule on WLI had a sensitivity of 91.3 %, specificity of 92.9 %, and accuracy of 91.9 % for detection of peritoneal metastasis. Pathological examination showed that a brown spot detected on NBI correlated with dilated vessels around cancer cells. Vascular endothelial growth factor was expressed in 76.2 % of peritoneal metastases. CONCLUSIONS: NBI was more sensitive for the detection of dilated vessels than WLI. NBI could be a useful tool for the diagnosis of peritoneal metastasis during SL.

Comparison of fluid leakage from four different cuffed pediatric endotracheal tubes using a pediatric airway simulation model.

This study used an airway model to compare the ability of a pediatric endotracheal tube with a taper-shaped cuff to prevent microaspiration relative to endotracheal tubes with conventional cuffs. Four different types of 5.0-mm inner diameter cuffed pediatric endotracheal tubes (taper-shaped cuff [Taper], high-volume low-pressure [Hi-Lo], middle-volume low-pressure [Intermediate], and low-volume low-profile [Lo-Pro]) were fixed within vertically placed acrylic tubes. The cuffs were maintained at 10, 20, or 30 cmH2 O pressure and 3 mL of simulated stomach contents was added to the top of the cuffs. The volume of leakage around the cuffs after 5 min and 4 h was measured. After 5 min, the volume of leakage was significantly lower with the Taper than with the Hi-Lo, Intermediate, or Lo-Pro at all pressure settings. After 4 h, leakage was significantly lower with the Taper than with the other three tubes regardless of initial cuff pressure (P < 0.05).

[Difficult airway management using the air-Q in a patient with Klippel-Feil syndrome].

Patients with Klippel-Feil syndrome (KFS) frequently encounter difficult airway management due to skeletal abnormalities, including fusion of two or more vertebrae and short neck. We report successful tracheal intubation using the air-Q supraglottic airway device (air-Q). A 46-year-old woman (height, 149 cm; weight, 62 kg) with KFS was scheduled to undergo vertebral arch plasty for cervical spondylotic myelopathy. She could open her mouth sufficiently but could not tilt her head due to C1-3 fusion. Following administration of fentanyl 100 microg and propofol 120 mg, mask ventilation was achieved with jaw thrust maneuver. We then administered rocuronium 50 mg for immobilization and attempted tracheal intubation using the Pentax-AWS Airwayscope with a thin pediatric Intlock. However, we could not target the glottis, and ventilation via a size 3 i-gel or size 3.5 air-Q was unsuccessful. Using a size 2.5 air-Q, sufficient ventilation was finally achieved. We performed fiberoptic tracheal intubation through the air-Q using a tube with an internal diameter of 6.0-mm. We then exchanged the 6.0-mm tracheal tube with a 7.0-mm spiral tube using a 10 Fr tracheal tube introducer.

[Successful awake tracheal intubation in the sitting position using the Pentax-AWS Airwayscope in a patient with hypopharyngeal cancer and gastroesophageal regurgitation].

We report the successful awake tracheal intubation in a patient with hypopharyngeal cancer and gastroesophageal regurgitation with the TaperGuard Evac tracheal tube (TaperGuard) and Pentax-AWS Airwayscope (AWS). A 63-year-old man with hypopharyngeal cancer with invasion to the glottis was scheduled for total laryngectomy under general anesthesia. He had undergone thoracic esophagectomy and could not maintain supine position due to severe gastroesophageal regurgitation. To avoid vomiting after induction of anesthesia, we planned awake intubation in the sitting position with the AWS. After topical anesthesia with 8% lidocaine and infusion of fentanyl and continuous dexmedetomidine, the AWS was inserted into his mouth in the sitting position from the cranial side. The AWS allowed visualizing the glottis avoiding the cancer, leading to safe placement of the tracheal tube.

[Shift of the i-gel position after chest compression: comparison of fixation methods using Durapore tape, Multipore tape, or a fixation strap].

BACKGROUND: The i-gel (Intersurgical, Wokingham, U.K.) is a newly developed, non-inflatable supraglottic device characterized by its soft, gel-like, and transparent mask made of thermoplastic elastomer. Although i-gel can be useful in emergency airway management during chest compression, the instability after insertion remains a problem. METHODS: We investigated the effectiveness of three fixation methods using a manikin and automated chest compressor. RESULTS: After 5-minute chest compression, i-gel without fixation was shifted by 0.56 +/- 0.17 cm, which was greater than with Durapore tape (0.28 +/- 0.08 cm), Multipore tape (0.26 +/- 0.05 cm), or a fixation strap (0.04 +/- 0.05 cm). The shift of the position was smaller with strap fixation compared to Durapore or Multipore tape fixation. CONCLUSIONS: A fixation strap may be useful in stabilizing the inserted position of i-gel during cardiopulmonary resuscitation.

Effect of miR-122 and its target gene cationic amino acid transporter 1 on colorectal liver metastasis.

Control of liver metastasis is an important issue in the treatment of colorectal cancer (CRC). MicroRNAs have been shown to be involved in the development of many cancers, but little is known about their role in the process of colorectal liver metastasis. We compared miRNA expression between primary colorectal tumors and liver metastasis to identify those involved in the process of metastasis. Cancer cells were isolated from formalin-fixed paraffin-embedded primary CRC samples and their corresponding metastatic liver tumors in six patients using laser capture microdissection, and miRNA expression was analyzed using TaqMan miRNA arrays. The most abundant miRNA in liver metastasis compared with primary tumors was miR-122. Immunohistochemical analysis revealed that the expression levels of cationic amino acid transporter 1 (CAT1), a negative target gene of miR-122, were lower in liver metastases than primary tumors (P < 0.001). Expression levels of CAT1 in 132 primary tumors were negatively correlated with the existence of synchronous liver metastasis (P = 0.0333) and tumor stage (P < 0.0001). In an analysis of 121 colon cancer patients without synchronous liver metastasis, patients with CAT1-low colon cancer had significantly shorter liver metastasis-free survival (P = 0.0258) but not overall survival or disease-free survival. Overexpression of miR-122 and concomitant suppression of CAT1 in the primary tumor appears to play important roles in the development of colorectal liver metastasis. Expression of CAT1 in the primary CRC has the potential to be a novel biomarker to predict the risk of postoperative liver metastasis of CRC patients.

Usefulness of three-dimensional angiographic analysis of perigastric vessels before laparoscopic gastrectomy.

BACKGROUND: Recognition of perigastric vessel anatomy is important to safely perform gastric surgery, especially in the case of laparoscopic gastrectomy. This study was designed to reevaluate the efficacy of preoperative three-dimensional (3D) angiography reconstructed from enhanced multidetector-row computed tomography (MDCT) data and to classify right gastric artery (RGA) branching patterns. METHODS: Perigastric vessel anatomy was preoperatively analyzed using MDCT-based 3D angiography reconstructed by computer software in patients undergoing laparotomic (n = 75) and laparoscopic (n = 25) gastrectomy. Results were compared with intraoperative findings in all cases, and were also compared with maximum intensity projection (MIP) imaging, which is similar to conventional angiography, in 10 patients. RESULTS: Preoperative diagnoses by 3D angiography were identical to intraoperative findings. The rates of branching patterns of the celiac artery and left gastric vein were comparable with previous reports. The detection rate of the right gastric artery (RGA) was 77.0%. Branching patterns of the hepatic artery were classified into four types: right hepatic artery (RHA) + left hepatic artery (LHA) type, replaced RHA + LHA type, RHA + replaced LHA type, and replaced RHA + replaced LHA type. RGA ramification patterns were classified into three types according to hepatic arterial running patterns: distal (68.8%), proximal (14.3%), and caudal (16.9%). Because of vessel overlapping, RGA ramified points were misdiagnosed under MIP images in two of ten cases (20%). CONCLUSIONS: Preoperative 3D angiography is useful for a new system of classifying RGA ramification patterns into three types. With this system, surgeons can perform laparoscopic gastrectomy with lymph node dissection more safely.

Proteomic analysis of cerebrospinal fluid before and after intrathecal injection of steroid into patients with postherpetic pain.

Postherpetic neuralgia (PHN) is the most frequent complication of herpes zoster, and the risk of it increases with age. By comparing proteomes of the cerebrospinal fluid (CSF) before and after the treatment, it may be possible to identify proteins that play a role in PHN and to predict responses to various treatments. To address this issue, we enrolled eight outpatients with PHN over 55 years of age and treated them with intrathecal methylprednisolone and lidocaine four times every week, collecting CSF samples before the treatment at each visit. We used 2D DIGE to investigate differentially expressed proteins in the CSF before and after repetitive treatments individually. Of 145 differentially expressed spots, the levels of nine proteins were decreased by the treatment including lipocalin-type prostaglandin D synthase (L-PGDS), and five were increased by it. The time course of alterations in the L-PGDS concentration in the CSF of each patient, detected by a pairwise and sandwich ELISA by SPR constructed here was well correlated with that by 1DE Western blots with anti-L-PGDS antibody, but was not related with that of the pain relief. The present study demonstrates that the real-time ELISA was precise and sensitive enough to measure L-PGDS in the CSF and that the steroid treatment decreased the L-PGDS concentration in CSF.

In vivo optical coherence tomography of very late drug-eluting stent thrombosis compared with late in-stent restenosis.

BACKGROUND: Autopsy findings have suggested delayed arterial healing as a primary cause of very late stent thrombosis (VLST) after drug-eluting stent (DES) implantation. METHODS AND RESULTS: Optical coherence tomography of DES-treated lesions that developed VLST (n = 6) was compared with that of DES-treated lesions that developed late in-stent restenosis (L-ISR: n = 32) among patients with recurrent ischemia >1 year after DES implantation (mean, 37 ± 17 months), and with the stented segment without any evidence of VLST or L-ISR (no-event: n = 20; mean, 38 ± 19 months). The proportion of uncovered and malapposed struts in each stented segment was evaluated. A total of 961 frames, 9,763 struts were analyzed. The proportion of uncovered struts was higher in the VLST group than in the L-ISR group and the no-event group (29.2 ± 22.8%, 7.9 ± 9.7%, and 7.6 ± 8.0%, respectively; P = 0.0002). The proportion of malapposed struts was higher in the VLST group than in the no-event group (7.3 ± 8.7% vs 1.1 ± 2.4%, P = 0.01). Two patients in the VLST group had lower rates of uncovered and malapposed struts, but this involved lipid-laden-like neointima with disruptions. CONCLUSIONS: Delayed neointimal coverage and incomplete stent apposition were frequently observed in the DES-treated lesions that developed very late thrombosis. Lipid-laden-like neointima with disruption within the DES may be another possible mechanism for very late thrombosis.

Defining the treatment strategy for uncomplicated appendicitis based on patient satisfaction feedback: A cross-sectional study.

BACKGROUND: Two surgical strategies are available for appendicitis: emergency laparoscopic appendectomy and interval laparoscopic appendectomy. However, timing of surgical intervention remains debatable. This study aimed to compare the surgical outcomes of emergency laparoscopic appendectomy and interval laparoscopic appendectomy and conduct a questionnaire survey to investigate the use of emergency laparoscopic appendectomy and patient satisfaction with regard to treatment. METHODS: We included 162 patients who underwent laparoscopic appendectomy at our hospital. Outcomes were assessed by operation time, blood loss, postoperative fasting time, length of hospital stay, and complication rate. Patient satisfaction was measured by questionnaire addressing degree of satisfaction, presurgery anxiety, and length of hospital stay. RESULTS: Of 162 patients, 74 (46%) and 88 (54%) received emergency and interval laparoscopic appendectomy, respectively. No significant difference was observed in the operation time, blood loss, length of hospital stay, or complication rate. Among 66 patients who responded to the questionnaire (28 emergency, 38 interval), a significant difference was observed only in the degree of satisfaction regarding the timing of the surgical intervention (p = 0.04). CONCLUSION: Surgical outcomes of emergency and interval appendectomy were equivalent; however, patient satisfaction favored emergency appendectomy, suggesting it is a preferable approach for the treatment of uncomplicated appendicitis.

Surgical intervention for imatinib and sunitinib-resistant gastrointestinal stromal tumors.

Imatinib mesylate is an effective treatment for recurrent or metastatic gastrointestinal stromal tumors (GISTs), but secondary resistance has been reported. The tyrosine kinase inhibitor sunitinib malate has shown efficacy in imatinib-resistant GISTs, and has been used as second-line therapy for recurrent or metastatic GISTs. However, it is often difficult to treat patients with imatinib- and sunitinib-resistant GISTs. In this report, we describe a case of surgically resected liver and peritoneal recurrences of GISTs that arose polyclonally and were resistant to imatinib and sunitinib. A 67-year-old man was referred to our hospital with multiple recurrent GISTs after failed imatinib treatment. Sunitinib was administered at 50 mg/day for 4 weeks with 2-week intervals between treatments. Some of the recurrent GISTs were sensitive, but others were resistant, and progressive disease was diagnosed. Extended left hepatectomy and peritoneal tumorectomy were performed. Histologically, tumors sensitive to sunitinib showed degenerative changes, while the resistant tumors consisted of KIT-positive, viable GIST cells. The primary mutation in all the tumors consisted of a deletion at nucleotides 555-560 with an E554D point mutation at exon 11 of the c-kit gene. The sunitinib-resistant liver and peritoneal tumors had different point mutations: T to G and T to A, respectively, although both resulted in an N822K amino acid alteration, indicating the polyclonal evolution of recurrent GISTs. Thus, if R0 resection is expected, surgical intervention under the control of imatinib or sunitinib should be considered for the control of metastatic or recurrent GISTs.

Postoperative bile leakage managed by interventional intrabiliary ethanol ablation.

We report a case of postoperative bile leakage that was successfully managed by intrabiliary ethanol ablation. A 68-year-old man with peritoneal and liver metastases from a jejunal gastrointestinal stromal tumor (GIST), which were refractory to molecular-targeted agents, underwent extended left lobectomy and peritoneal tumor resection. Bile leakage from the drainage tube persisted at a constant volume of 100 ml per day. On the 20th postoperative day, fistulography through a drainage tube and endoscopic cholangiography revealed biliary leakage from the bile ducts of segments 5 and 1. Since these bile ducts did not communicate with the proximal hilar bile ducts, two 5F balloon catheters were separately advanced into the leaking bile ducts via the drainage tube on day 30, and 1 ml absolute ethanol was injected into both of these catheters for 10 minutes. After three sessions of ethanol ablation, the bile leakage stopped. Although the bile leakage from segment 1 relapsed five days later, it gradually decreased and then stopped again until day 70. Intrabiliary ethanol ablation using the interventional technique is useful for managing bile leakage after hepatectomy when the leaking distal bile duct is isolated from the proximal biliary tree.