Laparoscopic transabdominal approach for resection of presacral epidermoid cyst in an obese man: a case report.

BACKGROUND: Complete resection of presacral epidermoid cysts is recommended due to the potential for infection or malignancy. Transsacral and transabdominal approaches have been used to treat presacral tumors. However, there are no standard surgical approaches to resection. We present the case of a presacral epidermoid cyst in an obese male patient who underwent laparoscopic transabdominal resection. CASE PRESENTATION: A 44-year-old man was referred to our hospital for treatment of a cystic tumor on the pelvic floor. Contrast-enhanced computed tomography revealed a 45 × 40-mm tumor on the left ventral side of the rectum, right side of the ischial spine, dorsal side of the seminal vesicles, and in front of the 5th sacrum. Enhanced magnetic resonance imaging revealed a multilocular cystic tumor with high and low signal intensities on T2-weighted images. The tumor was diagnosed as an epidermoid cyst. We considered the transsacral or laparoscopic approach and decided to perform a laparoscopic-assisted transabdominal resection since the tumor was in front of away from the sacrum, and a transsacral approach would result in a larger scar due to poor visibility from the thickness of the buttocks. The entire tumor was safely resected under laparoscopic guidance, because the laparoscopic transabdominal approach can provide a good and magnified field of view even in a narrow pelvic cavity with small skin incisions, allowing safe resection of the pelvic organs, vessels, and nerves while observing the tumor contour. CONCLUSIONS: The laparoscopic transabdominal approach is an effective method for treating presacral tumors in obese patients.

Aortoesophageal fistula due to esophageal cancer: a case report of successful management.

BACKGROUND: Aortoesophageal fistula (AEF) is a rare but potentially life-threatening condition. The best treatment for the AEF due to esophageal carcinoma is still unresolved. Here, we report a rare case of AEF caused by esophageal cancer, that was successfully treated with emergency thoracic endovascular aortic repair (TEVAR), followed by esophagectomy and gastric tube reconstruction. CASE PRESENTATION: A 64-year-old man presented with loss of consciousness and hypotension during chemoradiotherapy for advanced esophageal cancer. Enhanced computed tomography showed extravasation from the descending aorta into the esophagus at the tumor site. We performed emergency TEVAR for the AEF, which stabilized the hemodynamics. We then performed thoracoscopic subtotal esophagectomy on day 4 after TEVAR to prevent graft infection, followed by gastric tube reconstruction on day 30 after TEVAR. At 9 months after the onset of AEF, the patient continues to receive outpatient chemotherapy and leads a normal daily life. CONCLUSION: TEVAR is a useful hemostatic procedure for AEF. If the patient is in good condition and can continue treatment for esophageal cancer, esophagectomy and reconstruction after TEVAR should be performed to prevent graft infection and maintain quality of life.

[A Patient Who Had Postoperative Three-Field Lymph Node Recurrence of Cancer of the Esophagogastric Junction Obtains Complete Response by DCF Treatment].

A 64-year-old woman underwent left-thoracoabdominal esophagectomy and esophagojejunostomy for cancer of the esophagogastric junction. The pathological examination of the resected specimen showed a poorly squamous cell carcinoma (SCC). The pathological stage was pT3, pN1, sM0, and fStage Ⅲ. Three months after surgery, an SCC antigen related to a tumor marker was found to be outside the normal range, and CT showed lymph node recurrence of the three fields(No. 101R, No. 104RL, No. 106recRL, No. 106pre, and No. 16b1). Because the lymph node recurrence was in the three fields, we performed systemic chemotherapy with docetaxel, cisplatin(CDDP), and 5-fluorouracil(5-FU)(collectively, DCF). After the patient received 2 courses of DCF therapy, the lymph nodes where the recurrent occurred decreased in size(partial response), and SCC became within normal range. She received additional chemotherapy with 2 courses of DCF and achieved a complete response. Currently, she has been alive without recurrence for 7 years and 9 months after 4 courses of DCF therapy. We think that we can select DCF therapy as a first-line treatment for lymph node recurrence alone but not for CRT with FP.

Feasibility of International Proposed Standardized Enteral Connector for Semi-Solid Formula Feeding.

BACKGROUND/AIMS: The current study was undertaken to assess if the semi-solid formulas could be used with a new ENFit connector with similar force to current percutaneous endoscopic gastrostomy (PEG) tubes. METHODS: Experiment 1: We measured the applied pressure (force) needed to compress the syringe containing 7 viscous semi-solid formulas with a 20 Fr PEG tube and low-profile tube through the ENFit connector or the current connector. Experiment 2: This experiment was conducted to evaluate the compression force through 2 connectors in 3 infusion velocity, 7 PEG tube types with 2 semi-solid formulas. RESULTS: Experiment 1: The force needed to compress the syringe through the ENFit connector was higher in 3 semi-solid formulas with a 20 Fr low-profile tube; otherwise, there were no significant differences. Experiment 2: Each formula required a higher force in the ENFit connector in 6 settings out of 21. CONCLUSIONS: The ENFit connector will likely not show any remarkable change in the force to administer the semi-solid formula. However, a higher force was required under some conditions in the prototype ENFit connector. Further investigation of sensory test is needed to confirm the feasibility of the ENFit connector for using the semi-solid formulas.

Interstitial pneumonia in a patient treated with TAS-102 for metastatic colorectal cancer: a case report.

BACKGROUND: TAS-102, a new treatment option for patients with metastatic colorectal cancer that is refractory or intolerant to standard therapies, has been improving survival with acceptable tolerability and adverse events. Adverse hematological events associated with TAS-102 treatment were extensively profiled in the RECOURSE trial, but pulmonary toxicities associated with TAS-102 therapy are distinctly uncommon. In a recent early post-marketing phase vigilance on TAS-102 in Japan, seven cases of pulmonary disease were reported, but patient follow-up in this study was incomplete. Here, we present the first case of interstitial lung disease occurring in association with TAS-102 treatment. CASE PRESENTATION: A 57-year-old Japanese man who had previously received two standard treatments was admitted in 2014, at which time we administered TAS-102 (110 mg/day) as a third-line chemotherapy. He was safely treated with TAS-102 for the first planned cycle; however, approximately 4 days after receiving the second cycle of TAS-102, he complained of high fever and subsequent dyspnea with severe hypoxemia and went to the emergency room. A chest X-ray revealed diffuse coarse reticular shadows with ground-glass opacity on both lungs. Furthermore, a chest computed tomography scan showed thickening of the bronchovascular bundles with extensive ground-glass opacification and pleural effusions in both lung fields. In addition, a peripheral blood lymphocyte stimulation test with TAS-102 showed higher values compared with control samples. Consequently, we suspected drug-induced interstitial pneumonia, and discontinued treatment. Our patient was given an initial administration of high-dose methylprednisolone (1000 mg/day) for 3 days and oxygen. Our patient was discharged with oral prednisolone (20 mg/day) and improved symptomatically and radiologically. CONCLUSIONS: These findings suggest that interstitial pneumonia is a rare complication of TAS-102 chemotherapy, but the possibility of interstitial pneumonia should always be considered when a patient presents with a respiratory disorder while undergoing TAS-102 systemic chemotherapy. Prompt discontinuation of TAS-102 and treatment with high-dosage corticosteroids is needed to avoid exacerbating respiratory symptoms.

Preventive effects of amino-acid-rich elemental diet Elental® on chemotherapy-induced oral mucositis in patients with colorectal cancer: a prospective pilot study.

PURPOSE: The prospective pilot study was designed to evaluate the preventive effects of amino-acid-rich elemental diet (ED), Elental(®), on chemotherapy-induced oral mucositis in patients with colorectal cancer. The factors influencing its efficacy are also investigated. METHODS: A total of 22 eligible patients with colorectal cancer experiencing grade 1-3 oral mucositis during treatment with fluorouracil-based chemotherapy entered the current study. Their average age was 67 years. There were 10 male and 12 female. The PS was 0 in the majority of patients. Patients received two courses of the same chemotherapy regimen and Elental(®) concurrently after recovery to grade 0 or 1 oral mucositis. RESULTS: FOLFOX6 + bevacizumab in 8 patients, FOLFIRI + bevacizumab in 8 patients, FOLFIRI + panitumumab in 1 patient, FOLFIRI in 1 patient, XELOX + bevacizumab in 2 patients, and S-1 + cetuximab in 2 patients were used as first-line (16 cases) or as second-line (6 cases) chemotherapy. Dose reduction of 5-fluorouracil (5-FU) or oral fluoropyrimidine was performed in the 2 patients achieving grade 3 oral mucositis and in the 3 patients achieving grade 2 oral mucositis. The maximum grade of oral mucositis decreased in 18 of the 22 patients during the first treatment course with Elental(®) (p = 0.0002) and in 20 of the 22 patients in the second course (p < 0.0001). Multivariate analyses found that the dose reduction in 5-FU or oral fluoropyrimidine, ED intake, and the prior administration of ED were each a significant factor for the preventive efficacy on oral mucositis. CONCLUSION: The amino-acid-rich elemental diet Elental(®) may be useful as a countermeasure for 5-FU-based chemotherapy-induced oral mucositis in patients with colorectal cancer.

[Stevens-Johnson syndrome induced by regorafenib in a patient with progressive recurrent rectal carcinoma].

A 55-year-old man with rectal carcinoma underwent lower anterior resection. Eight years after surgery, multiple metastases were detected in the liver, lung, and abdominal lymph nodes. The metastatic cancers were resistant to standard chemotherapy. Thus, regorafenib was administered to the patient. The patient presented symptoms of Stevens-Johnson syndrome (SJS) nine days after regorafenib administration, and hence, treatment was terminated. To treat SJS, he received oral and topical steroid therapies. SJS is an important adverse event that hinders the continuation of regorafenib treatment. Thus, it is necessary to continually check the patient's skin condition carefully, especially at early stages of treatment. To our knowledge, this is the first report of SJS arising during the course of regorafenib treatment.

Ultrasound-guided rectus sheath block for single-incision laparoscopic cholecystectomy.

INTRODUCTION: Single-incision laparoscopic cholecystectomy (SILC) is increasingly applied for cholecystectomy and has been reported as safe and feasible, with short-term operative outcomes equivalent to four-port cholecystectomy. Although many investigators in randomized studies have noted the cosmetic advantages of SILC, the benefit of decreased pain in SILC remains controversial. Therefore, this study aimed to assess the efficacy of the rectus sheath block in SILC with respect to subjective pain. METHODS: From April 2010 to March 2012, 75 patients with symptomatic gallstone or gallbladder polyps were assigned to one of three groups: (i) four-port laparoscopic cholecystectomy (n = 29); (ii) SILC (n = 15); and (iii) rectus sheath block in SILC (n = 30). We evaluated the operative details, length of hospital stay, and the need and usage of analgesia. Postoperative pain was recorded at 2, 6, 12, and 24 h after surgery based on a visual analog scale. RESULTS: There was no difference with regard to age, ASA score, BMI, duration of operation, or length of hospital stay among the three groups. A significantly lower pain score was observed in the rectus sheath block in SILC group than in the SILC group at 2 and 6 h after operation. The pain score and need for analgesia were similar between the SILC group and the four-port cholecystectomy group. CONCLUSION: SILC using an ultrasound-guided rectus sheath block significantly reduces postoperative pain.

Effect of preoperative administration of methylpredonisolone and ulinastatin on tumor cell metastasis after surgical stress.

Using a rat laparotomy stress model, we conducted a comparative analysis of postoperative organ metastasis after administration of ulinastatin (UTI) or methylprednisolone (MP), which have an inhibitory effect on cytokine production. The subjects were classified into 4 groups: 1) minimal laparotomy group (C group), 2) major laparotomy group (L group), 3) preoperative MP intravenous administration + major laparotomy group (MP group), and 4) preoperative UTI intravenous administration + major laparotomy group (UTI group). Either MP or UTI was administered intravenously before surgery, and RI-labeled cells were injected into the portal vein immediately after laparotomy to collect tissue specimens in order to measure radiation dosage. Then, the concentrations of serum IL-2 and IL-6, liver interleukin 1 beta (IL-1ß) and interleukin 10 (IL-10), and liver E-selectin were measured. In addition natural killer cell, (NK cell) activation and neoplastic nodules on the liver surface at 3 weeks after surgery were also measured. The adhesion rate of malignant cells to the liver was higher in the L group than in the C group, higher in the MP group than the L group, and lower overall in the UTI group. The concentration of IL-1ß and IL-6 were decreased in the MP and UTI groups compared to the L group. IL-2 was decreased significantly in the MP group compared with the C and L groups. E-selectin expression level decreased in the UTI group compared with the L group. NK cell activation decreased in the MP group compared with the C group and L group, but no differences were observed between the UTI and L groups. The number of tumor nodules on the surface of the liver increased in the MP group compared with the L group, and decreased in the UTI group compared with the L group. Postoperative alleviation of invasive reaction was suggested in both the MP and UTI groups. However, preoperative administration of MP increased metastasis while that of UTI inhibited metastasis. MP was considered to have decreased anti-tumor immunocompetence and promoted metastasis, while UTI was considered to have inhibited the expression of adhesive molecules and decreased metastasis.

Heat-shock pre-treatment reduces liver injury and aids liver recovery after partial hepatectomy in mice.

BACKGROUND: Heat-shock proteins (HSPs) are members of a chaperone protein family reported to modify stress responses. The aim of this study was to clarify the hypothesis of whether pre-treatment with heat shock reduces liver damage and influences liver regeneration after partial hepatectomy. MATERIALS AND METHODS: Mice (N=6) were divided into two groups: the control group underwent partial hepatectomy without heat shock pre-treatment, the heat shock (HS) group underwent partial hepatectomy 12 hours after pre-treatment with heat shock. Mice were sacrificed at different time points after hepatectomy, remnant liver and blood were collected for further analyses in blood samples and liver tissues. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin-6 (IL6), and tumor necrosis factor-alpha (TNFα) were measured using enzyme-linked immunosorbent assay (ELISA). We used tissue samples for several experiments: staining by 5-bromo-2-deoxyuridine (BrdU), evaluation of cytokines, transcription factors and signal-transduction associated proteins. RESULTS: HSP70 levels in the liver were clearly increased from 6 h to 72 h after heat shock treatment. Serum ALT and AST levels were significantly reduced in the HS group compared to the control group after partial hepatectomy. Liver regeneration rate and BrdU labeling index were significantly higher in the HS group than in the control group after partial hepatectomy. IL6 and TNFα in serum and liver tissues were significantly reduced in the HS group compared to the control group after hepatectomy. We did not detect phosphorylation of signal transducer and activator of transcription-3 (STAT3) protein by western blotting. Binding activities of transcription factors: nuclear factor-interleukin-6 (NF-IL6) and nuclear factor-kappa B (NF-kB) were significantly lower in the HS group than in the control group after hepatectomy. CONCLUSION: Pre-treatment with heat shock appears to reduce liver injury and promote liver regeneration, as HSP70 can reduce the inflammatory response and up-regulate liver regeneration without IL6 STAT signaling pathway in the liver after partial hepatectomy.

Multicenter Phase II Study of a New Effective S-1 and Irinotecan Combination Schedule in Patients with Unresectable Metastatic or Recurrent Colorectal Cancer.

INTRODUCTION: This multicenter phase II study determined the efficacy and safety of new daily oral S-1 and weekly irinotecan (CPT-11) combination schedule in patients with previously untreated advanced or recurrent colorectal cancer. PATIENTS AND METHODS: Patients received first-line chemotherapy comprising S-1 80 mg/m(2)/day given on days 3 to 7, 10 to 14, and 17 to 21 and 60 mg/m(2) CPT-11 administered intravenously on days 1, 8, and 15 of a 28-day cycle. RESULTS: A total of 45 eligible patients were enrolled in this study. The overall response rate was 48.9%. Median progression-free survival and median overall survival was 8.1 months and 20.9 months, respectively. The rates of grade 3 or 4 toxicity were as follows: neutropenia, 8.9%; anemia, 4.4%; anorexia, 6.7%; and diarrhea, 6.7%. CONCLUSIONS: This new S-1 and irinotecan combination schedule appeared to be an effective, well-tolerated, and convenient regimen in patients with advanced colorectal cancer as compared with conventional regimens such as FOLFIRI and IRIS.

Randomized controlled trial comparing antioxidant-enriched enteral nutrition with immune-enhancing enteral nutrition after esophagectomy for cancer: a pilot study.

PURPOSE: The objective of this study was to compare the effects of two types of enteral supplements, an antioxidant-enriched enteral nutrition (AeEN) and an immune-enhancing enteral nutrition (IeEN), on the nutrition, immunoinflammatory response, antioxidant capacity and clinical outcomes in patients after esophagectomy for cancer. METHODS: Patients (n = 20) undergoing esophagectomy for cancer were randomized in this single-center, open-label study. Two types of enteral supplements were used for 5 days before surgery and 7 days after surgery. The circulating levels of nutritional markers, immunoinflammatory markers, oxidative stress markers, and the antioxidant capacity were compared throughout the perioperative period, and the patients' clinical outcomes were also compared. RESULTS: The circulating levels of nutritional markers decreased after surgery, but the changes were not significantly different between the AeEN group and the IeEN group throughout the perioperative period. Surgery increased the immunoinflammatory markers, and the levels were not significantly different between the groups after surgery. Surgery also increased the levels of oxidative stress markers, but there were no significant differences between the groups throughout the study period. CONCLUSIONS: The results of this pilot study suggest that AeEN and IeEN have a similar effect on nutrition, the immunoinflammatory response, antioxidant capacity and clinical outcomes after esophagectomy for cancer. These findings, therefore, warrant further studies on a larger scale.

The effect of starvation on blood stream cancer cell metastasis to the liver in rat after laparotomy.

BACKGROUND: Preoperative malnutrition worsens the prognosis of cancer patients. However, it is not certain how preoperative malnutrition affects postoperative hematogenous metastasis. We examined the influence of preoperative starvation on liver metastasis in rats using intra-vascular injection of AH109A hepatoma cells. METHODS: Male donryu rats were divided into Fasting and Control groups. Rats received laparotomy and (125)I-iodo-deoxyuridine labeled AH109A hepatoma cells were inoculated via superior mesenteric vein. Radioactivity in the organs, macroscopic liver metastasis, white blood cell count, leukocyte count, NK cell activity, endogenous serum corticosterone and ACTH concentration and mRNA expression of cytokine in the liver and brain were evaluated at certain time points. RESULTS: 48hours preoperative starvation reduced body weight and induced a state of malnutrition. Accumulation of radioactivity in the liver was more than 4 times higher, and the number of liver metastases was 3.5 times higher in the Fasting than in the Control group. Preoperative starvation caused an almost 2 fold increase in plasma endogenous corticosterone levels and a 66% reduction in white blood cell and lymphocyte counts. Postoperative hypothalamus pituitary adrenal axis response was preserved. In addition, inflammatory cytokine expression in the liver was suppressed in the starved animals, suggesting that preoperative starvation led to a state of cellular immunosuppression, which would be an important factor for liver metastasis. CONCLUSION: Preoperative malnutrition by 48 hours starvation reduced inflammatory cytokine response and cellular immunity, resulting in an increase in hematogenous liver metastasis.

[A trial using maximum preoperative chemotherapy for metastatic colorectal cancer].

There are chemotherapy methods applied before operation, before and after operation, or after operation for metastatic colorectal cancer. But the correct times and periods, etc., for their administration have not been obvious. We perform maximum preoperative chemotherapy to control micrometastases, and afterwards surgically remove the metastatic lesions[including radiofrequency ablation(RFA)]. Complications after operation and the severity of pathological liver damage etc., were investigated by comparing 14 patients who received maximum preoperative chemotherapy(group A), with 4 patients for whom 6 courses of FOLFOX+bevacizumab(BV)therapy(group B)were planned. ICG15 before liver resection and bleeding during liver resection were not significantly different(p=0. 26 and p=0. 60, respectively). No severe complication after operation was seen and pathological liver damage was minor in both groups. No interference of maximum preoperative chemotherapy with BV to metastatic colorectal cancer was suggested from the point of view of complications after operation and the severity of pathological liver damage. Further investigation with many more patients is necessary.

[A case of remnant liver metastases after resection of liver metastases from rectal cancer following treatment with 5-FU, L-OHP and CPT-11, with markedly effective treatment by cetuximab plus S-1].

FOLFOX or FOLFIRI are commonly used as first- or second-line chemotherapy for unresectable colorectal cancer or its metastases.Recently, it had become a trend to add bevacizumab or cetuximab(Cmab)limited to the K-ras wild-type or panitumumab(Pmab)limited to the K-ras wild-type.At the present time, a common third-line chemotherapy is CPT-11 plus Cmab limited to the K-ras wild-type, or Cmab/Pmab.However, the results are unsatisfactory.With Cmab plus S-1 we treated a case of remnant liver metastases from rectal cancer which was a K-ras wild-type, after treating 5-FU, L-OHP and CPT-11. The tumor marker dropped and 7 focuses of liver metastases disappeared after 6 courses of treatment(complete response: CR in)and CR was achieved after 9 courses treatment.After 10 courses of treatment, a new lesion appeared on S5 of the liver and we performed percutaneous radiofrequency ablation.

[Efficacy of Elental on prevention for chemotherapy-induced oral mucositis in colorectal cancer patients].

BACKGROUND: The present study was designed to evaluate the preventive effects of elemental diet Elental (ED) on chemotherapy-induced stomatitis in patients with colorectal cancer. MATERIALS AND METHODS: A total of 23 patients with colorectal cancer experiencing grade 1-3 stomatitis during treatment with chemotherapy (2- or 3-week per cycle) entered the current study. Their average age was 67 years, ranging from 44 to 84 years. RESULTS: A total of 22 patients received the same chemotherapy regimen, but also received more than 80 g of Elental (ED) (including 1, 932 mg of L-glutamine), per day. FOLFOX, FOLFIRI or XELOX-based chemotherapy was used. A dose reduction of 5-FU, capacitabine or S-1 was performed in 5 patients who experienced grade 2 or 3 stomatitis. The maximum grade of stomatitis decreased in 18 of the 22 patients after the first treatment course, and decreased in 20 of 22 patients after the second course with ED.The preventive efficacy of ED on stomatitis was noted in a dose-dependent manner.Similarly, the maximum grade of neutropenia decreased in 10 of 11 patients after their first or second treatment course with ED. CONCLUSION: We conclude that ED can significantly decrease the severity of chemotherapy-induced stomatitis in colorectal cancer patients in association with the control of neutropenia.

[Liver histology and surgical outcomes after preoperative chemotherapy in colorectal cancer liver metastases].

We aimed to assess hepatic histopathological responses to preoperative chemotherapy in patients with colorectal liver metastasis. We selected all patients(n=34)with colorectal liver metastases between September 2006 and March 2009. The preoperative chemotherapy group was significantly associated with tumor regression, inflammatory response, sinusoidal dilatation compared with non-chemotherapy group. There was no difference in the rate of postoperative complications and hospital stay. Prolonged preoperative systemic chemotherapy alters liver parenchyma, but it does not increase postoperative complications. This should be taken into consideration before deciding a major liver resection in patients who have received preoperative chemotherapy.

Circulating endothelial progenitor cells in metronomic chemotherapy using irinotecan and/or bevacizumab for colon carcinoma: Study of their clinical significance.

The aim of the present study was to clarify the antitumor efficacy of metronomic chemotherapy using irinotecan (CPT-11) combined with or without bevacizumab against colon cancer, and the significance of circulating endothelial cell (CECs) and endothelial progenitor cells (CEPs) as a surrogate marker for metronomic chemotherapy. KM12SM cells were implanted into the subcutis of nude mouse. After confirming that the implanted tumors had grown 5 mm in size, group A received an intraperitoneal injection of 40 mg/kg CPT-11 every two weeks for 4 weeks [conventional maximum-tolerated dose (MTD)], group B received 10 mg/kg twice weekly (metronomic), group C received 10 mg/kg twice weekly combined with 5 mg/kg bevacizumab twice weekly (metronomic + anti-angiogenic), and the control group received 0.2 ml of PBS every week. Serial changes of CECs and CEPs in peripheral blood and microvessel density (MVD) in the tumor tissues were evaluated. The results showed that the antitumor activity in group B and in group C was significantly higher than that in group A. A significant inhibition in CEPs on day 15 in the metronomic therapy groups B and C was noted when compared to that in the control group, while there was no significant difference in CECs and CEPs between the groups on days 4 and 8. The MVD on day 15 in metronomic groups was significantly lower than that in group A. In conclusion, metronomic chemotherapy of CPT-11 with or without bevacizumab for colon cancer was more effective than the MTD therapy via anti-angiogenic effects. Sequential measurement of CEPs may be a predictive factor for the efficacy and a decisive factor for the optimal dose of metronomic therapy in colon cancer.

Increased claudin-1 protein expression contributes to tumorigenesis in ulcerative colitis-associated colorectal cancer.

BACKGROUND: The molecular and morphological alterations of the tight junctions in ulcerative colitis (UC)-associated colorectal cancer are still poorly understood. The possible involvement of claudin-1 (CL-1), one of the major tight junctional proteins, was investigated in the tumorigenesis of UC-associated CRC. PATIENTS AND METHODS: A total of 39 patients with UC underwent surgical treatment from January 2001 until October 2009 at Kurume University Hospital in Fukuoka. CRC tissue specimens were analyzed to determine whether the expression of CL-1 correlates with clinicopathological factors and to determine the role of CL-1 and ß-catenin in the alteration of tight junctions during tumorigenesis. RESULTS: The operations were 30 of elective surgery and 9 of emergency surgery. Colectomy was performed in five patients (12.8%) because of UC-associated CRC, and in another patient (2.6 %) because of high-grade dysplasia. The immunostaining pattern of the high-grade dysplasia and UC-associated CRC for CL-1 showed much stronger and more diffuse staining in comparison to the normal or UC colonic mucosa. The expression of ß-catenin was also positive or up-regulated in all of the UC-associated CRC and high-grade dysplasia tissue specimens. CONCLUSION: These observations suggested that CL-1 plays a pivotal role in the regulation of cellular morphology and behavior in UC. We speculate that increased CL-1 expression may be involved in the early stages of transformation in UC-associated neoplasia. CL-1 protein may therefore be a good candidate for surveillance of patients with UC.