Developmental changes in GABAergic and glycinergic synaptic transmission to rat motoneurons innervating jaw-closing and jaw-opening muscles.

Trigeminal motoneurons (MNs) innervating the jaw-closing and jaw-opening muscles receive numerous inhibitory synaptic inputs from GABAergic and glycinergic neurons, which are essential for oromotor functions, such as the orofacial reflex, suckling, and mastication. The properties of the GABAergic and glycinergic inputs of these MNs undergo developmental alterations during the period in which their feeding behavior proceeds from suckling to mastication; however, the detailed characteristics of the developmental patterns of GABAergic and glycinergic transmission in these neurons remain to be elucidated. This study was conducted to investigate developmental changes in miniature inhibitory postsynaptic currents (mIPSCs) in masseter (jaw-closing) and digastric (jaw-opening) MNs using brainstem slice preparations obtained from Wistar rats on postnatal day (P)2-5, P9-12, and P14-17. The frequency and amplitude of glycinergic mIPSCs substantially increased with age in both the masseter and digastric MNs. The rise time and decay time of glycinergic mIPSCs in both MNs decreased during development. In contrast, the frequency of GABAergic components in masseter MNs was higher at P2-5 than at P14-17, whereas that in the digastric MNs remained unchanged throughout the postnatal period. The proportion of currents mediated by GABA-glycine co-transmission was higher at P2-5, and then it decreased with age in both MNs. These results suggest that characteristics related to the development of inhibitory synaptic inputs differ between jaw-closing and jaw-opening MNs and between GABAergic and glycinergic currents. These distinct developmental characteristics may contribute to the development of feeding behaviors.

Postnatal Maturation of Glutamatergic Inputs onto Rat Jaw-closing and Jaw-opening Motoneurons.

Motoneurons that innervate the jaw-closing and jaw-opening muscles play a critical role in oro-facial behaviors, including mastication, suckling, and swallowing. These motoneurons can alter their physiological properties through the postnatal period during which feeding behavior shifts from suckling to mastication; however, the functional synaptic properties of developmental changes in these neurons remain unknown. Thus, we explored the postnatal changes in glutamatergic synaptic transmission onto the motoneurons that innervate the jaw-closing and jaw-opening musculatures during early postnatal development in rats. We measured miniature excitatory postsynaptic currents (mEPSCs) mediated by non-NMDA receptors (non-NMDA mEPSCs) and NMDA receptors in the masseter and digastric motoneurons. The amplitude, frequency, and rise time of non-NMDA mEPSCs remained unchanged among postnatal day (P)2-5, P9-12, and P14-17 age groups in masseter motoneurons, whereas the decay time dramatically decreased with age. The properties of the NMDA mEPSCs were more predominant at P2-5 masseter motoneurons, followed by reduction as neurons matured. The decay time of NMDA mEPSCs of masseter motoneurons also shortened remarkably across development. Furthermore, the proportion of NMDA/non-NMDA EPSCs induced in response to the electrical stimulation of the supratrigeminal region was quite high in P2-5 masseter motoneurons, and then decreased toward P14-17. In contrast to masseter motoneurons, digastric motoneurons showed unchanged properties in non-NMDA and NMDA EPSCs throughout postnatal development. Our results suggest that the developmental patterns of non-NMDA and NMDA receptor-mediated inputs vary among jaw-closing and jaw-opening motoneurons, possibly related to distinct roles of respective motoneurons in postnatal development of feeding behavior.

[A Case of Breast Mucinous Carcinoma with Bladder Metastasis Effectively Treated with Endocrine Therapy and Chemotherapy].

A 57-year-old Japanese woman underwent partial mastectomy of the right breast and sentinel lymph node biopsy in July 2005. The diagnosis was mucinous carcinoma with negative margins and no lymph node metastases(pT1cN0M0, pStage Ⅰ A). Postoperative adjuvant therapy included radiation therapy and oral administration of anastrozole for 5 years. In December 2015, we observed enlargement of left supraclavicular lymph nodes; a needle biopsy revealed lymph node metastases from breast cancer. We administered toremifene and the swelling disappeared. The patient was subsequently referred to the hospital for urinary frequency in November 2016. Imaging demonstrated a bladder tumor. Transurethral biopsy of bladder revealed adenocarcinoma with mucin production consistent with breast primary. After systemic chemotherapy(UFT, eribulin), endocrine therapy(fulvestrant), and molecular targeted therapy(palbociclib), her urologic symptoms were relieved. However, 2 years and 8 months after diagnosis of bladder metastasis, the patient showed disease progression and decided to discontinue all chemotherapy and pursue palliative care. We also present a review and discussion of the relevant literature.

TSPAN8, identified by Escherichia coli ampicillin secretion trap, is associated with cell growth and invasion in gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common human cancers. Genes expressed only in cancer tissue, especially on the cell membrane, will be useful biomarkers for cancer diagnosis and therapeutics. METHODS: To identify novel genes encoding transmembrane protein specifically expressed in GC, we generated an Escherichia coli ampicillin secretion trap (CAST) library from diffuse-type GC cell line MKN-45. CAST is a survival-based signal sequence trap method that exploits the ability of mammalian signal sequences to confer ampicillin resistance to a mutant ß-lactamase lacking the endogenous signal sequence. RESULTS: By sequencing 1,536 colonies, we identified 23 genes encoding the transmembrane protein present in GC. Among these genes, TSPAN8 (also known as CO-029 and TM4SF3) gene, which encodes transmembrane protein tetraspanin 8, was emphasized as a candidate. Immunohistochemical analysis of tetraspanin 8 in human GC tissues revealed that 72 (34 %) of 210 GC cases were positive for tetraspanin 8, and microvessel density was significantly higher in tetraspanin 8-positive GC than in tetraspanin 8-negative GC. Furthermore, univariate and multivariate analyses revealed that tetraspanin 8 expression is an independent prognostic classifier of patients with GC. TSPAN8 knockdown by siRNA reduced the invasion of GC cell line. The reduction of invasiveness was retrieved by the tetraspanin 8-containing exosome. CONCLUSION: These results suggest that tetraspanin 8 is involved in tumor progression and is an independent prognostic classifier in patients with GC.

Expression of DDX27 contributes to colony-forming ability of gastric cancer cells and correlates with poor prognosis in gastric cancer.

Previously, we have reported that gain at chromosome 20q13 is the most common genomic copy number aberration in gastric cancer (GC) (29/30 cases), and that among the genes located in this region, we have identified DDX27, whose expression level shows the highest correlation with genomic copy number, as a candidate therapeutic target for GC. Here, we analyzed the clinicopathological significance of DDX27 using immunohistochemistry and studied its functions using knockdown assays. We found that DDX27 was frequently upregulated in GC tissues (98 of 140 cases, 70%), and significantly associated with venous invasion and liver metastasis. Furthermore, multivariate analysis of GC patients showed that high expression of DDX27 was independently associated with poorer prognosis. In functional assays, knockdown of DDX27 reduced the ability of GC cells to form colonies both on conventional plates and soft agar, but had little effect on their invasiveness. We also found that knockdown of DDX27 reduced the viability of GC cells through inhibition of cell cycle progression independently of apoptosis. Interestingly, DDX27 depletion induced accumulation of TP53 in a TP53 wild-type cell line, AGS, but not in a TP53-deleted cell line, 44As3, although DDX27 knockdown commonly reduced the viability of both, indicating the TP53-dependent and independent cell cycle control of DDX27. Thus, our results suggest that expression of DDX27 contributes to colony formation by GC cells through cell cycle control and may be a potential therapeutic target for GC patients with chromosome gain at 20q13.

Comparing incidence of enterocolitis after laparoscopic and open low anterior resection for stage II/III rectal cancer.

INTRODUCTION: We recently observed an increased incidence of severe enterocolitis following laparoscopic low anterior resection (LAR) in some patients with stage II/III rectal cancer. This study aimed to examine the influence of laparoscopic LAR on postoperative enterocolitis compared with open LAR for Stage II/III rectal cancer. METHODS: From April 2002 to March 2012, we evaluated 65 patients with stage II/III cancer of the upper or lower rectum who underwent LAR. Among these, 27 patients underwent open LAR and 38 underwent laparoscopic LAR. First, we compared short-term outcomes between the two groups. Next, we evaluated the incidence of postoperative enterocolitis in the laparoscopic LAR group. The clinicopathological factors were examined by univariate and odds ratio (OR) analysis. RESULTS: Univariate analysis revealed significant differences in the occupancy rate, tumor location, depth of tumor invasion, operative time, amount of intraoperative blood loss, and postoperative enterocolitis between the laparoscopic and open groups. Postoperative enterocolitis developed in 6 of 38 patients (15.8%) in the laparoscopic group and in no patient in the open group. The occurrence of postoperative enterocolitis was significantly associated with BMI (≥28 kg/m(2) ), operative time, and wound infection in the laparoscopic LAR group (OR: 0.11, 95% confidence interval: 0.044-0.280, P < 0.05; OR: 1.40, 95% confidence interval: 1.068-1.835, P < 0.05; and OR: 15.0, 95% confidence interval, 1.752-128.310, P < 0.05, respectively). CONCLUSION: Postoperative enterocolitis occurred more frequently after laparoscopic LAR than after open LAR in patients with stage II/III rectal cancer. Clinical management in the perioperative period of laparoscopic LAR is necessary to prevent postoperative enterocolitis in obese patients and those with a prolonged operative time.

NRD1, which encodes nardilysin protein, promotes esophageal cancer cell invasion through induction of MMP2 and MMP3 expression.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide. In the present study, to identify novel prognostic markers or therapeutic targets for ESCC, we reviewed a list of genes with upregulated expression in ESCC compared with normal esophagus, as identified by our serial analysis of gene expression (SAGE) analysis. We focused on the NRD1 gene, which encodes the nardilysin protein. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in 34 ESCC tissue samples revealed that mRNA expression of NRD1 was upregulated in 56% of ESCC tissue samples. Immunohistochemical analysis of nardilysin in 109 ESCC tissue samples demonstrated that 43 (39%) ESCC cases were positive for nardilysin. Nardilysin-positive ESCC cases were more advanced in terms of T classification (P = 0.0007), N classification (P = 0.0164), and tumor stage (P < 0.0001) than nardilysin-negative ESCC cases. Furthermore, nardilysin expression was significantly associated with poorer prognosis (P = 0.0258). Univariate and multivariate analyses revealed that nardilysin expression is an independent prognostic classifier of patients with ESCC. The invasiveness of NRD1-knockdown TE1 and TE5 esophageal cancer cell lines was less than that of the negative control siRNA-transfected cell lines. Expression of MMP2 and MMP3 mRNA was significantly lower in NRD1-knockdown TE5 cells than in negative control siRNA-transfected cells. These results suggest that nardilysin is involved in tumor progression, and is an independent prognostic classifier in patients with ESCC.

Long-term survival after resection of brain metastases from esophagogastric junction adenocarcinoma: report of two cases and review of the literature.

The prognosis for brain metastasis from primary esophageal or gastric cancer is often poor because of late detection and a lack of effective treatments. We encountered two cases of long-term survival after resection of brain metastasis that was detected >1 year after primary esophagogastric junction adenocarcinoma resection. Both patients underwent total gastrectomy, middle to lower esophagectomy, and Roux-en-Y reconstruction using the jejunum, and intrathoracic anastomosis was performed via right thoracotomy and laparotomy for primary tumor resection as well as brain metastasis resection followed by CyberKnife irradiation. They remained recurrence free-one remains alive after 6.5 years, while the other died of myocardial infarction 4 years after surgery. The present cases emphasize that long-term survival in patients with brain metastasis from gastric cancer can be expected after resection and stereotactic radiosurgery of brain metastasis detected >1 year after the resection of primary gastric adenocarcinoma.

MiR-29c is downregulated in gastric carcinomas and regulates cell proliferation by targeting RCC2.

BACKGROUND: Previously, using miRNA microarray, we have found that miR-29c is significantly downregulated in advanced gastric carcinoma. In the present study, we investigated whether miR-29c functions as a tumor-suppressor miRNA in gastric carcinoma cells. For this purpose, we verified the downregulation of miR-29c in gastric carcinoma tissues, and assessed the biological effect of miR-29c on gastric carcinoma cells. RESULTS: In miR-29c-transfected cells, both proliferation and colony formation ability on soft agar were significantly decreased. Although apoptosis was not induced, BrdU incorporation and the proportion of cells positive for phospho-histone H3 (S10) were significantly decreased in miR-29c-transfected cells, indicating that miR-29c may be involved in the regulation of cell proliferation. To explain the mechanism of growth suppression by miR-29c, we explored differentially expressed genes (>2-fold) in miR-29c-transfected cells in comparison with negative control transfected cells using microarray. RCC2, PPIC and CDK6 were commonly downregulated in miR-29c-transfected MKN45, MKN7 and MKN74 cells, and all of the genes harbored miR-29c target sequences in the 3'-UTR of their mRNA. RCC2 and PPIC were actually upregulated in gastric carcinoma tissues, and therefore both were identified as possible targets of miR-29c in gastric carcinoma. To ascertain whether downregulation of RCC2 and/or PPIC is involved in the growth suppression by miR-29c, we transfected siRNAs against RCC2 and PPIC into MKN45 and determined cell viability, the rate of BrdU incorporation, and caspase activity. We found that RCC2-knockdown decreased both cell viability and BrdU incorporation without any increase of caspase activity, while PPIC-knockdown did not, indicating that downregulation of RCC2 may be at least partly responsible for the growth suppression by miR-29c. CONCLUSIONS: Our findings indicate that miR-29c may have tumor-suppressive functions in gastric carcinoma cells, and that its decreased expression may confer a growth advantage on tumor cells via aberrant expression of RCC2.

p-Cresyl sulfate causes renal tubular cell damage by inducing oxidative stress by activation of NADPH oxidase.

The accumulation of p-cresyl sulfate (PCS), a uremic toxin, is associated with the mortality rate of chronic kidney disease patients; however, the biological functions and the mechanism of its action remain largely unknown. Here we determine whether PCS enhances the production of reactive oxygen species (ROS) in renal tubular cells resulting in cytotoxicity. PCS exhibited pro-oxidant properties in human tubular epithelial cells by enhancing NADPH oxidase (nicotinamide adenine dinucleotide phosphate-oxidase) activity. PCS also upregulated mRNA levels of inflammatory cytokines and active TGF-ß1 protein secretion associated with renal fibrosis. Knockdown of p22(phox) or Nox4 expression suppressed the effect of PCS, underlining the importance of NADPH oxidase activation on its mechanism of action. PCS also reduced cell viability by increasing ROS production. The toxicity of PCS was largely suppressed in the presence of probenecid, an organic acid transport inhibitor. Administration of PCS for 4 weeks caused significant renal tubular damage in 5/6-nephrectomized rats by enhancing oxidative stress. Thus, the renal toxicity of PCS is attributed to its intracellular accumulation, leading to both increased NADPH oxidase activity and ROS production, which, in turn, triggers induction of inflammatory cytokines involved in renal fibrosis. This mechanism is similar to that for the renal toxicity of indoxyl sulfate.

Hypomanic episode during recurrent gastric cancer treatment: report of a rare case and literature review.

S-1 plus cisplatin is the standard chemotherapy for recurrent gastric cancer. While depression and delirium are frequent in cancer patients, hypomania during chemotherapy is rare. We describe a rare case of hypomania during S-1 plus cisplatin treatment for recurrent gastric cancer. A 66-year-old woman, with no previous psychiatric disorder, received S-1 plus cisplatin for recurrent gastric cancer. She showed peculiar behavior. Physical examination, urine, blood and imaging findings were normal. There was no gastric cancer progression. During psychiatric consultation, she behaved inappropriately. However, she behaved normally while performing daily activities. She manifested a persistently elevated, expansive or irritable mood, clearly different from her usual non-depressed state, meeting hypomania diagnostic criteria. Her condition did not require chemotherapy discontinuation or additional medication. During the second and subsequent S-1 plus cisplatin cycles, symptoms were stable. Cancer patients often have adjustment disorders, depression and delirium, but rarely hypomania. Our patient showed no significant changes in blood biochemistry and brain and whole body imaging. While S-1 plus cisplatin-induced hypomania cannot be excluded, hypomanic symptoms did not improve during the chemotherapy rest period, nor was there deterioration during subsequent cycles, suggesting drug-induced mania to be unlikely. Possible onset mechanisms include manic defense phenomena, common with stressful life events. There are no reports of recurrent gastric cancer patients experiencing hypomania during S-1 or S-1 plus cisplatin therapy, i.e. our patient represents a rare course. Clinicians should recognize psychosis or mood disorders during gastric cancer treatment. Further accumulation of such rare cases might elucidate pathological mechanisms underlying hypomania in cancer patients.

[A case of reversible posterior leukoencephalopathy syndrome(RPLS)induced by modified FOLFOX6].

We report here a case of reversible posterior leukoencephalopathy syndrome(RPLS)induced by modified FOLFOX6(mFOLFOX6). The patient was a 43-year-old woman who had sigmoid colon cancer with multiple liver metastases. Treatment with mFOLFOX6 was started. Early in the morning of day 11, the patient was transported by ambulance to the hospital due to nausea with headache, disturbed consciousness, and visual disturbance. The patient experienced sudden, severe nausea and subsequently presented generalized tonic-chronic seizures. The seizures subsided after treatment. On the evening of day 11, another episode of generalized tonic-chronic seizures occurred. Status epilepticus developed and tracheal intubation was performed for airway protection. Cranial MRI showed increased signal intensity in both occipital lobes, centered on the boundary between the gray and white matter on FLAIR images. Her condition stabilized with no seizure recurrence following intubation. Although hypertension was present on admission to the emergency room, blood pressure gradually fell to within the normal range without antihypertensive treatment. She was extubated on day 18. There were no neurologic sequelae. Cranial MRI on day 40 showed that the increased intensity in both occipital lobes had almost disappeared. Because the patient's condition was characterized by a reversible central nervous system disorder, RPLS was diagnosed.

Multicenter, phase II clinical trial of cancer vaccination for advanced esophageal cancer with three peptides derived from novel cancer-testis antigens.

BACKGROUND: Since a phase I clinical trial using three HLA-A24-binding peptides from TTK protein kinase (TTK), lymphocyte antigen-6 complex locus K (LY6K), and insulin-like growth factor-II mRNA binding protein-3 (IMP3) had been shown to be promising for esophageal squamous cell carcinoma (ESCC), we further performed a multicenter, non-randomized phase II clinical trial. PATIENTS AND METHODS: Sixty ESCC patients were enrolled to evaluate OS, PFS, immunological response employing ELISPOT and pentamer assays. Each of the three peptides was administered with IFA weekly. All patients received the vaccination without knowing an HLA-A type, and the HLA types were key-opened at the analysis point. Hence, the endpoints were set to evaluate differences between HLA-A*2402-positive (24(+)) and -negative (24(-)) groups. RESULTS: The OS in the 24 (+) group (n = 35) tended to be better than that in the 24(-) group (n = 25) (MST 4.6 vs. 2.6 month, respectively, p = 0.121), although the difference was not statistically significant. However, the PFS in the 24(+) group was significantly better than that in the 24(-) group (p = 0.032). In the 24(+) group, ELISPOT assay indicated that the LY6K-, TTK-, and IMP3-specific CTL responses were observed after the vaccination in 63%, 45%, and 60% of the 24(+) group, respectively. The patients having LY6K-, TTK-, and IMP3-specific CTL responses revealed the better OS than those not having CTL induction, respectively. The patients showing the CTL induction for multiple peptides have better clinical responses. CONCLUSIONS: The immune response induced by the vaccination could make the prognosis better for advanced ESCC patients. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT00995358.

Small cell carcinoma of gastro-oesophageal junction with remarkable response to chemo-radiotherapy.

Small cell carcinoma of the gastrointestinal tract is rare, and no effective strategy has yet been established. On the basis of regimens reportedly effective for small cell lung cancer, we performed chemotherapy with cisplatin plus etoposide in combination with radiotherapy to relieve obstruction, in a patient with small cell carcinoma of the gastro-oesophageal junction. Chemotherapy was switched to carboplatin plus etoposide due to renal toxicity. No distant metastases were detected and lesion spread was limited. A complete response, with no evidence of recurrence to date, was achieved. Curative resection was suggested but refused by the patient. He has been closely followed up in our outpatient clinic for more than a year and has shown no evidence of recurrence since the completion of treatment. Although cisplatin plus etoposide is a standard chemotherapy regimen for small cell carcinoma, carboplatin plus etoposide may be effective in cases in which cisplatin is contraindicated due to renal toxicity.

Morphology of the epithelium of the lower rectum and the anal canal in the adult human.

The anal canal is an important body part clinically. However, there is no agreement about the epithelium of the anal canal, the anal transitional zone (ATZ) epithelium in particular. The aim of this study is to clarify the structure of the epithelium of the human lower rectum and anal canal. Intact rectum and anus obtained from patients who underwent surgery for rectal carcinoma were examined by light and scanning electron microscopy (LM and SEM). By LM, three types of epithelium were observed in the anal canal: simple columnar epithelium, stratified squamous epithelium, and stratified columnar epithelium. The lower rectum was composed of simple columnar epithelium. SEM findings showed stratified squamous epithelium that consisted of squamous cells with microridges, changing to simple columnar epithelium consisting of columnar cells with short microvilli at the anorectal line. LM and SEM observations in a one-to-one ratio revealed that the area of stratified columnar epithelium based on LM corresponded to the anal crypt and sinus. In conclusion, the epithelium of the human anal canal was fundamentally composed of simple columnar epithelium and stratified squamous epithelium. We found no evidence of the ATZ.

Interaction between two sulfate-conjugated uremic toxins, p-cresyl sulfate and indoxyl sulfate, during binding with human serum albumin.

Recently, p-cresyl sulfate (PCS) has been identified as a protein-bound uremic toxin. Moreover, the serum-free concentration of PCS, which is associated with its efficacy of hemodialysis, appears to be a good predictor of survival in chronic kidney disease (CKD). We previously found that PCS interacts with indoxyl sulfate (IS), another sulfate-conjugated uremic toxin, during renal excretion via a common transporter. The purpose of this study was to further investigate the interaction between PCS and IS on the binding to human serum albumin (HSA). Here, we used ultrafiltration to show that there is only one high-affinity binding site for PCS, with a binding constant on the order of 10(5) M(-1) (i.e., comparable to that of IS). However, a binding constant of the low-affinity binding site for PCS is 2.5-fold greater than that for IS. Displacement of a fluorescence probe showed that PCS mainly binds to site II, which is the high-affinity site for PCS, on HSA. This finding was further supported by experiments using mutant HSA (R410A/Y411A) that displayed reduced site II ligand binding. A Klotz analysis showed that there could be competitive inhibition between PCS and IS on HSA binding. A similar interaction between PCS and IS on HSA was also observed under the conditions mimicking CKD stage 4 to 5. The present study suggests that competitive interactions between PCS and IS in both HSA binding and the renal excretion process could contribute to fluctuations in their free serum concentrations in patients with CKD.

Radical endoscopic resection is unsuitable for most synchronous, multiple and early gastric cancers.

BACKGROUND/AIMS: It remains unclear whether synchronous, multiple, early gastric cancers can be radically resected with endoscopic resection. METHODOLOGY: Patients who underwent gastrectomy for early gastric cancer were included in this study and divided into two groups: a solitary gastric cancer group and a multiple gastric cancer group. The clinicopathological features of patients in each group were compared and the criteria for endoscopic resection were subsequently investigated. RESULTS: A total of 244 patients were included in the present study. The solitary and multiple gastric cancer groups included 228 patients (93.4%) and 16 patients (6.6%), respectively. The multiple gastric cancer group included 35 lesions, including a greater number of larger tumors and protruded- type tumors, as well as increased incidence of submucosal and lymphatic invasion. Only 2 of 16 cases (12.5%) in the multiple gastric cancer group met the criteria for endoscopic resection. Eleven cases were excluded due to submucosal invasion and three cases were excluded due to undifferentiated histopathological type tumors. CONCLUSIONS: To be suitable for radical endoscopic resection, prompt detection of early gastric cancer is essential, before they become multiple gastric cancers and invade the submucosa.

How should we treat gastric cancer in the very elderly?

BACKGROUND/AIMS: We aimed to clarify the clinicopathological features of gastric cancer in very elderly patients and to identify appropriate surgical therapy for them, focused particularly on their prognosis. METHODOLOGY: Patients who underwent gastrectomy for gastric cancer in Oita University Hospital were included in this study. The patients were divided into two groups: the very elderly group (80 years or older) (E group) and the middle-aged group (ranging from 40 to 79 years) (M group). Their clinicopathological features and postoperative survival were compared. RESULTS: Type 3,4 macroscopic types, INFγ and number of dissected lymph nodes were significantly less in the E group than in the M group (p=0.0092, p=0.0077, p=0.0475, respectively). Overall survival and disease-free survival were shorter for the E group (p=0.0898, p=0.0566, respectively). When other cause-related deaths were considered to be lost to follow-up, there was no significant difference between the E group and the M group. CONCLUSIONS: Whenever radical resection is possible, surgical resection for gastric cancer, even in the very elderly, should not be denied. Nevertheless, surgeons should try to do less invasive surgery, especially for the very elderly.

Cytokeratin 7 is a predictive marker for survival in patients with esophageal squamous cell carcinoma.

BACKGROUND: Patients diagnosed with stage II and III esophageal squamous cell carcinoma (ESCC) have variable prognosis. This group would benefit greatly from the discovery of prognostic markers that are capable of identifying individuals for whom adjuvant treatment would be advantageous. The aim of this study was to investigate the impact of immunohistochemically detected cytokeratin 7 (CK7) expression on disease-free survival, overall survival (OS), or therapeutic outcome in patients with ESCC. METHODS: Immunohistochemical analysis of CK7 was performed on 225 surgically resected specimens of stage 0-III ESCC. RESULTS: In total, 20 (9%) of 225 ESCC cases were positive for CK7. In stage 0-III ESCC patients, CK7 expression was statistically significantly associated with OS, independent of clinical covariates, including tumor, node, metastasis system stage. In stage II and III ESCC patients (n = 124), CK7 expression was significantly associated with poorer OS (P = 0.0377). Furthermore, in stage II and III ESCC patients who did not receive adjuvant chemotherapy (n = 73), CK7 expression was significantly associated with poorer OS (P = 0.0003). CK7 expression was not associated with therapeutic outcome in patients with stage II and III ESCC who received adjuvant chemotherapy. In patients with CK7-positive ESCC (n = 16), receipt of adjuvant chemotherapy tended to be beneficial for patients with stage II and III ESCC (P = 0.0654). CONCLUSIONS: Immunohistochemical analysis of CK7 will help to identify high-risk patients.

Desmocollin 2 is a new immunohistochemical marker indicative of squamous differentiation in urothelial carcinoma.

AIMS: Urothelial carcinoma (UC) with squamous differentiation tends to present at higher stages than pure UC. To distinguish UC with squamous differentiation from pure UC, a sensitive and specific marker is needed. Desmocollin 2 (DSC2) is a protein localized in desmosomal junctions of stratified epithelium, but little is known about its biological significance in bladder cancer. We examined the utility of DSC2 as a diagnostic marker. METHODS AND RESULTS: We analysed the immunohistochemical characteristics of DSC2, and studied the relationship of DSC2 expression with the expression of the known markers uroplakin III (UPIII), cytokeratin (CK)7, CK20, epidermal growth factor receptor (EGFR), and p53. DSC2 staining was detected in 24 of 25 (96%) cases of UC with squamous differentiation, but in none of 85 (0%) cases of pure UC. DSC2 staining was detected only in areas of squamous differentiation. DSC2 expression was mutually exclusive of UPIII expression, and was correlated with EGFR expression. Furthermore, DSC2 expression was correlated with higher stage (P = 0.0314) and poor prognosis (P = 0.0477). CONCLUSIONS: DSC2 staining offers high sensitivity (96%) and high specificity (100%) for the detection of squamous differentiation in UC. DSC2 is a useful immunohistochemical marker for separation of UC with squamous differentiation from pure UC.