[Brain Metastasis and Leptomeningeal Carcinomatosis after Surgery for Esophageal Cancer-A Case Report].

A 70-year-old man had undergone thoracoscopic esophagectomy following neoadjuvant chemotherapy for thoracic esophageal squamous cell carcinoma 3 years before presentation. He was undergoing whole-brain irradiation following surgery for a solitary brain metastatic tumor. The chief complaint was left leg pain during irradiation. FDG-PET/CT and MRI revealed metastases in bilateral cauda equina S1 nerve roots. Cerebrospinal fluid examination also revealed malignant cells. He received chemotherapy with 2 courses of 5-fluorouracil and cisplatin following 30 Gy of spinal irradiation. To control neurological symptoms, 4 courses of intrathecal chemotherapy with methotrexate, cytarabine, and betamethasone were performed. However, he gradually weakened and died 8 months after brain metastasis and 7 months after leptomeningeal carcinomatosis. The multidisciplinary treatment using irradiation and systemic and intrathecal chemotherapies could improve the survival of patients with leptomeningeal carcinomatosis of esophageal squamous cell carcinoma.

[Effect of Proteinuria in Patients Receiving Anti-VEGF Therapy for Advanced Colorectal Cancer].

Grade 2 or 3 proteinuria was observed in 54 patients out of 158 metastatic colorectal cancer patients receiving anti-VEGF therapy. Patients with diabetes and hypertension were risk for severe proteinuria. ARBs were more frequently used in patients with severe proteinuria. However, they could not reduce proteinuria. The examination of protein/creatinine ratio was useful for continuing anti-VEGF therapy.

Low-dose immunoglobulin G is not associated with mortality in patients with sepsis and septic shock.

BACKGROUND: The administration of low-dose intravenous immunoglobulin G (IVIgG) (5 g/day for 3 days; approximate total 0.3 g/kg) is widely used as an adjunctive treatment for patients with sepsis in Japan, but its efficacy in the reduction of mortality has not been evaluated. We investigated whether the administration of low-dose IVIgG is associated with clinically important outcomes including intensive care unit (ICU) and in-hospital mortality. METHODS: This is a post-hoc subgroup analysis of data from a retrospective cohort study, the Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study. The JSEPTIC DIC study was conducted in 42 ICUs in 40 institutions throughout Japan, and it investigated associations between sepsis-related coagulopathy, anticoagulation therapies, and clinical outcomes of 3195 adult patients with sepsis and septic shock admitted to ICUs from January 2011 through December 2013. To investigate associations between low-dose IVIgG administration and mortalities, propensity score-based matching analysis was used. RESULTS: IVIgG was administered to 960 patients (30.8%). Patients who received IVIgG were more severely ill than those who did not (Acute Physiology and Chronic Health Evaluation (APACHE) II score 24.2 ± 8.8 vs 22.6 ± 8.7, p < 0.001). They had higher ICU mortality (22.8% vs 17.4%, p < 0.001), but similar in-hospital mortality (34.4% vs 31.0%, p = 0.066). In propensity score-matched analysis, 653 pairs were created. Both ICU mortality and in-hospital mortality were similar between the two groups (21.0% vs 18.1%, p = 0.185, and 32.9% vs 28.6%, p = 0.093, respectively) using generalized estimating equations fitted with logistic regression models adjusted for other therapeutic interventions. The administration of IVIgG was not associated with ICU or in-hospital mortality (odds ratio (OR) 0.883; 95% confidence interval (CI) 0.655-1.192, p = 0.417, and OR 0.957, 95% CI, 0.724-1.265, p = 0.758, respectively). CONCLUSIONS: In this analysis of a large cohort of patients with sepsis and septic shock, the administration of low-dose IVIgG as an adjunctive therapy was not associated with a decrease in ICU or in-hospital mortality. TRIAL REGISTRATION: University Hospital Medical Information Network Individual Clinical Trials Registry, UMIN-CTR000012543 . Registered on 10 December 2013.

Single-incision thoracoscopic surgery using a chest wall pulley for lung excision in patients with primary spontaneous pneumothorax.

PURPOSE: The aim of the study was to evaluate the feasibility and compare the outcomes of single-incision thoracoscopic surgery using a chest wall pulley for lung excision (PulLE) vs. those of conventional video-assisted thoracic surgery (cVATS) in patients with primary spontaneous pneumothorax (PSP). METHODS: Sixty-nine patients who underwent PulLE (n = 34) or cVATS (n = 35) between January 2009 and December 2013 were enrolled in this study. PulLE was performed as follows. After making a 17- to 25-mm single incision in the 6th intercostal space (6ICS) at the median axillary line, the visceral pleura near the bulla was sutured for traction. The parietal pleura at 3ICS was then sutured from the thoracic cavity to serve as the chest wall pulley and a traction thread was passed through the pulley. By manipulating the traction thread, it was possible to move the lesion to an arbitrary site for excision. The postoperative scar was nearly invisible. RESULTS: The operative time, duration of postoperative drainage, and postoperative hospital stay were equivalent for PulLE vs. cVATS. There was no significant difference in postoperative recurrence rates. CONCLUSIONS: PulLE has cosmetic benefits over cVATS and is easy to perform. We believe our novel procedure has the potential to become the standard operative treatment for PSP.

Visual cognitive function in infants with intractable epilepsy before and after surgery.

PURPOSE: One purpose of pediatric epilepsy surgery is to improve psychomotor development. However, few methods are available for evaluating cognitive function in infants with severe developmental delays. We used the following battery of tests to evaluate visual cognitive function of infants following surgery for intractable epilepsy. METHODS: The following battery of tests were used to evaluate eight patients before and 1 month after surgery: (1) Erhardt Developmental Vision Assessment (EDVA); (2) evaluation of ocular pursuit for a flashing LED toy; (3) three visual acuity tests preferential looking procedure, optokinetic nystagmus, and Sheridan's Test for Young Children and Retarded balls vision test; and (4) existing developmental test. RESULTS: EDVA scores and ocular pursuit score with a flashing LED toy showed the same trends with developmental age as the existing developmental tests. However, in some patients, the EDVA score and ocular pursuit score improved greatly, whereas the developmental age changed very little. CONCLUSIONS: These tests are suitable for patients with intractable epilepsy and severe developmental delay. By performing these tests before and after surgery, small cognitive changes occurring soon after the surgery may be detected.

[Evaluation of 2 ports video-assisted thoracoscopic surgery (VATS) using endo-close for primary spontaneous pneumothorax].

We aimed to assess the perioperative outcomes of 2 ports video-assisted thoracoscopic surgery(VATS) using Endo-Close (2 ports VATS) in patient for the primary spontaneous pneumothorax(PSP) compared to conventional 3 ports VATS in our hospital. 31 consecutive patients(11;2 ports VATS and 20;3 ports VATS) since 2009 were enrolled in this study. Endo-Close is a device that for pulling the anchoring thread by puncture 1.5 cm incision at the level of the 7th intercostal space( ICS) at the median axillary line( MAL) for camera port, a 1.5 cm incision at the level of the 4th ICS at the anterior axillary line for working port, and 2 mm puncture at the level of the 5th ICS at the MAL using the Endo-Close were placed for this procedure. Compared with 3 ports VATS, equivalent results were obtained by the present procedure;operation time(58.6±18.3 minutes vs 63.0±15.1 minutes, NS), duration of drainage after operation(1.0±0 days vs 1.3±0.5 days, NS), postoperative hospital stay(3.0±1.5 days vs 3.7±1.4 days, NS) significantly.Blood loss was minimal in both cases. In conclusion, 2 port VATS using Endo-Close proved to be feasible method in surgical treatment for PSP.

[Experience of DMAT rescue activity by doctor-helicopter in Tohoku Area after the earthquake].

We operated rescue activities in Tohoku area after the earthquake of March 11th, 2011. From our hospital, a doctor-helicopter flew to the staging care unit at Hanamaki airport with two members of the disaster medical assistance team (DMAT), one of whom was an anesthesiologist. The helicopter carried ten patients by nine flight missions, who were the victims of tsunami after the earthquake. There were seven doctor-helicopters from all over Japan and did the missions based at Hanamaki airport. The missions was quite different from our usual job as an anesthesiologist, but we could transfer the patients safely by using some knowledge of stabilizing the unstable patients as flight doctors. We report the details of our activities by our doctor-helicopters in Tohoku area.

[Pleuroperitoneal communication with liver cirrhosis and chronic kidney disease needed hemodialysis successfully treated by video-assisted thoracoscopic surgery; report of a case].

A 59-year-old man treated with hemodialysis for liver cirhhosis and chronic kidney disease developed right pleural effusion and ascites. Ascites always decreased after thoracocentesis for pleural effusion. In spite of repeated treatment with chest tube drainage, massive pleural effusion reappeared. Under the diagnosis of pleuroperitoneal communication, surgical repair of the diaphragm by video assisted thoracoscopic surgery (VATS) were performed. Bulla and pin hole were found and they were resected and sutured. Surgery was safely and successfully accomplished though the patient had Child-Pugh B liver cirhhosis. Pleural effusion disappeared after surgery.

[A case of pneumonia due to Enterococcus faecium after near drowing].

A 73-year-old man admitted for near drowning was found after 24 hours of mild therapeutic hypothermia to have pneumonia. Blood gas analysis showed metabolic acidosis, hypercapnia, and hyponatremia. Chest X-ray and computed tomography (CT) showed bilateral mainly lower-lobe consolidation. After being treated with 13.5 g of tazobactam/piperacillin and 1.0-1.25 g of vancomycin per day for two weeks, the man recovered from his severe respiratory failure. Enterococcus faecium was isolated twice from sputum and raising the dose of vancomycin was effective, but it took 10 days to wean him from ventilator support. While this case may be rare, therapeutic hypothermia and near drowning together were considered predisposing factors in the severity of the pneumonia caused by E. faecium. The possibility of pneumonia due to vancomycin-resistant Enterococci should thus be considered in similar cases.

A case of Spigelian hernia after laparoscopic incisional hernia repair.

Laparoscopic ventral hernia repair with intraperitoneal onlay mesh reinforcement is often performed in clinical practice. We herein describe a patient who developed a Spigelian hernia at the edge of the mesh due to rupture of the muscular layer in the abdominal wall. A 69-year-old woman developed a left-sided abdominal bulge 15 months after laparoscopic ventral hernia repair. CT showed a 33-mm defect in the abdominal wall at the lateral edge of the left abdominal rectus muscle with an intestinal prolapse through the defect. She was diagnosed with a Spigelian hernia and underwent operation. The hernia orifice was located at the aponeurosis of the transverse abdominal muscle where the thread had been used to fix the mesh through all layers of the abdominal wall. This report details a case of a Spigelian hernia after laparoscopic ventral hernia repair.

Multidetector computed tomography for preoperative identification of left gastric vein location in patients with gastric cancer.

BACKGROUND: The area near the left gastric vein (LGV) is a challenging site at which to perform dissection of the lymph nodes during gastrectomy. Therefore, knowledge of the precise location of the LGV is important. The objective of this study was to examine the usefulness of multidetector computed tomography (MDCT) for the identification of the LGV. METHODS: Eighty-one patients with gastric cancer underwent MDCT, which was performed with contrast media in 76 patients and without contrast media in 5 patients. A 5-mm thin slice of the frontal image was reconstructed. These images were examined preoperatively to detect the location of the LGV. Upon gastrectomy, the LGV was identified and its location compared to that determined by MDCT. RESULTS: The LGV was identified by MDCT in 76 of the 81 patients (93.8%). The LGV was subsequently located during the operation in all 81 patients. The LGV was located dorsal to the common hepatic artery in 40 patients (49.4%), ventral to the common hepatic artery in 18 patients (22.2%), ventral to the splenic artery in 17 patients (21.0%), dorsal to the splenic artery in 2 patients (2.5%) and in other positions in 4 patients (4.9%). In all patients, the location of the LGV detected using MDCT was consistent with that identified during gastrectomy. In the 4 patients with relatively unusual locations of the LGV, these 4 LGV variants were identified preoperatively by MDCT. CONCLUSION: MDCT was useful for identifying the location of the LGV prior to gastrectomy.

[A successfully resected case of rectal cancer with liver metastases treated with mFOLFOX6 and bevacizumab].

A sixties-man had complained of melena. Colonoscopy revealed type 2 tumor at rectum. Computed tomography (CT)demonstrated lymph node metastasis in front of sacrum and two low density areas which were suspected metastases in the liver. The patient was diagnosed stageIV rectal cancer and resected primary focus and lymph node metastasis.[ Ra-RS, ant, type 2, moderately differentiated adenocarcinoma, ly1, v3, pSE, pN2, sH1(Grade C), sP0, pM1(No. 270)]without liver resection. It was due to high level of CEA and remote lymph node metastasis. The patient was treated with mFOLFOX6 and bevacizumab after the operation. The level of CEA decreased to normal level and CT revealed a partial response after 4 cycles of systemic chemotherapy. Liver resection was performed safely. Histological response was Grade 2 at liver metastases.

[A case of curatively resected biliary tract cancer with peritoneal dissemination through effective response to chemotherapy of S-1].

The patient is a 55-year-old woman who has biliary tract cancer with peritoneal dissemination (T3N1P2M0, Stage IV b). Since a curative operation was deemed impossible, we conducted chemotherapy using S-1. S-1 (120 mg/day) was administered for 2 weeks and then chemotherapy was discontinued for 1 week, which was regarded as one course. After 2 courses of the chemotherapy, CT scan showed that the metastatic lymph node and tumor of peritoneal dissemination were reduced in size, and that there was no ascites. Left lobectomy of the liver, cholecystectomy, and partial resection of omentum were carried out. The pathological diagnosis was also curative (pT1, pN0, pP0, Stage I). We think this case shows the possibility of S-1 for patients with unresectable biliary tract cancer.

Characteristics, treatments, and outcomes of severe sepsis of 3195 ICU-treated adult patients throughout Japan during 2011-2013.

Severe sepsis is a major concern in the intensive care unit (ICU), although there is very little epidemiological information regarding severe sepsis in Japan. This study evaluated 3195 patients with severe sepsis in 42 ICUs throughout Japan. The patients with severe sepsis had a mean age of 70 ± 15 years and a mean Acute Physiology and Chronic Health Evaluation II score of 23 ± 9. The estimated survival rates at 28 and 90 days after ICU admission were 73.6 and 56.3 %, respectively.

Antithrombin Supplementation and Mortality in Sepsis-Induced Disseminated Intravascular Coagulation: A Multicenter Retrospective Observational Study.

Supplemental doses of antithrombin (AT) are widely used to treat sepsis-induced disseminated intravascular coagulation (DIC) in Japan. However, evidence on the benefits of AT supplementation for DIC is insufficient. This multicenter retrospective observational study aimed to clarify the effect of AT supplementation on sepsis-induced DIC using propensity score analyses. Data from 3,195 consecutive adult patients admitted to 42 intensive care units for severe sepsis treatment were retrospectively analyzed; 1,784 patients were diagnosed with DIC (n = 715, AT group; n = 1,069, control group). Inverse probability of treatment-weighted propensity score analysis indicated a statistically significant association between AT supplementation and lower in-hospital all-cause mortality (n = 1,784, odds ratio [95% confidence intervals]: 0.748 [0.572-0.978], P = 0.034). However, quintile-stratified propensity score analysis (n = 1,784, odds ratio: 0.823 [0.646-1.050], P = 0.117) and propensity score matching analysis (461 matching pairs, odds ratio: 0.855 [0.649-1.125], P = 0.263) did not show this association. In the early days after intensive care unit admission, the survival rate was statistically higher in the propensity score-matched AT group than in the propensity score-matched control group (P = 0.007). In DIC patients without concomitant heparin administration, similar results were observed. In conclusion, AT supplementation may be associated with reduced in-hospital all-cause mortality in patients with sepsis-induced DIC. However, the statistical robustness of this connection was not strong. In addition, although the number of transfusions needed in patients with AT supplementation increased, severe bleeding complications did not.

[A case of Guillain-Barré Syndrome complicated with Fat Embolism syndrome].

A 22-year-old man was admitted to our ICU for treatment of fat embolism syndrome complicated with multiple bone fractures. Acute respiratory distress syndrome developed, and the patient received steroid therapy. During the steroid therapy, symmetrical proximal muscle weakness of all four limbs without sensory abnormalities and autonomic nervous system dysfunction developed. Cerebrospinal fluid showed albuminocytologic dissociation. Blood examination showed herpes simplex virus and cytomegalovirus infection. The patient was diagnosed as having Guillain-Barré syndrome, but he recovered completely one month after admission. It is thought that the prolonged steroid therapy for acute respiratory distress syndrome in this case induced viral infection that might have caused Guillain-Barré syndrome.

Significance of Akt phosphorylation on tumor growth and vascular endothelial growth factor expression in human gastric carcinoma.

OBJECTIVE: Hypoxia is known to be a prevalent stress stimulus and increases the transcription of vascular endothelial growth factor (VEGF) mediated by hypoxia inducible factor-1alpha (HIF-1alpha). We investigated the role of phosphatidyl inositol-3 OH kinase (PI3K)-Akt signaling in the regulation of HIF-1alpha and VEGF expression in human gastric adenocarcinoma. METHODS: The growth-inhibitory and apoptosis-inducing effects of the LY294002 PI3K inhibitor were analyzed in four gastric cancer cell lines and in vivo. The regulatory mechanism of VEGF and HIF-1alpha expression under hypoxic conditions was examined in the cell cultures. In 88 gastric cancer tissue samples, phosphorylated Akt and VEGF expression were analyzed immunohistochemically. RESULTS: LY294002 suppressed cell proliferation but induced apoptosis with decreased levels of phosphorylated Akt. HIF-1alpha expression and VEGF secretion were induced under hypoxic conditions and VEGF protein secretion was significantly decreased by treatment with LY294002. In tumor samples, phosphorylated Akt expression was detected in 57% of the tumors, which was correlated with high VEGF expression, angiogenesis, clinicopathological parameters as well as a poor outcome. CONCLUSIONS: These findings suggest that phosphorylated Akt (Ser473) reflects the grade of malignancy in human gastric adenocarcinomas, not only in terms of tumor growth but also with respect to tumor angiogenesis.

Studies on the prevalence of human papillomavirus in pregnant women in Japan.

AIMS: In order to evaluate the prevalence of human papillomavirus (HPV) in the pregnant population in Japan. METHODS: We examined cervical swabs of 1,183 pregnant women for HPV DNA using a PCR-RFLP method during October, 2000 and February, 2001. The overall prevalence of HPV in 1,183 pregnant women was analyzed and stratified by age. RESULTS: The overall prevalence of HPV in pregnant women was 12.5% (148 of 1,183 cases). The prevalence in pregnant women younger than 25 years (22.6%, 28 of 124 cases) was significantly higher compared with that in pregnant women > or =25 years (11.3%, 120 of 1057 cases, P< 0.0005). CONCLUSIONS: The data indicate a significantly higher prevalence of HPV infection in younger pregnant Japanese women.

Mutational analysis of TP53 and p21 in familial and sporadic ovarian cancer in Japan.

OBJECTIVE: To investigate whether somatic mutations in cell cycle checkpoint genes, TP53 and p21, are involved in the development of ovarian cancer with or without BRCA1 germline mutation. METHODS: We analyzed somatic genetic alterations of TP53 and p21 in 46 ovarian cancer patients with BRCA1 germline mutations and 93 sporadic patients, using direct sequencing for the entire coding sequences in TP53 and p21. RESULTS: TP53 somatic mutations were detected in 25 of the 46 BRCA1 cases and 40 of the 93 sporadic cases (54.3% vs. 43.0%). In contrast, p21 somatic mutations were detected in 1 of the 46 BRCA1 cases and 2 of the 93 sporadic cases (2.2% vs. 2.2%). TP53 mutations in sporadic cases more frequently occurred in exons 6-11 than those in cases with germline BRCA1 mutations (84.4% vs. 56.3%: P = 0.013). The proportion of sporadic cases with TP53 mutations in non-serous tumors (e.g. endometrioid, clear cell, or mucinous) was significantly lower than that in serous tumors (18.5% vs. 53.0%: P = 0.0038). However, there was no significant difference between the proportion of BRCA1 cases with TP53 mutation in non-serous and in serous tumors (37.5% vs. 57.9%). CONCLUSIONS: Our results suggest that somatic mutation of TP53 plays less of a role in the carcinogenesis of sporadic non-serous tumors than in that of sporadic serous tumors or BRCA1-related tumors. Furthermore, p21 somatic mutation appears to be less involved in the development of ovarian cancer than TP53 somatic mutation.

Mutational analysis of the estrogen receptor-alpha gene in familial ovarian cancer.

AIM: The genetic region of 6q25 containing the estrogen receptor-alpha (ER-alpha) gene is lost in a significant number of ovarian tumors. The aim of this study was to identify how inherited variation in the ER-alpha gene contributes to susceptibility to familial ovarian cancer. METHODS: DNA obtained from 18 cases of familial ovarian cancer without mutation of the BRCA1 and BRCA2 genes, 20 cases with BRCA1 mutation, 20 cases of sporadic ovarian cancer, and 19 controls were screened for mutations in the coding region of the ER-alpha gene using direct sequencing. RESULTS: Two germline missense variants at codons 307 [GCC(Ala)-->TCC(Ser)] and 347 [ACC(Thr)-->TCC(Ser)] were detected in two unrelated cases with BRCA1 mutation, but not in all other cases tested. Three polymorphisms in codon 10 [TCT-->TCC(Ser)], codon 325 [CCC-->CCG(Pro)], and codon 594 [ACA-->ACG(Thr)] were identified in this series, and a higher frequency of the allele TCC at codon 10 and a lower frequency of the allele CCG at codon 325 were observed in familial cases without BRCA1 mutation, compared with those in familial cases with BRCA1 mutation, in both the sporadic cases and in the controls. CONCLUSIONS: We could not detect pathogenic mutations of the ER-alpha gene in ovarian cancer cases without BRCA1 mutation. However, association analyses of two polymorphisms suggest that the ER-alpha gene or a gene located close to the ER-alpha locus might be related to susceptibility of familial ovarian cancer without BRCA1 mutation.