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Nonspecific esophageal motility disorder (NEMD) is a vague category that includes patients with poorly defined contraction abnormalities observed during esophageal manometry. This study investigated the therapeutic effects of the video-assisted thoracoscopic surgery (VATS) approach using long myotomy and fundopexy for NEMD.The VATS approach using myotomy and fundopexy was performed for 4 patients of NEMD between 2005 and 2008. A total of 4 patients with NEMD that underwent treatment at our institution were analyzed retrospectively.The patients included 2 males and 2 females with a median age of 48 years (range 21-74 years). The median duration of NEMD symptoms was 58 months (range 4-108 months). Dysphagia was a primary symptom in all patients. Chest pain was a primary symptom in 3 of 4 patients (75 %). Treatment with medication was attempted before the operation. The median operative time was 344.5 min (range 210-476 min). The median time before starting oral feeding was 2.5 days (range 2-22 days). All patients achieved a significant improvement of their previous condition.The VATS approach using myotomy and fundopexy for NEMD is a good treatment in cases resistant to medication and balloon dilation.

CD47 inhibits phagocytosis and its overexpression is correlated with poor prognosis in patients with several types of cancer. It has also been reported that CD47 expression in multiple sclerosis is regulated by microRNAs. However, the regulatory mechanism of CD47 in cancer tissues has not been yet clarified. Re-analysis of a public microarray database revealed that miR-133a is downregulated in esophageal squamous cell carcinoma (ESCC). Moreover, in silico algorithms predicted that miR-133a is a regulator of CD47. The purpose of this study was to clarify the clinical significance of CD47 and its regulatory mechanism by miR-133a in ESCC. Quantitative real-time RT-PCR was used to evaluate CD47 and miR-133a expression in 102 cases of curative resected ESCC and adjacent non-cancerous tissue. The regulation of CD47 by miR-133a was examined with precursor miR-133a-transfected cells. A mouse xenograft model was used to investigate the ability of miR-133a to suppress tumor progression. High expression levels of CD47 were associated with lymph node metastasis (P=0.049). Multivariate analysis showed that CD47 expression was an independent prognostic factor (P=0.045). miR-133a expression was significantly lower in cancer tissues compared to adjacent non-cancerous tissues (P

We evaluated treatment strategies for Stage II/III (non-T4) advanced esophageal cancer in high-risk (HR) patients and analyzed the relationship between E-PASS scoring system (E-PASS) and HR patients retrospectively. The subjects were 85 patients who received the treatment for Stage II/III (non-T4) advanced esophageal cancer between 2006 and 2010 in our institute. The patients were divided into the HR and non high-risk (NHR) group. In this study, HR patients were defined as satisfying at least one of the following criteria; over 75 years old, performance status ≥ 2, presence of sever heart, respiratory, liver, renal dysfunction and diabetes mellitus. Using these criteria, there were 35 patients (41%) in the HR group. In the HR group, the ratio of surgical treatment was significantly lower than that in the NHR group (p0.01), and minimal invasive surgery was performed. In the patients who underwent surgery, there was no difference in morbidity rate and overall survival between the HR and the NHR group. A preoperative risk score (PRS) in E-PASS system was positively correlated with HR patients satisfying our classification( rs=0.63, p0.01). Our results indicated that overall survival of the HR patients was not inferior to that of the NHR patients, even if minimal invasive surgical methods were performed for the HR patients with Stage II/III (non-T4) advanced esophageal cancer. Moreover, we found that our HR classification would be a useful index to decide the treatment for Stage II/III (non-T4) advanced esophageal cancer, as well as the PRS in E-PASS.

Heat shock proteins (HSPs) are well known as tumor rejection antigens, most notable of which is HSP70. HSP110 is classified as a member of the HSP70/DnaK superfamily. The objective of this study was to clarify the clinicopathological and prognostic significance of Heat Shock Protein 110 expression and T lymphocyte infiltration in esophageal cancer.Immunohistochemical staining of HSP110, CD4 and CD8 were performed on surgical specimens obtained from 124 patients with esophageal cancer.The expression of HSP110 correlated inversely with depth of invasion (p0.0001), lymph node metastasis (p=0.0163), pathological stage (p0.0001), lymphatic invasion (p=0.0104), blood vessel invasion (p=0.0027), infiltrative growth pattern (p=0.0368) and correlated positively with CD4+ T lymphocyte infiltration (p=0.0018). Reduction of HSP110 expression was significantly correlated with poor prognosis (p=0.0010).The present findings suggest that HSP110 expression and T lymphocyte infiltration is a significant prognostic factor for esophageal cancer.

Esophageal motility disorders are classified primary and secondary, and primary esophageal motility disorders are classified esophageal achalasia and other diseases by manometry. An esophageal emptying disorder associated with insufficient relaxation of the lower esophageal sphincter (LES) and elimination of peristaltic waves on the esophageal body is the major abnormality of achalasia. Esophagogram, endoscopy, and manometry are used for diagnosis. As pharmacological therapy, administration of a calcium channel blocker or nitrate is useful. The pharmacological therapy is not recommended as long-term basic therapy but as a temporary treatment. At 1st, the balloon dilation method is chosen in treatment of achalasia Surgical treatment is indicated in the following cases: (1) Patients uneffected by balloon dilation, (2) Flask type with grade II to III dilation, and sigmoid type, (3) the gradual progression to the pathophysiological stage, (4) young patients, (5) complicated with esophageal cancer. Laparoscopic Heller-Dor procedure is the most popular surgical procedure, recently. It is somewhat difficult to perform surgical treatment for this functional disease. We should select the most suitable individualized treatment with efficient comprehension of the pathophysiological situation.

Chemoradiotherapy for advanced esophageal cancer is a standard treatment alongside surgical treatment. Although numerous investigators have attempted to identify the predictive markers for chemoradiosensitivity, there appear to be few candidates that can be applied in clinical use. Using biopsy specimens, we investigated the apoptotic index (AI) prior to treatment and following a radiation dose of 10 Gy to detect the early response to chemoradiotherapy in 28 patients with esophageal squamous cell carcinoma. Molecular markers, including p53, p21, bax, bcl-2, HSP27, HSP70, HSP90, Ku70, Ku86 and HIF-1α, were also examined by immunohistochemical staining. The patients were divided into two groups depending on the response to chemoradiotherapy: a responder group (RG) (n=19) that included the patients with complete or partial response, and a non-responder group (NRG) (n=9), that included patients with stable or progressive disease. In the RG and NRG, the AI of pretreatment was 4.7±5.3 (mean ± SD, cells/1,000 cells) and 5.9±3.7, respectively. The apoptotic index ratio (AIR), which was determined by dividing the AI following 10 Gy radiation by the pretreatment AI, was higher in the RG compared to the NRG (4.7±4.5 versus 1.9±1.4, p=0.03). When the cut-off value of AIR was set at 2.4, the sensitivity, specificity and accuracy were 74, 78 and 76%, respectively. Among the molecular markers we examined immunohistochemically, a positive p53 expression in the pretreatment evaluation was associated with the efficacy of chemoradiotherapy (p=0.08). Regarding the expression of other molecular markers, no significant correlations were found in RG and NRG. In the present study, the results indicated that AIR is useful for the prediction of chemoradiosensitivity in esophageal squamous cell carcinoma.

Background Ghrelin is a peptide hormone predominantly produced by endocrine cells in the oxyntic mucosa of the stomach and is an endogenous ligand for the growth hormone secretagogue receptor. Ghrelin plays an important role in regulating appetite, food intake, and energy metabolism. We investigated the correlation between clinicopathologic factors and plasma ghrelin concentration before and after esophagectomy with gastric tube reconstruction for esophageal cancer treatment. Methods The study group comprised 25 patients (22 men, three women, age range 46–78 y) with esophageal cancer who underwent esophagectomy with gastric tube reconstruction between 1999 and 2007. Blood samples were collected before and three times after the operation. Plasma concentrations of ghrelin were determined using a sandwich-type enzyme immunoassay kit. Results Plasma ghrelin concentrations were significantly decreased to 38.7% of the preoperative concentration at postoperative d 7. Plasma ghrelin concentrations recovered slightly over 6–24 mo postoperatively. After 36 mo or longer, ghrelin concentrations had returned to preoperative levels. There was no relationship between ghrelin concentrations and gender, location of tumor, tumor stage, operative procedure, and reconstruction route at each time point. There was a significant relationship between the decrease in body mass index and decrease in plasma ghrelin in patients at 6–24 mo after esophagectomy ( P Conclusions Plasma ghrelin concentrations decrease on a temporary basis after esophagectomy with gastric tube reconstruction and are associated with body weight loss after surgery.

A 74-year-old woman was admitted to Gunma University Hospital because of dysphagia symptoms. A gastrointestinal contrast study demonstrated a large esophageal hiatal sliding hernia affecting the passage of barium at the lower end of the esophagus. Manometric studies showed hypotensive pressure in the lower esophageal sphincter (LES) and relaxation failure of the LES during swallowing. We diagnosed a combination of sliding hiatal hernia with nonspecific esophageal motility disorder (NEMD). Thoracoscopically assisted Heller myotomy and Dor fundoplication by abdominal open surgery were then performed. The patient is currently well and is free from dysphagia symptoms. Treatment with combination thoracoscopic and abdominal open surgery was effective. We report here the first case of combined hiatal hernia with NEMD treated by thoracoscopic and abdominal open surgery.

A 60-year-old woman with right lower abdominal pain was admitted to our hospital. Computed tomography demonstrated right hydronephrosis and an irregular mass of 4 x 3 cm adjacent to the ileocecal region and iliopsoas muscle. Preoperative serum soluble anti-interleukin-2 receptor antibody was elevated (689 U/ml). Laparotomy showed an appendiceal tumor invading the cecum, mesocolon, right ureter, and duodenum. Right hemicolectomy with partial resection of the right ureter was performed. Histologic examination revealed diffuse infiltration of centrocyte-like cells, scattered plasma cells, and immunoblasts. The centrocyte-like cells were immunohistochemically positive for CD20 and CD79a, and were negative for BCL2, CD3, CD5, and CD10; this was compatible with primary mucosa-associated lymphoid tissue (MALT) lymphoma. The patient has shown a favorable course without recurrence for 2 years postoperatively. This is the sixth documented case of primary MALT lymphoma of the appendix. The spectrum of sites in which gastrointestinal MALT lymphomas occur should be expanded to include the appendix.

CD151 is a member of the tetraspanins and has recently been reported as a promoter of the malignant progression of cancer. The purpose of this study was to clarify the clinicopathological outcome and prognostic significance of the immunohistochemical expression of CD151 in esophageal squamous cell carcinoma (ESCC).We evaluated the significance of CD151 expression by immunohistochemistry in 138 surgically resected ESCC and the association of CD151 expression with clinicopathological features.Seventy-five (51.7%) ESCC showed a positive expression of CD151, which indicated a significant association with tumor depth (P = 0.004), lymph node metastasis (P = 0.002), distant metastasis (P = 0.025), and lymphatic invasion (P = 0.046), as well as the Ki-67 labeling index (P = 0.011). The 5-year survival rate of ESCC patients with CD151-positive expression was significantly lower than with CD151-negative expression (positive, 43.1%; negative, 63.8%; P = 0.003). Multivariate analysis showed that positive CD151 expression was not an independent factor for poor survival (P = 0.096).CD151 expression is associated with tumor proliferation and invasiveness in ESCC.

Karyopherin-alpha 2 (KPNA2) is a member of the importin alpha family and has recently been reported to play an important role in tumorigenesis and tumor progression. The aim of the current study was to elucidate the clinicopathological significance of immunohistochemical expression of KPNA2 in esophageal squamous cell carcinoma (ESCC).KPNA2 expression was investigated by immunohistochemistry in 116 surgically resected ESCC, and the association of KPNA2 expression with clinicopathologic features was also examined.Sixty (51.7%) ESCCs demonstrated positive expression of KPNA2. Positive expression of KPNA2 showed a significant association with poor differentiation (p=0.015), tumor depth (p=0.001), lymphatic invasion (p0.001), venous invasion (p0.001), and tumor stage (p=0.008). Positive expression of KPNA2 was also significantly associated with Ki-67 labeling index (p=0.039). Univariate analysis revealed that the prognosis of the ESCC patients whose tumors demonstrated positive expression of KPNA2 was significantly poorer than that of those that did not (p=0.009). Multivariate analysis revealed that only tumor depth and the presence of lymph node metastasis, which are strong prognostic factors in ESCC, were independently associated with poor prognosis in this study.KPNA2 expression is associated with poor differentiation, tumor invasiveness, and tumor proliferation in ESCC.

The role and potential usefulness of positron emission tomography (PET) scanning in certain tumors has been widely investigated in recent years. (18)F-FAMT (L-[3-(18)F]-α-methyltyrosine) is an amino acid tracer for PET. This study investigated whether PET/CT with (18)F-FAMT provides additional information for preoperative diagnostic workup of esophageal squamous cell carcinoma compared with that obtained by (18)F-FDG (fluorodeoxyglucose) PET or CT.PET/CT studies with (18)F-FAMT and (18)F-FDG were performed as a part of the preoperative workup in 21 patients with histologically confirmed esophageal squamous cell carcinoma.For the detection of primary esophageal cancer, (18)F-FAMT-PET exhibited a sensitivity of 76.2%, whereas the sensitivity for (18)F-FDG-PET was 90.5% (P = 0.214). (18)F-FAMT uptake in primary tumors showed significant correlation with depth of invasion (P = 0.005), lymph node metastasis (P = 0.045), stage (P = 0.031), and lymphatic invasion (P = 0.029). In the evaluation of individual lymph node groups, (18)F-FAMT-PET exhibited 18.2% sensitivity, 100% specificity, 71.9% accuracy, 100% positive predictive value, and 70.0% negative predictive value, compared with 24.2%, 93.7%, 69.8%, 66.6%, and 70.2%, respectively, for (18)F FDG-PET. CT exhibited 39.4% sensitivity, 85.7% specificity, 69.8% accuracy, 59.1% positive predictive value, and 73.0% negative predictive value. The specificity of (18)F-FAMT-PET is significantly higher than that of (18)F-FDG-PET (P = 0.042) and CT (P = 0.002). (18)F-FAMT-PET did not have any false-positive findings compared to those with (18)F-FDG-PET.Our findings suggest that the addition of (18)F-FAMT-PET to (18)F-FDG-PET and CT would permit more precise staging of esophageal cancer.

To compare mRNA levels in cancer cells and protein levels in cancerous tissue in order to evaluate the expression of dihydropyrimidine dehydrogenase (DPD).The materials were resected specimens of primary colorectal cancer (n=88) and synchronous liver metastasis (n=15). The expression of DPD mRNA in cancer cells was quantified by reverse-transcriptase polymerase chain reaction (RT-PCR) using cancer cells obtained by micro-dissection of paraffin-embedded specimens (Danenberg tumor profiling method). The protein level of DPD was determined by enzyme -linked immunosorbent assay (ELISA).There was no relationship between the level of DPD mRNA and the level of DPD protein in primary colorectal cancers and liver metastases. The level of DPD protein tended to be higher in liver metastases than in primary lesions (p=0.08) without a significant relationship between the two values. There was no relationship between primary colorectal lesions and liver metastases in terms of the expression of DPD mRNA. The efficacy of 5-fluorouracil (5-FU or UFT)/Leucovorin did not correlate with the expression level of DPD mRNA or DPD protein of primary lesions (n=18).We should note the discrepancy of results between the two different methods and the lack of a relationship between the levels of DPD expression in primary lesions and liver metastases, when considering the efficacy of 5-FU-based regimens according to the DPD expression level in primary colorectal cancers.

We examined 155 patients who received a first-line modified FOLFOX6 ( mFOLFOX6) regimen for unresectable or recurrent colorectal cancer regarding oxaliplatin-related allergic reactions and prognosis of patients who developed such allergic reactions. Twenty eight patients (18.1%) developed a total of 44 allergic reactions (2.9%): The first allergic reactions were grade 1 in nine, grade 2 in seventeen, and grade 3 in two. The median number of cycles of mFOLFOX6 until the first allergic reaction was 8.5 (range, 1-25). Compared with non-allergic group patients (n=127), allergic group patients (n=28) had mFOLFOX6 regimen more frequently (p=0.01) and higher rate of introduction to second-line FOLFIRI regimen (p0.01). When analysis was restricted to patients who were given a second-line FOLFIRI regimen, the response rate and disease control rate associated with FOLFIRI treatment did not differ significantly between the two groups. However, the allergic group patients tended to show longer disease-free survival (p=0.16) and showed longer overall survival after the start of second-line treatment (p=0.03). In addition, the allergic group patients showed a longer overall survival after the start of mFOLFOX6 (p=0.03). These results suggest that allergic reactions in the first-line mFOLFOX6 treatment might not be a poor prognostic factor, considering the efficacy of second-line FOLFIRI regimen.

This retrospective study was performed to clarify problems associated with surgery for local recurrence of rectal cancer in recent years when new anticancer drugs have come out to be available. We compared the background characteristics and treatment outcomes of patients who underwent resective surgery (resection group, n=9) and those who received chemotherapy comprised of new aniticancer drugs (chemotherapy group, n=5) for intrapelvic recurrence of rectal cancer between 1997 and 2008. In the resection group, the types of surgery included were abdomino-perineal resection in 1, posterior exenteration in 4, total pelvic exenteration in 4 and 5 who underwent sacrectomy. In the chemotherapy group, chemotherapy was continued to second-line treatment in 4 patients and third-line in 1. Oxaliplatin was given to 3 patients, irinotecan to 3, and Leucovorin to 5. The two groups did not significantly differ regarding various background factors including age, sex, stage at resection of the primary lesion, and the interval between resection of the primary lesion and detection of recurrence. The overall survival period after the start of treatment for recurrence did not significantly differ between the two groups (p=0.73). Patient's selection seems to have become a more important factor for resective surgery for intrapelvic recurrence of rectal cancer in recent years when the efficacy of new anticancer drugs is expected.

This retrospective study was performed to evaluate the outcomes of 12 patients with brain metastasis from colorectal cancer treated between 1999 and 2008. The range of patients was 33-72 years old (median: 64 years old). The male to female ratio was 2:1. The primary site was the colon in 4 patients and rectum in 8 patients. The site of brain metastasis was the cerebrum in 8 and cerebellum in 4. All brain lesions were metachronously detected. Three patients had a single lesion each, while the remaining 9 had multiple lesions. The range of the period from the resection of the primary lesion to the detection of brain metastasis was 144-2,062 days (median: 868 days). The types of treatment included whole brain radiotherapy after cerebral metastatectomy in three patients with a single lesion, whole brain radiotherapy only in 7 patients with multiple lesions, and modified FOLFOX6 (mFOLFOX6) regimen combined with whole brain radiation in recently treated two patients with multiple brain and lung metastases. The median overall survival period was 107 days. The longest survivor was a patient who survived for 505 days after the start of mFOLFOX6 plus radiation therapy. It appears that how we control metastases has become more important in recent years. For example, using new drugs, extracranial metastases of controllable cancer have become better controllable over longer periods.

This retrospective study was performed to clarify whether or not ovarian metastasis from colorectal cancer should be classified into peritoneal metastasis. We compared patient background data and prognosis between patients with ovarian metastasis (ovarian group, n=16) and female patients with peritoneal metastasis without involving ovaries (peritoneal group, n=22) treated between 1998 and 2008. The two groups did not significantly differ in terms of other clinicopathological factors evaluated. The median overall survival period was 13.8 months for the ovarian group and 16.7 months for the peritoneal group (p=0.96). The 3-year overall survival rate was 48.6%, 46.9%, and 11.5% for patients with ovarian metastasis only (P2), those with minute peritoneal metastasis without involving ovaries (P1), and those with multiple (numerous) peritoneal metastasis without involving ovaries (P3) (p=0.13), respectively. These results suggest that it is valid to classify ovarian metastasis as peritoneal metastasis. However, further collection of data may be needed to conclude that solitary ovarian lesion(s) would be classified into P2.

This retrospective study was performed to examine the outcomes of patients with liver metastasis of colorectal cancer, who received mFOLFOX6 regimen prior to hepatic metastatectomy. The reasons for introducing mFOLFOX6 prior to hepatectomy were unresectable hepatic lesions in two patients, presence or suspicion of extrahepatic lesions in four patients, and patient's refusal for hepatectomy in one patient. The mean number of cycles of administering mFOLFOX6 was 12.7 (range 10-18), two patients received additional FOLFIRI regimen after mFOLFOX6 treatment. The therapeutic efficacy revealed complete response in two, partial response in two, and stable disease in two by RECIST criteria. Histological examination revealed that six from 15 resected nodules were classified into grade 3. Histological examination of the non-cancerous liver tissue revealed stage I sinusoidal dilation (Rubbia-Brandt's classification) in five and grade 1 steatohepatitis (Brunt's classification) in two who received additional FOLFIRI regimen. Blood loss and duration of surgery of the subjects were identical to those (n=17) who underwent hepatic metastatectomy without preoperative chemotherapy during the same study period. It does not seem easy to determine the optimal timing of hepatic metastatectomy after FOLFOX treatment in clinical practice. However, our results suggest that preoperative FOLFOX treatment may have little adverse impact on the safety of hepatic metastatectomy.

Considering the advantages and disadvantages of lateral lymph node dissection in patients with lower rectal cancer, it would be ideal to select candidates for lateral lymph node dissection by preoperative imaging study. This preliminary study was performed to examine whether it would be possible to predict lateral lymph node metastasis by their sizes in patients with lower rectal cancer. In study-1, we measured the maximal and minimal diameter of 17 lateral lymph nodes from 2 patients on the paraffin-embedded slides and compared them to the diameters of the fresh specimen. In study-2, a relationship between the size of lateral lymph nodes and the presence of metastasis was examined in 259 lateral lymph nodes from 35 patients. The mean reduction rate after paraffin embedding was 56.8% (34.7-78.8) for the maximal diameter and 62.0% (36.7-80.5) for the minimal diameter. The maximal (p0.01) and minimal diameters (p0.01) were significantly greater in the nodes positive for metastasis than in the negative nodes. The area under the receiver operating curve was significantly greater for the minimal diameter than for the maximal diameter( p=0.07). The sensitivity, specificity, and accuracy for predicting metastasis was 78.6%, 83.7%, and 83.4%, respectively when the cut off of the minimal diameter was set at 3.41 mm, which corresponds to 5.50 mm in living bodies. In conclusion, determining the minimal diameter of the lateral lymph nodes by preoperative imaging studies may be useful for selecting candidates for lateral lymph nodes dissection.

To assess current trends and problems in chemotherapy for elderly patients with unresectable gastric cancer.Patients with unresectable gastric cancer were divided into two groups: an elderly group aged 70 years or older (n=28), and a control group aged younger than 70 years (n=46). The feasibility, safety, and efficacy of chemotherapy were compared between the two groups. The induction rate for a first-line treatment did not differ between the groups (89% for the elderly group versus 93% for the control group). A regimen comprising S-1 and cisplatinum (CDDP) was selected most frequently as the first-line treatment in both groups. When an analysis was restricted to patients given S-1 and CDDP, the elderly group showed fewer cycles of CDDP administration, a higher rate of grade 3 or worse adverse events, a lower rate of switching to a second-line treatment, and a shorter overall survival than the control group, although the p values did not reach a significant level. Among patients aged 70 years or more, those given S-1 alone showed an overall survival equivalent to that for patients given S-1 and CDDP. In conclusion, in clinical practice, it seems appropriate to consider whether the S-1+CDDP regimen is the most optimal first-line treatment for elderly patients with gastric cancer.

This retrospective study was performed to examine the frequency of PSK administration in patients with Stage III rectal cancer in clinical practice, and the effect of PSK on patient outcome. The subjects were 71 patients with Stage III rectal cancer who received postoperative adjuvant chemotherapy comprising fluoropyrimidines between April 1997 and March 2006. The frequency of PSK administration and factors affecting recurrence, disease-free survival, and overall survival were examined. The frequency of concomitant use of PSK with fluoropyrimidines was 79% (56 patients). Among the patients who were given PSK, the frequency of concomitant use of UFT alone was higher in Stage III a patients, while the rate of concomitant use of fluoropyrimidines and Leucovorin was higher in Stage III b patients (p0.01). Multivariate analyses revealed that the only predictive factor affecting recurrence, disease-free survival, and overall survival was Stage III b. Although the rate of concomitant use of PSK in adjuvant chemotherapy for patients with Stage III rectal cancer was high, we did not evaluate the effect of PSK because there was a marked bias in relation to the subclassification of Stage III disease and the use of Leucovorin in these subjects. Prospective randomized trials with stratification of Stage III disease will be needed in the future to validate the efficacy of PSK.

Tissue-engineered cartilage may be expected to serve as an alternative to autologous chondrocyte transplantation treatment. Several methods for producing cartilaginous tissue have been reported. In this study, we describe the production of scaffold-free stiff cartilaginous tissue of pig and human, using allogeneic serum and growth factors. The tissue was formed in a mold using chondrocytes recovered from alginate bead culture and maintained in a medium with transforming growth factor-beta and several other additives. In the case of porcine tissue, the tear strength of the tissue and the contents of proteoglycan (PG) and collagen per unit of DNA increased dose-dependently with transforming growth factor-beta. The length of culture was significantly and positively correlated with thickness, tear strength, and PG and collagen contents. Tear strength showed positive high correlations with both PG and collagen contents. A positive correlation was also seen between PG content and collagen content. Similar results were obtained with human cartilaginous tissue formed from chondrocytes expanded in monolayer culture. Further, an in vivo pilot study using pig articular cartilage defect model demonstrated that the cartilaginous tissue was well integrated with surrounding tissue at 13 weeks after the implantation. In conclusion, we successfully produced implantable scaffold-free stiff cartilaginous tissue, which characterized high PG and collagen contents.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms affecting the gastrointestinal tract. Esophageal GISTs are very rare, but recognition of esophageal GISTs has been increasing recently. We report a patient with an esophageal GIST that showed increased uptake on 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET). In this case, preoperative diagnosis was assumed to be esophageal cancer, but postoperative histopathological and immunohistochemical examination showed it to be a malignant GIST. We also found an activating mutation of kit in this patient; the mutation type was an in-frame deletion of a portion of the juxtamembrane domain (exon11). FDG-PET is useful not only for evaluating the bioactivity but also the malignant potential of esophageal GISTs.

BACKGROUND: Metabolic tumor activity using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was believed to have a predictive value for patient outcome in malignancies. The objective of the current study was to assess the prognostic effectiveness of the highest standardized uptake value (SUV) in the primary or regional area (peak SUV) and the number of PET-positive lymph nodes in esophageal cancer. METHODS: The authors retrospectively reviewed their experience with 184 consecutive esophageal cancer patients imaged preoperatively using FDG-PET scanning. RESULTS: The median peak SUV was 4.5 (range, 1.4-21.9). The survival curve was analyzed using the median peak SUV as the cutoff value. Comparison of each group and clinicopathologic characteristics revealed significant associations between peak SUV and each of the following factors: tumor status (P < .001), lymph node status (P < .001), metastatic status (P < .05), stage of disease (P < .001), number of PET-positive lymph nodes (P < .001), and the number of histologically positive lymph nodes (P < .001). The 5-year overall survival (OS) rate for patients having FDG uptake with a peak SUV ≥4.5 was 47% and that for patients with a peak SUV

The objective of this study was to clarify the participation of heat-shock protein 70 (HSP70) and the humoral immune system in antitumor immunity in esophageal cancer.Immunohistochemical staining for HSP 70, and CD4(+) T-, CD8(+) T-, B- and plasma cells was performed on surgical specimens obtained from 125 patients with esophageal cancer. An enzyme-linked immunosorbent assay (ELISA) was then performed to measure serum anti-HSP70 antibodies in the azygos vein.The expression of HSP 70 correlated inversely with depth of invasion (p0.0001), pathological stage (p0.0001) and blood vessel invasion (p0.001), and there was a positive correlation between HSP70 and CD4(+) T-, CD8(+) T-, B- and plasma cells. Of these, the B- and plasma cells had the strongest correlation to HSP70 expression. Serum anti-HSP70 antibody levels in the azygos vein correlated with HSP70 expression, and B and plasma cell infiltration. Patients positive for HSP70, and B- and plasma cell infiltration had good prognosis compared to other cases. According to multivariate analyses, simultaneous occurrence of HSP70 expression, and B- and plasma cell infiltration is a stronger prognostic factor than simultaneous occurrence of HSP70 expression, and CD4(+) T- and CD8(+) T-cell infiltration.It is suggested that the HSP70-humoral immune cell system might play an important role in antitumor effects in patients with esophageal cancer.

Cap43 protein has been proven to be upregulated by nickel compounds or hypoxic stress, often during cell differentiation or cell growth arrest. However, the function of this gene remains unknown. Although, several studies have been performed, none of these have evaluated the expression of Cap43 in esophageal cancer. To clarify its function and role in esophageal cancer, a clinical archive of cancer specimens was examined for the expression of Cap43 by immunohistochemistry. The expression level of Cap43 protein was also investigated by Western blotting and mRNA by realtime RT-PCR using esophageal cancer cell lines. Immunohistochemistry results showed that overexpression of Cap43 was correlated with malignant status of esophageal cancer and that was considered as an independent prognostic marker. Interestingly, adenocarcinoma of the esophagus did not express Cap43. In esophageal cancer cell lines, Western blotting and real-time RT-PCR, showed a variation in the expression level of Cap43 and there was no obvious correlation between protein and mRNA levels. The present report shows for the first time that the expression of the Cap43 gene has a function in tumor progression and that its expression correlates independently with patient survival. Cap43 gene could be considered as a new and important cancer marker.

To compare mRNA levels in cancer cells and protein levels in cancerous tissue in terms of the expression of thymidine phosphorylase(TP).The materials were resected specimens of primary colorectal cancer(n=84)and synchronous liver metastasis(n=15). The expressions of TP mRNA in cancer cells was quantified by reverse-transcriptase polymerase chain reaction(RT-PCR)using cells obtained by microdissection of paraffinembedded specimens(Danenberg tumor profiling method). The protein level of TP was determined by enzyme-linked immunosorbent assay(ELISA).There was a weak relationship between TP mRNA levels and TP protein levels in primary colorectal cancers(p=0.04), but these factors did not correlate with each other in liver metastases. There was no relationship between primary colorectal lesions and synchronous liver metastases in terms of TP mRNA levels and TP protein levels. In relation to the efficacy of 5-fluorouracil(or UFT)/Leucovorin, the mRNA level of the primary lesion was marginally higher in the order of patients with PD(n=11), SD(n=3), and CR/PR(n=4)(p=0.05). However, the TP protein level did not correlate with therapeutic efficacy.The different methods of determining the expression of TP in colorectal cancer specimens do not correlate with each other and may cause different therapeutic results after 5-fluorouracil-based chemotherapy.

Cell cycle regulators, such as cyclinD1 and p53, play major roles in the tumor response to radiation and chemotherapy in esophageal squamous cell carcinoma (SCC). Pin1-mediated prolyl-isomerization potentiates cell cycle progression and cell proliferation, including the regulation of cyclinD1 and p53. Herein, we investigated the effect of Pin1 in association with cyclinD1 and p53 on the sensitivity of esophageal SCC to chemoradiotherapy (CRT). The expression levels of Pin1, cyclinD1 and p53 were examined immunohistochemically in endoscopic biopsy specimens from 68 advanced esophageal SCC patients before CRT to determine whether their expression levels predicted the clinical effectiveness of CRT in individual cancers. Forty-six of the 68 patients (67.6%) had an effective response to CRT, whereas 22 patients (32.4%) had an ineffective response. There was no significant correlation between clinical responses and expression levels of cyclinD1 or p53. However, the clinical response of the high Pin1 expression group was significantly higher than that of the low expression group (P=0.0200). Moreover, our data indicate that the combined immunohistochemical evaluation of Pin1, cyclinD1 and p53 expression in pretreatment biopsy samples is a useful indicator of sensitivity to CRT in advanced esophageal SCC. Thus, Pin1 may influence cyclinD1 and p53 functions and predict CRT sensitivity.

This retrospective study was performed to clarify the efficacy and safety of FOLFOX regimen in aged patients with nonresectable colorectal cancer.We had 92 patients with nonresectable colorectal cancer between December 2005 and March 2008. The rate of introducing modified FOLFOX6 (mFOLFOX6) regimen was compared among the patients aged 75 years or older (n = 22, aged group) and those aged 74 years or younger (n = 55, younger group). In addition, relative dose intensity (RDI), therapeutic efficacy, and adverse events in the patients who were given the regimen, we compared between the groups.The rate of introducing the regimen was significantly lower in the aged group (36%, n = 8) than in the younger group (79%, n = 55) (p0.01). The RDI tended to be lower in the aged group (68.0% versus 79.9%, p=0.10). There were no significant differences in the response rate, disease-control rate, progression-free survival, and overall survival between the groups. The rate of adverse events (or = grade 3) was not different between the groups ( 50% versus 51%).Similar to younger patients the mFOLFOX6 regimen is feasible, safe and effective in the selected aged patients, although the dose reduction may be needed for such patients.

Surgical resection has been the standard treatment recommended for respectable pulmonary metastasis from colorectal cancer. However, we should evaluate again the indication of bilateral thoracotomy and repeat resection of pulmonary metastatic lesions, because these surgical interventions may deteriorate the patients' quality of life. This retrospective study was performed to address this issue.The subjects were 39 patients who underwent pulmonary metastatectomy of colorectal cancer between May 1990 and January 2007. The prognosis was evaluated according to the types of thoracotomy, bilateral thoracotomy (n=5), repeat pulmonectomy (n=6), and single thoracotomy (n=28). In addition, the impact of new anticancer drugs (5-fluorouracil+Leucovorin, S-1, irinotecan, and oxaliplatin) on survival after thoracotomy was examined.The patients undergoing bilateral thoracotomy showed a significantly shorter survival after the last thoracotomy than those in other groups (p=0.03). The survival time after the initial thoracotomy was not different between patients who received new anticancer drugs (n=11) and those without (n=28, p=0.58).Bilateral pulmonary metastatectomy from colorectal cancer appears to have little benefit on survival, while a repeat metastatectomy may cause a long-term survival. A further collection of cases is needed to conclude whether the new anticancer drugs would be useful for prolonging the patients' survival after pulmonary metastatectomy.

This retrospective study was performed to clarify the frequency and clinical significance of hepatic lymph-node metastasis in patients with synchronous liver metastasis from colorectal cancer, in relation to the grading system of liver metastasis classified by the 7th Edition of General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum and Anus. Hepatic lymph-node metastasis was histologically examined in 61 patients with synchronous liver metastasis whose primary lesion was resected. The incidence of hepatic lymph-node metastasis for all patients was 26%. The frequency was 8% in Grade A (n=13), 20% in Grade B (n=15), and 36% in Grade C (n=33) (p=0.09). Among patients classified in Grade A/Grade B, the patients with hepatic lymph-node metastasis showed a shorter survival time than those without metastasis (p0.01). Among patients in Grade C, there was no significant difference in survival times between the patients with hepatic lymph-node metastasis and those without metastasis (p=0.59). In conclusion, the incidence of hepatic lymph-node metastasis should be considered regardless of the Grade of liver metastasis from colorectal cancer.

We investigated the clinical significance of chemo-radiotherapy (CRT) and chemotherapy (CT) in patients with primary metastatic esophageal cancer.Twenty-six patients with esophageal cancer received CRT (n =21) or CT alone (n=5) as a first treatment for para-aortic lymph node and/or hematogenous metastases. The therapeutic effect, duration of treatment, changes in performance status before and after treatment, and survival were analyzed retrospectively.The median duration of treatment was 2.9 months for CRT and 2.3 months for CT. The response rate was 76% in patients who underwent CRT and 20% in patients who underwent CT. In 18 patients (69%), the level of performance status showed no change after treatment in comparison with that before treatment. The median survival time was 5.6 months after CRT and 5.8 months after CT (p=0.91).These results suggest that the majority of patients with extremely advanced esophageal cancer can tolerate CRT or CT well without compromising their performance status within their limited life expectancy.

This retrospective study evaluated the prognosis of patients undergoing resection of both hepatic and pulmonary metastases from colorectal cancer. The subjects were 14 patients who underwent resection of both hepatic and pulmonary metastases from colorectal cancer between January 1991 and January 2008. The range of patient age at first metastatectomy was 48- 73-years-old (median 59). The ratio of males to females was 4 to 3. Hepatic metastatectomy proceeded to pulmonary metastatectomy in 10 cases, while pulmonary metastatectomy was performed first in 4 cases. The median duration of relapse-free survival and overall survival after the second metastatectomy was 11.2 months and 20.4 months, respectively. The overall survival after the second metastatectomy tended to correlate with the relapse-free survival after the first metastatectomy (rs=0.55, p=0.08). In conclusion, relapse-free survival after the first metastatectomy should be considered when a second metastatectomy is scheduled in patients with both hepatic and pulmonary metastases from colorectal cancer.

Chemotherapy is potentially hazardous for patients with liver dysfunction. Although FOLFOX regimen is one of the standard chemotherapies for nonresectable liver metastases of colorectal cancer, the safety of this regimen has not been established yet in patients with obstructive jaundice associated with multiple liver metastases. We report a case of nonresectable liver metastases of rectal cancer treated by modified FOLFOX6 regimen after percutaneous transhepatic biliary drainage for obstructive jaundice, which was caused by hepatic lymph-node metastasis. Five days after giving a birth, a 32-year-old woman underwent Hartmann's procedure for perforation of rectal cancer associated with multiple liver metastases. She was admitted again to receive chemotherapy 35 days after surgery, but the level of total bilirubin was elevated (3.9 mg/dL). Since the total bilirubin level was not rapidly decreased after PTBD, the modified FOLFOX6 regimen was started with a 70% dose. After an introduction of mFOLFOX6 treatment, a biliary-stenting was successfully performed, and the mFOLFOX6 continued with a full dose starting from the 5th cycle. Although the therapeutic efficacy after an additional 8-cycle was classified as stable disease (SD), she did not show any sign of adverse effects except for grade 1 neurotoxicity.

This retrospective study was performed to evaluate the administration and effect of PSK in patients with stage III colorectal cancer in clinical practice.The subjects were 55 patients with stage III colorectal cancer who received adjuvant chemotherapy, comprising UFT in 44, UFT/calcium folinate (Leucovorin) in 4 and 5-FU/levofolinate calcium (l-LV) in 7, between April 2000 and December 2006. The rate of administering PSK, disease-free survival time, and overall survival time were evaluated.The rate of administering PSK was 82%. There was no significant difference in disease-free survival and overall survival between patients who received PSK and those without. Among the patients in stage IIIa, the patients who received PSK tended to show a longer overall survival time than those without PSK (p =0.15).The rate of administering PSK is high in patients with stage III colorectal cancer. But further cases would be needed to evaluate the effect of PSK with 5-FU-based adjuvant chemotherapy.

Gornet et al.(2002) reported that patients who received chemotherapy containing oxaliplatin for metastatic colorectal cancer experienced exacerbation of neurotoxicity after surgical resection and suggested that the possible mechanism behind exacerbation of neurotoxicity was perioperative transfer of accumulated platinum from the red blood cells into the plasma. However, no further reports about this issue have been published.We investigated changes of neurotoxicity after resection in three patients who received modified FOLFOX6 therapy prior to surgery. In addition, changes of the total plasma, ultrafiltrate, and erythrocyte platinum levels were determined by inductively coupled plasma mass spectrometry.Exacerbation of neurotoxicity was not seen in any of the patients postoperatively. The platinum concentrations of all samples did not change significantly from before surgery to 4, 24, and 48 hours postoperatively.Further assessment of patients is needed to draw a definite conclusion, but our preliminary data suggest that the risk of neurotoxicity exacerbation due to perioperative changes of the platinum pool is low.

Objective: Vascular endothelial growth factor (VEGF)-C is known to be associated with angiogenesis and lymphangiogenesis in various cancers. However, little is known about the clinical significance of determining the blood level of VEGF-C in patients with colorectal cancer. Methods: Plasma levels of VEGF-C in patients with colorectal cancer (n ¼ 127) and normal healthy volunteers (n ¼ 23) were determined by the sandwich enzyme-linked immunosorbent assay. Results: The plasma VEGF-C concentration did not significantly differ between patients with colorectal cancer and healthy controls (P ¼ 0.53). However, subgroup analysis showed that deeper tumor invasion (P ¼ 0.04), more severe lymphatic invasion (P ¼ 0.03) and venous invasion (P , 0.01) were correlated with an elevated level of plasma VEGF-C. Among the patients (n ¼ 109) who underwent potentially curative surgery, the plasma level of VEGF-C was higher in patients who developed recurrence (n ¼ 35) than in those who did not (n ¼ 74) (P ¼ 0.04). In addition, disease-free (P ¼ 0.02) and overall survival times (P ¼ 0.02) were shorter in patients with a high level (.1840 pg/ml) of plasma VEGF-C than in those with a low level (1840 pg/ml) when the cut-off value was determined on the basis of the median value in colorectal cancer patients. Multivariate analysis with the Cox proportional hazard model demonstrated that the plasma VEGF-C level along with Dukes’ stage was an independent factor affecting overall survival (P ¼ 0.03). Conclusion: These results suggest that determining the plasma level of VEGF-C would be useful for predicting lymphatic invasion, venous invasion and poor outcome of patients with colorectal cancer.

Carbonic anhydrase 9 (CA9) is a protein to be upregulated under exposure to hypoxic conditions. Hypoxic conditions are known to be associated with resistance to chemotherapy and radiotherapy, and with poor cancer prognosis. We examined CA9 expression in surgical specimens from oesophageal squamous cell carcinoma (ESCC) patients (n=127) using immunohistochemistry and real-time RT-PCR. We also examined CA9 expression and cell proliferation in ESCC cell lines (TE-2, TE-8 and TE-15) and an immortalised human oesophageal cell line (CHEK-1) using real-time RT-PCR, Western blotting, ELISA and MTT assay. Immunohistochemistry, high expression of CA9 was found in 63 of the 127 primary tumour specimens and was correlated with poor outcome (P=0.0003) and more aggressive/less favourable clinicopathological parameters (tumour size (P=0.0235), tumour depth (P

The purpose of the present study was to assess the contribution of simultaneous functional/anatomical imaging using integrated 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT), compared with PET alone for the evaluation of initial lymph node staging in esophageal cancer. We studied 167 consecutive patients with thoracic esophageal squamous cell carcinoma (SCC) who had radical esophagectomy performed between January 1999 and April 2007. For individual nodal group evaluation, PET/CT showed 46.0% sensitivity (p

Small leucine-rich proteoglycans, such as biglycan, and their side chain sulfated glycosaminoglycans (GAGs), have been suggested to be involved in bone formation and mineralization processes. The present study was designed to investigate whether chondroitin sulfate (CS), one of the GAG, and its oversulfated structures coupled with bone morphogenetic protein-4 (BMP-4) alter the differentiation and subsequent mineralization of MC3T3-E1 osteoblastic cells. CS-E, one of the oversulfated CS structure, enhanced cell growth, alkaline phosphatase (ALP) activity, collagen deposition, and mineralization whereas heparin enhanced only ALP activity and mineralization. As well as CS-E, CS-H, and CPS also enhanced the mineralization of the cells. CS-E enhanced the mineralization of the cells by interacting with protein in the conditioned medium. CS-E induced mineralization was significantly inhibited by an antibody against BMP-4. The addition of exogenous BMP-4 further increased the capacity of CS-E to enhance mineralization. Fluorescence correlation spectroscopy method using fluoresceinamine-labeled GAG revealed that the oversulfated GAGs have a high affinity for BMP-4. The disaccharide analysis of the cells indicated that MC3T3-E1 cells are capable of producing oversulfated structures of CS by themselves. The lack of CS from the cells after chondroitinase treatment resulted in the inhibition of mineralization. These results in the present study indicate that oversulfated CS, which possesses 4,6-disulfates in N-acetyl-galactosamine, binds to BMP-4 and promotes osteoblast differentiation and subsequent mineralization.

Circulating vascular endothelial growth factor-C (VEGF-C) levels were measured in patients with esophageal cancer to assess the value of VEGF-C as a biomarker for predicting tumor recurrence.Preoperative serum samples were acquired from 80 patients and healthy volunteers who served as normal controls. VEGF-C levels were assessed using enzyme-linked immunosorbent assay (ELISA).The preoperative serum VEGF-C level in patients with esophageal cancer was significantly higher than in healthy volunteers. Furthermore, patients with recurrence had significantly higher preoperative serum VEGF-C levels than patients without recurrence, and a high preoperative serum VEGF-C level was found to be an independent risk factor for recurrence, in addition to lymph node metastasis.Preoperative VEGF-C levels may reflect malignancy, such as lymph node metastasis, and predict recurrence in patients with esophageal cancer. Therefore, the preoperative VEGF-C level may be a useful biomarker for choice of multimodality therapy.

We reported an elderly case of squamous cell carcinoma of the anal canal which showed complete response following radiotherapy alone. An 86-year-old man complaining of anal bleeding and pain was admitted. Colonoscopy showed a type 1 tumor just above the dentate line. Biopsy revealed squamous cell carcinoma. Serum SCC Level before treatment was elevated (8.4 ng/mL). Magnetic resonance imaging did not show any metastatic lesions. Since the patient and his family members refused a surgical intervension and chemotherapy, he received an external radiotherapy (total dose: 60 Gy) to the pelvic space and showed complete response after radiotherapy. He is alive without evidence of recurrence about three years after the radiation, although serum SCC is slightly elevated.

We examined five cases of pseudomyxoma peritonei with treatments of cytoreduction surgery, abdominal lavage and intraperiotoneal administration of cisplatin (CDDP). These primary lesions contained one case of pancreas and four cases of appendix. Histological types contained one case of well differentiated adenocarcinoma and four cases of signet ring cell carcinoma. All cases underwent a resection of primary lesion and muconodule, abdominal lavage with saline and 5% glucose or low molecule dextran solution. CDDP was administered into the abdominal space during and after the surgery, a total amount of 100 to 400 mg/body. There were no cases of collected ascites within one year, except one case that we could not follow. There was a possibility that a short-term quality of life was improved by multidiciplinary therapy containing cytoreduction surgery and intraperiotoneal administration of CDDP.

We report a case of squamous cell carcinoma of the anal canal which showed complete response following chemoradiotherapy. A 54-year-old woman was diagnosed as having squamous cell carcinoma of the anal canal (T2N0M0 stage II). Chemoradiotherapy comprising peroral tegafur/uracil and external radiotherapy (60 Gy) to the pelvic space resulted in complete response 4 months after the initiation of the treatment. PET-CT showed recurrence in paraortic lymph node, right sacral and left pubic bone 11 months after the initiation of treatment, although the primary lesion did not relapse. The patient is now given 5-fluorouracil/cisplatin in addition to external radiotherapy (57.5 Gy) to the metastatic lymph node. This case suggests that we should take measures to prevent distant metastases in the treatment of squamous cell carcinoma of the anal canal.

This retrospective study was performed to examine the relationship between the size and metastasis of hepatic lymph node in patients with liver metastasis of colorectal cancer.We analyzed a total of 163 hepatic lymph nodes that were removed during surgery from 55 patients with synchronous liver metastasis of colorectal cancer, who underwent resection of primary tumor without any residual lesions except for liver metastasi (e) s. The relationship between the size and metastasis was examined on paraffin-embedded specimens.The maximal and minimal diameters were significantly greater in positive lymph nodes (n=35) than in negative lymph nodes (n=128). The area under the curve of receiver operating curve for predicting metastasis by size was 0.69. The sensitivity, specificity, and accuracy were 62.9%, 60.9%, and 61.4%, respectively, when the cutoff value was set at 7 mm.These findings suggest that selecting patients with hepatic lymph node metastasis based on the size of lymph nodes would be difficult.

After esophagectomy a swallowing abnormality is the predominant symptom for esophageal cancer. The aims of this study were to examine (i) oropharyngeal swallowing by comparing pre- and postoperative period, and (ii) the relationship between oropharyngeal swallowing and the alimentary reconstruction route after esophagectomy.We studied 27 patients in the upright position using videofluoroscopy in the lateral projection. Each patient was studied during 10 mL barium swallows in the pre- and post-operative period.Of the 27 patients studied, alimentary reconstruction with the retrosternal route (RS group) was performed in 8 patients, that with posterior mediastinal route (PM group) in 8 patients, and the intrathoracic (IT group) esophagogastrostomy inside the posterior mediastinum in 11 patients. With regard to the maximal extent of structural movement, the superior and anterior excursion of the hyoid bone was significantly reduced postoperatively among all groups. The maximal extent of the cricopharyngeal opening was significantly reduced postoperatively in the RS group, but not in the IT group. The changes in the peri-operative structural movement were the lowest in the RS group.A new-onset oropharyngeal swallowing abnormality following retrosternal reconstruction after esophagectomy may have appeared because the change in the peri-operative movement was the lowest. The results of the swallowing evaluation using videofluoroscopy suggest that to avoid oropharyngeal swallowing abnormalities the intrathoracic or cervical anastomosis with posterior mediastinal route should be chosen as reconstruction after esophagectomy if possible.

Self-expandable metallic stents (SEMS) have been used for many years in the palliation of esophageal cancer symptoms. Stent migration is one of the most recognized complications of SEMS. To prevent SEMS migration, this study reported the use of endoscopic clips, and carefully analyzed the patients who underwent implantation.From January 2000 to December 2002, nine patients consecutively underwent SEMS implantation. After successful placement of the SEMS and to maintain its position, endoscopic clips were used to fix the branch of the upper end of the stent to the esophageal mucosa.Stent implantation was technically successful in all patients, three of whom had strictures and six of whom had digestive-respiratory fistulas. No stent migration was observed in any of the patients, and dysphagia improved significantly after stent placement. Five patients did, however, experience delayed complications, two in the form of obstructions, two with recurrent fistulas, and one with a perforation.In conclusion, this new technique is recommended as endoscopic clipping can diminish the risks of stent migration, in particular those associated with esophago-respiratory fistulas without luminal obstruction.

Little is known about the expression levels of thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and orotate phosphoribosyltransferase (OPRT) in diffusely infiltrating colorectal cancer. We semiquantified the mRNA levels of these enzymes in colorectal cancer specimens from 10 patients with diffusely infiltrating type and 20 patients with other types (control) matched by the maximal diameter and pathological stage, using the Dannenberg tumor profiling method. The relative expression of these enzymes did not significantly differ between diffusely infiltrating and other types of tumors. There were no significant relationships among the relative expression of the four enzymes in the diffusely infiltrating tumors, while the following three combinations were found to be correlated with each other in the control tumors: TS versus TP,TS versus DPD, and TP versus DPD. In 5 patients who received 5-fluorouracil-based chemotherapy for evaluable lesions, there were no specific relationships between the expression of these enzymes and therapeutic response. In conclusion, diffusely infiltrating colorectal cancer does not appear to have any characteristics in terms of the expression of these enzymes, which may not alter the effect of 5-fluorouracil-based chemotherapy.

We report a case of a granular cell tumor (GCT) covered by squamous cell carcinoma (SCC) in the esophagus. A 69-year-old Japanese man was admitted to our hospital for treatment of superficial esophageal cancer detected by upper gastrointestinal endoscopy. Endoscopic examination revealed a shallow ulcer in the esophagus, 28–32 cm from the incisor teeth. The pathological findings of a biopsy of the lesion were moderately differentiated SCC. Thus, we performed partial esophagectomy with two-field (thoraco-abdominal) lymph node dissection. Microscopic examination of the surgical specimen revealed intraepithelial SCC with minimal invasion, and a GCT, 3 × 1 mm in size, in the submucosa just beneath the SCC. Cytoplasmic granules in the GCT were positive for periodic acid-Schiff. Immunohistochemically, the GCT was strongly positive for S-100 protein. To our knowledge, this is the first published report of a GCT covered by SCC in the esophagus.