Spontaneous intercostal artery bleeding occurring simultaneously in numerous vessels during antithrombotic therapy with mechanical circulatory support: a case report.

BACKGROUND: Intercostal artery bleeding often occurs in a single vessel; in rare cases, it can occur in numerous vessels, making it more difficult to manage. CASE PRESENTATION: A 63-year-old Japanese man was admitted to the emergency department owing to sudden chest and back pain, dizziness, and nausea. Emergency coronary angiography revealed myocardial infarction secondary to right coronary artery occlusion. After intra-aortic balloon pumping, percutaneous coronary intervention was performed in the right coronary artery. At 12 hours following percutaneous coronary intervention, the patient developed new-onset left anterior chest pain and hypotension. Contrast-enhanced computed tomography revealed 15 sites of contrast extravasation within a massive left extrapleural hematoma. Emergency angiography revealed contrast leakage in the left 6th to 11th intercostal arteries; hence, transcatheter arterial embolization was performed. At 2 days after transcatheter arterial embolization, his blood pressure subsequently decreased, and contrast-enhanced computed tomography revealed the re-enlargement of extrapleural hematoma with multiple sites of contrast extravasation. Emergency surgery was performed owing to persistent bleeding. No active arterial hemorrhage was observed intraoperatively. Bleeding was observed in various areas of the chest wall, and an oxidized cellulose membrane was applied following ablation and hemostasis. The postoperative course was uneventful. CONCLUSION: We report a case of spontaneous intercostal artery bleeding occurring simultaneously in numerous vessels during antithrombotic therapy with mechanical circulatory support that was difficult to manage. As bleeding from numerous vessels may occur during antithrombotic therapy, even without trauma, appropriate treatments, such as transcatheter arterial embolization and surgery, should be selected in patients with such cases.

Anatomical information of the lenticulostriate arteries on high-resolution 3D-TOF MRA at 3 T: comparison with 3D-DSA.

PURPOSE: As the lenticulostriate arteries (LSAs) perfuse neurologically important areas, it is necessary to accurately assess the origin and number of the LSAs before surgery. Although three-dimensional time-of-flight MR angiography (3D-TOF MRA) is a non-invasive procedure, it requires high-resolution (HR) images to depict the LSAs with a small diameter. Therefore, we performed 3D-TOF MRA with the maximum HR (HR-MRA) using a 3 T scanner to examine whether a good depiction of the LSAs, equivalent to that of digital subtraction angiography (DSA), could be obtained. METHODS: Our study group comprised 16 consecutive patients who underwent HR-MRA and 3D-DSA. In both studies, we evaluated the localization of the origin from M1, M2, or A1 segments, their number of stems, and depiction. RESULTS: There was no significant difference in the visualization of the LSAs between HR-MRA and 3D-DSA (P values; M1, M2, and A1 = 0.39, 0.69, and 0.69, respectively), and both the number of stems and the localization of the origin of the LSAs corresponded between the two examinations. CONCLUSION: HR-MRA at 3 T can depict the LSA well. It reveals the number of the LSA stems and the LSA origin comparatively with DSA.

Metastatic lung tumor from hepatocellular carcinoma with tumor thrombus invasion in the pulmonary vein: a case report.

BACKGROUND: Metastatic lung tumor with a tumor thrombus in the peripheral pulmonary vein is very rare. We present a case of a metastatic lung tumor from hepatocellular carcinoma (HCC) with tumor thrombus invasion in the pulmonary vein that was diagnosed preoperatively and underwent complete resection by segmentectomy. CASE PRESENTATION: A 77-year-old man underwent laparoscopic lateral segment hepatectomy for HCC eight years ago. Protein induced by vitamin K absence or antagonist-II remained elevated from two years ago. Contrast-enhanced chest computed-tomography (CT) showed a 27 mm nodule in the right apical segment (S1). He was pathologically diagnosed with a metastatic lung tumor from HCC via transbronchoscopic biopsy. We planned to perform right S1 segmentectomy. Before surgery, contrast-enhanced CT in the pulmonary vessels phase for three-dimensional reconstruction showed that the tumor extended into the adjusting peripheral pulmonary vein, and we diagnosed tumor thrombus invasion in V1a. The surgery was conducted under 3-port video-assisted thoracic surgery. First, V1 was ligated and cut. A1 and B1 were cut. The intersegmental plane was cut with mechanical staplers. Pathological examination revealed moderately-differentiated metastatic HCC with tumor thrombus invasions in many pulmonary veins, including V1a. No additional postoperative treatments were performed. CONCLUSIONS: As malignant tumors tend to develop a tumor thrombus in the primary tumor, it might be necessary to perform contrast-enhanced CT in the pulmonary vessel phase to check for a tumor thrombus before the operation for metastatic lung tumors.

Effect of an Ultrahigh b Value of 3000 s/mm2 and the Minimal Echo-time on Image Quality and the T2 Shine-through Effect in Diffusion-weighted Imaging of the Liver at 3T: Phantom and Clinical Pilot Studies.

PURPOSE: To assess the effect of an ultrahigh b value of 3000 s/mm2 and the minimal TE of 53 ms on image quality and T2 shine-through effect in liver diffusion-weighted imaging (DWI) using a 3-Tesla MRI scanner with a peak gradient of 100 mT/m. METHODS: At b values of 1000 and 3000 s/mm2 and at the minimal (44-53 ms) and routine TEs (70 ms), DWI of our original phantom and liver DWI in 10 healthy volunteers and 26 patients with 35 hepatic hemangiomas were acquired with this scanner, and the quantified SNR of the phantom and the hepatic parenchyma in the volunteers and the contrast-to-noise ratio (CNR) of the hepatic hemangiomas were calculated; two independent readers qualitatively graded the overall image quality in the volunteers and determined the presence or absence of the T2 shine-through effect related to the hemangiomas in the patients. We compared the SNR and subjective overall image quality between the minimal and routine TEs and the CNR and incidence of the T2 shine-through effect between b values of 1000 and 3000 s/mm2. Inter-reader agreement was also evaluated. RESULTS: The SNR at both b values was significantly higher, and the subjective overall image quality at a b value of 3000 s/mm2 was significantly better at the minimal TE than at the routine TE (P < 0.05 for all). The CNR at both TEs and the incidence of the T2 shine-through effect at the minimal TE were significantly lower at a b value of 3000 s/mm2 than at a b value of 1000 s/mm2 (P < 0.05 for all). Inter-reader agreement was excellent. CONCLUSION: Liver DWI at the ultrahigh b value can reduce the T2 shine-through effect with improvement of image quality using the minimal TE.

Denoising using deep-learning-based reconstruction for whole-heart coronary MRA with sub-millimeter isotropic resolution at 3 T: a volunteer study.

PURPOSE The aim of this study was to assess the usefulness of denoising deep-learning-based reconstruction (dDLR) to improve image quality and vessel delineation in noncontrast 3-T wholeheart coronary magnetic resonance angiography (WHCMRA) with sub-millimeter isotropic resolution (Sub-mm) compared with a standard resolution without dDLR (Standard). METHODS For 10 healthy volunteers, we acquired the WHCMRA with Sub-mm with and without dDLR and Standard to quantify signal- (SNR) and contrast-to-noise ratio (CNR) and vessel edge signal response (VESR) in all the 3 image types. Two independent readers subjectively graded vessel sharpness and signal homogeneity of 8 coronary segments in each patient. We used Kruskal- Wallis test with Bonferroni correction to compare SNR, CNR, VESR, and the subjective evaluation scores among the 3 image types and weighted kappa test to evaluate inter-reader agreement on the scores. RESULTS SNR was significantly higher with Sub-mm with dDLR (P < .001) and Standard (P=.005) than with Sub-mm without dDLR and was comparable between Sub-mm with dDLR and Standard (P=.511). CNR was significantly higher with Sub-mm with dDLR (P < .001) and Standard (P=.005) than with Sub-mm without dDLR and was comparable between Sub-mm with dDLR and Standard (P=.560). VESR was significantly greater with Sub-mm with (P=.001) and without dDLR (P=.017) than with Standard and was comparable between Sub-mm with and without dDLR (P=1.000). In the proximal, middle, distal, and all the coronary segments, the subjective vessel sharpness was significantly better with Sub-mm with dDLR than Sub-mm without dDLR and Standard (P < .001, for all) and was comparable between Sub-mm without dDLR and Standard (P > .05); the subjective signal homogeneity was significantly improved from Sub-mm without dDLR to Standard to Sub-mm with dDLR (P < .001). The inter-reader agreement was excellent (kappa=0.84). CONCLUSION Application of dDLR is useful for improving image quality and vessel delineation in the WHCMRA with Sub-mm compared with Standard.

Aseptic Meningitis after Amenamevir Treatment for Herpes Zoster in the First Branch of the Trigeminal Nerve.

Amenamevir has been approved for the treatment of herpes zoster (HZ); however, its therapeutic efficacy against central nervous system (CNS) infection may be insufficient due to its low spinal fluid permeability. We herein report a case of aseptic meningitis in a 91-year-old Japanese man treated with amenamevir for HZ in the trigeminal nerve region. Several cases of CNS infection have been reported in patients receiving amenamevir treatment for HZ. Patients with CNS complications often have skin rashes near the trigeminal region. Thus, we should be alert for signs of CNS infection when administering amenamevir to patients with such rashes.

Long-Term Outcomes of Longitudinal Efficacy Study With Tolvaptan in ADPKD.

INTRODUCTION: The effects of long-term and uninterrupted tolvaptan treatment on autosomal dominant polycystic kidney disease (ADPKD) are unclear. Therefore, a more than 3-year continuous treatment study was performed. METHODS: From the Kyorin University cohort, 299 patients were surveyed and 179 patients were indicated for tolvaptan having a total kidney volume (TKV) ≥750 ml, TKV slope ≥5%/yr, and estimated glomerular filtration rate (eGFR) ≥15 ml/min per 1.73 m2. Among 179 patients, 118 patients consented to the study. RESULTS: Retrospective pretreatment and prospective on-treatment periods had a median of 1.8 and 4.0 years, respectively. During the 5 treatment-years, the log10(TKV) slope/yr decreased from the pretreatment period (P < 0.0001) and the estimated height-adjusted TKV growth rate α (eHTKV-α, %/yr) decreased from baseline (P < 0.0001). The decline in eGFR improved in female patients (P < 0.0001), but not in males (P = 0.6321). Furthermore, during the 5 treatment-years, eGFR remained significantly better in the group with a percent decrease in eHTKV-α from baseline to the first treatment-year ≥ the median (2.94%) than in the group with a decrease <2.94%. The free-water clearance was higher in males than in females irrespective of treatment. CONCLUSION: The TKV growth rate decreased in 4 years with tolvaptan in both sexes. The insignificant effects of tolvaptan on the eGFR slope in males were likely due to androgen stimulation of cystogenesis and analytical difficulty of longitudinal changes in nonlinear trajectories of eGFR. The larger decrease in eHTKV-α in the first year was related to a better renal prognosis. The vasopressin-mediated water reabsorption was activated more in females than males irrespective of tolvaptan administration.

PKD1-Associated Arachnoid Cysts in Autosomal Dominant Polycystic Kidney Disease.

OBJECTIVES: the prevalence of intracranial aneurysms and arachnoid cysts is higher in patients with autosomal dominant polycystic kidney disease (ADPKD) than in the general population. A genotype correlation was reported for intracranial aneurysms, but it is unclear for arachnoid cysts. Therefore, the genotype correlation with intracranial aneurysms and arachnoid cysts was investigated in ADPKD. MATERIALS AND METHODS: intracranial aneurysms and arachnoid cysts were screened by magnetic resonance imaging (MRI), and PKD genotypes were examined using next-generation sequencing for 169 patients with ADPKD. RESULTS: PKD1-, PKD2- and no-mutation were identified in 137, 24 and 8 patients, respectively. Intracranial aneurysms and arachnoid cysts were found in 34 and 25 patients, respectively, with no significant difference in frequency. Genotype, sex, estimated glomerular filtration rate and age at ADPKD diagnosis significantly affected the age at brain MRI. The proportional hazard risk analyzed using the age at brain MRI adjusted by these four variables was 5.0-times higher in the PKD1 group than in the PKD2 group for arachnoid cysts (P = 0.0357), but it was not different for intracranial aneurysms (P = 0.1605). Arachnoid cysts were diagnosed earlier in the PKD1 group than in the PKD2 group (54.8 vs 67.7 years, P = 0.0231), but no difference was found for intracranial aneurysms (P = 0.4738) by Kaplan-Meier analysis. CONCLUSIONS: this study demonstrated the correlation between arachnoid cysts and PKD1 mutation. The reported association of arachnoid cysts with advanced renal disease may be due to the common correlation of these factors with PKD1 mutation.

Imaging Identification of Rapidly Progressing Autosomal Dominant Polycystic Kidney Disease: Simple Eligibility Criterion for Tolvaptan.

BACKGROUND: Tolvaptan was approved for the treatment of autosomal dominant polycystic kidney disease (ADPKD). However, the official indication of "rapidly progressive disease" is described differently in the clinical guidelines. We aim to define "rapidly progressive disease" by risk of ESRD, which is evaluated using estimated height-adjusted total kidney volume (HtTKV) growth rate. METHODS: The risk of ESRD was retrospectively analyzed in 617 initially non-ESRD adults with ADPKD and observed with standard of care between 2007 and 2018. The estimated annual growth rate of the HtTKV, termed as eHTKV-α (%/year), is derived from the following equation: [HtTKV at age t] = K(1 + eHTKV-α/100)t, where K = 150 mL/m is used in Mayo Imaging Classification and K = 130 mL/m is proposed for individually stable eHTKV-α value from baseline. The accuracy of eHTKV-α to predict ESRD for censored ages was analyzed using time-dependent receiver-operating characteristic curves (ROC). The cutoff point of initially measured eHTKV-α to predict ESRD was assessed using Kaplan-Meier and Cox's proportional hazards models. Performance characteristics of the cutoff point for censored ages were calculated using time-dependent ROC and validated by the bootstrap method. RESULTS: The area under the time-dependent ROC of eHTKV-α to predict ESRD at age 65 was 0.89 ± 0.04 (K = 130). The mean renal survival was less than 70 years at eHTKV-α ≥4.0%/year (K = 130). Mean renal survival was approximately 12 years shorter, and hazard ratio of ESRD was more than 5-time higher at this cutoff point than at lower point. Time-dependent sensitivity for age 65 and cutoff point of 4.0%/year (K = 130) was 93.4 ± 0.3%. Between cutoff points ≥4.0%/year (K = 130) and ≥3.5%/year (K = 150), there was no significant difference in performance characteristics and accuracy to predict ESRD. CONCLUSION: eHTKV-α well predicts ESRD. Initially, measured eHTKV-α ≥4.0%/year (K = 130) defines high-risk ESRD. Without additional conditions, a single eHTKV-α cutoff point identifies subjects that are most likely to benefit from tolvaptan.

Colonic varices treated with embolization after pancreatoduodenectomy with portal vein resection: a case report.

BACKGROUND: Pancreatoduodenectomy with resection of the portal vein or superior mesenteric vein confluence has been safely performed in patients with pancreatic head cancer associated with infiltration of the portal vein or superior mesenteric vein. In recent years, left-sided portal hypertension, a late postoperative complication, has received focus owing to increased long-term survival with advances in chemotherapy. Left-sided hypertension may sometimes cause fatal gastrointestinal bleeding because of the rupture of gastrointestinal varices. Here, we present a case of colonic varices caused by left-sided portal hypertension after pancreatoduodenectomy with portal vein resection. CASE PRESENTATION: A 69-year-old man diagnosed with pancreatic head cancer was referred to our department for surgery after undergoing chemotherapy with nine courses of gemcitabine and nab-paclitaxel. Computed tomography showed a mass 25 mm in diameter and in contact with the portal vein. He had undergone subtotal stomach-preserving pancreatoduodenectomy with portal vein resection. Four centimeters of the portal vein had been resected, and end-to-end anastomosis was performed without splenic vein reconstruction. We had to completely resect the right colic vein, accessary right colic vein, and middle colic vein due to tumor invasion. The pathological diagnosis was ypT3, ypN1a, ypM0, and ypStageIIB, and he was administered TS-1 as postoperative adjuvant chemotherapy. Seven months after therapeutic radical surgery, he presented with melena with progressive anemia. Computed tomography revealed transverse colonic varices. He was offered interventional radiology. Trans-splenic arterial splenic venography showed that transverse colonic varices had developed as collateral circulation of the splenic vein and inferior mesenteric vein system. An embolic substance was injected into the transverse colonic varices, which halted the progression of the anemia caused by melena. Fifteen months after therapeutic radical surgery, local recurrence of the tumor occurred; he died 28 months after the surgery. CONCLUSIONS: When subtotal stomach-preserving pancreatoduodenectomy with portal vein resection is performed without splenic vein reconstruction, colonic varices may result from left-sided portal hypertension. Interventional radiology is an effective treatment for gastrointestinal bleeding due to colonic varices, but it is important to be observant for colonic necrosis and new varices.

Minimally invasive surgery for esophageal cancer after esophageal perforation.

Both esophageal rupture and esophageal cancer are life-threatening diseases. We report a case of esophageal cancer that occurred after esophageal rupture was treated with thoracoscopic and laparoscopic surgery. A 76-year-old man presented with vomiting followed by epigastric pain and was diagnosed with spontaneous esophageal rupture. Laparoscopic and thoracoscopic surgery were performed. Primary closure was completed with a fundic patch, and thoracic lavage was performed. Ten months later, his condition was diagnosed as squamous cell carcinoma of the abdominal esophagus. He underwent thoracoscopic esophageal resection in the prone position, and a gastric conduit was created laparoscopically. The pathological finding was superficial esophageal carcinoma without lymph node metastasis. The patient's postoperative course was uneventful, and there was no recurrence at 21 months of follow-up.

Prognostic significance of pathologic complete response and Ki67 expression after neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Recent studies have indicated that response to chemotherapy and the prognostic impact of a pathologic complete response (pCR) after neoadjuvant chemotherapy differ among breast cancer subtypes. METHODS: Women with Stage I to III breast cancer treated with anthracycline and taxane-based neoadjuvant chemotherapy (four cycles of docetaxel every 3 weeks followed by four cycles of FEC every 3 weeks) between 2006 and 2011 were retrospectively analyzed. Trastuzumab was concurrently added to docetaxel for HER2-positive breast cancer. Expression of estrogen receptor (ER), progesterone receptor (PgR), HER2, and Ki67 was examined by immunohistochemistry in pre- and post-treatment specimens. Predictive factors for neoadjuvant chemotherapy and prognosis were analyzed by breast cancer subtype. RESULTS: Of 64 patients, 30 (47 %) were ER-positive (ER+) HER2-negative (HER2-), including eight as luminal A (Ki67 labeling index (LI) <14 %) and 22 as luminal B (Ki67 LI ≥ 14 %) subtypes, 11 (17 %) were ER+ HER2-positive (HER2+), 12 (19 %) were ER-negative (ER-) HER2+, and 11 (17 %) were ER- HER2-. The clinical response rates were significantly higher in luminal B, ER+ HER2+, and ER- HER2+ subtypes compared with luminal A subtype. Patients whose tumors contained high Ki67 expression effectively responded to neoadjuvant chemotherapy. Ki67 LI was a predictive marker for pCR, and all patients whose tumors achieved pCR are currently disease-free. Furthermore, high Ki67 expression in post-treatment tumors was strongly correlated with poor disease-free and overall survival regardless of subtype. CONCLUSIONS: It is necessary to establish additional strategies to improve survival for patients whose residual tumors show high Ki67 expression after neoadjuvant chemotherapy.

Surgical resection of colorectal recurrence of gastric cancer more than 5 years after primary resection.

INTRODUCTION: Intestinal metastasis from gastric cancer is rare, although the most common cause of secondary neoplastic infiltration of the colon is gastric cancer. However, little data is available on recurrence or death in patients with gastric cancer surviving >5 years post-gastrectomy. Here we report two cases of lower intestinal metastasis from gastric cancer >5 years after primary resection and discuss with reference to the literature. PRESENTATION OF CASE: Case 1: A 61-year-old man with a history of total gastrectomy for gastric cancer 9 years earlier was referred to our hospital with constipation and abdominal distention. We diagnosed primary colon cancer and subsequently performed extended left hemicolectomy. Histological examination revealed poorly differentiated adenocarcinoma resembling the gastric tumor he had 9 years earlier. The patient refused postoperative adjuvant chemotherapy and remained alive with cancerous peritonitis and skin metastases as of 17 months later. Case 2: A 46-year-old woman with a history of total gastrectomy for gastric cancer 9 years earlier presented with constipation. She also had a history of Krukenberg tumor 3 years earlier. We diagnosed metastatic rectal cancer and subsequently performed low anterior resection and hysterectomy. Pathological examination revealed poorly differentiated tubular adenocarcinoma, resembling the gastric tumor. The patient remained alive without recurrence as of 17 months later. DISCUSSION: We found 19 reported cases of patients with resection of colon metastases from gastric cancer. Median disease-free interval was 74 months. CONCLUSION: Resection of late-onset colorectal recurrence from gastric cancer appears worthwhile for selected patients.

Method for the validation of immunohistochemical staining using SCID mouse xenografts: expression of CD40 and CD154 in human non-small cell lung cancer.

This report proposes a concept for the standardization of immunohistochemical evaluation. Immunohistochemical staining has several problems associated with the sensitivity of the technical process and standardization of the assessment of potent staining. We provided data focusing on this concept through immunostaining for CD154 in non-small cell lung cancer (NSCLC). We used two types of anti-CD154 antibody as primary antibodies in immunohistochemical staining, as previously reported. Western blot analysis confirmed strong CD154 expression in the cultured cell line PC10, but not in LK2. We also assessed CD154 expression in SCID mouse xenografts of these cell lines. SCID xenograft data on western blot analysis were consistent with those of cultured cell lines. These xenografts could thus be used as positive or negative tissue controls for CD154 immunostaining. Primary antibodies should therefore be confirmed as recognizing target lesions, while control tissue specimens should be objectively confirmed as having target products using another experimental method. Our method would allow results to be unified at more than one laboratory and could act as an objective control assessment method in immunohistochemistry.

The CD40-CD154 interaction would correlate with proliferation and immune escape in pancreatic ductal adenocarcinoma.

BACKGROUND: CD40 and CD154 are associated with lymphocyte signaling pathways and they are also expressed in some malignant neoplasms, but the significance in pancreatic cancer is unknown. METHODS: Eighty pancreatic cancer specimens were stained immunohistochemically, and the results were correlated with the patients' clinicopathologic features. Subsequently, in vitro analysis of CD40-CD154 signaling was performed. RESULT: Immunohistochemical analysis of tumor cells showed that 29 patients (36.3%) were positive for CD40, and 17 patients (21.3%) had very high CD154 expression. The survival of patients who had very high CD154 expression was significantly better than that of others (P = 0.0198). Univariate and multivariate analysis revealed that very high CD154 expression in cancer cells was not an independent, favorable prognostic factor (risk ratio, 0.493; P = 0.0224). On in vitro proliferation assay, the growth of PK-45P and KP-4 cells was blocked by CD40 and CD154 blocking antibodies. Moreover, on in vitro cytokine assay, Th-2 cytokines from PK-45P and SUIT-2 were blocked by CD40 or CD154 blocking antibody. CONCLUSION: These results suggest that the CD40-CD154 interaction would correlate with cell proliferation and secretion of cytokines in PDAC cells, and CD154 overexpression could be a favorable prognostic factor in PDAC patients.

Adenovirus-mediated eukaryotic initiation factor 4E binding protein-1 in combination with rapamycin inhibits tumor growth of pancreatic ductal adenocarcinoma in vivo.

Over-expression of eIF4E indicates a poor prognosis in different tumors. In the present study, we investigated the frequency of eIF4E, 4E-BP1 and phosphorylated 4E-BP1 expression in PDAC cell lines, gastric carcinoma (GC) cell lines and human embryonic pancreatic cells, as well as gene therapy using translation repressor gene 4E-BP1 in combination with the mTOR inhibitor rapamycin. We also assessed the significance of eIF4E expression in 80 PDAC cases. Combination therapy of adenovirus vector-delivered 4E-BP1 gene and rapamycin was administered to determine their growth inhibition effect in vitro and in vivo in mice. Our study revealed that all PDAC cell lines, GC cell lines and human embryonic pancreas-derived cells expressed the 25-kDa eIF4E protein (MIAPaca-2 cells also expressed the 13-kDa protein 4E-BP1). The 80 PDAC specimens showed a heterogeneous pattern of eIF4E staining. No significant correlation between eIF4E expression and TNM classification was found. Adenovirus vectors Ad-4E-BP1 and Ad-GFP efficiently showed transgenic expression with hyperphosphorylation of 4E-BP1; however, insignificant growth inhibition of the PDAC and GC cell lines was observed. Combination therapy with rapamycin significantly inhibited proliferation and tumor growth in vitro as well as in vivo. Therefore, combination of Ad 4E-BP1 and rapamycin may be a more effective adjuvant therapy.

Up-regulation of CD40 with juxtacrine activity in human nonsmall lung cancer cells correlates with poor prognosis.

BACKGROUND: CD40 and its ligand, CD154, play a regulatory role in several signaling pathways among lymphocytes. Recently, it was reported that CD40 is expressed in several malignant tumors. However, the clinical impact of CD40 expression in nonsmall cell lung cancer has not been studied widely. METHODS: One hundred twenty-nine surgical specimens of nonsmall cell lung cancer were assessed immunohistochemically for CD40 and CD154 expression, and that expression was correlated with patients' clinicopathologic parameters and outcome. Subsequently, in vitro analysis of CD40-CD154 signaling was performed. RESULTS: Immunohistochemical staining of tumor cells confirmed that 67 patients (51.9%) were positive for CD40, and 76 patients (58.9%) were positive for CD154. The survival of patients who had tumors that were negative for CD40 was significantly better than the survival of patients who had tumors that were positive for CD40 (P = .0004). Multivariate analysis using a Cox regression model indicated that CD40 expression in cancer cells is an independent, unfavorable prognostic factor (risk ratio, 1.855; P = .0403). By using an in vitro juxtacrine growth factor assay, the growth of LK2 cells (CD40-positive/CD154-negative) was accelerated by CD154-positive cancer cells, such as PC10 cells (CD40-negative/CD154-positive), by a juxtacrine mechanism. CONCLUSIONS: The current results suggested that CD40 expression in tumors is associated with a poor prognosis and that the juxtacrine interaction of CD40-CD154 among cancer cells facilitates the development of malignant potential in nonsmall cell lung cancer.

Primary small cell carcinoma of the common bile duct, in which surgical treatment was performed after neoadjuvant chemotherapy: report of a case.

Primary small cell carcinoma of the hepatobiliary tract is rare. Most cases occur in the gallbladder or in the ampulla of Vater, and such cases in the common bile duct (CBD) are extremely rare. We herein report a case of small cell carcinoma arising in the CBD. In this case, neoadjuvant chemotherapy followed by pylorus-preserving pancreaticoduodenectomy showed an excellent response. To our knowledge, this is the first reported case of small cell carcinoma of the CBD in which a radical resection was performed after successful neoadjuvant chemotherapy.