[Gallbladder Necrosis after Surgery for Stanford Type A Aortic Dissection in an Elderly Patient:Report of a Case].

An 86-year-old woman who suffered from cardiac tamponade due to acute Stanford type A aortic dissection was admitted to our hospital. An emergency operation was performed uneventfully. She suffered from abdominal pain 13 days after the operation. Computed tomography( CT) scan revealed pericholecystic fluid and unclear gallbladder wall, revealing acalculous necrotizing cholecystitis. We performed open cholecystectomy and abdominal cavity drainage. No gallstones were observed. She underwent intensive treatment. She was discharged without complications 44 days after the cholecystectomy.

[Internal Hernia Accompanying Intestinal Necrosis after Aortic Arch Replacement:Report of a Case].

A 76-year-old man with thoracic aortic aneurysm was admitted to our hospital. Aortic arch replacement was performed uneventfully. He suffered from abdominal pain 17 days after the operation. Computed tomography (CT) scan revealed a strangulated bowel obstruction, and we performed emergent open abdominal surgery. During the operation, we found an adhesion between the greater omentum and the retroperitoneum. The small intestine was intussuscepted into this site, and strangulated with necrosis of a 35-cm length. We performed a partial resection of the small intestine. We encountered rare strangulated bowel obstruction after open heart surgery due to adhesion of the great omentum in a patient without a history of abdominal surgery.

Establishment of a novel method to evaluate peritoneal microdissemination and therapeutic effect using luciferase assay.

Peritoneal dissemination is a major cause of recurrence in patients with malignant tumors in the peritoneal cavity. Effective anticancer agents and treatment protocols are necessary to improve outcomes in these patients. However, previous studies using mouse models of peritoneal dissemination have not detected any drug effect against peritoneal micrometastasis. Here we used the luciferase assay to evaluate peritoneal micrometastasis in living animals and established an accurate mouse model of early peritoneal microdissemination to evaluate tumorigenesis and drug efficacy. There was a positive correlation between luminescence intensity in in vivo luciferase assay and the extent of tumor dissemination evaluated by ex vivo luciferase assay and mesenteric weight. This model has advantages over previous models because optimal luciferin concentration without cell damage was validated and peritoneal microdissemination could be quantitatively evaluated. Therefore, it is a useful model to validate peritoneal micrometastasis formation and to evaluate drug efficacy without killing mice.

Control of primary lesions using resection or radiotherapy can improve the prognosis of metastatic colorectal cancer patients.

BACKGROUND: Control of the primary lesions in metastatic colorectal cancer (mCRC) is still controversial. For rectal cancer patients, not only resection but also irradiation is expected to provide palliative effects. We investigated the effects of resection and irradiation of primary lesions (local control) on the prognosis of mCRC patients. PATIENTS: Forty-seven patients with mCRC at our institute were examined, with 34 in the local controlled group and 13 in the uncontrolled group. RESULTS: The median survival time (MST) of the local controlled and uncontrolled groups were 2.90 and 1.39 years (P = 0.028). Cox proportional hazard regression analysis showed that local control was an independent prognostic factor (P < 0.05). The patients who underwent primary lesion resection had significantly longer MST (2.90 vs. 1.39 years, P = 0.032) than those in the uncontrolled group. In rectal cancer patients, the patients who underwent irradiation to control the primary lesions had a significantly longer MST than the uncontrolled patient group (1.97 vs. 1.39 years, P = 0.019). CONCLUSIONS: Local control of primary lesions may improve the prognosis in mCRC patients. In rectal cancer patients with metastasis, not only resection but also irradiation of the primary lesions may be a useful therapeutic strategy. J. Surg. Oncol. 2016;114:75-79. © 2016 Wiley Periodicals, Inc.

KPNA2 over-expression is a potential marker of prognosis and therapeutic sensitivity in colorectal cancer patients.

BACKGROUND: Karyopherin α 2 (KPNA2) is a member of the Karyopherin α family and has recently been reported to play an important role in tumor progression. The aim of the current study was to elucidate the clinicopathological significance of KPNA2 over-expression in colorectal cancer (CRC). PATIENTS AND METHODS: KPNA2 expression was evaluated by immunohistochemistry in 122 surgically resected CRC and 13 biopsy specimens obtained at colonoscopy during screening for preoperative hyperthermochemoradiation therapy (HCRT). The association between KPNA2 expression and clinicopathological features and preoperative HCRT efficacy were examined. RESULTS: The high and low KNPA2 expression groups were comprised of 91 (74.6%) and 31 CRC patients, respectively. A significant association was observed between high expression and lymphatic invasion (P = 0.0245). KPNA2 high expression group had decreased overall survival (P = 0.00374). Multivariate analysis demonstrated high KPNA2 expression was independently associated with poor prognosis. Histological examinations revealed 11 (84.6%) and 2 (15.4%) of cases were KPNA2 positive and negative, respectively. Pathological complete response (pCR) was observed in 9.1% of KPNA2-positive cases and 100% of KPNA2-negative cases. CONCLUSION: High KPNA2 expression was found to be associated with poor prognosis and resistance to HCRT.

MicroRNA-7 expression in colorectal cancer is associated with poor prognosis and regulates cetuximab sensitivity via EGFR regulation.

MicroRNA-7 (miR-7) has been reported to be a tumor suppressor in all malignancies including colorectal cancer (CRC). However, its significance for CRC clinical outcomes has not yet been explored. The potential for miR-7 to act as a tumor suppressor by coordinately regulating the epidermal growth factor receptor (EGFR) signaling pathway at several levels was examined. We investigated the tumor inhibitory effect of miR-7 in CRC, with particular focus on the relationship between miR-7 and the EGFR pathway. Quantitative reverse transcription-PCR was used to evaluate miR-7 expression in 105 CRC cases to determine the clinicopathologic significance of this miRNA. The regulation of EGFR by miR-7 was examined with miR-7 precursor-transfected cells. Furthermore, we investigated whether miR-7 suppresses proliferation of CRC cells in combination with cetuximab, a monoclonal antibody against EGFR. Multivariate analysis indicated that low miR-7 expression was an independent prognostic factor for poor survival (P = 0.0430). In vitro assays showed that EGFR and RAF-1 are direct targets of miR-7, which potently suppressed the proliferation of CRC cells, and, interestingly, that the growth inhibitory effect of each of these was enhanced by cetuximab. miR-7 is a meaningful prognostic marker. Furthermore, these data indicate that miR-7 precursor, alone or in combination with cetuximab, may be useful in therapy against CRC.

Feasibility of Reduced Port Laparoscopic Colectomy for Colon Cancer.

BACKGROUND/AIMS: Reduced port laparoscopic surgery has recently emerged as a method to improve the cosmetic results of conventional laparoscopic surgery. We reported our technique of reduced port laparoscopic colectomy using 3-port and short-time outcomes. METHODOLOGY: Between 2005 and 2012, we performed 161 reduced port laparoscopic colectomies using the 3-port technique. Data analyzed in-cluded age, gender, body mass index (BMI), duration of surgery, number of harvested lymph nodes, and duration of hospital stay. RESULTS: All of the cases were successfully performed using the 3-port procedure. The median durations of surgery and postoperative hospital stay were 140 mm (range 75-463 mm) and 9 days (range 5-38 days), respectively. No mortality was associated with this technique. CONCLUSION: Reduced port laparoscopic colectomy is feasible and may have advantages over conventional laparoscopic colectomy.

Clinicopathological Features of Second Primary Colorectal Cancer Incidentally Identified by 18F-FDG-PET.

As positron emission tomography using F18-fluorodeoxyglucose (FDG-PET) is becoming a common imaging modality the number of colorectal cancers incidentally detected by FDG-PET is expected to increase. In this study, we investigated the clinicopathological features of 15 cases of second primary colorectal cancer incidentally detected by PET during other cancer evaluation in patients who underwent surgery. We also discussed the significance of FDG-PET in evaluating cancer status. None of the patients had undergone FDG-PET for suspected colorectal disease; 6 were being evaluated by FDG-PET for lung cancer, 5 for nasopharyngeal or laryngeal cancer, 3 for gastrointestinal cancer, and 1 for uterine cancer. The average tumor size was 36.1 ± 14.4 mm (range, 25-70 mm) and the mean maximum standardized uptake value (SUVmax) was 11.9 ± 6.0 (range, 3.0-29.6). Although 4 cases (26.7%) had distant metastasis, 3 (20%) were Tis or T1 cancer, 3 (20%) were T2 cancer. Of the 15 cases, 6 (40%) could have been underwent laparoscopic surgery. Our study found that asymptomatic cases of colorectal cancer can be detected by FDG-PET during evaluation for other cancer. Therefore, in some cases, FDG-PET is useful for detecting second primary colorectal cancer at a relatively early and curable stage.

Addition of Bevacizumab to First-Line Chemotherapy for Metastatic Colorectal Cancer.

BACKGROUND/AIMS: We evaluated the efficacy and safety of bevacizumab for metastatic colorectal cancer patients. METHODOLOGY: All unresectable metastatic colorectal cancer patients who began receiving bevacizumab at participating facilities from 2006 to 2011 were retrospectively analyze to determine the safety and efficacy. The primary end points were Progression Free Survival (PFS) and Overall Survival (OS). The secondary end points were adverse events. RESULTS: A total of 101 patients were enrolled in the study. The primary tumor site was the colon in 53 patients and the rectum in 48 patients. The most common metastatic sites were the liver (63.4%), lung (31%), and peritoneum (10%). In first-line therapy, 76 (75.2%) patients received the FOLFOX regimen. Among these patients, 33 (43.4%) patients received FOLFOX alone, and 43 (56.6%) received FOLFOX plus bevacizumab. The addition of bevacizumab to first-line chemotherapy was associated with increases in median PFS (12.5 vs. 6.0 months; P = .00001) and median OS (24.0 vs. 16.0 months; P = 0.0221). The risks of adverse events were not significantly increased with the addition of bevacizumab. CONCLUSIONS: The addition of bevacizumab to first-line therapy in CRC patients provided clinically significant patient benefit, including statistically significant improvement in OS and a favorable tolerability profile.

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.

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.

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.

Low level of stromal lectin-like oxidized LDL receptor 1 and CD8+ cytotoxic T-lymphocytes indicate poor prognosis of colorectal cancer.

BACKGROUND: Lectin-like oxidized LDL receptor-1 (LOX-1) has been identified as a new marker for functional myeloid-derived suppressor cells (MDSCs) that exhibit an immunosuppressive phenotype in the tumor microenvironment (TME). However, the role of LOX-1+ cells in the TME of colorectal cancer (CRC) remains unknown. AIM: This study aimed to determine the expression and significance of LOX-1 in the TME of clinical CRC specimens. METHODS AND RESULTS: We performed immunohistochemical and genetic analyses of LOX-1, CD8, KRAS, and BRAF in 128 resected CRC specimens and determined the expression of IFN-γ and IL-10 using real-time reverse transcription-polymerase chain reaction. We analyzed the correlation between LOX-1, TME factors, gene alteration, clinicopathological factors, and disease prognosis. The co-expression pattern of LOX-1, hematopoietic markers, and a fibroblast marker was evaluated using multiplex immunofluorescence staining. Low stromal LOX-1 expression and low intratumoral CD8+ cytotoxic T-lymphocyte (CTL) status correlated with poor prognosis. Moreover, stromal LOX-1-low/CD8+ CTL-low status was the most important independent prognostic factor of poor overall survival. Most of the LOX-1+ stromal cells were positive for CD163+ , indicating they were CD163+ M2 macrophages. CONCLUSIONS: The MDSC marker, LOX-1, was mainly expressed by M2 macrophages in CRC tissues. LOX-1+ macrophages and CD8+ CTLs may serve as useful biomarkers for predicting the prognosis of CRC.

Implication of duration of clinical presentation on tumor progression and short-term recurrence in patients with early breast cancer.

Breast cancer growth is dependent on time and it may be of utmost importance to take into consideration the duration of clinical symptoms in order to predict which patients are at high risk for disease recurrence. The aim of this study was to determine the association between duration of clinical symptoms and disease recurrence in patients with breast cancer. A total of 139 consecutive patients with primary breast cancer who underwent a radical breast operation were retrospectively investigated and the association between recurrence and the duration of symptoms was investigated. The duration of clinical signs was defined as the time from the onset of symptoms to the date of surgery. The breast cancer cases were divided into two groups on the basis of symptom duration (≤6 and >6 months). The mean duration of symptoms was 191.0±242.6 days. Of the 139 cases, 36 (25.9%) had a duration of symptoms of >6 months. In the univariate analysis, a statistically significant association with long symptom duration was observed for disease recurrence. Of the 139 patients, 6 (4.3%) developed recurrent disease. The univariate analysis revealed that long duration of symptoms and nuclear grade were significantly associated with recurrence. In conclusion, our results indicated that breast cancer progression is dependent on time. A long duration of symptoms (>6 months) may be considered as an indicator of tumor progression and a strong prognostic factor in breast cancer patients.

Significance of lymphatic invasion combined with size of primary tumor for predicting sentinel lymph node metastasis in patients with breast cancer.

BACKGROUND/AIM: Lymphatic invasion (ly) may mainly reflect the selective affinity of breast cancer cells for lymph nodes. We conducted the present study to investigate whether the presence of lymphatic invasion is a predictor of sentinel lymph node (SLN) metastasis in clinically node-negative breast cancer. PATIENTS AND METHODS: We retrospectively evaluated the cases of 202 consecutive female patients with clinically node-negative primary breast cancer who underwent a radical breast operation with SLN biopsy. We examined the relationship between SLN metastasis and the significance of clinicopathological factors, including lymphatic invasion. RESULTS: Among the 202 patients, 49 (24.3%) had SLN metastasis. The univariate and multivariate analyses revealed that the size of the tumor and lymphatic invasion were independent risk factors for SLN metastasis. Among the 96 patients who were ly-negative and had a tumor size of less than 20 mm, only 5 (5.2%) had 1-2 metastases within the SLN. Among the 34 patients who were ly-negative and had a tumor size of less than 10 mm, there were no patients with SLN metastasis. CONCLUSION: Our results suggest that the presence of lymphatic invasion combined with the size of the primary cancer could be considered a strong risk factor for SLN metastasis in clinically node-negative breast cancer, and patients with a tumor size of less than 20 mm and clinically node-negative breast cancer may avoid axillary lymph node dissection after SLN biopsy. There is also a possibility that SLN biopsy could be unnecessary for patients with clinically node-negative breast cancer who are ly-negative and have a tumor size of less than 10 mm.

Prophylactic and informational abdominal drainage is not necessary after colectomy and suprapromontory anastomosis.

Several randomized prospective studies in western countries regarding the usefulness of prophylactic drainage have concluded that prophylactic abdominal drainage tubes are unnecessary. In Japan, however, longitudinal and vascular margins are rather different from in western countries. Furthermore, body mass index and volume of mesentery differed. Thus, although it is a retrospective study, it is worth investigating the usefulness of prophylactic drainage in the Japanese context. Two hundred sixty patients underwent colectomy and suprapromontory anastomosis. Prophylactic drainage tubes were inserted in 124 cases (47%) and not inserted in 136 cases (53%). In terms of postoperative complications, no statistically significant difference was found between the with-drainage and the without-drainage groups. The incidence of the abscess formation was not statistically different in the with-drainage group (4.0%) or the without-drainage group (0.7%). We concluded that the prophylactic and informational drainage tubes are not necessary even in Japanese cases of suprapromontory anastomosis, which typically have a wide resection and regional lymphadenectomy containing the roots of regional vessels.

Tumor response and negative distal resection margins of rectal cancer after hyperthermochemoradiation therapy.

BACKGROUND: The safety of regional hyperthermia has been tested in locally advanced rectal cancer. The aim of this study was to assess the effects of shorter distal margins on local control and survival in rectal cancer patients who were treated with preoperative hyperthermochemoradiation therapy (HCRT) and underwent rectal resection by using the total mesorectal excision (TME) method. PATIENTS AND METHODS: Ninety-three patients with rectal adenocarcinoma who received neoadjuvant HCRT (total radiation: 50 Gy) were included in this study. Surgery was performed 8 weeks after HCRT, and each resected specimen was evaluated histologically. Length of distal surgical margins, status of circumferential margins, pathological response, and tumor node metastasis stage were examined for their effects on recurrence and survival. RESULTS: Fifty-eight (62.4%) patients had tumor regression, and 20 (21.5%) had a pathological complete response. Distal margin length ranged from 1 to 55 mm (median, 21 mm) and did not correlate with local recurrence (p=0.57) or survival (p=0.75) by univariate analysis. Kaplan-Meier estimates of recurrence-free survival and local recurrence for the <10 mm versus ≥10 mm groups were not significantly different. Positive circumferential margins and failure of tumors to respond were unfavorable factors in survival. CONCLUSION: Distal resection margins that are shorter than 10 mm but are not positive appear to be equivalent to longer margins in patients who undergo HCRT followed by rectal resection with TME. To improve the down-staging rate, additional studies are needed.