Investigation of risk factors associated with the development of depressive symptoms in healthy subjects exposed to long-term stress: A prospective study of the Japanese Antarctic research expedition wintering party.

BACKGROUND: Stressors induce depression together with parenting experienced in childhood, personality traits, and sleep. In this study, we investigated factors associated with the development of depression in a long-term stressful environment, namely, the Antarctic Research Expedition wintering party, by comparing 2 groups, the depression and nondepression groups. METHODS: A self-administered questionnaire was used to survey 91 members of the Japanese Antarctic Research Expedition who spent winters in the Antarctic base. Psychological evaluations of depression, anxiety, and sleep were performed using a questionnaire every 3 months during the participants' stay in Antarctica. The primary endpoint was the occurrence of minor or major depression, as evaluated by the PHQ-9 score. RESULTS: Participants with a PHQ-9 score of 5 or more during their stay in Antarctica were defined as the depression group (25 subjects), and participants with a PHQ score of 4 or less were defined as the nondepression group (43 subjects). Compared with the nondepression group, the depression group had significantly higher scores for predeparture PHQ-9, state and trait anxiety, sleep disturbance, and neuroticism. Multivariable logistic regression analyses showed that higher predeparture scores of subthreshold depressive symptoms and neuroticism were found to be significant predictors of the occurrence of depression during their stay in Antarctica. CONCLUSIONS: This study prospectively showed that subthreshold depressive symptoms and neuroticism, which were suggested as risk factors in previous studies, were confirmed to be risk factors for depression. The results of our study are expected to contribute to the understanding of depression in harsh environments.

Incomplete bowel obstruction caused by sigmoid colon cancer in an inguinal hernia: a case report.

BACKGROUND: Most colon cancers that develop in the intestinal tract within the inguinal hernia sac are identified by incarceration. However, treatment methods for these cases vary depending on the pathology. Cases showing perforation or abscess formation require emergency surgery for infection control, while cases with no infection generally involve oncological resection, with laparoscopic surgery also being an option. We encountered a case of Incomplete bowel obstruction secondary to sigmoid colon cancer within the hernial sac. We report the process leading to the selection of the treatment method and the surgical technique, along with a review of the literature. CASE PRESENTATION: A 79-year-old man presented to our hospital complaining of a left inguinal bulge (hernia) and pain in the same area. The patient had the hernia for more than 20 years. Using computed tomography, we diagnosed an incomplete bowel obstruction caused by a tumor of the intestinal tract within the hernial sac. Since imaging examination showed no signs of strangulation or perforation, we decided to perform elective surgery after a definitive diagnosis. After colonoscopy, we diagnosed sigmoid colon cancer with extra-serosal invasion; however, we could not insert a colorectal tube. Although we proposed sigmoid resection and temporary ileostomy, we chose the open Hartmann procedure because the patient wanted a single surgery. For the hernia, we simultaneously used the Iliopubic Tract Repair method, which does not require a mesh. Eight months after the surgery, no recurrence of cancer or hernia was observed. CONCLUSIONS: We report a case of advanced sigmoid colon cancer with a long-standing inguinal hernia that later became incomplete bowel obstruction. Although previous studies have used various approaches among the available surgical methods for cancer within the hernial sac, such as inguinal incision, laparotomy, and laparoscopic surgery, most hernias are repaired during the initial surgery using a non-mesh method. For patients with inguinal hernias that have become difficult to treat, the complications of malignancy should be taken into consideration and the treatment option should be chosen according to the pathophysiology.

Relationship between Urinary Metabolomic Profiles and Depressive Episode in Antarctica.

Antarctic expeditions have a high risk of participant depression owing to long stays and isolated environments. By quantifying the stress state and changes in biomolecules over time before the onset of depressive symptoms, predictive markers of depression can be explored. Here, we evaluated the psychological changes in 30 participants in the Japanese Antarctic Research Expedition using the Patient Health Questionnaire-9 (PHQ-9). Urinary samples were collected every three months for a year, and comprehensive urinary metabolomic profiles were quantified using liquid chromatography time-of-flight mass spectrometry. Five participants showed major depressive episodes (PHQ-9 ≥ 10) at 12 months. The urinary metabolites between these participants and the 25 unaffected participants were compared at individual metabolite and pathway levels. The individual comparisons showed the most significant differences at 12 months in 14 metabolites, including ornithine and beta-alanine. Data from shorter stays showed less significant differences. In contrast, pathway and enrichment analyses showed the most significant difference at three months and a less significant difference at longer stays. These time transitions of urinary metabolites could help in the development of urinary biomarkers to detect subjects with depressive episodes at an early stage.

[Surgical Case of Ulcerative Colitis Accompanied with Rectal Cancer Combined with Transanal Minimally Invasive Surgery].

A46 -year-old man developed ulcerative colitis at the age of 19 years. Although the colitis was medically treated, it relapsed and repeated over time. Periodic lower gastrointestinal endoscopy revealed lower rectal cancer, and he was referred to our department of surgery. Previous steroid therapy induced diabetes, and he was obese, with a height of 170.3 cm, weight of 89.6 kg, and BMI of 30.89 kg/m2, indicating that laparoscopic dissection near the anus would be difficult to perform. Therefore, the patient was scheduled for transanal minimally invasive surgery(TAMIS). The surgery involved as much laparoscopic rectal dissection as possible in the ventral to dorsal direction, followed by the TAMIS procedure. Dissection was started from the dentate line, and, after the closure of the anal stump, GelPOINT was placed, and made continuous with the previous dissection layer by applying the technique of down-to-up total mesorectal excision(TME)by TAMIS. The large intestine was excised through a small abdominal incision to create an ileal pouch, hand-sewn anastomosis was performed transanally to create a temporary colostomy, and the surgery was completed. Regarding TAMIS-TME several problems remain to be solved, including an understanding of its unique anatomy and the mastery of single-port surgical techniques. However, the herein reported patient with a high BMI had a definite indication for TAMIS-TME.

Photodynamic therapy for biliary tract organ via a novel ultra-small composite optical fiberscope.

Photodynamic therapy (PDT) is a method used treat tumors via utilizing photodynamic reactions between photosensitive substances with tumor affinity and lasers. For overall bile duct cancers, PDT has been demonstrated to resolve stenosis and improve prognosis; however, when limited to intrahepatic bile duct cancers, modifications to the laser irradiation are necessary as surrounding hepatocytes incorporate a large amount of photosensitive substances. Furthermore, the intrahepatic bile duct is thin, and a guide sheath and thin fiber are necessary to transport laser irradiation probes to the target region. In the present study, a parallel-type ultra-small composite optical fiberscope (COF) with an outer diameter of 1 mm or smaller was developed to target a thin intrahepatic bile duct. PDT was performed using an animal model and talaporfin sodium (Laserphyrin), which is rapidly excreted by hepatocytes and is suitable for use with a long-wavelength laser due to its high tissue penetrating ability. The results demonstrated that Laserphyrin does not cause necrotic changes in the normal biliary tract mucosa. In addition, COF images of sufficient quality were acquired. The present results suggest that COF may be used for the treatment of deep bile duct lesions.

Liver metastasis is established by metastasis of micro cell aggregates but not single cells.

Cancer cell engraftment in the target organ is necessary to establish metastasis. Clinically, lymph node metastasis of single cells has been confirmed using cytokeratin staining. In the current study, a LacZ-labeled cancer cell line was used to visualize intrahepatic metastasis of single cells or liver micrometastasis. KM12SM-lacZ stably expressing LacZ was prepared with a highly metastatic colon cancer cell line, KM12SM. KM12SM-lacZ was injected into the spleen of nude mice and following 1 week the spleen was excised. The liver was then examined for metastasis following 1, 2 or 3 weeks. Confirmation of liver metastasis was completed by observing the grade of metastasis. Grade-1 metastasis (DNA level), human DNA in liver tissue was detected; Grade-2 metastasis (metastasis of single cells), confirmed by X-gal staining; Grade-3 metastasis (histopathological micrometastasis), diagnosed by light microscopy and Grade-4 metastasis (typical metastasis), easily detected macroscopically or by hematoxylin and eosin staining. The Grade-1 metastasis detection rates 1, 2 and 3 weeks following splenectomy were 50, 100 and 100%, respectively. Grade-2 metastasis was not detected by microscopy. The Grade-3 metastasis detection rates for 1, 2 and 3 weeks were 75, 100 and 100%, respectively. Micrometastasis was observed in the portal vein lumen and wall. The Grade-4 metastasis detection rates were 50, 100 and 100% for 1, 2 and 3 weeks respectively. Cancer cells were present in vessels surrounding the main tumor. In conclusion, a specific number of cancer cell aggregates may be necessary to establish hematogenous metastasis.

A phase II trial of neoadjuvant chemoradiotherapy with intensity-modulated radiotherapy combined with gemcitabine and S-1 for borderline-resectable pancreatic cancer with arterial involvement.

PURPOSE: Chemoradiotherapy using intensity-modulated radiotherapy (IMRT) is expected to provide a powerful alternative to conventional chemotherapy with a low incidence of adverse events. This study evaluated the efficacy of intensity modulated radiotherapy in combination with gemcitabine and S-1 as neoadjuvant chemoradiotherapy (NACRT) for borderline-resectable pancreatic cancer with arterial involvement (BR-A). METHODS: A total of 27 patients with BR-A were enrolled in this study between February 2012 and September 2015. IMRT was administered at 50.4 Gy in 28 fractions with concurrent gemcitabine at a dose of 600 mg/m2 and S-1 at a dose of 60 mg. RESULTS: Only one patient (3.5%) experienced gastrointestinal adverse events at grade 3 or higher. Nineteen patients (70.3%) underwent resection, and R0 resection was achieved in 18 patients (94.7%). Thirteen patients (68.4%) developed distant metastasis at the initial site of recurrence after resection. Local recurrence developed in only one of these patients (7.7%). The median overall survival and 1-year survival rates were 22.4 months and 81.3%, respectively. CONCLUSIONS: Concurrent IMRT with gemcitabine and S-1 for patients is feasible as NACRT for BR-A with low gastrointestinal toxicity. IMRT can be employed as a standard radiotherapy to provide more effective NACRT with powerful chemotherapy drugs.

Serum Metabolomic Profiles for Human Pancreatic Cancer Discrimination.

This study evaluated the clinical use of serum metabolomics to discriminate malignant cancers including pancreatic cancer (PC) from malignant diseases, such as biliary tract cancer (BTC), intraductal papillary mucinous carcinoma (IPMC), and various benign pancreaticobiliary diseases. Capillary electrophoresismass spectrometry was used to analyze charged metabolites. We repeatedly analyzed serum samples (n = 41) of different storage durations to identify metabolites showing high quantitative reproducibility, and subsequently analyzed all samples (n = 140). Overall, 189 metabolites were quantified and 66 metabolites had a 20% coefficient of variation and, of these, 24 metabolites showed significant differences among control, benign, and malignant groups (p < 0.05; Steel-Dwass test). Four multiple logistic regression models (MLR) were developed and one MLR model clearly discriminated all disease patients from healthy controls with an area under receiver operating characteristic curve (AUC) of 0.970 (95% confidential interval (CI), 0.946-0.994, p < 0.0001). Another model to discriminate PC from BTC and IPMC yielded AUC = 0.831 (95% CI, 0.650-1.01, p = 0.0020) with higher accuracy compared with tumor markers including carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), pancreatic cancer-associated antigen (DUPAN2) and s-pancreas-1 antigen (SPAN1). Changes in metabolomic profiles might be used to screen for malignant cancers as well as to differentiate between PC and other malignant diseases.

The Straightened Splenic Vessels Method Improves Surgical Outcomes of Laparoscopic Distal Pancreatectomy.

BACKGROUND: In laparoscopic distal pancreatectomy (LDP), isolating the splenic artery and vein requires advanced techniques. This study aimed to assess the efficacy of a novel method termed the 'straightened splenic vessels' (SSV) method for isolating the splenic vessels in LDP. METHODS: In SSV, to adjust the instrument axis, the splenic artery was straightened by grasping 2 points of its nerve sheath. Then, the layer between the splenic artery's nerve sheath and the pancreatic parenchyma was dissected. Next, the pancreas was mobilized from body to tail, and the splenic vein was straightened by 3-point retraction before isolation. To evaluate this method's efficacy, we investigated 51 patients who underwent LDP. RESULTS: In 39 patients who underwent LDP with splenectomy, the mean operating time was significantly shorter in the SSV group than in the conventional group (p = 0.004). In 12 patients who underwent LDP with preserving the splenic vessels, the mean intraoperative blood loss in the SSV group was 27.6 ml, which was significantly lower than that in the conventional group (p = 0.012). CONCLUSION: This method may be applied as a standard procedure with little blood loss and short operation time for LDP. Larger prospective studies are needed to further evaluate the feasibility.

Prospective evaluation of a new biflanged metal stent for the treatment of pancreatic fluid collections (with videos).

BACKGROUND AND AIMS: EUS-guided transluminal drainage (EUS-TD) and sequential direct endoscopic necrosectomy (DEN) for pancreatic fluid collections (PFCs) by using a dedicated biflanged metal stent (BFMS) has been reported as a useful alternative to using plastic stents or a conventional metal stent. However, current dedicated BFMSs have limitations. Recently, a new BFMS with solidly constructed biflanges and various stent lengths matched to the PFC condition has been developed. Herein, we prospectively evaluated this new BFMS for the treatment of PFCs. METHODS: From July 2015 to July 2016, EUS-TD by using the new BFMS was performed in 12 patients for PFCs (4 patients with pancreatic pseudocysts, 8 patients with walled-off necrosis). When clinical resolution could not be achieved, DEN was performed the following day. RESULTS: The stent was deployed successfully with a median procedure time of 16 minutes (range 11-24 minutes) and with no procedure-related adverse events in any patients (12/12, 100%). DEN via the stent was achieved in all patients in whom they were attempted (4/4,100%). Spontaneous stent migration or stent dislocation during DEN was not observed in any patients. Two WON patients died from spontaneous pseudoaneurysm rupture and multiple organ failure. The PFCs in the other 10 patients completely resolved, and later the stent was removed with no difficulty in 9 patients after a median time of 48 days (range 30-180 days). CONCLUSIONS: The new BFMS is technically feasible and safe for the treatment of PFCs. (Clinical trial registration number: UMIN000021347.).

[Two Cases of Non-Occlusive Mesenteric Ischemia That Developed after Chemotherapy].

Non-occlusive mesenteric ischemia(NOMI)causes intestinal necrosis due to irreversible ischemia of the intestinal tract despite the absence of organic obstruction in the mesenteric blood vessels. The disease has extremely poor prognosis. We encountered 2 cases of NOMI hypothesized to have developed after chemotherapy; thus, we report these cases considering the available literature. Case 1: A7 9-year-old man. The patient complained of abdominal pain during the first week after introducing docetaxel for local recurrence of prostate cancer. Abdominal computed tomography(CT)revealed mesenteric ischemia and intestinal emphysema. The patient was diagnosed with NOMI, and an emergency operation was performed. Upon laparotomy, the small intestine; ascending, transverse, and descending colon; recto sigmoid; and gall bladder appeared mottled necrotic. As such, all these were excised. He was admitted back to the hospital 3 weeks after surgery due to pneumonia. Case 2: A7 4-year-old man. Combination chemotherapy of docetaxel, cisplatin, and 5-FU was given for oropharyngeal cancer. After 1 week, fever and abdominal pain were noted. Abdominal contrast CT examination was performed, and mesenteric ischemia was confirmed as NOMI. Emergency surgery was performed on the same day. The entire ileum was discolored with mottling, and it was determined to be necrotic. Thus, it was excised. Postoperative course is good, and the patient was followed up after discharge from the hospital. Before NOMI onset in both cases, docetaxel was used to treat myelosuppression. Considering the patient conditions, the association between NOMI onset and docetaxel was suspected. In general, mesenteric ischemia after administration of anticancer drugs is rare, and only a few cases have been reported.

[A Case of T4 Esophageal Cancer with Refractory Chylothorax Developed Postoperatively].

A 65-year-old man was diagnosed as having middle thoracic esophageal cancer(c-T3N2M0, stage III ), and neoadjuvant chemoradiotherapy was performed.We performed surgical therapy.However, tumor and #113 lymph node invasion into the aortic arch was observed; therefore, it was judged that curative resection was difficult, and R2 surgery was performed instead. Postoperative diagnosis was Mt, CRT-type 5b, s-T4(aortic arch)N4(#113)M0, stage IV a.After surgery, pleural effusion was abundant and was diagnosed as chylothorax.Even though intestinal rest and octreotide administration were performed as a conservative treatment, chylothorax was not improved.Therefore, thoracoscopic thoracic duct ligation was performed on 8POD.After that, pleural effusion was still sustained, and pleural adhesions were performed.However, it did not prove to be effective.Furthermore, when Lipiodol lymphangiography was performed to identify the leakage site, the leakage of contrast medium was observed from the remaining lymph node.After lymphangiography twice(in total), pleural effusion disappeared, and the patient was discharged on the 75POD.In this case, we report an example in which lymph leakage disappeared due to lymphangiography for diagnostic purpose, while no improvement was observed in the lymphatic leakage from the remaining metastatic lymph node in T4 esophageal cancer with R2 surgery, nor with some treatments for chylothorax, including thoracic duct ligation.

[A Case Where Function Preservation Was Possible for Quadruple Cancer Metastasis].

The patient was a 69-year-old man visited our hospital because of fecal occlt blood test at medical checkup and diagnosed with rectal cancer and gastric cancer. The patient underwent super low anterior resection for rectal cancer cStage III b and underwent endoscopic submucosal dissection(ESD)for early gastric cancer. In 1 year after surgery the patient had recurrence of gastric cancer after ESD and recurrent gastric cancer was additionally resected. In 1 year and 4 months after surgery pulmonary metastasis was recognized and the patient underwent pulmonary segmentectomy. In 5 years after surgery renal cell carcinoma was recognized and the patient underwent partical renal excision. In 8 years after surgery esophagus cancer was recognized and the patient underwent radical chemoradiationtherapy and completed local complete remission. Current the patient is alive without relapse. We report a case where function preservation was possible for quadruple cancer by appropriate preoperative and postoperative examination and appropriate treatment.

RhoA activity increases due to hypermethylation of ARHGAP28 in a highly liver-metastatic colon cancer cell line.

Certain cell lines exhibit metastatic ability (highly metastatic cell lines) while their parent cell lines have no metastatic ability. Differences in methylation, which are not derived from differences in the gene sequence between cell lines, were extensively analyzed. Using an established highly metastatic cell line, KM12SM, and its parent cell line, KM12C, differences in the frequency of methylation were analyzed in the promoter regions of ~480,000 gene sites using Infinium HumanMethylation450. The promoter region of the Rho GTPase-activating protein 28 (ARHGAP28) gene was the most markedly methylated region in KM12SM compared with KM12C. ARHGAP28 is a GTPase-activating protein (GAP), and it converts activated RhoA to inactivated RhoA via GTPase. RhoA activity was compared between these two cell lines. The activated RhoA level was compared using western blot analysis and G-LISA. The activated RhoA level was higher in KM12SM compared to KM12C for western blot analysis and G-LISA analysis. RhoA is a protein involved in cytoskeleton formation and cell motility. RhoA, for which ARHGAP28 acts as a GAP, is possibly a factor involved in the metastatic ability of cancer.

[Radiofrequency Ablation Combined with Hepatectomy for the Treatment of Liver Metastases from Colorectal Cancer].

OBJECTIVE: We evaluated hepatectomy combined with radiofrequency ablation(RFA)in patients with liver metastases from colorectal cancer for which curative resection is difficult. METHODS: This study included 13 patients who underwent hepatectomy combined with RFA for liver metastases from colorectal cancer in or before 2015. RESULTS: In 11 patients who were determined to have achieved a complete curative resection, the 50%survival time was 35.4 months, and the 5-year overall survival (OS)rate was 33%. Recurrence at the RFA site was observed in 4 patients. There were 2 patients with a long-term survival of 5-years or longer. The reasons for concomitant use of RFA include deviation from the Makuuchi criteria in 4 patients, control of disease progression in 3 patients, non-curative surgery in 2 patients, difficulty in performing surgical procedures in 2 patients, and refusal by 1 patient, while the reason was unknown in 1 patient. DISCUSSION: Hepatectomy combined with RFA was selected in patients in whom curative hepatectomy was impossible. Although their 5-year OS rate was lower than that of patients who undergo hepatectomy alone, local control was relatively favorable. CONCLUSION: These results suggest that hepatectomy combined with RFA for liver metastases from colorectal cancer might be effective in selected cases.

[Examination to Determine Predictive Factors of Effectiveness of Surgical Treatment for Both Pulmonary and Hepatic Metastasis from Colorectal Cancer].

In recent years, several colorectal patients with pulmonary and hepatic metastasis, if resectable, have been found to experience long-term survival. In the present study, we extracted predictive factors, selected patients for whom a good prognosis could be anticipated, and examined the indications for surgery. From January 1986 to December 2014, we conducted a multivariate analysis of 18 patients who underwent surgical resection for pulmonary and hepatic metastases, with overall survival(OS)as the dependent variable, and clinicopathological factors as explanatory variables. The 5-year survival rate of the pulmonary and hepatic resection group was 32.0%. No significant difference was noted observed in CEA levels, number of metastatic pulmonary nodes, tumor diameter, synchronic, and metachronous tumors. A significant difference was only observed for disease-free interval(DFI)following resection of the primary lesion. The area under the receiver operating characteristic(ROC)curve revealed that the optimum cut-off value following resection of the primary lesion was a DFI of 762 days. When comparing the OS of the group with DFI<762 days and the group with DFI<762 days using a Kaplan-Meier curve, we found that survival was significantly prolonged. Therefore, surgery is indicated for colorectal cancer patients with pulmonary and hepatic metastasis, and who have DFI>2 years following resection of the primary lesion, and prolonged survival can be expected following surgery.

[A Case of Advanced Rectal Cancer in Which Combined Prostate Removal and ISR Using the da Vinci Surgical System with Preoperative Chemotherapy Allowed Curative Resection].

A 53-year-old male presented with a chief complaint of dyschezia.Lower gastrointestinal endoscopy confirmed the presence of a type II tumor in the lower part of the rectum, and a biopsy detected a well-differentiated adenocarcinoma.As invasion of the prostate and levator muscle of the anus was suspected on diagnostic imaging, surgery was performed after preoperative chemotherapy.With no clear postoperative complications, the patient was discharged 26 days after surgery. After 24 months, the number of urination ranged from 1 to 6, with a Wexner score of 6 and a mild desire to urinate in the absence of incontinence.At present, the patient is alive without recurrence.When combined with chemotherapy, robotassisted surgery allows the curative resection of extensive rectal cancer involving the suspected invasion of other organs.In this respect, it is likely to be a useful method to conserve anal and bladder function.

[Four Patients Who Underwent Lateral Lymph Node Dissection by an Extraperitoneal Approach for Lateral Lymph Node Recurrence FollowingSurg ery for Rectal Cancer].

To date, the surgical approach for recurrent rectal cancer has often involved highly invasive procedures. We report our experience of 4 patients who underwent lateral lymph node dissection via an extraperitoneal approach for lateral lymph node recurrence following surgery for rectal cancer. Patient 1 was a 60-year-old woman who, 6 months after surgery, underwent surgery for lateral lymph node recurrence in 1 node. Patient 2 was a 71-year-old man who underwent surgery after colostomy for rectal cancer and 4 courses of FOLFIRI+panitumumab resulted in a PR. Five months later, he underwent left lateral lymph node dissection. Patient 3 was a 78-year-old man who underwent postoperative adjuvant chemotherapy. Ten months later he underwent colostomy closure+left lateral lymph node dissection. Patient 4 was a 66-year-old man who underwent colostomy closure+lateral lymph node dissection with concurrent resection of the right internal artery. In 3 out of 4 patients, meal intake was recommenced on day 4 after surgery, and the patients were discharged without any complications. Furthermore, 3 out of the 4 patients were recurrence-free at 19 months. We believe that our results with regards to complications and duration until meal recommencement were better than those for conventional surgery for lymph node recurrence.