Associated expression of α2,3sialylated type 2 chain structures with lymph node metastasis in distal colorectal cancer.

PURPOSE: One of the typical modifications on the surface of cancer cells is sialylation of terminal carbohydrates. The expression of several types of sialylation of glycoconjugates was investigated in colorectal cancer. METHODS: The cancer tissue specimens obtained from 65 colorectal cancer patients were stained with sialic acid-binding lectins from Maackia amurensis (MAM), Sambucus sieboldiana (SSA), Maackia amurensis agglutinin (MAA) and monoclonal antibodies, and compared with their clinicopathological features. RESULTS: Cancer tissue specimens from 44.6% of patients had positive staining with MAM, which recognized α2,3sialylated type 2 chain (NeuAcα2,3Galß1,4GlcNAcßR) structures, but normal colorectal mucosa showed only weak staining with MAM was observed. More lymph node metastases and lymphatic invasion were seen in patients with positive staining with MAM (P < 0.01), while not with other lectins or antibodies that recognized sialylated glycoconjugates or sialyl Lewis-related antigens. The five-year survival rate of patients with MAM-positive staining was significantly lower than that with MAM-negative staining when including T0-1 cases, but there was no difference in cases with T2-4. There was no difference in the patients' survival rates when the tissues were stained with MAA, SSA or PNA lectins. CONCLUSION: α2,3Sialylated type 2 chain structures were predominantly expressed in colorectal tissues associated with the malignant transformation, in particular, with lymphatic spread of distal colorectal adenocarcinomas.

Feasibility of solo laparoscopic colorectal resection.

BACKGROUND/AIMS: To demonstrate the feasibility of solo laparoscopic colorectal resection (SLCR) is performed by the laparoscopist only. This study is an evaluation of the feasibility of SLCR for patients with colorectal cancer. METHODOLOGY: Fifty-one consecutive patients received SLCR from 2008 to 2009. The procedure was performed with four trocars and one laparoscopist. The short-term outcomes and complications were investigated retrospectively. RESULTS: The median age of the patients was 67 years (range 42-81). The median operating time for SLCR was 168 minutes (range 90-268). For one patient (1.96%) conversion to open surgery was required. Anastomotic leakage developed in 1 (1.96%) patient and ileus developed in 2 (3.9%). The median postoperative hospital stay was 8 (range 6-60) days without in-hospital deaths. CONCLUSIONS: In our experience, SLCR for patients with colorectal cancer is feasible and compares favorably with the standard technique. The diminished need for human operative assistance provides significant economic and organizational benefits.

Extranodal metastasis predicts poor survival in advanced colorectal cancer.

BACKGROUND/AIMS: The prognostic significance of extranodal metastasis (ENM) in colorectal cancer (CRC) is disregarded by the TNM classification system. The influence of ENM on survival among locally advanced CRC patients was examined. METHODOLOGY: We reviewed retrospectively the clinical course of 263 patients who underwent surgical resection of locally advanced CRC at our Department between 2005 and 2009. We analyzed the prognostic factors with special reference to the clinicopathological factors of primary tumors. RESULTS: Thirty-eight cases of ENM were detected among patients with CRC. Compared with ENM negative cancers, ENM-positive cancers were associated with poorer tumor differentiation grade (p=0.026) and higher prevalence of TNM-stage (p<0.0001), T-status (p=0.024), N-status (p<0.0001) and postoperative recurrence (p<0.0001). In univariate analysis, TNM-stage (p<0.0035), T-status (p=0.002), N-status (p<0.0024) and positive ENM (p<0.0001) were significant predictors of poor survival. Multivariate analyses showed a positive ENM to be a highly significant independent predictor of mortality (HR=1.98, 95% CI=1.23- 3.23, p=0.0053). Survival analyses using Kaplan-Meier curves demonstrated that patients with ENM-positive cancers had significantly poorer survival than patients with ENM-negative cancers. Patients with ENM-negative cancers did not show significantly different survival from patients with node-negative cancers (p=0.272, data not shown). CONCLUSIONS: ENM appears to be a strong independent negative prognostic factor of poor survival in locally advanced CRC.

The efficacy of fondaparinux for the prophylaxis of venous thromboembolism after resection for colorectal cancer.

BACKGROUND/AIMS: The advantages of combined pharmacological and physical methods for venous thromboembolism (VTE) prophylaxis after colorectal surgery have not been clearly determined. The aim of this study is to compare the efficacy and safety of fondaparinux combined with intermittent pneumatic compression (IPC) with IPC alone for VTE prophylaxis after resection for colorectal cancer. METHODOLOGY: Between June 2008 and March 2010, 137 consecutive patients with colorectal cancer (CRC) who underwent colorectal resection in our surgical unit were enrolled in the study. Patients were divided into 2 groups. The IPC group was treated with IPC alone as controls. The fondaparinux group was treated with IPC and received subcutaneous injections of fondaparinux once daily. The aim of this study was to compare the efficacy and safety of fondaparinux combined with IPC with IPC alone for VTE prophylaxis. RESULTS: The demographic variables and risk factors, operating time, blood loss and length of the postoperative hospital stay were similar in the two groups. No clinically evident VTE, critical bleeding, and postoperative death occurred during the study period. No adverse reactions due to fondaparinux were observed. CONCLUSIONS: In patients undergoing resection of colorectal cancer, receiving fondaparinux and IPC thromboprophylaxis was highly effective, well tolerated and safe. The use of combined modalities for VTE prophylaxis is justified in patients at high risk of VTE.

Scheduled prospective tri-weekly modified FOLFOX6 maintenance chemotherapy in the treatment of metastatic colorectal cancer.

BACKGROUND/AIMS: Oxaliplatin, which is effective for colorectal cancer (CRC) in combination with 5-fluorouracil (5-FU) and leucovorin (LV), is widely used for metastatic CRC. With the increasing use of oxaliplatin, however, serious adverse events have been experienced, including hematologic and neurologic toxicities. The aim of this study was to evaluate whether tri-weekly modified FOLFOX6 (mFOLFOX6) maintenance chemotherapy is associated with a low incidence of severe hematologic and neurologic toxicities in the treatment of patients with metastatic CRC. METHODOLOGY: We developed a new treatment regimen with mFOLFOX6 biweekly for 8-10 consecutive cycles (induction phase) followed by a 3-week rest period, after which treatment was resumed with cycles of tri-weekly mFOLFOX6 at standard doses (maintenance phase). Validity and complications were investigated retrospectively. RESULTS: Twenty-nine patients were enrolled in this study. The median progression-free survival (PFS) and overall survival (OS) times were 9.4 months and 23 months, respectively. All patients had peripheral neuropathy during treatment, but grade 3 neurotoxicity was observed in only 2 patients (6.9%). CONCLUSIONS: mFOLFOX6 maintenance chemotherapy was associated with a very low incidence of grade 3 hematologic and neurologic toxicities. The toxicities associated with PFS and OS were comparable to those reported in the treatment of patients with metastatic CRC. A tri-weekly mFOLFOX maintenance strategy of alternative treatment with a less-toxic regimen may reduce toxicity and maintain efficacy.

Effectiveness of intraperitoneal hyperthermo-chemotherapy for malignant peritoneal mesothelioma and estimation of its effect by repeated FDG-PET: a case report.

Malignant peritoneal mesothelioma is a rare neoplasm derived from the peritoneum of the abdominal cavity. Here, we report on a case of malignant peritoneal mesothelioma that expanded aggressively after initial surgery, followed by successful treatment with cytoreductive surgery, intra-abdominal hyperthermo-chemotherapy, to allow the patient to perform daily activities with reduced symptoms. The therapeutic effects were monitored by FDG-PET/CT. The patient, a 55-year-old female, was referred to our hospital with a diagnosis of pelvic tumor. Laparotomy and cytoreductive surgery revealed the diagnosis of malignant mesothelioma. The tumor progressed rapidly in the abdominal cavity, so cytoreduction and intra-abdominal hyperthermo-chemotherapy were performed as strong local therapies. In addition, monthly hyperthermo-chemotherapy was performed. The patient lived for 21 months after the first surgery. Severe bowel obstruction and malignant ascites did not appear. Cancerous pain was controllable throughout this portion of her life. In conclusion, we experienced a case of malignant peritoneal mesothelioma and treated it with hyperthermo-chemotherapy. This treatment helped the patient to maintain daily activities throughout the remainder of her life. Thus, hyperthermo-chemotherapy can be considered an option in the treatment of malignant peritoneal mesothelioma.

Cell to cell interaction in clusters enhances thermosensitivity in HT29 human colon cancer cells.

BACKGROUND/AIMS: Tumor cells at high density are considered to be resistant to hyperthermia. Our objective in this study was to investigate hyperthermia sensitivity of clusters, cancer cell aggregation, compared with that of monolayer cells. METHODOLOGY: Colon carcinoma cells HT29 were cultured on poly 2-hydroxyethyl methacrylate-coated dishes for 7 days and the clusters were selected by a 40µm pore filter. To detect the cell reproductive potential, a colony formation assay was performed in HT29 cells from a monolayer and from clusters after exposure to cis-diamino-dichloroplatinum, fluorouracil and/or hyperthermia. Western blotting was used to analyze the induction of heat shock protein expression by hyperthermia. RESULTS: Histological findings of the clusters less than 400µm in diameter showed dividing cells and no secondary central necrosis. Cluster cells were more sensitive to hyperthermia than monolayer cells (p<0.0001). However, cluster formation induced cis-diamino-dichloroplatinum resistance (p<0.0001). The enhancement of hyperthermia sensitivity in clusters was not observed when the cells were heated after dispersion to single cells (p<0.0001). No difference of heat-induced HSP70/72 and HSP27 expression between cluster cells and monolayer cells was found. CONCLUSIONS: Cluster formation induced hyperthermia sensitivity, and cell-to-cell interaction in the clusters might enhance hyperthermia sensitivity.

The progression potential of peritoneal dissemination nodules from gastrointestinal tumors.

It is necessary to examine the characteristics of the dissemination nodules to establish a therapeutic strategy for peritoneal dissemination from digestive malignancy. Ki-67 expression as a proliferation marker in peritoneal dissemination nodules was investigated. The subjects were 15 patients with gastrointestinal cancers who underwent resection of the primary tumor and disseminated nodules. The expression of Ki-67 in both primary tumor and peritoneal dissemination nodule from each patient was evaluated by immunohistochemistry. Ki-67 labeling index in the original tumor was higher than that in the disseminated nodule in 13 of 15 patients (P < 0.0001). The mean value of Ki-67 labeling index was 42.2% in the 15 original tumors and 18.7% in the 15 disseminated nodules. Proliferative activity in the disseminated nodules was lower than that in the primary tumors. Further examination about characteristics of cancer dissemination is needed to treat patients with peritoneal metastasis.

Characterization of special propulsive contractions during rectal evacuation in a canine model of intestinal extrinsic denervation and rectal transection.

PURPOSE: The mechanism for the initiation of giant migrating contractions (GMCs) associated with defecation is not well known. The aim of this study was to describe the characteristics of special propulsive contractions (SPCs), such as GMCs, during evacuation in four experimental dog models, with emphasis on denervation. MATERIALS AND METHODS: Twenty healthy dogs were used in this study, and they were divided into four groups, i.e., control (underwent force transducer implantation alone), denervation (underwent transection of the descending nerve fibers along the caudal mesenteric artery (CMA)), transection (underwent transection of the rectum, which corresponds to transection of the enteric nerve fibers), and denervation-plus-transection (underwent transection of the descending nerve fibers along the CMA and transection of the rectum). Colonic contractile activities were continuously recorded on a computer. Five force transducers were implanted at the serosal surfaces of the colon (C1-R). The consistency of dog feces was checked daily. The parameters of rectal relaxation (RR), defecation characteristics, and SPCs, such as motility index (MI), duration, and frequency, were measured. RESULTS: In the control and denervation groups, GMCs were observed with evacuation, and RR occurred synchronously with the initiation of GMCs. On the other hand, in the transection and denervation-plus-transection groups, strong force contractions without RR occurred only during evacuation. The MI and duration of the transection and denervation-plus-transection groups were higher than those of other groups (p < 0.05). The frequency of SPCs was the highest in the denervation-plus-transection group. CONCLUSIONS: In conclusion, the continuity of enteric nerves is necessary for the occurrence of GMCs and rectal relaxation (RR).

Case of Bochdalek hernia in the elderly: success with laparotomy.

Bochdalek hernia is usually diagnosed in pediatric patients and not in the elderly. In adults, there are some cases resulting in misdiagnosis of pneumonia, pleural effusion, congenital bulla, and pneumothorax by chest roentgenogram. We present here a rare case of Bochdalek hernia in an elderly patient who suffered from sudden back pain and had the hernia repaired with laparotomy.

Management of bile leakage caused by clip displacement from cystic duct stumps.

BACKGROUND/AIMS: Cystic duct leakage (CDL) is one of the most common complications after laparoscopic cholecystectomy (LC). We retrospectively examined 3 patients with CDL that were treated with endoscopic stenting. METHODOLOGY: From January 1995 to December 2004, 1127 LCs were performed. CDL occurred in 3 cases and a closed suction drain was inserted in 2 of those 3 cases. RESULTS: The duration from LC to endoscopic retrograde cholangiopancreatography (ERCP) was 2 to 4 days, and the patient without the drain experienced the longest waiting time. Hospital stay was almost identical for all 3 cases. There was an immediate improvement after the procedure. CONCLUSIONS: It is important to employ accurate technical surgical procedures to prevent complications. ERCP with stent placement and sphincterotomy is an easy and safe diagnostic and therapeutic procedure for CDL, and has a high success rate in resolving leaks.

P16 protein abnormality in Epstein-Barr virus-associated gastric carcinomas.

BACKGROUND: The Epstein-Barr virus (EBV) has been detected in lymphoepithelioma of the nasopharynx and lymphoepithelioma-like carcinomas in various organs. Ten percent of gastric carcinomas, including lymphepithelioma-like carcinoma and adenocarcinoma, are associated with EBV infection. The p16 protein is a cyclin-dependent kinase (CDK) inhibitor that decelerates the cell cycle, inactivating the CDKs that phosphorylate retinoblastoma (Rb) protein. MATERIALS AND METHODS: To clarify the relationship between p16 overexpression and EBV-associated gastric carcinomas, immunohistochemical analysis of p16 and detection of EBV by in situ hybridization were performed on 238 formalin-fixed and paraffin-embedded samples of gastric carcinomas. RESULTS: The non-expression of p16 protein in EBV-positive and -negative carcinoma was 81.5% (53 out of 65 samples) and 26.6% (46 out of 173 samples), respectively (p < 0.001). CONCLUSION: We suggest that the carcinogenesis of EBV-associated gastric cancers may be closely associated with a p16 abnormality.

Poorly cohesive adenocarcinoma of the ampulla of Vater: a case report.

A 47-year-old Japanese male was submitted to pancreaticoduodenectomy for an ampullary cancer. Pathologically, the ampullary cancer was poorly cohesive adenocarcinoma without tubular structure. Moreover, locoregional lymph nodes were swollen with hypervascularity, plasmacytes infiltration, and hemorrhage. Our case seems to be different from usual poorly differentiated adenocarcinoma.

A case of mixed adenoneuroendocrine carcinoma of the stomach with focal intestinal metaplasia and hypergastrinemia.

Among neuroendocrine neoplasms, mixed exocrine and endocrine characteristics with at least 30% of each component are classified into mixed adenoneuroendocrine carcinoma (MANEC), according to the 2010 World Health Organization classification. We experienced a rare case of MANEC of the stomach with focal intestinal metaplasia and hypergastrinemia. A 76-year-old Japanese male was diagnosed as having gastric adenocarcinoma and underwent total gastrectomy. The pathologic diagnosis was MANEC of the stomach accompanied by unusual mucosal atrophy without Helicobacter pylori infection, the characteristics of which were different from both type A and type B atrophic gastritis. The patient has a history of long-term use of a proton pump inhibitor. Additional serum chemistry examination using preoperatively obtained plasma from the patient revealed hypergastrinemia. The mechanism of gastric MANEC carcinogenesis is still unclear, but that might be correlated with unusual intestinal metaplasia and hypergastrinemia in this case.

Evaluation of abdominal circumference and salivary amylase activities after unsedated colonoscopy using carbon dioxide and air insufflations.

OBJECTIVE: To assess and compare abdominal distention and stress in unsedated colonoscopy using carbon dioxide (CO2 ) and air insufflations. METHODS: Two hundred and five patients underwent colonoscopic examinations without sedation using either CO2 or air insufflation. Abdominal circumference and salivary amylase (sAMY) activities before and 0 and 15 min after colonoscopy were measured by a nurse who was blinded to the grouping of the patients. RESULTS: In all, 102 and 103 patients were randomly recruited in the CO2 and air insufflation groups, respectively. sAMY activities before and 0 and 15 min after colonoscopy were not significantly different between the two groups. Abdominal circumference measured immediately and 15 min after colonoscopy was significantly smaller in CO2 insufflation group than in the air insufflation group (81.2 cm vs 84.0 cm, and 79.7 cm vs 83.6 cm, respectively; P <0.05). The increasing ratio of abdominal circumference immediately after colonoscopy was not significantly different between the two groups; however, the ratio at 15 min after colonoscopy using CO2 insufflation was significantly lower than that in the air insufflation group (1.007 vs 1.028, P <0.001). CONCLUSION: sAMY activities after unsedated colonoscopy using CO2 insufflation were not improved; however, CO2 insufflation decreases abdominal circumference after colonoscopy compared with air insufflation.

[Endocrine cell carcinoma (atypical carcinoid) of the ileocecal region adjacent to an adenocarcinoma].

An 86-year-old woman was admitted because of right lower abdominal pain. A 7 by 6 cm tumor palpable in the right lower quadrant was poorly mobile. Abdominal CT scan showed a huge tumor with a strong enhancement effect. Barium enema and colonoscopic examination revealed a submucosal tumor located from the cecum to the ascending colon on the oral side. An undifferentiated adenocarcinoma was suspected after examination of the biopsy specimen, right hemicolectomy was performed. The tumor invaded the retroperitoneal membrane. Histological examination showed a very atypical carcinoid tumor with central necrosis invading the veins. Pathohistologically, the huge tumor was diagnosed as endocrine cell carcinoma or atypical carcinoid. Furthermore, an elevated lesion, 2.5 cm in size, was revealed in the cecum closed to the huge tumor. Histological examination showed that the polypoid lesion was early moderately differentiated adenocarcinoma. There was no transition between the two tumors. The patient was discharged, but died of local recurrence 9 months after the surgery. Endocrine cell carcinoma of the large bowel is rare, in particular of the ileocecal region. Endocrine cell carcinoma of the ileocecal region adjacent to an adenocarcinoma without transition had not been reported previously in Japan.

Retroperitoneal liposarcoma with leiomyosarcomatous differentiation.

We herein describe a 60-year-old Japanese man with a giant retroperitoneal liposarcoma undergoing leiomyosarcomatous differentiation. He was admitted to our hospital because of a 5-month history of dysphagia and abdominal distention. Abdominal computed tomography showed a giant tumor that occupied the entire retroperitoneal space. The majority of the mass was lipomatous and low density; both a heterogenous and solid mass were also present. A giant retroperitoneal liposarcoma was diagnosed, and tumor resection was performed. At surgery, the tumor was mostly isolated from the retroperitoneum and other organs. Histopathologically, the tumor comprised well-differentiated and dedifferentiated liposarcoma with heterologous differentiation of the leiomyosarcomatous components, which is a rare phenomenon in liposarcoma. The patient was alive 3 years after the first treatment, although he has had 3 local recurrences (approximately one recurrence yearly) and has been treated by repeated resection and radiotherapy.

Intrahepatic biliary dilatation caused by a small simple hepatic cyst: report of a case.

Biliary obstruction caused by small simple cysts is very rare. We present a case of biliary dilatation caused by a simple cyst with a 4-cm diameter. The patient was a 75-year-old woman referred to our hospital for evaluation of a cystic tumor associated with peripheral biliary duct dilatation in the left segment of the liver. Computed tomography and magnetic resonance imaging showed that the cyst probably communicated with the intrahepatic bile duct. Malignant tumors, including intrahepatic papillary neoplasms of the bile duct, could not be ruled out; therefore, we performed surgery with the patient's consent. Histopathologic examination of the resected liver showed that the cystic lesion was a simple cyst. The finding that even small simple cysts can obstruct the biliary tract is important for the management of cystic lesions of the liver.

Recurrent, spontaneous esophageal ruptures associated with antiphospholipid antibody syndrome: report of a case.

A 52-year-old man was admitted to our hospital with a spontaneous esophageal rupture (Boerhaave syndrome) and was successfully treated. Eight years after the first incident, he was readmitted with a recurrent rupture. Recurrence of Boerhaave syndrome is extremely rare, with only 7 cases reported in the English literature. During treatment, the patient was also diagnosed with antiphospholipid syndrome (APS). Although APS is known to cause a variety of symptoms due to vascular thrombosis, recurrence of Boerhaave syndrome, coincident with APS, has never been reported. The pathogenesis of Boerhaave syndrome has not been clearly determined. This report serves to increase awareness of the risk of APS, which results in an increased risk of spontaneous rupture of the esophagus.

Mucosal esophageal squamous cell carcinoma with intramural gastric metastasis invading liver and pancreas: a case report.

A 59-year-old Japanese man was admitted to our hospital because of a 1-month history of dysphagia. Endoscopic examination revealed a superficial esophageal squamous cell carcinoma and a giant gastric tumor. Computed tomography showed that the gastric tumor was directly invading the liver and pancreas. Because of the risk of the gastric tumor causing obstruction and bleeding, we performed a subtotal esophagectomy, proximal gastrectomy, left lateral segmentectomy of liver, and pancreatosplenectomy with gastric tube reconstruction. Final pathological findings were superficial esophageal carcinoma penetrating the muscularis mucosae with an intramural gastric metastasis directly invading the liver and pancreas. The patient received postoperative adjuvant chemotherapy, yet died 8 months postoperatively of complications of local recurrence. Early-stage esophageal carcinoma with intramural gastric metastasis is very rare. To our knowledge, this is the first case of mucosal esophageal carcinoma with intramural gastric metastasis directly invading other organs.