Short-term outcomes of robotic tumor-specific mesorectal resection of rectal cancer: surgical techniques in mesorectal division using rolling division of the mesorectum.

BACKGROUND: This study aims to report our surgical techniques for robot-assisted laparoscopic anterior resection, specifically focusing on mesorectal division using rolling division of the mesorectum, and to elucidate short-term outcomes at a single institution. Tumor-specific mesorectal excision (TSME) is commonly performed for resection of a tumor located in the upper rectum. However, especially in a narrow pelvis, it is difficult to perform appropriate mesorectal division at an adequate distance from the tumor in robot-assisted laparoscopic anterior resection. METHODS: Retrospective case series of patients with rectal cancer who underwent robot-assisted TSME using rolling division of mesorectum. Patient characteristics, perioperative clinical results, surgical and pathological details were recorded. RESULTS: A total of 198 patients underwent robot-assisted TSME for rectal cancer using rolling division of mesorectum between May 2019 and December 2023.The tumor was located in the upper rectum in 45 patients, middle rectum in 115 patients and lower rectum in 38 patients. The types of resections were 40 high anterior resection and 158 low anterior resections. The median operation time was 175 (range 109-310) min, and median mesorectal division time was 24 (range 15-45) min. Median blood loss was 3 (range 0-20) ml; no patients required blood transfusion. The overall complication rate of Clavien-Dindo classification grades I-IV was 7.1%. Anastomotic leakage was observed in two patients (1.0%) with grade III. There was no surgical mortality in this series. CONCLUSION: This robotic technique for anterior resection is a feasible and reliable procedure for achieving sufficient and safe TSME in this cohort.

[Neutrophil-Lymphocyte Ratio as a Prognostic Indicator in Patients Treated with Nivolumab for Gastric Cancer].

BACKGROUND: Immune checkpoint inhibitors(nivolumab)have been recommended as third-line chemotherapy for advanced gastric cancer(AGC)according to the Guidelines of Gastric Cancer(5th edition). Therefore, they have been used in daily clinical practice. On the other hand, the neutrophil-lymphocyte ratio(NLR)has been reported to be associated with the prognosis of cancer patients. METHODS: Twenty patients treated with nivolumab for AGC between January 2018 and November 2019 were retrospectively examined. RESULTS: Median age of the 20 patients(18 males, 2 females)was 70 years(55- 84 years). Nivolumab was administered as second-, third-, fourth-, and fifth-line therapy in 1, 11, 7, and 1 case, respectively. The best tumor response evaluation was observed in PR 1, SD 7 and PD 10 cases. Median overall survival(OS)was 10 months, and median progression-free survival(PFS)was 3 months. No serious adverse events occurred. Compared to the NLR>2.0 group, OS significantly prolonged(2.2 months vs 21.9 months)and PFS tended to prolong(1.4 months vs 6.2 months)in the NLR≤2.0 group. CONCLUSION: NLR may be an effective prognostic factor in patients with AGC receiving nivolumab treatment.

Galectin-3 Mediates Tumor Cell-Stroma Interactions by Activating Pancreatic Stellate Cells to Produce Cytokines via Integrin Signaling.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is characterized by activated pancreatic stellate cells (PSCs), abundance of extracellular matrix (ECM), and production of cytokines and chemokines. Galectin 3 (GAL3), a ß-galactoside-specific lectin, contributes to PDAC development but its effects on the stroma and cytokine production are unclear. METHODS: The effect of recombinant human GAL3 (rGAL3) on activation of PSCs, production of cytokines, and ECM proteins was determined by proliferation, invasion, cytokine array, and quantitative polymerase chain reaction. We assessed co-cultures of PDAC cells with GAL3 genetic alterations with PSCs. Production of interleukin 8 (IL8) and activities of nuclear factor (NF)-κB were determined by enzyme-linked immunosorbent assay and luciferase reporter analyses. We studied the effects of inhibitors of NF-κB and integrin-linked kinase (ILK) on pathways activated by rGAL3. RESULTS: In analyses of the Gene Expression Omnibus database and our dataset, we observed higher levels of GAL3, IL8, and other cytokines in PDAC than in nontumor tissues. Production of IL8, granulocyte-macrophage colony-stimulating factor, chemokine ligand 1, and C-C motif chemokine ligand 2 increased in PSCs exposed to rGAL3 compared with controls. Culture of PSCs with PDAC cells that express different levels of GAL3 resulted in proliferation and invasion of PSCs that increased with level of GAL3. GAL3 stimulated transcription of IL8 through integrin subunit beta 1 (ITGB1) on PSCs, which activates NF-κB through ILK. Inhibitors of ILK or NF-κB or a neutralizing antibody against ITGB1 blocked transcription and production of IL8 from PSCs induced by rGAL3. The GAL3 inhibitor significantly reduced growth and metastases of orthotopic tumors that formed from PDAC and PSC cells co-implanted in mice. CONCLUSION: GAL3 activates PSC cells to produce inflammatory cytokines via ITGB1signaling to ILK and activation of NF-κB. Inhibition of this pathway reduced growth and metastases of pancreatic orthotopic tumors in mice.

Diagnostic accuracy of EUS in differentiating mucosal versus submucosal invasion of superficial esophageal cancers: a systematic review and meta-analysis.

BACKGROUND: The prognosis of esophageal cancer (EC) depends on the depth of tumor invasion and lymph node metastasis. EC limited to the mucosa (T1a) can be treated effectively with minimally invasive endoscopic therapy, whereas submucosal (T1b) EC carries relatively high risk of lymph node metastasis and requires surgical resection. OBJECTIVE: To determine the diagnostic accuracy of EUS in differentiating T1a EC from T1b EC. DESIGN: We performed a comprehensive search of MEDLINE, SCOPUS, Cochrane, and CINAHL Plus databases to identify studies in which results of EUS-based staging of EC were compared with the results of histopathology of EMR or surgically resected esophageal lesions. DerSimonian-Laird random-effects model was used to estimate the pooled sensitivity, specificity, and likelihood ratio, and a summary receiver operating characteristic (SROC) curve was created. SETTING: Meta-analysis of 19 international studies. PATIENTS: Total of 1019 patients with superficial EC (SEC). INTERVENTIONS: EUS and EMR or surgical resection of SEC. MAIN OUTCOME MEASUREMENTS: Sensitivity and specificity of EUS in accurately staging SEC. RESULTS: The pooled sensitivity, specificity, and positive and negative likelihood ratio of EUS for T1a staging were 0.85 (95% CI, 0.82-0.88), 0.87 (95% CI, 0.84-0.90), 6.62 (95% CI, 3.61-12.12), and 0.20 (95% CI, 0.14-0.30), respectively. For T1b staging, these results were 0.86 (95% CI, 0.82-0.89), 0.86 (95% CI, 0.83-0.89), 5.13 (95% CI, 3.36-7.82), and 0.17 (95% CI, 0.09-0.30), respectively. The area under the curve was at least 0.93 for both mucosal and submucosal lesions. LIMITATIONS: Heterogeneity was present among the studies. CONCLUSION: Overall EUS has good accuracy (area under the curve ≥0.93) in staging SECs. Heterogeneity among the included studies suggests that multiple factors including the location and type of lesion, method and frequency of EUS probe, and the experience of the endosonographer can affect the diagnostic accuracy of EUS.

Protein kinase D1 promotes anchorage-independent growth, invasion, and angiogenesis by human pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases. Novel molecularly targeted therapies are urgently needed. Here, we extended our studies on the role of protein kinase D1 (PKD1) in PDAC cell lines. Given that Panc-1 express moderate levels of PKD1, we used retroviral-mediated gene transfer to create a Panc-1 derivative that stably over-expresses PKD1 (Panc-1-PKD1). Reciprocally, we used shRNA targeting PKD1 in Panc-28 to produce a PKD1 under-expressing Panc-28 derivative (Panc-28-shPKD1). Our results demonstrate that Panc-1-PKD1 cells exhibit significantly increased anchorage-independent growth in soft agar and increased in vitro invasion compared with Panc-1-mock. Reciprocally, Panc-28-shPKD1 cells show a significant decrease in anchorage-independent growth and invasiveness, as compared with Panc-28-mock cells. The selective PKD family inhibitor CRT0066101 markedly decreased colony-forming ability and invasiveness by either Panc-1-PKD1 or Panc-28-mock cells. Secretion of the pro-angiogenic factors vascular endothelial growth factor (VEGF) and CXC chemokines (CXCL8) was significantly elevated by PKD1 over-expression in Panc-1 cells and reduced either by depletion of PKD1 via shRNA in Panc-28 cells or by addition of CRT0066101 to either Panc-1-PKD1 or Panc-28-mock cells. Furthermore, human umbilical vein endothelial cell (HUVEC) tube formation was significantly enhanced by co-culture with Panc-1-PKD1 compared with Panc-1-mock in an angiogenesis assay in vitro. Conversely, PKD1 depletion in Panc-28 cells decreased their ability to induce endotube formation by HUVECs. PDAC-induced angiogenesis in vitro and in vivo was markedly inhibited by CRT0066101. Our results lend further support to the hypothesis that PKD family members provide a novel target for PDAC therapy.

IGF-1 mediates PTEN suppression and enhances cell invasion and proliferation via activation of the IGF-1/PI3K/Akt signaling pathway in pancreatic cancer cells.

BACKGROUND: Type-1 insulin-like growth factor (IGF-1) up-regulates cell proliferation and invasiveness through activation of PI3K/Akt signaling pathway. IGF-1 also down-regulates the tumor suppressor chromosome 10 (PTEN). We investigated the mechanism by which IGF-1 affects cell proliferation and invasion by suppression of PTEN phosphorylation and interaction with PI3K/PTEN/Akt/NF-small ka, CyrillicB signaling pathway in pancreatic cancer. MATERIALS AND METHODS: The expression of IGF-1 receptor (IGF-1R) and PTEN in five pancreatic cancer cell lines was determined by RT-PCR and Western blot. Proliferation and invasion were investigated by WST-1 assay and Matrigel-double chamber assay. Pancreatic cancer cells were transfected with PTEN siRNA to investigate which signaling pathway correlates in regulation of cancer cell proliferation and invasion. RESULTS: Five pancreatic cancer cell lines expressed PTEN and IGF-1R in mRNA and protein levels. Suppression of PTEN phosphorylation strongly enhanced cell proliferation and invasion stimulated with IGF-1 via activation of PI3K/Akt/NF-small ka, CyrillicB signaling pathway. In addition, knockdown of PTEN by siRNA transfection also enhanced activation of PI3K/Akt/NF-small ka, CyrillicB pathway, subsequently up-regulating cell invasiveness and proliferation. CONCLUSIONS: The IGF-1/PI3K/PTEN/Akt/NF-small ka, CyrillicB cascade may be a key pathway stimulating metastasis of pancreatic cancer cells. We suggest that interfering with the functions of IGF-1/PI3K/Akt/NF-small ka, CyrillicB might be a novel therapeutic approach to inhibit aggressive spread of pancreatic cancer.

Cancer cell-derived IL-1α promotes HGF secretion by stromal cells and enhances metastatic potential in pancreatic cancer cells.

BACKGROUND AND OBJECTIVES: Interleukin (IL)-1α and hepatocyte growth factor (HGF) play an important role in pancreatic cancer proliferation, angiogenesis, and invasiveness. The aim of this study was to investigate the cooperative role of HGF and IL-1α in metastatic processes promoted by interactions between pancreatic cancer cells and stromal cells. METHODS: Expression of IL-1α and HGF mRNA and protein was determined by RT-PCR and ELISA. The effect of HGF on metastatic potential was evaluated by proliferation, invasion, and angiogenesis assays using an in vitro system consisting of co-cultured tumor cells and stromal cells. RESULTS: IL-1α expression was closely correlated with metastatic potential, and cancer cell-derived IL-1α significantly promoted HGF expression by fibroblasts (P < 0.01). HGF not only enhanced the invasiveness and proliferation of pancreatic cancer cells, but also enhanced migration and proliferation of human umbilical vein endothelial cells (HUVECs). HGF significantly enhanced HUVEC tube formation (P < 0.01). Furthermore, the high liver-metastatic pancreatic cancer cell line (BxPC-3), which secretes IL-1α, significantly enhanced HUVEC tube formation compared with the low liver-metastatic cell line (Capan-2), which does not produce IL-1α (P < 0.01). CONCLUSION: Autocrine IL-1α and paracrine HGF co-enhance the metastatic potential of pancreatic cancer cells via both IL-1α and HGF signaling pathways.

Proteasome inhibitor MG132 inhibits angiogenesis in pancreatic cancer by blocking NF-kappaB activity.

Since angiogenesis enables solid tumors, including pancreatic cancer (PaCa), to grow and metastasize, the development of anti-angiogenic agents is currently one of the urgent issues. Proteasome inhibitors are well known for inhibiting nuclear factor-kappa B (NF-kappaB) activity in various cancer cells, but little is known about their biologic mechanisms against angiogenesis in PaCa. We divided human PaCa cell lines into high-angiogenic (BxPC-3 and SW 1990) and low-angiogenic (MIA PaCa-2 and Capan-2) groups. The high-angiogenic PaCa cell lines constitutively expressed high NF-kappaB activity and produced high levels of vascular endothelial growth factor (VEGF) and interleukin 8 (IL-8). The conditioned media from BxPC-3 significantly enhanced both proliferation of and tube formation by human umbilical vein endothelial cells (HUVECs) and these enhancements were significantly inhibited by the proteasome inhibitor MG132 treatment. Collectively, MG132 blocked PaCa-derived VEGF and IL-8 production through inhibition of NF-kappaB activity. Thus, proteasome inhibitors may prove beneficial as anti-angiogenic therapy for PaCa. Our studies show that MG132, a proteasome inhibitor, significantly blocked pancreatic-cancer-associated angiogenesis through inhibition of NF-kappaB and NF-kappaB-dependent proangiogenic gene products VEGF and IL-8.

CXCL8/IL-8 and CXCL12/SDF-1alpha co-operatively promote invasiveness and angiogenesis in pancreatic cancer.

CXC-chemokines are involved in the chemotaxis of neutrophils, lymphocytes and monocytes. However, role of these chemokines in tumorigenesis, especially with regard to interaction between tumor and its microenvironment, has not been clearly elucidated. The purpose of this study was to analyze the co-operative role of CXCL8 and CXCL12 in the tumor-stromal interaction in pancreatic cancer (PaCa). Using enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR), we initially confirmed the expression of ligands and receptors, respectively, of CXC-chemokines in PaCa and stromal cells. We examined the co-operative role of CXCL8 and CXCL12 in proliferation/invasion of PaCa and human umbilical vein endothelial cells (HUVECs), and in HUVEC tube-formations through tumor-stromal interaction by MTS, Matrigel invasion, and angiogenesis assays, respectively. We detected expression of CXCR4, but not CXCR2, in all PaCa cells and fibroblasts. PaCa cells secreted CXCL8, and fibroblast cells secreted CXCL12. CXCL8 production in PaCa was significantly enhanced by CXCL12, and CXCL12 production in fibroblasts was significantly enhanced by co-culturing with PaCa. CXCL8 enhanced proliferation/invasion of HUVECs but did not promote proliferation/invasion of PaCa. Both recombinant and PaCa-derived CXCL8 enhanced tube formation of HUVECs that were co-cultured with fibroblast cells. CXCL12 enhanced the proliferation/invasion of HUVECs and the invasion of PaCa cells but had no effect on tube formation of HUVEC. We showed that PaCa-derived CXCL8 and fibroblast-derived CXCL12 cooperatively induced angiogenesis in vitro by promoting HUVEC proliferation, invasion, and tube formation. Thus, corresponding receptors CXCR2 and CXCR4 are potential antiangiogenic and antimetastatic therapeutic targets in PaCa.

PTEN regulates angiogenesis through PI3K/Akt/VEGF signaling pathway in human pancreatic cancer cells.

Phosphoinositide 3-kinase (PI3K) pathway exerts its effects through Akt, its downstream target molecule, and thereby regulates various cell functions including cell proliferation, cell transformation, apoptosis, tumor growth, and angiogenesis. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) has been implicated in regulating cell survival signaling through the PI3K/Akt pathway. However, the mechanism by PI3K/PTEN signaling regulates angiogenesis and tumor growth in vivo remains to be elucidated. Vascular endothelial growth factor (VEGF) plays a pivotal role in tumor angiogenesis. The effect of PTEN on VEGF-mediated signal in pancreatic cancer is unknown. This study aimed to determine the effect of PTEN on both the expression of VEGF and angiogenesis. Toward that end, we used the siRNA knockdown method to specifically define the role of PTEN in the expression of VEGF and angiogenesis. We found that siRNA-mediated inhibition of PTEN gene expression in pancreatic cancer cells increase their VEGF secretion, up-modulated the proliferation, and migration of co-cultured vascular endothelial cell and enhanced tubule formation by HUVEC. In addition, PTEN modulated VEGF-mediated signaling and affected tumor angiogenesis through PI3K/Akt/VEGF/eNOS pathway.

Interleukin-1alpha secreted by pancreatic cancer cells promotes angiogenesis and its therapeutic implications.

BACKGROUND: Previously we reported the critical role of interleukin (IL)-1alpha in liver metastasis from pancreatic cancer (PaCa). However, its role in angiogenesis and metastasis, particularly as it relates to the interaction between tumor and stromal cells, was not clearly elucidated. To further investigate, we initially compared vascular endothelial cell migration and tube formation in human PaCa cell lines that differed in metastatic potential. We then compared the effects of IL-1alpha derived from PaCa cells on the same processes. MATERIALS AND METHODS: Expression of IL-1alpha mRNA and protein in PaCa cells was measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. IL-1alpha mRNA and protein were detected only in predominantly liver-metastatic PaCa cells. Next, we examined differences in migration and tube formation by human umbilical vein endothelial cells (HUVECs) in the various PaCa cells using invasion and angiogenesis assays, respectively. Furthermore, we determined the effects of IL-1alpha secreted by PaCa cells on migration and tube formation by HUVECs using coculture experiments. RESULTS: Expression of IL-1alpha mRNA and protein was observed only by the highly liver-metastatic PaCa cell lines BxPC-3 and SW 1990. Both HUVEC migration and tube formation were significantly enhanced by coculture with metastatic PaCa cells and IL-1alpha (P < 0.01). Similarly, blockade of IL-1alpha by its antagonist inhibited HUVEC migration and tube formation (P < 0.01). CONCLUSIONS: Our results indicate that IL-1alpha secreted by PaCa cells plays an important role in metastasis through vascular endothelial cell invasion and angiogenesis. Thus, blocking IL-1alpha is a potential novel therapeutic strategy in PaCa.

IL-1alpha secreted by colon cancer cells enhances angiogenesis: the relationship between IL-1alpha release and tumor cells' potential for liver metastasis.

BACKGROUND AND OBJECTIVES: Interleukin (IL)-1alpha plays an important role in colon cancer progression and angiogenesis. We here asked whether IL-1alpha derived from cancer cells modulates vascular endothelial cell growth, migration and tubule formation. METHODS: The existence of IL-1alpha mRNA and protein in colon cancer cell lines (WiDr, HT-29, Caco-2, COLO 320) were investigated with RT-PCR and ELISA. Proliferation and invasion were investigated by MTS assay and Matrigel-double chamber assay. To answer our main question, we performed angiogenesis assay used an in vitro model consisting of co-cultivated tumor cells and stromal cells. RESULTS: IL-1alpha mRNA and protein were detected in highly metastatic colon cancer cells (WiDr and HT-29). Recombinant IL-1alpha significantly enhanced growth and invasiveness of human umbilical vein endothelial cells (HUVEC) (P < 0.01). Moreover, HUVEC growth and migration were significantly enhanced by WiDr compared to control (without co-culture) or Caco-2 (P < 0.05). Exogenous rIL-1alpha significantly enhanced HUVEC tube-like formation in a dose-dependent manner (P < 0.01) in a HUVEC/fibroblast co-cultivation system. Moreover, WiDr significantly enhanced HUVEC tubule formation compared with control or Caco-2 (P < 0.01). CONCLUSION: Based on these findings, we conclude that colon cancer cell-derived IL-1alpha up-regulates angiogenesis by modulating stromal cells within the tumor cells' microenvironment.

Interleukin-1alpha enhances angiogenesis and is associated with liver metastatic potential in human gastric cancer cell lines.

BACKGROUND: To better understand the underlying mechanism of liver metastasis formation in human gastric cancer, we evaluated the angiogenic capabilities of human gastric cancer cell lines with different metastatic potentials as well as the role of interleukin (IL)-1alpha in the angiogenic process. MATERIALS AND METHODS: Reverse transcription-polymerase chain reaction was used to detect the expression of IL-1alpha and vascular endothelial growth factor (VEGF) mRNA in gastric cancer cell lines with different liver metastatic potentials. Levels of VEGF secreted by human gastric cancer cells were measured by enzyme-linked immunosorbent assay. We also examined how gastric cancer cells with different metastatic potentials influence the proliferation and tube formation of human umbilical vein endothelial cells (HUVECs) using the Premix WST-1 cell proliferation assay system and an angiogenesis assay, respectively. RESULTS: IL-1alpha expression levels were significantly correlated with liver metastatic potential in gastric cancer cell lines. Levels of VEGF secreted by gastric cancer cells appear to be regulated by IL-1alpha through IL-1 receptor Type 1 and were correlated with liver metastatic potential. Both HUVEC proliferation and tube formation were strongly enhanced by coculture with high liver-metastatic gastric cancer cells and were enhanced to a similar extent by culture in the presence of IL-1alpha. In contrast, blockade of IL-1alpha inhibited both HUVEC proliferation and angiogenesis. CONCLUSIONS: IL-1alpha may play a role in liver metastasis of gastric cancer via enhanced vascular endothelial cell proliferation and angiogenesis.

Loss of PTEN expression is associated with colorectal cancer liver metastasis and poor patient survival.

BACKGROUND: The tumour suppressor phosphatase and tensin homolog (PTEN) is an important negative regulator of cell-survival signaling. To evaluate the correlation between PTEN expression and clinicopathological characteristics of colorectal cancer patients with and without liver metastases, we investigated PTEN expression in primary colorectal cancer and colorectal cancer liver metastases. METHODS: Sixty-nine pairs of primary colorectal cancer and corresponding liver metastasis specimens were analyzed immunohistochemically, and the correlation between immunohistochemical findings and clinicopathological factors was investigated. Seventy primary colorectal cancer specimens from patients without liver metastases were used as controls. RESULTS: PTEN was strongly expressed in 44 (62.9%) colorectal cancer specimens from patients without liver metastases. In contrast, PTEN was weakly expressed in 52 (75.4%) primary colorectal cancer specimens from patients with liver metastases, and was absent in liver metastases. Weak PTEN expression in colorectal cancer tissues was significantly associated with advanced TNM stage (p < 0.01) and lymph node metastasis (p < 0.05). PTEN expression was significantly stronger in primary colorectal cancer specimens from patients without liver metastases. Furthermore, among colorectal cancer patients with liver metastases, the 5-year survival rate was significantly higher in patients with positive PTEN expression compared to those with negative PTEN expression (p = 0.012). CONCLUSION: Our results suggest that loss of PTEN expression is involved with colorectal cancer aggressive capacity and that diagnostic evaluation of PTEN expression may provide valuable prognostic information to aid treatment strategies for colorectal cancer patients.

Antiproteases in preventing the invasive potential of pancreatic cancer cells.

The process of tumor progression and metastasis involves degradation of the extracellular matrix and is governed by an intricate balance of proteases, their activators and their inhibitors, in which malignant cells are permitted to infiltrate the adjacent structures and gain access to lymph and blood vessels. These proteases can be broadly categorized into three families: matrix metalloproteinases, serine proteinases and cysteine proteinases, all of which have all been implicated in these processes. The presence of neural invasion is often considered to be a poor prognostic sign; however, the cellular mechanisms underlying this propensity for perineural invasion are unknown. We recently researched the relationship between the glial cell line-derived neurotrophic factor and perineural invasion by human pancreatic cancer cells. We also confirmed that NF-kappa B is a part of the signaling pathway from the glial cell line-derived neurotrophic factor in human pancreatic cancer cells, and documented the inhibitory effect of gabexate mesilate, a well-known non-physiological synthetic serine protease inhibitor, for pancreatic cancer invasion. Recent studies on the role of proteases and protease inhibitors in pancreatic cancer invasion are also reviewed.

Posterior mediastinal angioleiomyoma: report of a case.

We describe a case of mediastinal angioleiomyoma in an asymptomatic 72-year-old man, who was admitted to our hospital for a mediastinal tumor discovered during an annual medical examination. The tumor was evaluated by computed tomography (CT) and magnetic resonance imaging (MRI). Unenhanced CT scans demonstrated a tumor that was adjacent to the descending aorta. The tumor was partially enhanced in the early phase of contrast-enhanced CT, and in the late phase there was additional tumor enhancement. With MRI, the tumor displayed a homogeneous low signal intensity on the T1-weighted image and a homogeneous very high signal intensity on the T2-weighted image. Contrast-enhanced MRI demonstrated the same enhancement pattern as CT. The examination results led to a preoperative diagnosis of posterior mediastinal hemangioma, and the patient underwent surgery. The tumor originated from the supreme intercostal vein, and was diagnosed as an angioleiomyoma by histopathologic examination. Because mediastinal angioleiomyomas are very rare, they are difficult to diagnose preoperatively. However, we believe that CT and MRI can be of significant help in the differential diagnosis.

Successful paclitaxel-based chemotherapy for an alpha-fetoprotein-producing gastric cancer patient with multiple liver metastases.

BACKGROUND: Alpha-fetoprotein (AFP)-producing gastric cancer is known to frequently cause multiple liver metastases and to have an extremely poor prognosis. CASE PRESENTATION: A 64-year-old Japanese man admitted to our hospital was diagnosed with gastric cancer with liver metastases. He underwent a total gastrectomy with splenectomy, and pathological stage IV disease according to the classification proposed by the Japanese Gastric Cancer Association was assigned. The histological diagnosis was poorly differentiated adenocarcinoma, and tumor production of AFP was confirmed by immunohistochemical staining. Following surgery, the patient received combination chemotherapy consisting of TS-1 and paclitaxel. Initially, AFP levels decreased dramatically and computed tomography (CT) revealed regression of liver metastases. However, multiple new liver metastases appeared and serum AFP levels increased after 5 months. A regimen of 5-FU plus paclitaxel followed by paclitaxel monotherapy was used next. Serum AFP levels once again decreased and CT showed regression or disappearance of liver metastases. The patient currently has a very good quality of life, and is receiving weekly paclitaxel monotherapy as an outpatient. No progression of liver metastases has been observed to date. CONCLUSION: We consider this rare case to have significant value with respect to treatment of AFP-producing gastric cancer with multiple liver metastases, and propose that combining surgery with chemotherapeutic agents such as paclitaxel may lead to a better prognosis in such cases.

Eversion stripping of the esophagus with intraesophageal insufflation-A case report.

INTRODUCTION: Patients with esophageal cancer frequently cannot tolerate thoracotomy due to their overall debilitated condition. Moreover, some patients have severe adhesions in the thoracic cavity. Eversion stripping of the esophagus is an option for resection in these patients. PRESENTATION OF CASE: A 64-year-old man was admitted to our institution with the chief complaint of epigastric pain. Endoscopic examination showed a protruding lesion 22cm from the incisors, with a superficial and circumferential mucosal irregularity on the distal side of the lesion. Biopsy revealed squamous cell carcinoma. Clinical stage was T1b(sm)N0M0, cStage I. In addition to the poor pulmonary status of the patient, adhesions in the intrathoracic cavity were predicted. The decision was made to perform esophageal resection without a thoracotomy. In order to ensure complete invagination of the esophagus, the esophagus was insufflated prior to stripping. The stripping process was observed with a gastroscope. During the stripping, the esophagus did not bunch up, and stripping was smooth and with minimal resistance. DISCUSSION: The stripping resection of the esophagus is an important option for the esophageal surgeon. In this case report, we describe a new eversion stripping method of the esophagus. This easy and reliable stripping method incorporates intraesophageal insufflation. CONCLUSION: The indications for blunt esophageal dissection without thoracotomy have been decreasing. On the other hand, our method seems to be useful in optimal case of stripping of esophagus.

Resection of the Gastric Tube Reconstructed through the Retrosternal Route without Sternotomy.

With advances of combined modality therapy, prognoses in esophageal cancer have been improving. After resection of esophageal cancer, the development of gastric tube cancer is a risk. While such cancer in an early stage can be cured endoscopically, total gastric tube resection is indicated in advanced stages. A 68-year-old man underwent subtotal esophagectomy reconstructed with a gastric tube through the retrosternal route. Gastric cancer was found one and a half years postoperatively. The gastric tube was resected without sternotomy. This is the first report of a patient undergoing resection of the gastric tube reconstructed through the retrosternal route without sternotomy.

The stem cell factor/c-kit receptor pathway enhances proliferation and invasion of pancreatic cancer cells.

BACKGROUND: The transmembrane protein c-kit is a receptor tyrosine kinase (KIT) and KIT is expressed in solid tumors and hematological malignancies such as gastrointestinal stromal tumor (GIST), small-cell lung cancer and chronic myelogenous leukemia (CML). KIT plays a critical role in cell proliferation and differentiation and represents a logical therapeutic target in GIST and CML. In pancreatic cancer, c-kit expression has been observed by immunohistochemical techniques. In this study, we examined the influence of c-kit expression on proliferation and invasion using five pancreatic cancer cell lines. In addition, the inhibitory effect of imatinib mesylate on stem cell factor (SCF)-induced proliferation and invasion was evaluated. Finally, we also analyzed KIT and SCF expression in pancreatic cancer tissues using immunohistochemistry and correlated the results with clinical features. RESULTS: RT-PCR revealed that two pancreatic cancer cell lines, PANC-1 and SW1990, expressed c-kit mRNA. By Western blot analysis, c-kit protein was also present in those lines. In KIT-positive pancreatic cancer cell lines, proliferation and invasion were significantly enhanced by addition of SCF. In contrast, SCF did not enhance proliferation and invasion in the three KIT-negative lines (BxPC-3, Capan-2 and MIA PaCa-2). 5 muM imatinib mesylate significantly inhibited SCF-enhanced proliferation to the same extent compared with the control. Similarly, SCF-enhanced invasive ability was significantly inhibited by 5 muM imatinib mesylate. KIT was expressed in 16 of 42 clinical specimens by immunohistochemistry, and KIT expression was significantly related to venous system invasion. Furthermore, patients expressing both KIT and SCF had a somewhat lower survival. CONCLUSION: Our results demonstrated that the SCF-KIT pathway enhanced the proliferation and invasiveness in KIT-positive pancreatic cancer cell lines and that the enhanced proliferation and invasion were inhibited by imatinib mesylate. We propose that inhibitors of c-kit tyrosine kinase receptor have the potential to slow the progression of KIT-positive pancreatic cancers.