Clinical Utility and Characteristics of the LARS Score Compared to the CCIS.

PURPOSE: The low anterior resection syndrome (LARS) score (LS) has been widely validated and has become an international tool for evaluating postoperative bowel dysfunction. However, many physicians still use the conventional incontinence scores in LARS treatment. Moreover, interpretation of LS and its relationship with conventional incontinence scores are not yet well understood. Here we compared the LS with the Cleveland Clinic Incontinence Score (CCIS) to clarify the clinical utility and characteristics of the LARS score. METHODS: We performed a multicentre observational study, recruiting 246 rectal cancer patients following sphincter-preserving surgery. Patients completed the LS, CCIS, and SF36 questionnaires. RESULTS: The response rate was 76.4%, and a total of 180 patients were analysed. The LS was strongly correlated with the CCIS (P < 0.001, rs = 0.727). However, among 116 patients determined to not have incontinence (CCIS 0-5), 51 (44%) were diagnosed with LARS (29 with minor LARS and 22 with major LARS). Among 68 patients without LARS, only 3 were diagnosed as having incontinence (CCIS > 6). In comparison with background factors, aging and elapsed time were associated with only LS. High LS and CCIS both showed significant quality-of-life impairment as assessed by the SF-36. CONCLUSION: This is the first study to determine the difference in the numeric values between the CCIS and LS. The LS can be a convenient tool for LARS screening, identifying a wide range of patients with LARS, including those with incontinence evaluated by CCIS. Assessment using the CCIS may often underestimate LARS.

Incidental thyroid "PETomas": clinical significance and novel description of the self-resolving variant of focal FDG-PET thyroid uptake.

BACKGROUND: Recent series of incidental thyroid activity on fluorodeoxyglucose positron emission tomography (FDG-PET) in patients evaluated for nonthyroidal malignancy, which we refer to as a "PEToma," have suggested that such lesions are associated with a significant incidence of primary thyroid cancer. METHODS: We retrospectively reviewed 6457 FDG-PET scans performed on 4726 patients from May 2004 to March 2007. We reviewed the cases of patients whose PET or computed tomography (CT) radiology reports described PET uptake within the thyroid to identify incidence and malignant potential of PETomas and evaluate their clinical and histopathologic features. RESULTS: We found that 160 patients (3.4%) had incidental, abnormal FDG uptake in the thyroid gland, 103 of whom had focal uptake (the PEToma group). Of these patients, 50 (48%) underwent further investigations, including ultrasonography in 48, fine-needle aspiration cytology in 38 and computed tomography in 3. Ten patients underwent surgery, and papillary thyroid cancer was identified in 9. The remaining 53 patients with PETomas underwent no further investigation. Interestingly, 5 patients who had focal uptake within the thyroid showed either spontaneous resolution on repeat FDG-PET (self-resolving) or no focal lesion on subsequent ultrasonography (false-positive). CONCLUSION: The incidence of papillary thyroid cancer in the present series is similar to that in the literature. Although some patients will show self-resolving or false-positive focal thyroid uptake on FDG-PET, we believe that, if the patient's clinical status permits, the evaluation of patients with incidental thyroid PEToma should include ultrasonographic confirmation and fine-needle aspiration cytology.

Mucosal lymphatic vessels of the esophagus distant from the cancer margin: morphometrical analysis using 27 surgically removed specimens of squamous cell carcinoma located in the upper or middle thoracic esophagus.

PURPOSE: To clarify the configuration of the esophageal mucosal lymphatics distant from cancer using D2-40 immunohistochemistry. METHODS: D2-40 immunohistochemistry for human lymphatic epithelium was performed at sites about 10 cm anal from the pathologically examined margin of upper or mid- thoracic squamous cell carcinoma (27 patients). We measured the entire length of mucosal lymphatic vessels within a x10 objective field (1.2 mm along the muscularis mucosae). RESULTS: The present morphometrical study demonstrated significant individual differences in the amount of mucosal lymphatic vessels, within a range of more than 10-fold (8.4 mm-0.8 mm within an objective field). However, the difference in length of the mucosal lymphatic epithelium did not correlate with either N-factor, T-factor including cancer depth or prognosis. CONCLUSION: A higher density of pre-existing mucosal lymphatic vessels may not always be correlated with larger numbers of nodal metastases. Lymphatic proliferation or dilation induced by cancer seems to occur irrespective of whether pre-existing vessels are rich or sparse.

Inhibition of osteopontin reduces liver metastasis of human pancreatic cancer xenografts injected into the spleen in a mouse model.

PURPOSE: Pancreatic cancer is associated with the poorest prognosis of any digestive cancer due to the high incidence of liver metastasis. This study evaluated the possibility that osteopontin (OPN) RNA interference (RNAi) and anti-OPN antibody (Ab) could have antimetastatic effects. METHODS: The differential gene expression was measured in a parental cell line, HPC-3, and an established highly liver metastatic cell line, HPC-3H4. This study investigated the effect of OPN RNAi and anti-OPN Ab on the metastatic ability of HPC-3H4 to the liver. An OPN RNAi-expressing vector was introduced into HPC-3H4 cells (HPC-3H4/miOPN), in which OPN production was reduced to the level of the parental HPC-3 cells. Finally, the ability of anti-OPN Ab to suppress liver metastasis was investigated. RESULTS: Osteopontin was upregulated 11.1-fold in HPC-3H4 in comparison to HPC-3. The metastatic rate of HPC-3H4/miOPN was significantly reduced to 25% in comparison to the 100% metastatic rate of HPC-3H4 and control HPC-3H4/miNeg cells (P < 0.01). The metastatic rate of the group given anti-OPN Ab was 50%. CONCLUSION: OPN RNAi and anti-OPN Ab had remarkable inhibitory effects against liver metastasis by the pancreatic cancer cell line.

A new liver metastatic and peritoneal dissemination model established from the same human pancreatic cancer cell line: analysis using cDNA macroarray.

To elucidate the mechanisms of metastasis, we established two sublines HPC-1H5 with a highly liver metastatic cell line and HPC-1P5a with a highly peritoneal disseminating cell line, which were sequentially selected from the parental pancreatic cancer cell line HPC-1. Using these three cell lines, we investigated several biological properties and mRNA levels of differentially-expressed genes involved in cancer metastasis by cDNA macroarray. Microscopic findings for the three cell lines were the same. The tumorigenicity, in vitro growth ability, motile activity, adhesive activity and the production of IL-8 of metastatic sublines were higher than those of parental HPC-1 cells. Particularly, HPC-1H5 cells showed clearly higher levels of IL-8 expression and tumors of HPC-1H5 cells grew faster and bigger than those of HPC-1P5a cells. In cDNA macroarray analysis of HPC-1H5 cells, 22 genes were up-regulated and 44 genes were down-regulated compared with parental HPC-1 cells. In HPC-1P5a cells, 9 genes were up-regulated and 28 genes were down-regulated compared with parental HPC-1 cells. This study provides a demonstration of global gene expression analysis of pancreatic cancer cells with liver metastasis and peritoneal dissemination. Furthermore, our results provide a new insight into the study of liver metastasis and peritoneal dissemination of human pancreatic cancer.

A novel nude mouse model of liver metastasis and peritoneal dissemination from the same human pancreatic cancer line.

INTRODUCTION: Recently, several mice models have been used for investigating cancer metastasis. However, there are no metastatic and peritoneal dominated variants from the same parental cell line. AIM AND METHODOLOGY: To elucidate the mechanisms of metastasis, we established highly liver metastatic and peritoneal disseminated models in nude mice, and then characterized several factors related to metastasis in these cells. We established a series of well-characterized sublines that showed metastatic potentials to different organ sites of nude mice. Two sublines were selected sequentially from the parental pancreatic cancer cell line, HPC-4, resulting in a highly liver metastatic cell line, HPC-4H4, and a highly peritoneal disseminated cell line, HPC-4P4a. Using these three cell lines, we investigated several biologic properties and mRNA levels of differentially expressed genes involved in cancer metastasis. RESULTS: The tumorigenicity, the motile activity, and the adhesive activity of metastatic sublines were higher than those of parental HPC-4 cells. Macroscopic and microscopic findings and the DNA ploidy pattern were the same among the three cell lines. In addition, HPC-4H4 cells expressed clearly higher levels of vascular endothelial growth factor and IL-8 expression than did HPC-4P4a cells. In fluorescence-activated cell sorter analysis of adhesion molecules, the expression of integrin-alpha2 was enhanced in HPC-4 cells, integrin-alphavbeta5 was enhanced in HPC-4H4 cells, and integrin-alpha3 was enhanced in HPC-4P4a cells. Osteopontin, vascular endothelial growth factor, and hepatocyte growth factor were among the genes that were upregulated in HPC-4H4 cells compared with HPC-4P4a cells. HPC-4P4a cells did not metastasize to the liver by intrasplenic injection. Conversely, HPC-4H4 cells metastasized remarkably to the peritoneum by intraabdominal injection. CONCLUSION: These sublines are the first reported liver metastatic and peritoneal disseminated models derived from the same parental cell lines. The results of our study suggest that the process of hematogenous metastasis is not the same as that of peritoneal dissemination.

Gastric T-cell lymphoma associated with hemophagocytic syndrome.

BACKGROUND: Lymphoma-associated hemophagocytic syndrome (LAHS) occurs in mostly extra nodal non-Hodgkin's lymphoma. LAHS arising from gastrointestinal lymphoma has never been reported. Here we report a case of gastric T-cell lymphoma-associated hemophagocytic syndrome. CASE PRESENTATION: A 51-year-old woman presented with pain, redness of breasts, fever and hematemesis. Hematological examination revealed anemia. Gastroscopy revealed small bleeding ulcers in the stomach and the computed tomography scan showed liver tumor. She underwent total gastrectomy for gastrointestinal bleeding and the histopathology revealed gastric T-cell lymphoma. She continued to bleed from the anastomosis and died on the 8th postoperative day. Autopsy revealed it to be a LAHS. CONCLUSIONS: If Hemophagocytic syndrome (HPS) occurs in lymphoma of the gastrointestinal tract, bleeding from the primary lesion might be uncontrollable. Early diagnosis and appropriate treatment are needed for long-term survival.

A simple and safe procedure to repair rectal prolapse perineally using stapling devices.

Rectal prolapses are not life-threatening, however the bleeding and fecal incontinence associated with them significantly erode quality of life and can cause concern among patients' caregivers in nursing homes. Many procedures have been reported that repair rectal prolapses, and the procedure used depends on the severity of the prolapse; however, the treatments are yet to be established. Here we report a simple and safe procedure to repair rectal prolapse perineally using stapling devices. We performed this procedure on 5 patients within a short time. All patients were followed up for over 24 months and none had any recurrences of their rectal prolapses. No complications occurred during the operations and postoperative periods. Most patients who have prolapses are elderly and fragile, so the treatment must be easy, safe, and rapid. While rectal prolapse is not life-threatening, the goal of treatment is to alleviate its symptoms. The procedure we describe is consistent with this concept. We suggest that this procedure, which uses surgical stapling devices, might be a better option for the treatment of complete rectal prolapse. We will continue to surgically correct complete rectal prolapses and investigate the long-term outcomes of the procedure.

Inhibitory effect of endothelin A receptor blockade on tumor growth and liver metastasis of a human gastric cancer cell line.

BACKGROUND: With metastatic progression, gastric cancer is incurable. Using a DNA microarray, we performed differential gene expression analysis of established highly metastatic gastric cancer cell lines and compared the findings with those from a low-metastatic parental cell line. The results demonstrated that the endothelin A receptor (ET-A) gene was the only one from the highly metastatic cell lines that was generally up-regulated. METHODS: To investigate the role that ET-A plays in gastric cancer metastasis, we studied the effect of an ET-A-selective antagonist, YM598, on cell proliferation, tumor growth, and liver metastasis of the highly liver metastatic cell line AZ-H5c, established from the low metastatic human gastric cancer cell line AZ-521. RESULTS: An in vivo study using nude mice demonstrated that YM598 had a significant growth inhibition effect on AZ-H5c at doses of 0.5-10.0 mg/kg. The liver metastatic rate was also significantly reduced by YM598: control, 83.3%; 1 mg/kg dosage, 16.7%; 10 mg/kg, 20%; and pretreatment at 1 mg/kg, 16.7%. There was no evidence of gross toxicity resulting from the YM598 treatment. CONCLUSION: The ET-A blockade by YM598 had a strong inhibitory effect against tumor growth and liver metastasis of the gastric cancer cell lines. These data suggest that YM598 has potential as a novel therapeutic agent for inhibiting liver metastasis of gastric cancer.

A novel, easy, and safe technique to repair a stoma prolapse using a surgical stapling device.

A stoma prolapse is one of the late complications and often occurs when the stoma is made in an emergency situation. This complication is not lethal, but causes irritable stoma, skin trouble, and difficulty in stoma care. We herein report the case of a 48-year-old female with an end colostomy that was created as an emergency operation 4 months before. On admission, her colostomy protruded approximately 20 cm from the skin with marked redness, swelling, and erosion; it was impossible to treat manually. We repaired the prolapse successfully in a simple procedure with a Proximate Linear Cutter 100. Briefly, under mild sedation, the instrument was diagonally inserted into the prolapsed stoma and applied twice on both sides. Then, the base of each divided tissue was stapled and cut with the same device. Finally, the prolapse was completely repaired without major bleeding and severe pain. We have applied this novel technique successfully in 5 further cases, and there have been no complications or recurrences. This technique can be performed without spinal or general anesthesia and seems to be a very useful procedure for patients with prolapse of a stoma.

Biliary tract malignancy and chronic inflammation from the perspective of pancreaticobiliary maljunction.

This is a brief review of pancreaticobiliary maljunction. The basic treatment for this condition includes either cholecystectomy or extrahepatic bile duct resection. When the condition is accompanied by malignancies, a radical operation should be the first treatment option. Knowledge on molecular pathogenesis is gradually increasing. However, studies should be expanded to include larger patient cohorts, and other types of molecules should be carefully investigated and analyzed.

Vesico-ileosigmoidal fistula caused by diverticulitis: report of a case and literature review in Japan.

Enterovesical fistula is a relatively uncommon complication of colorectal and pelvic malignancies, diverticulitis, inflammatory bowel disease, radiotherapy, and trauma in Asian countries. A case of vesico-ileosigmoidal fistula and a literature review of this disease in Japan are presented. A 70-yr-old male was referred with complaints of urinary pain and pneumaturia. On admission, urinary tract infection and pneumaturia were presented. A barium enema demonstrated multiple diverticulum in his sigmoid colon and the passage of contrast medium into the bladder and ileum. Under the diagnosis of vesico-ileosigmoidal fistula due to suspected diverticulitis of the sigmoid colon, sigmoidectomy and partial resection of the ileum with partial cystectomy were performed. The histopathology revealed diverticulosis of the sigmoid colon with diverticulitis and development of a vesico-ileosigmoidal fistula. No malignant findings were observed. Until the year 2000, a total of 173 cases of vesico-sigmoidal fistula caused by diverticulitis had been reported in Japan. Pneumaturia and fecaluria are the most common types, presenting symptoms in 63% of the cases. Computed tomography, with a sensitivity of 40% to 100%, is the most commonly used diagnostic study. For patients with vesico-sigmoidal fistula, resection of the diseased sigmoid colon and partial cystectomy with primary anastomosis are the safest and most acceptable procedures, leading to the best results.

Giant peritoneal loose body in the pelvic cavity: report of a case.

This report describes a giant peritoneal loose body in the pelvic cavity. A 63-year-old man who was asymptomatic underwent a routine medical examination, which revealed a tumor in the pelvic space. Computed tomography and magnetic resonance imaging showed a smooth-surfaced mass with two marked calcifications in the central position. Preoperatively, we suspected a calcified leiomyoma originating from the wall of the sigmoid colon; however, at laparoscopic surgery we extracted a hard, egg-shaped mass 5 cm in diameter, with detached appendices epiploicae. Histological examination revealed that this peritoneal loose body was made up of thick layers of fibrous tissue with a few cellular components, and necrotic fat tissue in the central position. Small peritoneal loose bodies are occasionally found during laparotomy or autopsy, but such a large one is very unusual.

Endo-bowel clamp (PL540S) for safe rectal irrigation in laparoscopy-assisted rectal resection.

We describe a technique of rectal irrigation using an endo-bowel clamp (PL540S) in laparoscopy-assisted rectal resection. One of the major concerns associated with current techniques of laparoscopy-assisted rectal resection is accidental tumor spillage because it is difficult to perform the necessary procedures without grasping and manipulating the bowel and mesorectum near the tumor. Therefore, sufficient intraoperative rectal irrigation is essential for preventing intraluminal implantation of rectal cancer. However, this can be difficult, especially if the tumor is located in the rectum. By placing a PL540S before transection, it is possible to occlude the rectum completely and irrigate it effectively. We think that the PL540S is a valuable device in laparoscopic surgery for rectal cancer.

Septic thrombophlebitis of the portal and superior mesenteric veins as a complication of appendicitis: report of a case.

Pylephlebitis is extremely rare and associated with high mortality, even in this modern era. It usually occurs secondary to infection in the region drained by the portal systems or in the structure contiguous to the portal vein. We report a case of septic thrombophlebitis of the portal and superior mesenteric veins (SMV) with multiple liver abscesses caused by acute appendicitis with an abscess of the mesoappendix. We performed appendectomy and successfully removed the thrombi using a Fogarty catheter. Postoperative histopathological examination confirmed a diagnosis of appendicitis and septic thrombophlebitis of the portal vein and SMV. The patient recovered completely with appropriate medical and surgical treatment.

Gene expression screening using a cDNA macroarray to clarify the mechanisms of peritoneal dissemination of pancreatic cancer.

PURPOSE: Pancreatic cancer is associated with the poorest prognosis of any digestive cancer due to the high incidence of peritoneal dissemination, which is the cause of death in most cases. To determine the mechanisms of peritoneal dissemination in pancreatic cancer, we established a mouse model of high peritoneal dissemination. METHODS: A novel highly peritoneal-disseminating cell line was established from the human pancreatic cancer cell line; CAPAN-1. The new cell line, CAPAN-1P4a, was established from CAPAN-1 by repeated in vivo selection (four times) of the tumor cell line. To clarify the candidate genes implicated in peritoneal dissemination of pancreatic cancer, global gene expression screening was done using a cDNA macroarray. RESULTS: CAPAN-1P4a cells showed 100% metastasis 3 weeks after injection and high reproducibility in the inoculated mice. Twenty-seven genes were upregulated and 14 genes were downregulated in CAPAN-1P4a cells compared with CAPAN-1 cells. The genes differentially expressed in the two cell lines were included as tumor suppressor/apoptosis genes, regulatory transcription factor, membrane receptors, cell adhesion protein, membrane receptors, and so on. CONCLUSIONS: Our established CAPAN-1P4a model offers a new means of conducting global gene expression analysis of pancreatic cancer cells with peritoneal dissemination and it has the potential to provide new insights into the mechanism of peritoneal dissemination in human pancreatic cancer.

Transanal repair of rectourethral fistula after a radical retropubic prostatectomy: report of a case.

Rectourethral fistula occurred in a 64-year-old man after a radical prostatectomy. Despite conservative treatment the fistula did not close spontaneously. Eleven months after the original prostatectomy, an operation was performed. We chose the Latzko technique with slight modifications as follows. The patient was placed in the prone jackknife position. The fistula was found at a site about 6.0 cm from the anal verge. An elliptical area of rectal mucosa was incised about 1.5 cm from the fistulous orifice and subsequently the rectal mucosa was denuded. The submucosa was dissected above the fistula about 2.0 cm from the edge of the incision. The fistula was then closed with one layer of side-by-side absorbable 2-0 polyglactin sutures. The dissected rectal mucosal flap was brought down over the fistula and sutured in one layer to the distal edge of the rectal muscularis propria through the mucosa with 3-0 polyglactin sutures. On postoperative day 21 a retrograde urethrogram was made and it showed no leakage of urine via the rectum. This procedure is a simple, effective, and minimally morbid technique for the repair of rectourethral fistula after a radical prostatectomy, although it is only useful for the treatment of low rectourethral fistulas.

Malignant melanoma of the anorectum: report of four cases.

Four cases of anorectal malignant melanoma are reported in this paper. All patients underwent an abdominoperineal resection with lymph node dissection for a curative operation and received postoperative chemotherapy with dacarbazine, ranimustine, and vincristine, either with or without interferon-beta. One of these patients has been observed for more than 6 years postoperatively without any evidence of recurrence. The other three patients had advanced diseases at the time of diagnosis, and died within 3 years after operation. The prognosis of anorectal malignant melanoma is considered to be directly related to tumor size and depth. Therefore, a staging system and treatments based on the tumor size and depth (or thickness) are needed.