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A 42-year-old woman was admitted to our hospital because of a positive fecal occult blood test. Colonoscopy examination revealed an elevated lesion measuring 25mm in diameter at the terminal ileum. A histological diagnosis of neuroendocrine tumor(NET)was made based on biopsy specimens taken from the lesion. Since no apparent distant metastasis other than the ileocolic lymph nodes was noted, laparoscopy-assisted ileocecal resection with regional lymph node dissection was performed. In the resected material, NET(G2)limited to the subserosa layer was present. The NET tested positive for synaptophysin, chromogranin A, and CD56. Metastases in the paraileal lymph nodes was detected. NET metastasis to the ileum is frequent, even if the tumor is small in diameter; therefore, it is necessary to resect the tumor entirely and to dissect the regional lymph nodes.

An 80-year-old woman had undergone a right hemicolectomy for ascending colon cancer 9 months prior to the current presentation. CT and PET-CT showed a solitary tumor measuring 55mm in diameter at the uterus and rectum. Three 5mm ports and two 12mm two ports were placed. The sigmoid colon was mobilized using a medial approach as usual in laparoscopic surgery. The rectum and uterus were mobilized and were resected. We inserted the End-catchTM in from the vagina and removed the specimen. The patient had no abdominal pain and was discharged from the hospital 9 days after the operation.

A 59-year-old man underwent total gastrectomy(with D2 dissection)and cholecystectomy for gastric cancer and a submucosal tumor of the stomach. The specimen was immunohistochemically positive for c-kit, the Ki-67 label index was 10%, and the mitotic count was 20/HPF. Finally, the patient was diagnosed with high-risk gastrointestinal stromal cancer with normal type gastric cancer. After discharge from hospital, we started administration of TS-1 as adjuvant therapy for the gastric cancer. As multiple recurrences of the GIST in the abdomen developed, the patient underwent 3 radical local resections. Mutational analysis revealed a PDGFRA mutation in exon 18, which causes resistance to both imatinib and sunitinib. As he was refractory to imatinib, the patient received regorafenib. After a while, it caused liver failure, which required 7 rounds of plasmapheresis. The patient died from multiple organ failure resulting from multiple recurrences 4 years after the first surgery.

A n 85-year-old woman presented with a mass in the left breast. A3 7mm lobulated mass including enhancement of a cyst of 37mm was detected by sonography. An axillary lymph node had increased to 16 mm. Atypical cells dyed by light green and orange G were identified by fine needle aspiration and cytology. She was diagnosed with left breast cancer(cT2N1M0, Stage II B), histologically suspected to be squamous cell carcinoma. She underwent a left-breast-conserving surgery and axillary lymph node dissection. On pathology, a cyst of 34×30mm was noted. The tumor grew from inside the cyst to the surround- ing tissue and it had a trend for keratinocytes. Lymph node metastases affected 1/11. By immunostaining, the tumor was found to be ER(+), PgR(-), HER2(-), CK5/6(+), p40(+), mammaglobin(-), and GCDFP15(-). There was no component of ductal carcinoma. She received radiotherapy to the left breast and tamoxifen as an adjuvant therapy. Squamous cell carcinoma of the breast is rare. We encountered a case of pure squamous cell carcinoma of the breast in an elderly woman. We report this case with a discussion of the relevant literature.

Laparoscopic surgery is less invasive and has better cosmetic results. Laparoscopic liver resection(LLR)was covered by health insurance in April 2010, and has increasingly been performed in many hospitals, and also in cases of elderly patients. We report the results of laparoscopic liver resection for hepatocellular carcinoma(HCC)in patients ≥80 years old. From June 2010 through March 2016, 237 cases of laparoscopic hepatectomy for HCC were performed in our hospital, and 35 of 237 cases were patients ≥80 years old(the elderly group). The operation time in the elderly vs the non-elderly group was 321 minutes vs 340.9 minutes(p=0.4676), the blood loss was 447.2mL vs 331.5mL(p=0.6691), and the hospital stay after the operation was 18 days vs 16 days(p=0.6347). The 3 year disease free survival rate for stage I was 66.7% vs 58.6%(p= 0.1849), for stage II was 35.6% vs 31.8%(p=0.7538), for stage III was 33.3% vs 49.5%(p=0.8683), and for stage IV was 100% vs 32.4%(p=0.3452). Laparoscopic hepatectomy for HCC can be performed safely, even for patients ≥80 years old. Further studies are necessary to confirm the benefits of laparoscopic liver resection for elderly patients compared with the non-elderly.

A 69-year-old man with anemia underwent colonoscopy. Colonoscopy showed a black tumor, 2 cm from the anal verge. The biopsy specimen revealed malignant melanoma, which was preoperatively diagnosed as T1(SM), N0, M0, Stage I . We performed laparoscopic abdominoperineal resection. The tissue type and diagnosis were malignant melanoma, pT1b(10 mm), pN0, pM0, ly0, v0, pDM0, pPM0, pRM0, pStage I b, according to the Colon Cancer Handling Terms, 8th edition). The patient did not receive adjuvant chemotherapy. However, he survived postoperatively for 9 months, with no sign of recurrence.

We report the case of a 70-year-oldwoman with local recurrence of occult breast cancer after conserving therapy. Breast cancer metastasis to an axillary lymph node was suspected when she was 62-years-old. Even with mammography, ultrasound sonography, positron emission tomography/computedtomography, andmagnetic resonance imaging, the primary disease lesion could not be identified. She underwent axillary dissection, and received 5 years of endocrine therapy. Eight years after surgery, a new ipsilateral breast tumor was detectedusing ultrasoundsonography andvacuum assistedbiopsy, confirmedas invasive carcinoma. This time the patient had no distant metastases; therefore, she was diagnosed with local recurrence, and mastectomy with immediate breast reconstruction was performed. Breast conserving surgery aims to reduce the psychological burden on the patient but must be closely followed-up in case of local recurrence. Any incidences of local recurrence can also be treatedusing breast reconstruction surgery.

Pancreatic adenocarcinoma is one of the leading causes of cancer deaths in Japan.Albumin -bound paclitaxel (nab-paclitaxel)plus gemcitabine hydrochloride(GEM)combination chemotherapy provided significant improvements in the overall and progression-free survival in a phase III trial in Europe and America and a phase II trial in Japan.As a result, this combination therapy was approved for use in Japan.We evaluated the efficacy of nab-paclitaxel plus GEM with metastatic or recurrent pancreatic cancer.Between December 2014 and March 2016, 11 patients received nab-paclitaxel plus GEM as follows: nab-paclitaxel(125mg/m2 of body-surface area)followed by GEM(1,000mg/m2)on days 1, 8, and 15 every 4 weeks.The treatment was continued until disease progression, unacceptable adverse events, discontinuation as decided by the investigators, or patient refusal.The mean age was 65.6 years(range, 48-75 years), and 8 out of 11 patients were men.Ten patients had an Eastern Cooperative Oncology Group(ECOG)performance status(PS)of 0.Ten patients had metastatic disease.Only 4 patients had no prior therapy.The mean duration of treatment was 10.2 weeks(range, 2-41 weeks).The relative dose intensities of nab-paclitaxel and GEM were 90.6%(66.7-100%)and 87.5%(62.9-100%), respectively.The major Grade 3 or 4 hematological toxicities were leucopenia(54.5%), neutropenia(36.4%), anemia (27.3%), and thrombocytopenia(18.2%).The major grade 2 or 3 non-hematological toxicities were fatigue(45.6%), skin rash(27.3%), peripheral sensory neuropathy(9.1%), anorexia(9.1%), and stomatitis(9.1%).There were no treatmentrelated deaths.Interstitial lung disease was not observed.The 6 month progression-free and overall survival rate were 25.7% and 66.7%, respectively. The disease control rate was 90.9%(complete response, n=0; partial response, n=1; stable disease, n=9; progressive disease, n=1).Nab-paclitaxel plus GEM is well tolerated and associated with efficacy and improved survival outcomes.Nab -paclitaxel plus GEM can be the standard treatment for patients with metastatic pancreatic adenocarcinoma.

Pancreatic ductal carcinoma is a highly aggressive cancer, and chemotherapy is the standard therapy for pancreatic adenocarcinoma. We report curative resection for a case of pancreatic cancer with liver metastasis after chemotherapy. A 67-yearold woman presented with vomiting and weight loss, and was admitted to our hospital for an evaluation of pancreatic lesions. Computed tomography revealed a hypoattenuating tumor in the head of the pancreas. We would usually perform pancreatoduodenectomy based on a diagnosis of cStage III . However, this case was inoperable because we found 4 liver metastases during surgery, which we resected. Sixteen days after surgery, we administered FOLFIRINOX chemotherapy. The grade 2 toxicities were nausea, anorexia, diarrhea, and fatigue, but serious adverse events did not occur. After 7 courses of chemotherapy, no new metastases were noted. Therefore, radical subtotal stomach-preserving pancreatoduodenectomy was performed. The patient has survived without any recurrence for more than 17 months after hepatectomy.

Background Fetal goitrous hypothyroidism is mainly caused by maternal treatment of Graves' disease. Fetal goiter sometimes compresses the trachea and esophagus and may cause polyhydramnios, preterm labor, complications of labor and delivery, and neonatal respiratory disorder. Case presentation We report a case of fetal goitrous hypothyroidism in which the mother had Graves' disease, which was treated with propylthiouracil. Intra-amniotic levothyroxine (L-T4) administration was performed, and the fetal goiter decreased in size. A female infant was delivered without goiter and complications. Thyroid function was within the normal range. Conclusions Previous reports on fetal goitrous hypothyroidism that was treated with intra-amniotic L-T4 showed that patients who had intra-amniotic L-T4 administration were likely to have a good outcome compared with patients who did not have L-T4. Thyroid function of the mother and fetus should be carefully monitored and treated appropriately.

Background Esophageal cancer is frequently associated with multiple primary cancers and they are sometimes found simultaneously. The aim of this retrospective study was to clarify the clinical outcome of simultaneous surgery for patients with esophageal squamous cell cancer with multiple primary cancers. Methods Clinicopathologic features and surgical outcomes were compared between 14 simultaneous resections (SR group) and 108 single esophagectomy (E group) among 122 patients who underwent esophagectomy for esophageal squamous cell cancer in 2005–2013. Results The most common site of multiple primary cancers was the stomach (6 patients; 43%), followed by the stomach (5 patients; 36%), the lung (4 patients; 29%), the tongue, the colon, and the duodenum (1 patient; 7%). The number of multiple primary cancers was double (12 patients; 86%), triple (1 patient; 7%), and quadruple (1 patient; 7%). The incidence of antecedent and subsequent cancers didn’t differ between two groups. The SR group increased blood loss and prolonged operation time. However, there were no differences in postoperative morbidity, mortality and hospital days between the two groups. The SR group had shorter overall survival than the E group (3 years MST 54% vs 74%, Log rank P = 0.056) Conclusion The presence of synchronous cancers complicates the surgical resection of esophageal cancer. Although simultaneous surgery for patients with esophageal squamous cell cancer with multiple primary cancers was found to be comparably safe, the overall survival was poor than the single esophagectomy group. Treatment strategy condidering multidisciplinary approach is needed to improve the survival. Disclosure All authors have declared no conflicts of interest.

There are almost no reports about drug excretion management during colorectal cancer chemotherapy. Anticancer chemotherapeutic drugs excreted in urine and feces may exert toxic effects and promote teratogenesis, mutagenesis, and carcinogenesis. To assess the knowledge of patients about drug excretion, a questionnaire survey was performed among 45 patients receiving chemotherapy for colorectal cancer in our hospital; among them, 36 patients completed the survey. Most of the patients did not know about the excretion and toxic effects of anticancer drugs. The results indicate that patients should be instructed on the management ofexcretion during chemotherapy to minimize toxic exposure. We believe that unnecessary exposure of patients and their families to anticancer drugs should be minimized. This study highlights the importance of issuing guidelines regarding excretion management during cancer chemotherapy.

Background Cecal volvulus is an uncommon cause of acute abdomen in patients. Cecal volvulus is currently treated mostly with right hemicolectomy with laparotomy, which is an invasive surgical procedure. Less invasive techniques, such as endoscopic decompression, have a poor success rate. Case presentation We report a case of cecal volvulus in a 35-year-old male patient. He was successfully treated with single-site laparoscopic decompression by inserting a catheter through the amputated appendix, detorsion, and hemicolectomy. This approach was less invasive than the traditional approach and resulted in satisfactory outcomes and cosmesis. Conclusions Application of single-site laparoscopic colectomy to acute cecal volvulus is feasible using decompression of the dilated colon by inserting a catheter through the amputated appendix. To the best of our knowledge, this is the first report of this treatment.

Pancreatic adenocarcinoma is one of the leading causes of cancer-related deaths in Japan. oxaliplatin: L-OHP, irinotecan: CPT-11, fluorouracil: 5-FU, and Leucovorin: l-LV (FOLFIRINOX) combination chemotherapy provided significant improvements in overall and progression-free survival in a phase Ⅲ trial in France and in a phase Ⅱ trial in Japan. As a result, this combination therapy was approved for use in Japan. We evaluated the efficacy of FOLFIRINOX in metastatic or recurrent pancreatic cancer. Between October 2014 and July 2015, 10 patients received mFOLFIRINOX as follows: 2-hour infusion of LOHP at 85 mg/m2, 2-hour infusion of l-LV at 200 mg/m2 and infusion of CPT-11 over 90 min at 150 mg/m2, followed by continuous infusion of 5-FU over 46 hours at 2,400mg/m2. Prior to the treatment, a 5-hydroxytryptamine receptor antagonist, aprepitant, and dexamethasone were given. The treatment was repeated every 2 weeks until disease progression, unacceptable toxicity, discontinuation as decided by the investigators, or patient refusal. The mean age of the patients was 65.0 years (range, 59-75 years), and 4 out of 10 patients were men. Only 2 patients had no prior therapy. Nine patients had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0. Eight patients had metastasis and 2 had locally recurrent disease. The median number of treatment cycles was 5 (range, 1-14). The relative dose intensities of 5-FU, L-OHP and CPT-11 were 93.3% (range, 58.3-100%), 84.0% (range, 63.2-100%), and 76.0% (range, 44.4-83.3%), respectively. The major Grade 3 and 4 hematological toxicities were neutropenia (40%), leucopenia (30%), and thrombocytopenia(10%). The major Grade 2 and 3 non-hematological toxicities were diarrhea (30%), nausea (60%), and vomiting (10%). Serious adverse events occurred in 2 patients. Severe biliary tract infection causing sepsis was observed in 1 patient with a biliary stent. Overwhelming post-splenectomy infection was observed in 1 patient after distal pancreatectomy. No cases of interstitial lung disease were observed. The 6-month progression-free and overall survival rates were 59.3% and 61.7%, respectively. The overall response rate was 10%, and the disease control rate was 90%(complete response [CR], n=0; partial response [PR], n=1; stable disease [SD], n=8; progressive disease [PD], n=1). Although FOLFIRINOX is associated with increased treatment efficacy and survival outcomes, because of its severe toxicity it cannot be administered to all patients. FOLFIRINOX can be used as the standard treatment for patients with a good performance status.

The Guidelines for Colorectal Cancer Treatment list indication and curative resection criteria for the endoscopic resection of mucosal and submucosal invasive colorectal cancers. Here, we report the case of a woman who underwent endoscopic mucosal resection (EMR) but should have undergone curative resection because the submucosal invasion depth in this case was 1,200 mm; however, she did not undergo additional curative surgery. Although liver and lymph node metastases were observed 7 years later, we were able to resect all of these tumors after neoadjuvant chemotherapy. We strongly recommend additional curative surgery for patients who fulfill the criteria for curative resection after EMR because of the very high recurrence rates in such cases.

Systemic chemotherapy based on 5-fluorouracil (5-FU) is a standard treatment for unresectable or recurrent colorectal cancer. Although hyperammonemia is known as one of the adverse side effects of 5-FU, a disturbance of consciousness caused by hyperammonemia is not a usual finding. We encountered a case of 5-FU-related consciousness disturbance with respiratory depression. A woman in her sixties was diagnosed with metastatic cecum cancer, involving peritoneal dissemination and hydronephrosis due to retroperitoneal invasion. After resection of the primary lesion, systemic chemotherapy, including capecitabine, irinotecan, bevacizumab and cetuximab, was administered for the metastatic lesions. As a third-line of treatment, the mFOLFOX6 plus bevacizumab regimen was administered. On the second day of the first course, the patient complained of nausea and vomiting. On third day, her consciousness level was deteriorating. The level of ammonia in the blood was abnormally high. Therefore, we diagnosed consciousness disturbance caused by hyperammonemia resulting from high-dose 5-FU infusion. The symptom improved immediately after mechanical ventilation and intravenous infusion. Renal dysfunction is considered a risk factor for hyperammonemia caused by 5-FU, and it is necessary to pay particular attention in patients with renal dysfunction who receive chemotherapy with 5-FU.

The patient was an 86-year-old woman. She underwent right breast-conserving surgery and sentinel lymph node biopsy for breast cancer in August 2006. The pathological diagnosis was invasive ductal carcinoma, T1N0M0, Stage Ⅰ, ER (+), PgR (-), HER2 (-). She was treated with tamoxifen for 5 years as adjuvant therapy and showed no signs of recurrence. In November 2014, CA15-3 was elevated and an accumulation of FDG in the right paracolic sulcus was observed on PET-CT. Peritoneal metastasis of breast cancer was suspected, and an operation was performed for a definitive diagnosis. During the operation, the tumor was seen on the paracolic sulcus, and laparoscopic-assisted right hemicolectomy was performed. A poorly differentiated adenocarcinoma was diagnosed by pathological examination, and immunostaining results were as follows: CK7(+), CK20(-), mammaglobin (-), GCDFP-15 (-), ER (-), PgR (-), and HER2 (-). Because there was no original lesion other than the breast cancer, the tumor was diagnosed as a metastasis of breast cancer. The frequency of peritoneal metastasis of breast cancer is low. In this case, pathological diagnosis was necessary for a definitive diagnosis. A change of subtype was also confirmed, and the treatment strategy was decided appropriately. Surgical resection should be considered for peritoneal metastasis of breast cancer when the operation can be performed safely.

Pancreatic ductal carcinoma is a highly aggressive cancer, with one of the highest mortality rates among gastrointestinal cancers. Nab-paclitaxel plus gemcitabine (GEM) significantly improved overall survival, progression-free survival, and response rate in a phase Ⅲ trial in 151 community and academic centers in 11 countries. As a result, nab-paclitaxel plus GEM was approved for use in December 2014 in Japan. We report a case of a patient with pancreatic cancer who underwent this chemotherapy. A 47-year-old man was admitted to our hospital for evaluation of pancreatic lesions. Computed tomography revealed a hypoattenuating tumor in the body of the pancreas. After the patient underwent preoperative chemoradiotherapy under the diagnosis of cStage Ⅳa cancer, we planned to perform distal pancreatectomy. However, this case was inoperable because we found 3 liver metastases during surgery. On postoperative day 14, we treated the patient with nab-paclitaxel plus GEM. Grade 2 toxicities included neutropenia, diarrhea, and peripheral neuropathy, but serious adverse events did not occur. The progression-free survival was 5 months. He remained alive for 7 months after the chemotherapy. In patients with metastatic pancreatic adenocarcinoma, nab-paclitaxel plus GEM can be considered as the standard treatment.

The indications for duodenal stent placement for gastric outlet obstruction caused by gastric cancers remain controversial. We report the case of a patient with inoperable advanced gastric cancer with gastric outlet obstruction in whom oral intake could be prolonged for more than 2 years by duodenal stenting. A 60-year-old man diagnosed as having cStage Ⅳ gastric cancer with liver, peritoneum, and lymph node metastases underwent duodenal stent placement before first-line chemotherapy. After 8 months, the duodenal stent was found to be dislocated in the horizontal part of the duodenum due to tumor shrinkage. It was removed immediately by endoscopy. The patient was able to take a solid diet orally for the next 19 months, while receiving systemic chemotherapy.Duodenal stent placement proved useful in a patient who showed response to chemotherapy, despite the need for management of late complications. This approach is expected to be a first-line treatment option for gastric outlet obstruction caused by inoperable gastric cancer.

Laparoscopic surgery is less invasive and provides better cosmetic outcomes than conventional surgery. Laparoscopic liver resection has been covered by insurance since April 2010 and is increasingly performed in many hospitals. However, laparoscopic hepatectomy is sometimes difficult to perform safely in the case of HCC recurrence because adhesions restrict vision and manipulation of forceps. We report the results of laparoscopic hepatectomy for cases of HCC recurrence. From June 2010 through December 2014, 180 laparoscopic hepatectomy procedures for HCC were performed in our hospital; 33 were in patients with HCC recurrence. Of the 33 patients, 26 underwent pure laparoscopic partial hepatectomy. The median operative time was 242 min, the median bleeding amount was less than 5 g, and the median hospital stay after surgery was 12.0 days. In the group that underwent laparoscopic hepatectomy after open liver resection (12 patients), the median operative time was 303.5 min, the median bleeding amount was less than 5 g, and the median hospital stay after surgery was 9.0 days. Among the 21 patients that underwent laparoscopic hepatectomy after laparoscopic liver resection, the median operative time was 248 min (p=0.382), the median bleeding amount was less than 5 g (p=0.112), and the median hospital stay after surgery was 11.0 days (p=0.236). We could perform laparoscopic hepatectomy for cases of HCC recurrence. This procedure can be suitable for HCC recurrence, which sometimes requires poly-surgery.

A 58-year-old woman presented to our hospital with a huge hepatic mass. A CT scan showed an enhanced mass lesion on the fundus of the gallbladder and an enhanced mass ring on the gallbladder bed. Since FDG-PET showed no evidence of metastasis, we performed cholecystectomy, hepatectomy of S4a/5, and regional lymph node dissection. The immunohistochemical study of the specimen was positive for CK7, CK20, chromogranin A, and synaptophysin. The Ki-67 labeling index was 50%, and the SSTR2 score was 2+. The patient was diagnosed with neuroendocrine carcinoma. Since she was in poor condition and on hemodialysis, we started administration of somatostatin analog at the time of recurrence, and soon her diarrhea improved but the tumor increased in size.

Neurotrophin (NT)-4 is known to be an inducer of catagen in the hair cycle, but little is known of its role in the pathogenesis of androgenetic alopecia (AGA). We previously studied the gene expression of dermal papilla cells from AGA patients and controls and found that NT-4 was up-regulated in the AGA patients. In the present study, the etiological relationship between NT-4 and androgen, which is one of the causes of AGA, and the effect of an NT-4 inhibitor on hair growth were investigated. We established a NT-4 luciferase reporter assay system using a roughly 2-kb region upstream of the NT-4 transcriptional start site and investigated an accelerating effect of androgen on NT-4 transcription. We also screened for a NT-4 inhibitor by using the NT-4 reporter assay and evaluated the effects of NT-4 inhibitors on hair growth by using dihydrotestosterone (DHT)-implanted mice. The results show that transcriptional activity of NT-4 was accelerated by androgen, and extract of Hura crepitans L. inhibited the DHT-induced NT-4 transcriptional activation and ameliorated the retardation of hair regrowth by DHT-implanted mice. We also isolated the active ingredient in H. crepitans and found its structure to be that of 6,7-epoxy-5-hydroxyresiniferonol-14-(2,4-tetradecadienoate), i.e., daphne factor F3. These findings demonstrated that NT-4 activity accelerated by androgen might contribute to the pathogenesis of AGA and indicated that NT-4 inhibitors such as H. crepitans and daphne factor F3 might have a salutary effect on AGA.

844 Background: Obstructive colorectal cancer is an oncological emergency that requires emergency treatment. In Japan, laparoscopic resection after decompression with metallic-stent placement is becoming mainstream as a bridge to surgery (BTS). However, there are reports of worse prognoses due to stent placement, and the European Gastroenterology Society of Endoscopy guidelines do not recommend BTS. In our department, since 2011 the first choice of the treatment has been laparoscopic resection after decompression with a trans-anal or trans-nasal drainage tube. STo investigate the safety and short- and long-term results of laparoscopic resection after decompression with a drainage tube. Methods: Eighty-one cases of obstructive colorectal cancer that underwent surgery at our hospital from 2011 to 2016 were investigated with regards to the short- and long-term outcomes of treatment strategies for obstructive colorectal cancer. Results: The median age was 72 years old (39-94). The ratio of male to female was 46:29. The success rate of decompression was 86.7% (66 cases). Stages II, III and IV were involved in 25, 28 and 28 cases, respectively. The causes of the emergency operations were an inability to insert both the ileus tube and the stent (9.3%, 7 cases), and perforation (2.7%, 2 cases) when the trans-anal ileus tube was inserted. In the cases in which decompression was possible, the laparoscopic operation rate was 89.4% (56 cases) and the primary resection rate was 90.9% (59 cases). The median surgical time was 194 minutes (27-325), the median blood loss was 10 g (0-660 g),The median postoperative hospital stay was 14 days (5-147 days). The rate of anastomotic leak was 4.5%. There were no deaths within 30 and 90 days after surgery. The relapse free survival rate in Stage II and III were 72% and 67.9%, respectively. The median months of overall survival in Stage II, III and IV were 60.4, 56.3 and 18.7, respectively. Conclusions: A treatment strategy with laparoscopic resection followed by decompression with a drainage tube was performed feasibly and safely. At this time, the effects of a stent on oncological prognosis is unclear, and this strategy could be an effective treatment for obstructive colorectal cancer.

【症例】40歳代, 女性. 【臨床診断】軽度知的障害を伴う自閉症. 【症例報告】膵臓がんに対し, 膵頭十二指腸切除術を行った. 当初, 基礎疾患に自閉症を有することで医療者と患者・家族間の相互理解の困難さが予想されたため, 臨床心理士が介入した. 介入後, 障害が周術期にどのような影響を与えるか検討したところ, 医療者側に徐々に自閉症に対する認識が深まり, 患者の個別性に配慮したケアを行うことができた. 患者・家族に対しては, 臨床心理士が個別面接を繰り返し家族以外の理解者となるよう受容し, 共感的に支える関わりを継続したことで患者・家族の不安が軽減した. 【結語】臨床心理士の介入が, 患者・家族の精神的安定およびスタッフ教育に一定の効果をもたらした. Palliat Care Res 2010; 5(2): 323-326

Objective: In urological operations, many endourological procedures and pre-existing urinary tract infections may cause surgical complications. It is essential to identify the risk factors for surgical site infections (SSI) and determine additional influences. Patients and Methods: In the present retrospective investigation, a total of 324 patients who underwent open urological surgery between January 2003 and December 2007 at Anjo-Kosei Hospital were assessed for SSI along with possible associated factors. Results: Forty-four cases (13.6%) proved positive for SSIs during the surveillance period. Among these, 31 demonstrated incisional SSI and 13 demonstrated deep/organ space SSI. Greater age and body mass index, low preoperative haemoglobin levels, long preoperative hospital stay, prolonged operation time and increased blood loss during surgery were all positively associated with SSI in general. For the deep/organ space SSI cases, advanced age, low preoperative haemoglobin levels, long preoperative hospital stay and prolonged operation time were significant factors. Conclusion: This study identified several independent predictors of SSI in general, as well as deep/organ space infection, for urological open surgery at our hospital. The results provided a basis for urologists to decrease the incidence of urological SSI.

Summary Background Androgens cause regression of human hair follicles in the parietofrontal scalp, but the precise mechanisms by which they do so are unknown. Although many investigators have elucidated the effect of androgens on hair growth by using rodents and other animals, some of the evidence is conflicting. Objectives To investigate the effect of androgens on mouse hair regrowth and hair cycle by using androgen receptor knockout (ARKO) mice. Methods We examined the effects of dihydrotestosterone (DHT) on hair regrowth by using ARKO mice and wild-type (WT) littermates, compared the hair cycles in ARKO mice and WT littermates by histology and histomorphometry, and measured hair length and thickness in ARKO mice and WT littermates. Results DHT inhibited the hair regrowth of WT mice but not that of their ARKO littermates. The anagen phase in the second hair cycle was longer in ARKO mice than in their WT littermates. The hair of ARKO mice was longer and thicker than that of their WT littermates. Conclusions Androgens inhibit hair growth in mice, and this inhibition might be caused by androgen–androgen receptor signals.

Background The aim of the present study was to examine whether stanniocalcin 1 (STC1) affects cardiomyocytes under physiological or pathophysiological conditions. Methods and Results Using fresh isolated rat cardiomyocytes, the effects of STC1 on cell hypercontracture, cell shortening and Ca2+ transients were measured after exposing the cells to ouabain. STC1 alone did not affect cell shortening or the Ca2+ transient. Exposure to ouabain significantly increased the fraction of hypercontractured cells (40.5±1.4% vs 3.5±1.7% in the control, p

Long-standing inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn disease (CD), is a known risk factor for gastrointestinal (GI) cancer, especially colorectal cancer (CRC). However, the feasibility of chemotherapy for IBD-related GI cancer is not well understood in terms of efficacy and adverse events, because there are fewer GI cancer patients with IBD than without IBD.We retrospectively analyzed the medical records of eight IBD patients (CD = 5 and UC = 3) who received chemotherapy for IBD-related GI cancer between April 2003 and March 2013.The most common gastrointestinal adverse event was diarrhea (75%); 38% of patients experienced grade 3 diarrhea. Moreover, all grade 3 diarrhea occurred in patients with CD. The most common hematologic adverse events were anemia (75%), leukopenia (38%), and neutropenia (30%); 25% of patients experienced grade 3 neutropenia. The other severe adverse events were grade 3 AST and ALT elevation (13%).In this study, the incidence of grade 3 diarrhea was higher in patients with CD. The length and dysfunction of the small intestine is the most likely reason that diarrhea occurred more frequently in patients with CD.

Adipose-derived stem cell (ADSC) transplantation is expected to be a minimally invasive, but effective, treatment for postoperative enterocutaneous fistulas associated with poor blood flow and chronic inflammation. The aim of this study was to assess the safety and efficacy of a novel ADSC therapy for this condition. We conducted an open-label, single-arm exploratory phase I study to assess the safety and efficacy of a novel ADSC therapy. Using the Celution system, we isolated adipose-derived regenerative cells (ADRCs) containing abundant ADSCs from liposuction-obtained gluteal adipose tissue. A mixture of ADRCs and fibrin glue was subsequently transplanted into the fistula, and ADRCs were percutaneously and endoscopically injected around the fistula. We evaluated the safety and feasibility of ADRC transplantation and fistula closure in six patients (UMIN000007316). ADRC transplantation was completed in all patients. The fistula closure rates were 83.3 % at 4 and 12 weeks and 100 % at 24 weeks. All patients had grade 1 pain and subcutaneous hemorrhage at the liposuction sites, but no serious adverse events related to this procedure were observed. Transplantation of autologous ADRCs is safe, feasible and advantageous, as it can secure a sufficient cell count without culture or multiple passages, and will likely be effective for a postoperative enterocutaneous fistula.

A 70-year-old man presenting with melena was referred to our clinic. A clinical examination revealed a bulky tumor in the lower rectum. After ileostomy, 4 courses of capecitabine plus oxaliplatin (XELOX) therapy were administered as neoadjuvant chemotherapy. Computed tomography (CT) revealed significant reduction of the tumor. Laparoscopic super-low anterior resection with lateral lymph node dissection was performed. The pathological examination revealed no residual cancer cells, and a diagnosis of pathological complete response was made. The patient has been disease-free for 1 year after the operation. Neoadjuvant chemotherapy with XELOX might be promising for patients with locally advanced rectal cancer.

Solitary fibrous tumor (SFT) are relatively rare neoplasms that usually arise in the thoracic cavity in adults. Although many cases of extrathoracic SFT have been recently reported, SFT from the omentum is rare. A 32-year-old woman consulted a gynecologist complaining of irregular vaginal bleeding. Magnetic resonance imaging (MRI) revealed a tumor in the omentum, and the patient was admitted to our department. The patient underwent laparoscopic tumorectomy. The tumor size was 48 × 35 × 30 mm, and grayish-white nodules were observed. Histological examination showed hyperplastic spindle-shaped tumor cells with a pattern-less arrangement. Immunohistochemical staining showed the tumor was positive for CD34 and bcl-2, slightly positive for alpha smooth muscle actin(a-SMA), and negative for S-100 and c-kit. Accordingly, a diagnosis of SFT was made. The patient has not shown any recurrence 12 months after surgery. Most SFTs are benign, although there are some reports of recurring tumors. There are no clear guidelines for the treatment of SFT because of its rarity. Therefore, close long-term follow-up should be performed.

Single-incision laparoscopic surgery (SILS) is a promising new technique that is potentially applicable to Crohn's disease (CD). However, there is no consensus on the application of SILS for penetrating CD due to its complex pathology.We investigated the feasibility of SILS in 24 CD patients (12 with stricturing and 12 with penetrating CD) and compared the results between the two groups.There were 17 males and seven females [median age at the time of surgery, 41 (range 20-61) years old] included in the study. Sixteen patients underwent primary surgery, while eight received repeat surgery. Twenty patients had small bowel CD and four patients had ileocolonic CD. The indication for surgery was a fistula/abscess in 12 patients, stenosis in 10 and other indications in two cases. The total length of the operation and blood loss was 171 min (113-221 min) and 230 mL (30-400 mL) in the penetrating CD cases, and 149 min (111-186 min) and 90 mL (20-400 mL) in the stricturing CD cases. There were no significant differences in the length of the operation between the two groups, but the blood loss was significantly greater in the cases of penetrating CD. Conversion to open surgery was required in one patient with penetrating CD. Postoperative complications developed in one patient with stricturing CD.SILS could be performed safely not only in patients with stricturing CD, but also in those with penetrating CD.

Cell cycle-arrested cancer cells are resistant to conventional chemotherapy that acts on the mitotic phases of the cell cycle, although the molecular mechanisms involved in halting cell cycle progression remain unclear. Here, we demonstrated that RFPL4A, an uncharacterized ubiquitin ligase, induced G1 retention and thus conferred decreased sensitivity to chemotherapy in the human colorectal cancer cell line, HCT116. Long term time lapse observations in HCT116 cells bearing a "fluorescence ubiquitin-based cell cycle indicator" identified a characteristic population that is viable but remains in the G1 phase for an extended period of time (up to 56 h). Microarray analyses showed that expression of RFPL4A was significantly up-regulated in these G1-arrested cells, not only in HCT116 cells but also in other cancer cell lines, and overexpression of RFPL4A increased the G1 population and decreased sensitivity to chemotherapy. However, knockdown of RFPL4A expression caused the cells to resume mitosis and induced their susceptibility to anti-cancer drugs in vitro and in vivo. These results indicate that RFPL4A is a novel factor that increases the G1 population and decreases sensitivity to chemotherapy and thus may be a promising therapeutic target for refractory tumor conditions.

It is known that the process of amyloid fibril formation, including amyloid β (Aβ) and islet amyloid polypeptide, is generally associated with diseases, such as Alzheimer’s disease, type II diabetes, and prion diseases. However, many proteins form amyloid-like fibrils but do not associate with amyloidrelated diseases. Amyloid fibrils are elongated, insoluble structures of 7-10 nm in diameter found in extracellular plaques. Structural studies have shown that mature amyloid fibrils involve the alignment of short peptide segments, usually between 6 and 12 residues in length, from many protein monomers. Together, these aligned polypeptide stretches form the characteristic core structure of the amyloid fibril, the cross β sheet, in which β strands run perpendicular to the main axis of the fibril. Amyloid fibrils possess a characteristic UV absorbing spectrum at the peak of 540 nm with Congo red and a characteristic X-ray diffraction pattern. Thus, specific pattern of molecular interactions, rather than nonspecific hydrophobic interactions, lead to ordered structures. Nevertheless, common structural elements responsible for such organized structures have not been identified and the mechanism of amyloid fibril formation is unclear. Previously, we screened the synthetic peptide library derived from the laminin-111 sequence, and identified five amyloidgenic peptides, A119 (LSNIDYILIKAS, mouse laminin α1 chain, 1321-1332), A208 (AASIKVAVSADR, mouse laminin α1 chain, 2097-2108), AG97 (SAKVDAIGLEIV, mouse laminin α1 chain, 2942-2953), B133 (DISTKYFQMSLE, mouse laminin β1 chain, 1367-1378), and B160 (VILQQSAADIAR, mouse laminin β1 chain, 1607-1618) [1]. Laminins, major components of basement membranes, regulate multiple biological functions, including cell adhesion, migration, differentiation, neurite outgrowth, wound healing, angiogenesis, and tumor progression. Laminins are a family of heterotrimeric glycoproteins that consist of α, β, and γ chains. So far, five α, three β, and three γ chains have been identified and at least 16 laminin isoforms have been reported that are formed by various combinations of each chains. Here, we focused on the AG97 and B160 peptide, which exhibits amyloid-like fibril formation, heparin-dependent cell attachment activity, and neurite outgrowth activity. Our approach was to investigate the essential residues for fibril formation and cell behavior using alanine-substituted peptides.

Molecular photonics, information processing based on strong interactions of photons and molecules, has attracted much attention, since it can fully utilize many superior properties of both photons and molecules. We have developed polymeric materials showing ultrafast absorption changes in the visible to near-infrared regions including the telecommunication wavelength by photoinduced electron transfer and reverse reactions between substituted pyridinium and its counter anion. By selecting the counter anion we succeeded in making steady and ultrafast absorption changes. Time-resolved absorption and fluorescence spectroscopy upon femtosecond laser excitation revealed reaction mechanism and ultrafast dynamics. In order to fully utilize such photoresponses in molecular photonics, we proposed guided wave mode (GWM) device composed of a prism, a low refractive index polymer film, and a photoresponsive polymer film. The reflectance in this GWM is controlled by many factors such as thickness values and complex refractive indices of two polymer layers as well as an incident angle and wavelength. We successfully achieved sensitive, all optical, and very fast control of reflectance by means of photoinduced complex refractive index changes upon femtosecond laser excitation.

Tetrasubstituted indium or gallium phthalocyanines and their dimers bridged with various ligands were dispersed in a polymer thin film, which was spin-coated on silver thin film vacuum-evaporated on a glass slide. All-optical reflectance control was achieved by complex refractive index changes upon photoexcitation of phthalocyanines by nanosecond laser in such a guided mode geometry. They gave rise in less than ns pulse width, and a few to a few tens of microseconds decay characteristic to the lifetime of the excited triplet state. Repeated and reversible reflectance changes were achieved. Axially bridged phthalocyanine dimers showed almost the same photoresponses as monomers.

The calcium ion regulates many aspects of neuronal migration, which is an indispensable process in the development of the nervous system. Calmodulin (CaM) is a multifunctional calcium ion sensor that transduces much of the signal. To better understand the role of Ca2+-CaM in neuronal migration, we investigated mouse precerebellar neurons (PCNs), which undergo stereotyped, long-distance migration to reach their final position in the developing hindbrain. In mammals, CaM is encoded by three non-allelic CaM (Calm) genes (Calm1, Calm2 and Calm3), which produce an identical protein with no amino acid substitutions. We found that these CaM genes are expressed in migrating PCNs. When the expression of CaM from this multigene family was inhibited by RNAi-mediated acute knockdown, inhibition of Calm1 but not the other two genes caused defective PCN migration. Many PCNs treated with Calm1 shRNA failed to complete their circumferential tangential migration and thus failed to reach their prospective target position. Those that did reach the target position failed to invade the depth of the hindbrain through the required radial migration. Overall, our results suggest the participation of CaM in both the tangential and radial migration of PCNs.

Interferon-α (IFN-α) is used clinically to treat hepatocellular carcinoma (HCC), although the detailed therapeutic mechanisms remain elusive. In particular, IFN-α has long been implicated in control of the cell cycle, but its actual point of action has not been clarified. Here, using time lapse imaging analyses of the human HCC cell line HuH7 carrying a fluorescence ubiquitination-based cell cycle indicator (Fucci), we found that IFN-α induced cell cycle arrest in the G0/G1 phases, leading to apoptosis through an IFN-α type-2 receptor (IFNAR2)-dependent signaling pathway. Detailed analyses by time lapse imaging and biochemical assays demonstrated that the IFN-α/IFNAR2 axis sensitizes cells to apoptosis in the S/G2/M phases in preparation for cell death in the G0/G1 phases. In summary, this study is the first to demonstrate the detailed mechanism of IFN-α as an anticancer drug, using Fucci-based time lapse imaging, which will be informative for treating HCC with IFN-α in clinical practice.

In low anterior resections, anastomosis continues to present major problems. Although the single-stapling technique (SST) is considered to be superior to the double-staple technique (DST) in terms of leakage and stenosis, SST requires suturing, which is particularly difficult during laparoscopic surgery. A simpler and safer method of anastomosis is needed. In this study, we developed a pre-ligation SST (L-SST) that does not require suturing and evaluated the usefulness of L-SST in an ex vivo and an in vivo porcine model.Porcine rectums were ligated using SurgiTie™ and sharply resected instead of using a linear stapler. The burst pressures of the closed rectums after using a linear stapler and SurgiTie™ (each group; n = 5) and the burst pressures of the anastomoses performed with L-SST and DST (each group; n = 4) were measured. During in vivo porcine laparoscopic surgery, we performed and evaluated the feasibility of L-SST.After completing the anastomosis with L-SST, the ligated portion using SurgiTie™ was completely removed. The stump closed using SurgiTie™ was much stronger than that closed using a stapler (131.2 and 25.6 mmHg, respectively; P = 0.01). The average burst pressure of the anastomoses performed with L-SST was 33.8 mmHg, whereas that performed with DST was 30.5 mmHg. We did not find significant difference between these two groups (P = 0.88). We also confirmed the feasibility of L-SST in an in vivo porcine laparoscopic surgery model.We developed a novel SST, the L-SST. We were able to perform L-SST successfully using an ex vivo porcine rectum and during in vivo porcine laparoscopic surgery.

Although simultaneous resection of primary colorectal cancer and synchronous liver metastases is reported to be safe and effective, the feasibility of a laparoscopic approach remains controversial. This study evaluated the safety, feasibility, and short-term outcomes of simultaneous laparoscopic surgery for primary colorectal cancer with synchronous liver metastases. From September 2008 to December 2013, 10 patients underwent simultaneous laparoscopic resection of primary colorectal cancer and synchronous liver metastases with curative intent at our institute. The median operative time was 452 minutes, and the median estimated blood loss was 245 mL. Median times to discharge from the hospital and adjuvant chemotherapy were 13.5 and 44 postoperative days, respectively. Negative resection margins were achieved in all cases, with no postoperative mortality or major morbidity. Simultaneous laparoscopic colectomy and hepatectomy for primary colorectal cancer with synchronous liver metastases appears feasible with low morbidity and favorable outcomes.

An infant with truncus arteriosus (Van Praagh A3; isolated left pulmonary artery (LPA) and ductal origin of the LPA) had an extremely stenotic ductus arteriosus (DA) and the LPA could not be demonstrated. As a salvage operation, balloon angioplasty was performed for the stenotic DA at 8 days of age. The minimum lumen diameter of the DA increased from 0.7 to 2.7 mm. After the procedure, the LPA tree was well demonstrated and total pulmonary blood flow increased. Nitrogen inhalation was begun with a nasal positive airway pressure system in order to regulate pulmonary blood flow. Repeat balloon angioplasty was performed at 33 days of age for the restenosed DA. The infant's general condition was stabilized until undergoing pulmonary artery reconstruction and modified Blalock-Taussig shunt at 4 months of age, and definitive repair at 11 months of age. The combination of balloon angioplasty and nitrogen inhalation therapy enabled simultaneous growth of the LPA tree and regulation of total pulmonary blood flow, which could be a useful strategy for complex congenital heart diseases with unbalanced pulmonary blood flow. (Circ J 2007; 71: 445 - 447)

The mechanism behind the spatiotemporal control of cancer cell dynamics and its possible association with cell proliferation has not been well established. By exploiting the intravital imaging technique, we found that cancer cell motility and invasive properties were closely associated with the cell cycle. In vivo inoculation of human colon cancer cells bearing fluorescence ubiquitination-based cell cycle indicator (Fucci) demonstrated an unexpected phenomenon: S/G2/M cells were more motile and invasive than G1 cells. Microarray analyses showed that Arhgap11a, an uncharacterized Rho GTPase-activating protein (RhoGAP), was expressed in a cell-cycle-dependent fashion. Expression of ARHGAP11A in cancer cells suppressed RhoA-dependent mechanisms, such as stress fiber formation and focal adhesion, which made the cells more prone to migrate. We also demonstrated that RhoA suppression by ARHGAP11A induced augmentation of relative Rac1 activity, leading to an increase in the invasive properties. RNAi-based inhibition of Arhgap11a reduced the invasion and in vivo expansion of cancers. Additionally, analysis of human specimens showed the significant up-regulation of Arhgap11a in colon cancers, which was correlated with clinical invasion status. The present study suggests that ARHGAP11A, a cell cycle-dependent RhoGAP, is a critical regulator of cancer cell mobility and is thus a promising therapeutic target in invasive cancers.