The inositol 1,4,5-trisphosphate receptor (InsP3R) mediates Ca2+ signaling in epithelia and regulates cellular functions such as secretion, apoptosis and cell proliferation. Loss of one or more InsP3R isoform has been implicated in disease processes such as cholestasis. Here we examined whether gain of expression of InsP3R isoforms also may be associated with development of disease. Expression of all three InsP3R isoforms was evaluated in tissue from colorectal carcinomas surgically resected from 116 patients. Type I and II InsP3Rs were seen in both normal colorectal mucosa and colorectal cancer, while type III InsP3R was observed only in colorectal cancer. Type III InsP3R expression in the advancing margins of tumors correlated with depth of invasion, lymph node metastasis, liver metastasis, and TNM stage. Heavier expression of type III InsP3R also was associated with decreased 5-year survival. shRNA knockdown of type III InsP3R in CACO-2 colon cancer cells enhanced apoptosis, while over-expression of the receptor decreased apoptosis. Thus, type III InsP3R becomes expressed in colon cancer, and its expression level is directly related to aggressiveness of the tumor, which may reflect inhibition of apoptosis by the receptor. These findings suggest a previously unrecognized role for Ca2+ signaling via this InsP3R isoform in colon cancer.
Inositol 1,4,5-trisphosphate receptor; Calcium signaling; Colorectal cancer; Prognosis; Apoptosis
A 56-year-old woman with a history of gynecological surgery for cervical cancer 18 years previously was referred to our hospital for colicky abdominal pain, nausea and vomiting. Intestinal obstruction was diagnosed by contrast-enhanced computed tomography (CT) which showed dilation of the small intestine and suggested obstruction in the terminal ileum. In addition, CT showed a thick-walled cavitary lesion communicating with the proximal jejunum. 18F-fluorodeoxyglucose positron emission tomography showed abnormal uptake at the same location as the cavitary lesion revealed by CT. The patient underwent laparotomy for the ileus and resection of the cavitary lesion. At laparotomy, we found a retained surgical sponge in the ileum 60 cm from the ileocecal valve. The cavitary tumor had two fistulae communicating with the proximal jejunum. The tumor was resected en bloc together with the transverse colon, part of the jejunum and the duodenum. Microscopic examination revealed fibrous encapsulation and foreign body giant cell reaction. Since a retained surgical sponge without radiopaque markers is extremely difficult to diagnose, retained surgical sponge should be considered in the differential diagnosis of intestinal obstruction in patients who have undergone previous abdominal surgery.
Retained surgical sponge; Gossypiboma; Textiloma; Intestinal obstruction; Ileus
In animals, major classes of Rho guanine nucleotide exchange factors (GEFs) possess a Dbl (diffuse B-cell lymphoma)- homology (DH) domain that functions as a GEF-catalytic domain. However, no GEFs with the DH domain had been identified in plants. Recently, we found that the rice homolog of human SWAP70, Oryza sative (Os) SWAP70, containing the DH domain, exhibited GEF activity toward the rice Rho GTPase OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice.1 Arabidopsis contains a single SWAP70 gene. A T-DNA insertion mutant of Arabidopsis SWAP70 was morphologically wild type. Measurement of in planta growth of Pseudomonas syringae DC3000 hrcC, a mutant incapable of type III effector delivery, revealed enhanced growth of the pathogen in the atswap70 mutant, indicating that AtSWAP70 is required for PAMP-triggered immunity. In addition, the atswap70 mutation reduced the RPM1-mediated hypersensitive response. These results suggested that AtSWAP70 plays a role in both PAMP- and effector-triggered immunity in Arabidopsis.
GEF; Rop; GTPase; immunity; DH; defense; HR; PTI; ETI
We report a case of acute fulminant amoebic colitis that resulted in the development of a perianal ulcer in a 29-year-old Japanese homosexual man with acquired immunodeficiency syndrome (AIDS). The patient was admitted to our hospital with a persistent perianal abscess that was refractory to antibiotic therapy administered at another hospital. On admission, we observed a giant ulcer in the perianal region. At first, cytomegalovirus colitis was suspected by blood investigations. Ganciclovir therapy was initiated; however, the patient developed necrosis of the skin around the anus during therapy. We only performed end-sigmoidostomy and necrotomy to avoid excessive surgical invasion. Histopathological examination of the surgical specimen revealed the presence of trophozoite amoebae, indicating a final diagnosis of acute fulminant amoebic colitis. The patient’s postoperative course was favorable, and proctectomy of the residual rectum was performed 11 mo later. Amoebic colitis is one of the most severe complications affecting patients with AIDS. Particularly, acute fulminant amoebic colitis may result in a poor prognosis; therefore, staged surgical therapy as a less invasive procedure should be considered as one of the treatment options for these patients.
Acute fulminant amoebic colitis; Perianal ulcer; Acquired immunodeficiency syndrome; Cytomegalovirus colitis; Staged surgery
Growing evidence suggests that epicardial adipose tissue (EAT) may contribute to the development of coronary artery disease (CAD). In this study, we explored gender disparities in EAT volume (EATV) and its impact on coronary atherosclerosis.
The study population consisted of 90 consecutive subjects (age: 63 ± 12 years; men: 47, women: 43) who underwent 256-slice multi-detector computed tomography (MDCT) coronary angiography. EATV was measured as the sum of cross-sectional epicardial fat area on CT images, from the lower surface of the left pulmonary artery origin to the apex. Subjects were segregated into the CAD group (coronary luminal narrowing > 50%) and non-CAD group.
EATV/body surface area (BSA) was higher among men in the CAD group than in the non-CAD group (62 ± 13 vs. 33 ± 10 cm3/m2, p < 0.0001), but did not differ significantly among women in the 2 groups (49 ± 18 vs. 42 ± 9 cm3/m2, not significant). Multivariate logistic analysis showed that EATV/BSA was the single predictor for >50% coronary luminal narrowing in men (p < 0.0001). Predictors excluded were age, body mass index, hypertension, diabetes mellitus, and hyperlipidemia.
Increased EATV is strongly associated with coronary atherosclerosis in men.
Atherosclerosis; Gender difference; Epicardial adipose tissue; Obesity
The aim of this study was to evaluate the usefulness of urinary N1,N12-diacetylspermine (DiAcSpm) measured by the colloidal gold aggregation method as a tumor marker for colorectal cancer (CRC). The preoperative urine of 113 CRC patients was collected, and the urinary DiAcSpm was measured by a reagent kit for DiAcSpm determination based on colloidal gold aggregation using automatic biochemical analyzers. The urinary DiAcSpm levels significantly correlated with distant metastasis and Tumor-Node-Metastasis (TNM) stage. The positive rates of urinary DiAcSpm were significantly higher than those of serum carcinoembryonic antigen (CEA) or cancer antigen 19-9 (CA19-9) in stages 0+I, II, III and IV. The positive rates of urinary DiAcSpm were also significantly higher than those of serum CEA or CA19-9 in the early and advanced CRC groups according to the Japan Classification of Colorectal Cancer. Therefore, urinary DiAcSpm, measured by a reagent kit for DiAcSpm determination based on colloidal gold aggregation, may be useful as a non-invasive tumor marker in patients with CRC.
N1,N12-diacetylspermine; DiAcSpm; urine; tumor marker; colorectal cancer
Pylorus-preserving pancreatoduodenectomy has become a standard operation for distal and middle bile duct cancers. Bile duct cancer typically extends longitudinally and invades vertically. It frequently metastasizes to the lymph nodes and infiltrates the perineural spaces. The presence of residual cancer in the bile duct stump and lymph node metastases are significant prognostic factors. Negative surgical margins and D2 lymph node dissection are necessary for curative resection. The clinical course after portal vein resection for bile duct cancer with portal vein invasion is better than that of non-resectable bile duct cancer. Portal vein resection can therefore be useful. The efficacy of prophylactic portal vein resection is unclear. We describe here our methods for performing pylorus-preserving pancreatoduodenectomy for bile duct cancer.
Electronic supplementary material
The online version of this article (doi:10.1007/s00534-011-0480-8) contains supplementary material, which is available to authorized users.
Pancreatoduodenectomy; Bile duct cancer; Ampullary cancer; Lymph node dissection; Pancreaticojejunostomy
Cancer cells generally have a high rate of glycolysis and produce larger quantities of lactate as compared to the surrounding normal cells. Monocarboxylate transporter 4 (MCT4) is one of the proton pumps exchanging the lactate through the plasma membrane. The prognostic significance of MCT4 expression has not been evaluated in patients with colorectal cancer (CRC). Surgical specimens from 105 CRC patients were immunohistochemically stained using a polyclonal anti-MCT4 antibody. The relationships among the MCT4 expression, clinicopathological factors and prognosis were evaluated. A total of 53 (50.5%) of the 105 patients with CRC were determined to have tumors positive for MCT4 expression. The expression of MCT4 significantly correlated with the tumor size, depth of invasion, lymph node metastasis, distant metastasis and TNM staging. The survival rate of the patients who were positive for MCT4 expression was significantly lower than that of patients with negative MCT4 expression. Positive MCT4 expression was a significantly poor prognostic factor, as determined by both univariate and multivariate analyses. Therefore, positive MCT4 expression appears to be a useful marker for tumor progression and prognosis in patients with CRC.
monocarboxylate transporter; monocarboxylate transporter 4; colorectal cancer
Although metastasis or relapse is a leading cause of death for patients with gastric cancer, the hematogenous spread of cancer cells remains undetected at the time of initial therapy. The development of novel diagnostic molecular marker(s) to detect circulating gastric cancer cells is an issue of great clinical importance. We obtained peripheral blood samples from 10 patients with gastric cancer who underwent laparotomy and 4 healthy volunteers. Microarray analysis consisting of 30,000 genes or ESTs was carried out using eight gastric cancer tissues and normal gastric mucosae. We selected 53 genes up-regulated in gastric cancer compared to normal gastric mucosae from our microarray data set, and, among these, identified five candidate marker genes (TSPAN8, EPCAM, MMP12, MMP7 and REG3A) which were not expressed in peripheral blood mononuclear cells (PBMCs) from 4 healthy volunteers. We further carried out semi-quantitative nested reverse transcription-polymerase chain reaction (RT-PCR) for HRH1, EGFR, CK20 and CEA in addition to the five newly identified genes using PBMCs of patients with gastric cancer, and found that expression of one or more genes out of the nine was detected in 80% of the patients with gastric cancer. Moreover, the numbers of genes expressed in PBMCs were ≤2 and ≥2 in all vascular invasion-negative cases and in 5 of 6 positive cases, respectively, showing significant differences between the two groups (P=0.041). Nested RT-PCR analysis for the set of nine marker genes using PBMCs may provide the potential for detection of circulating gastric cancer cells prior to metastasis formation in other organs.
microarray; gastric cancer; molecular marker; nested RT-PCR; peripheral blood
Malignant fibrous histiocytoma (MFH) is a common sarcoma affecting soft tissues of the body, especially of the extremities or trunk. Prognosis of the abdominal MFH is usually poor.
A 52-year-old female presented to our surgical outpatient clinic with a lower abdominal tumor that had been gradually increasing in size. Clinical examination revealed a firm, irregularly surfaced, fixed, painless, child-head-sized tumor located in her lower abdomen. Computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen revealed a polycystic tumor at the lower abdomen which was 15 × 13 × 11 cm in diameter and encased the colorectum to the left back side. A barium enema and a colonoscopy showed direct invasion to the rectum. In 2001, the tumor had been excised along with a low anterior resection of the rectum because of direct invasion. The origin of this tumor was the mesorectum. The weight of the excised tumor was 1,500 g, including 800 ml of a brown fluid. A histopathological diagnosis revealed a common type of MFH, in which mitotic figures are frequently seen.
This patient has survived without recurrence, for approximately 8 years since the completed tumor resection. It is important to obtain a complete resection during the MFH treatment.
Heterotopic bone is rarely present in malignant tumors of the gastrointestinal tract. We herein report a case of rectal adenocarcinoma with heterotopic bone. A 46-year-old Japanese male presented to our hospital with abdominal distension and constipation. Colonoscopic examination showed an ulcerated polypoid tumor of the rectum which nearly obstructed the rectal lumen. Abdominal computed tomography showed a tumor of the rectum with calcified deposits. Low anterior resection with lateral lymph node dissection was performed under the tentative diagnosis of rectal cancer. Histological examination of the resected specimen showed mucinous carcinoma of the rectum with heterotopic bone. One of the metastatic lymph nodes dissected also showed heterotopic bone. In the present report, we describe this rare tumor and briefly review the pertinent literature regarding rectal cancer with heterotopic bone.
Rectum; Adenocarcinoma; Osseous metaplasia
autoimmune pancreatitis; diagnostic criteria; lymphoplasmacytic sclerosing cholangitis; IgG4
Proteus syndrome is an extremely rare congenital disorder that produces multifocal overgrowth of tissue. This report presents a surgical case of a large lipoma in the abdominal wall of a patient with Proteus syndrome. She was diagnosed with Proteus syndrome based on certain diagnostic criteria. The neoplasm increased in size gradually, producing hemihypertrophy of her left lower extremity and trunk, and spread to her retroperitoneum and her left abdominal wall. She experienced gradually progressive constipation, nausea, vomiting, and abdominal pain. Computed tomography (CT) of the abdomen demonstrated a large mass in the subcutaneous adipose tissue of the left lower abdominal wall which measured 12 cm × 8 cm x 6 cm in diameter and encased the left colon. This mass in the abdominal wall was excised. The weight of the excised mass was 1550 g. The histopathological diagnosis of this mass was lipoma. After surgery, the encasement of the left colon was improved, and the patient was able to move her bowels twice per day. The excision of the large lipoma in the abdominal wall contributed to the improved bowel passage in this patient with Proteus syndrome.
Proteus syndrome; Lipoma; Bowel obstruction; Abdominal wall; Bowel passage
We previously reported that survivin-2B, a splicing variant of survivin, was expressed in various types of tumors and that survivin-2B peptide might serve as a potent immunogenic cancer vaccine. The objective of this study was to examine the toxicity of and to clinically and immunologically evaluate survivin-2B peptide in a phase I clinical study for patients with advanced or recurrent breast cancer.
We set up two protocols. In the first protocol, 10 patients were vaccinated with escalating doses (0.1–1.0 mg) of survivin-2B peptide alone 4 times every 2 weeks. In the second protocol, 4 patients were vaccinated with the peptide at a dose of 1.0 mg mixed with IFA 4 times every 2 weeks.
In the first protocol, no adverse events were observed during or after vaccination. In the second protocol, two patients had induration at the injection site. One patient had general malaise (grade 1), and another had general malaise (grade 1) and fever (grade 1). Peptide vaccination was well tolerated in all patients. In the first protocol, tumor marker levels increased in 8 patients, slightly decreased in 1 patient and were within the normal range during this clinical trial in 1 patient. With regard to tumor size, two patients were considered to have stable disease (SD). Immunologically, in 3 of the 10 patients (30%), an increase of the peptide-specific CTL frequency was detected. In the second protocol, an increase of the peptide-specific CTL frequency was detected in all 4 patients (100%), although there were no significant beneficial clinical responses. ELISPOT assay showed peptide-specific IFN-γ responses in 2 patients in whom the peptide-specific CTL frequency in tetramer staining also was increased in both protocols.
This phase I clinical study revealed that survivin-2B peptide vaccination was well tolerated. The vaccination with survivin-2B peptide mixed with IFA increased the frequency of peptide-specific CTL more effectively than vaccination with the peptide alone, although neither vaccination could induce efficient clinical responses. Considering the above, the addition of another effectual adjuvant such as a cytokine, heat shock protein, etc. to the vaccination with survivin-2B peptide mixed with IFA might induce improved immunological and clinical responses.
There are accumulating reports that polyamines are involved in abiotic stress response. However, the role played by the polyamines is not fully elucidated. In the present studies, we assessed whether spermine among the polyamines plays a certain role against high salt and drought stresses using an Arabidopsis (acl5/spms) mutant plant that does not produce spermine, and found that it was hypersensitive to those stresses. In each case the hypersensitive phenotype was mitigated by application of exogenous spermine. The spermine-deficient mutant plants also showed a phenotype resembling Ca2+-deficiency. The NaCl-hypersensitivity and Ca2+-deficiency of acl5/spms double-knockout mutant resembled the phenotypes displayed by the AtGluR2- and CAX1-overexpressing transgenic plants. The two latter genes encode a glutamate receptor-type, Ca2+-ion influx channel at cytoplasmic membrane and a vacuolar Ca2+/H+ antiporter, respectively. The data suggest that regulated expression of the Ca2+-pathway members is critical to adapt to those stresses, and that spermine plays a certain role to control the stress-induced Ca2+ dynamics. Incorporating the current information from the literature, especially regarding action of polyamines on various ion channels, we present models describing a defensive role of spermine in high salt and drought stresses in Arabidopsis.
Arabidopsis thaliana; calcium ion; drought stress; high salt stress; ion channels; polyamine; spermine
Survivin is a member of the inhibitor of apoptosis protein (IAP) family containing a single baculovirus IAP repeat domain. It is expressed during fetal development but becomes undetectable in terminally differentiated normal adult tissues. We previously reported that survivin and its splicing variant survivin-2B was expressed abundantly in various types of tumor tissues as well as tumor cell lines and was suitable as a target antigen for active-specific anti-cancer immunization. Subsequently, we identified an HLA-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL) recognized by CD8+ cytotoxic T lymphocytes (CTLs). We, therefore, started a phase I clinical study assessing the efficacy of survivin-2B peptide vaccination in patients with advanced or recurrent colorectal cancer expressing survivin. Vaccinations with survivin-2B peptide were given subcutaneously six times at 14-day intervals. Of 15 patients who finished receiving the vaccination schedule, three suffered slight toxicities, including anemia (grade 2), general malaise (grade 1), and fever (grade 1). No severe adverse events were observed in any patient. In 6 patients, tumor marker levels (CEA and CA19-9) decreased transiently during the period of vaccination. Slight reduction of the tumor volume was observed in one patient, which was considered a minor responder. No changes were noted in three patients while the remaining eleven patients experienced tumor progression. Analysis of peripheral blood lymphocytes of one patient using HLA-A24/peptide tetramers revealed an increase in peptide-specific CTL frequency from 0.09% to 0.35% of CD8+ T cells after 4 vaccinations. This phase I clinical study indicates that survivin-2B peptide-based vaccination is safe and should be further considered for potential immune and clinical efficacy in HLA-A24-expression patients with colorectal cancer.
A 71-year-old Japanese woman complained of right upper abdominal fullness and pain. Computed tomography revealed a huge cyst in the right lobe of the liver, measuring 16 cm in diameter. She underwent laparoscopic deroofing of the liver cyst. On operation, needle aspiration of the cyst yielded clear serous fluid without any bile contamination. However, after the cyst was deroofed with laparoscopic coagulating shears, bile leakage was recognized from a tiny orifice in the cyst cavity. A catheter was inserted via the orifice for cholangiography, which demonstrated a communication with the biliary tract. The orifice was easily closed with a laparoscopic suturing device. Operation time was 5 hours and 30 minutes, and blood loss was 300 grams. Pathological examination of the liver cyst was consistent with a simple cyst. The postoperative course was uneventful, and the patient has had no recurrence to date at 13 months. Laparoscopic deroofing is a recommended treatment for a liver cyst even in the presence of cystobiliary communication.
Liver cyst; Laparoscopic deroofing; Biliary communication
A case of bile duct injury during laparoscopic cholecystectomy finally necessitating right hepatic lobectomy is reported to re-emphasize the importance of preoperative and intraoperative assessment of the biliary tree. A 47-year-old Japanese woman underwent laparoscopic cholecystectomy for cholecystolithiasis. On postoperative day 5, fever and right hypochondralgia developed, and CT revealed fluid collection at the right hypochondrium.
Percutaneous drainage was performed, and subsequent fistulography revealed a communication of the cystic cavity with the right posterior bile duct, which suggested injury of the aberrant hepatic duct. Conservative therapy, including the adaptation of fibrin glue, was performed, but closure of the fistula and cavity was not obtainable. Finally, a right hepatic lobectomy was performed four months after cholecystectomy. In this case, endoscopie retrograde cholangiopancreatography was unsuccessful preoperatively, and intraoperative cholangiography was not done. This case report re-emphasizes that the preoperative and intraoperative examination of the biliary tree is mandatory to avoid bile duct injury.
Laparoscopic cholecystectomy; Bile duct injury; Aberrant hepatic duct; Intraoperative cholangiography