Theoretical investigation of active listening behavior based on the echolocation of CF-FM bats.

Bats perceive the three-dimensional environment by emitting ultrasound pulses from their nose or mouth and receiving echoes through both ears. To determine the position of a target object, it is necessary to know the distance and direction of the target. Certain bat species that use a combined signal of long constant frequency and short frequency modulated ultrasounds synchronize their pinnae movement with pulse emission, and this behavior has been regarded as helpful for localizing the elevation angle of a reflective sound source. However, the significance of bats' ear motions remains unclear. In this study, we construct a model of an active listening system including the motion of the ears, and conduct mathematical investigations to clarify the importance of ear motion in direction detection of the reflective sound source. In the simulations, direction detection under rigid ear movements with interaural level differences was mathematically investigated by assuming that bats accomplish direction detection using the amplitude modulation in the echoes caused by ear movements. In particular, the ear motion conditions required for direction detection are theoretically investigated through exhaustive simulations of the pseudo-motion of the ears, rather than simulations of the actual ear motions of bats. The theory suggests that only certain ear motions, namely three-axis rotation, allow for accurate and robust direction detection. Our theoretical analysis also strongly supports the behavior whereby bats move their pinnae in the antiphase mode. In addition, we suggest that simple shaped hearing directionality and well-selected uncomplicated ear motions are sufficient to achieve precise and robust direction detection. Our findings and mathematical approach have the potential to be used in the design of active sensing systems in various engineering fields.

Patients with Non-Muscle-Invasive Bladder Cancer Previously Treated with Nephroureterectomy Have a High Risk of Recurrence after Bacillus Calmette-Guérin Intravesical Instillation Therapy.

BACKGROUND: There is a high incidence of intravesical recurrence after transurethral resection of bladder tumor for non-muscle-invasive bladder cancer (NMIBC). Intravesical instillation of bacillus Calmette-Guérin (BCG) is widely used to prevent recurrence and progression. There are two types of NMIBC: primary NMIBC and subsequent NMIBC after radical nephroureterectomy (RNU). We compared the clinical outcomes of BCG intravesical instillation therapy between the two types of NMIBC. PATIENTS AND METHODS: This study included a total of 357 patients, who received BCG intravesical instillation therapy to prevent recurrence of NMIBC (pTa/pT1) between 1991 and 2019. Among them, 34 patients had subsequent NMIBC after RNU, and the remaining 323 patients had primary NMIBC. This retrospective study analyzed 68 patients extracted by propensity score matching. Survival curves were estimated using the Kaplan-Meier method, and independent prognostic factors for survival were examined by the Cox proportional hazards model. RESULTS: The 3-year recurrence-free survival (RFS) rates in patients with primary NMIBC and subsequent NMIBC after RNU were 70.7% and 54.8%, respectively (p = 0.036). However, there were no significant differences between the two groups in progression-free survival and cancer-specific survival. Multivariate analysis of RFS showed that only a previous history of upper tract urothelial carcinoma was an independent prognostic and predictive factor. CONCLUSION: Patients with subsequent NMIBC after RNU treated with BCG intravesical instillation therapy have a higher risk of recurrence than those with primary NMIBC. Thus, stringent follow-up is necessary for patients with subsequent NMIBC after RNU.

Efficacy of Intravesical Instillation Therapy with Low-Dose Tokyo-172 Bacillus Calmette-Guérin to Prevent Recurrence of Non-Muscle-Invasive Bladder Cancer and Treat Carcinoma in situ: A Multi-Institutional Retrospective Study.

INTRODUCTION: There are various doses, durations, and strains of bacillus Calmette-Guérin (BCG) intravesical instillation therapy, but optimal treatment has not yet been established. We retrospectively investigated the efficacy and safety of low-dose BCG therapy for non-muscle-invasive bladder cancer (NMIBC) and carcinoma in situ (CIS) in a multicenter study. METHODS: From 1991 to 2019, 323 patients who received BCG therapy to prevent recurrence of NMIBC were analyzed as group A. Similarly, 147 patients who received BCG therapy for the treatment of CIS were analyzed as group B. Patients received low- or full-dose Tokyo-172 strain or full-dose Connaught strain, and the three strains were compared. Survival curves were estimated by the Kaplan-Meier method, and independent risk factors for intravesical recurrence were examined by multivariate logistic regression. RESULTS: Recurrence-free survival (RFS) in group A was significantly better for the Connaught strain than the low-dose Tokyo-172 strain (p = 0.026), but not between the low- and full-dose Tokyo-172 strains (p = 0.443). RFS of group B, cancer-specific survival, and progression-free survival in both groups did not show statistically significant differences. Logistic analysis of group A showed that for intravesical recurrence, only pT1 was a significant risk factor, and there were no differences between the BCG strain and dose and no significant factors in group B. There were also no differences in the completion rate in both groups, but adverse events such as urinary frequency and feeling of residual urine were significantly lower with the low-dose Tokyo-172 strain. CONCLUSION: There was no difference in efficacy between the low- and full-dose Tokyo-172 strains, but to minimize adverse events, the low-dose Tokyo-172 strain may be worth considering.

Analysis of echolocation behavior of bats in "echo space" using acoustic simulation.

BACKGROUND: Echolocating bats use echo information to perceive space, control their behavior, and adjust flight navigation strategies in various environments. However, the echolocation behavior of bats, including echo information, has not been thoroughly investigated as it is technically difficult to measure all the echoes that reach the bats during flight, even with the conventional telemetry microphones currently in use. Therefore, we attempted to reproduce the echoes received at the location of bats during flight by combining acoustic simulation and behavioral experiments with acoustic measurements. By using acoustic simulation, echoes can be reproduced as temporal waveforms (including diffracted waves and multiple reflections), and detailed echo analysis is possible even in complex obstacle environments. RESULTS: We visualized the spatiotemporal changes in the echo incidence points detected by bats during flight, which enabled us to investigate the "echo space" revealed through echolocation for the first time. We then hypothesized that by observing the differences in the "echo space" before and after spatial learning, the bats' attentional position would change. To test this hypothesis, we examined how the distribution of visualized echoes concentrated at the obstacle edges after the bats became more familiar with their environment. The echo incidence points appeared near the edge even when the pulse direction was not toward the edge. Furthermore, it was found that the echo direction correlated with the turn rate of the bat's flight path, revealing for the first time the relationship between the echo direction and the bat's flight path. CONCLUSIONS: We were able to clarify for the first time how echoes space affects echolocation behavior in bats by combining acoustic simulations and behavioral experiments.

[A Case of Rectal Cancer Diagnosed Based on Brain Metastasis and Had a Long-Term Prognosis by Radical Resections].

The patient was a 57-year-old man who visited the department of neurosurgery for headache and lightheadedness. He was admitted with a diagnosis of brain tumor based on imaging findings. Severe brain dysfunction and mild ataxia were observed, and craniotomy tumor resection was performed 5 days after admission. He was diagnosed with brain metastasis of colorectal cancer based on histopathological examination and endoscopic findings, and was therefore referred to our department. No extracranial metastases were observed, laparoscopic-assisted low anterior resection was performed 1 month after the craniotomy. The final diagnosis was rectal cancer(Ra), pT3N0M1a(BRA), Stage Ⅳa. Three months after the craniotomy, subsequent MRI examination revealed a new metastatic lesion inferior to the tumor excision cavity, and gamma knife radiosurgery was performed. However, because an increasing tendency was noted, craniotomy was performed again 7 months after the first craniotomy. Following operative treatment, follow up has been performed without adjuvant chemotherapy or prophylactic irradiation, the patient has survived without recurrence at 34 months postoperatively. Here, we report a valuable rare case of solitary brain metastasis of colorectal cancer in which prognosis could be expected by radical resections.

[Relationship between Degree of Obstruction of Colorectal Cancer and Nutritional and Immune Status].

This study examined the impact of the degree of occlusion in colorectal cancer during the perioperative period. The subjects included 207 patients who underwent elective colorectal cancer resection. The degree of obstruction at the first medical examination was evaluated using the ColoRectal Obstruction Scoring System(CROSS). We classified the subjects into two groups(CROSS score 0-2, CROSS score 3-4)and assessed their associations with clinicopathological factors, nutritional immune status, and postoperative course. Compared to the CROSS score 3-4 group, the CROSS score 0-2 group(42 subjects [20.3%])had a higher proportion of subjects with ≥2 lesions, T4, Stage classification Ⅳ, CEA >5.0 ng/mL, prognostic nutritional index( PNI)≤40, controlling nutritional status( CONUT) score ≥2, modified Glasgow prognostic score (mGPS)2, weight loss rate>2.3, mini nutritional assessment-short form(MNA®-SF)score <12, neutrophil lymphocyte ratio(NLR) ≥4.0, postoperative complications, and postoperative hospital stay >16 days( p<0.05). Our findings suggest that the degree of occlusion in colorectal cancer is associated with clinicopathological and nutritional/immune factors and is reflected by the postoperative course.

[Assessment of Curative Resection in Patients with Multiple Relapses of Colorectal Cancer].

We assessed the therapeutic effect of curative resection in patients with multiple relapses of colorectal cancer using the time to surgical failure(TSF)as an index. We included 24 patients who experienced recurrence after curative resection of primary colorectal cancer at our department between 1993 and 2015. Curative resection for multiple relapses was possible in these patients. The sites of recurrence included the liver, lungs, peritoneum, lymph nodes, localized, and brain in 9, 8, 3, 3, 2, and 1 patients, respectively. The relapse occurred in 2 organs in 2 patients. The TSF after curative resection of recurrent lesions was 25.6 months, with a 5-year TSF-free rate of 40.2%. The clinicopathological factors associated with poor prognosis were age B65 years at the time of recurrence, absence of distal metastasis at primary onset, and only 2 curative resections for relapses. However, there was no difference in prognosis because of the number of twice recurrent lesions. Therefore, curative resection should be proactively performed as long as feasible in colorectal cancer patients with multiple lesions or multiple relapses.

[A Case of Unresectable Ascending Colon Cancer Treated with a Newly Devised Bypass Method].

A 74-year-old man underwent a medical examination for anemia and had a positive fecal occult blood test. Ascending colon cancer was detected by colonoscopy. Since it was unresectable, a bypass operation was performed to prevent digestive symptoms prior to chemotherapy. The bypass was performed by cutting the ileum and attaching the oral side to the transverse colon with side to side anastomosis. The other end of the terminal ileum was anastomosed to the transverse colon on the oral side of the prior anastomosis, making a pretzel shaped bypass. There were no postoperative complications and the patient was treated with chemotherapy from postoperative day 23.

[A Case of Rectal Neuroendocrine Carcinoma That Developed Two Years after Curative Resection for Sigmoid Colon Cancer].

We report a rare case ofrectal neuroendocrine carcinoma(NEC)following sigmoidectomy of sigmoid colon cancer. NEC of the rectum is a rare disease. It has an extremely poor prognosis and a high potential for malignancy with hematogenous and lymph node metastases. A 90-year-old man who had carcinoma ofthe sigmoid colon 2 years ago was found to have rectal NEC based on endoscopy findings. He underwent the Hartmann operation. Histological and immunohistochemical analyses showed NEC. Four months after the surgery, he developed local recurrence with lymph node metastasis. He was not administered chemotherapy because ofhis old age. Although the patient needed strict outpatient care, he remained symptom-free 4 months after the Hartmann operation.

[Endoscopic Submucosal Dissection(ESD)as a "Loco-Regional Cancer Therapy" for Colorectal Tumors].

INTRODUCTION: Endoscopic submucosal dissection(ESD)for colorectal tumors has been covered by the national health insurance system in Japan since April 2012, and is widely used. We analyzed colorectal ESD cases we performed. PATIENTS AND METHODS: We investigated 515 patients with colorectal lesions(580 lesions)for whom ESD was performed between November 2005 and April 2017. Clinicopathological data, technical methods, complications, and outcomes were analyzed. RESULTS: Most tumors were found in the transverse colon(134 lesions). The average diameter was about 26 mm. The largest lesion was 120 mm. The en bloc resection rate was high(96.2%). The average operative time was 51 minutes. Among complications, the number of delayed major bleeding cases was 7(1.2%). Minor perforations occurred in 3 cases(0.5%). The perforation could be closed with endoscopic clips. About 70% of the cases were adenomas, and the remainder were carcinomas. One patient with carcinoma in situ showed a mucosal recurrence 4 months later and received repeat endoscopic treatment. The cure rate was 99.8%. Among 29 deep submucosal invasion cases, additional colectomy was performed in 21; 3 patients had persistent carcinoma in the colonic wall and another patient had lymph node metastasis. CONCLUSIONS: Colorectal ESD can be performed for all sites in the large intestine, and en bloc resection was possible for a large lesion. A good outcome was observed for "Loco-Regional Cancer Therapy" in early colorectal carcinoma.

[Assessment of Less Invasiveness Based on Serum CRP Level on Postoperative Day Three in Laparoscopic Surgery for Colorectal Cancer].

To evaluate the less invasiveness of laparoscopic surgery for colorectal cancer, we compared open and laparoscopic surgery for sigmoid or recto-sigmoid cancer operations undergoing the same procedures. One hundred forty-three patients curatively resected with D3 dissection were enrolled. All cases underwent the following procedure; high ligation of the inferior mesenteric artery(IMA)with median approach and double stapling technique(DST)for anastomosis. The clinicopathological factors were examined in 70 cases of open surgery(OC)and 73 cases of laparoscopic surgery(LAC). The mean age of all cases was 66(38-88)years, including 83 men and 60 women. The mean operation time was 189(82-413)minutes and the mean blood loss was 45(5-1,025)mL. Postoperative complications were reported in 45 cases including 10 cases with surgical site infection(SSI)and 10 cases with remote infection(RI). There was no difference in sex, BMI, PS, and ASA between the 2 groups; however, the patients were significantly older and the tumor maximum diameter significantly larger in the OC group. There was no significant difference in operation time but the blood loss was significantly lower in the LAC group. There were no differences in postoperative complications, first gait, WBC, and body temperature on postoperative day(POD)3, but the first flatus was earlier and the CRP level was significantly lower on POD 3 in the LAC group. There was no difference in the CRP level on POD 3 in the age, tumor diameter, and blood loss which showed a difference in the both group. Laparoscopic surgery was considered less invasive than open surgery because the serum CRP level was lower in the LAC group.

[A Case of Low-Grade Appendiceal Mucinous Neoplasm with Cecum Cancer].

The case was a 76-year-old man. He visited our hospital for a positive fecal occult blood test finding at a medical examination. A colonoscopy revealed a macroscopic, 30 mm, type-1 lesion in the cecum. We performed laparoscope-assisted ileocolic resection and D3 dissection, with a diagnosis of cecum cancer. In postoperative histopathological examination, the tumor in the cecum was diagnosed as a well-differentiated tubular adenocarcinoma. In addition, a low-grade appendiceal mucinous neoplasm(LAMN)was observed on the distal side of the appendix. The patient has survived for 9 months after surgery without recurrence. We report this case with a review of the literature.

[Efficacy of Laparoscopic Surgery for Elderly Patients with Colorectal Cancer Over 80 Years Old].

The efficacy of laparoscopic surgery for elderly patients aged over 80 years who have colorectal cancer was investigated concerning complications. Sixty-five patients over 80 years old who underwent colorectal cancer resection until January 2018 were enrolled. Factors that led to complication were analyzed retrospectively. Thirty-three men and 32 women were included, with a median age of 83 years. Forty-eight cases were located at the colon; and 17, at the rectum. The median operating time was 164 minutes, including 39 cases treated with the laparoscopic approach. Postoperative complications were observed in 28 cases(43.1%), of which 15(23.1%)had a Clavien-Dindo(CD)classification of Grade BⅡ. These cases had significantly prolonged postoperative hospital stay. Complications included 10 cases of incisional surgical site infection(SSI), 9 cases of ileus, 6 cases of melena, 2 cases of urinary infection, 2 cases of urinary disorder, and 1 case of postoperative death. Open surgery was the only significant factor associated with the incidence of CD classification of BⅡ(p=0.0330). Among the complications, the incisional SSI was reduced by laparoscopic surgery(p=0.0050). The number of laparoscopic surgeries reduced the incidence of CD classification BⅡ of complications in elderly patients aged over 80 years who had with colorectal cancer resection. The use of incisional SSI also decreased with the use of laparoscopic surgery. Laparoscopic surgery for colorectal cancer in elderly patients may lead to reduced complication rates.

[A Case of Lung Metastases from Rectal Cancer Treated for Quite Long with FOLFIRI plus Ramucirumab as a Late Line of Therapy].

We herein report a case of lung metastases from rectal cancer treated with FOLFIRI plus ramucirumab(Ram)therapy after salvage for a long time. A 44-year-old woman underwent low anterior resection for rectal cancer. Fifteen months after the surgery, mFOLFOX6 plus bevacizumab(BV)therapy was initiated for left obturator lymph node metastases. Although the target lesion shrunk, left lung metastasis was found 36 months after the surgery. Partial resection of the lung metastasis was performed, and carbon-ion radiotherapy for pelvic recurrence was administered. Following these treatments, mFOLFOX6 plus BV therapy was administered again for multiple lung metastases 42 months after the surgery. FOLFIRI plus BV therapy, TAS- 102 plus BV therapy, and regorafenib were then administered because of the disease progression. Although the best supportive care was provided after disease progression, FOLFIRI plus Ram therapy was initiated owing to the patient's wish. Although Grade 3 hematological toxicity was observed, severe digestive symptoms were not noted. Long-term administration(approximately 1 year, 21 courses)of the drugs was possible with withdrawal. The patient died due to disease progression 66 months after recurrence. We experienced a case in which FOLFIRI plus Ram therapy after salvage line could be administered for a quite long time. It has been suggested that anti-VEGF drugs with different targets may improve the prognosis even as a late line of therapy if it is tolerable.

[Impact of Postoperative Inflammatory Status on Colorectal Cancer Prognosis].

To clarify the prognostic impact of postoperative inflammatory status, serum CRP levels on POD3 after radical resection (POD3 CRP)were evaluated as an indicator of inflammatory response after surgery in patients with colorectal cancer. Of the colorectal cancer patients who underwent radical resection at our department between 2000 and 2015, 916 patients with Stage Ⅰto Ⅳdisease were included in the analyses. The patients were divided into 2 groups according to high and low POD3 CRP levels. The POD3 CRP levels of the patients were analyzed for the 75th percentile that was 12.16mg/dL(range, 0.06- 33.78). The cancer-specific 5-year survival rate was 80.6%in patients in the high group and 90.5%in those in the low group, indicating poor prognosis in patients with high values. POD3 CRP levels were an independent prognostic factor in the multivariate analysis. It was suggested that the degree of inflammation after surgery influences the postoperative prognosis after radical resection for colorectal cancer.

[Efficacy of Negative Pressure Wound Therapy for Post-Operative Wound Dehiscence after Resection of a Metastatic AbdominalWal lTumor from Cecal Cancer during Chemotherapy with Bevacizumab].

A 74-year-old man with recurrence of cecal cancer received systemic chemotherapy(CapeOX plus bevacizumab). After the administration of 9 courses, he reported sudden appearance of bloody bowel discharge. Endoscopic examination could not locate the bleeding point. A CT scan indicated that the small intestine was affected by the recurrence of cancer. Therefore, resection of the small intestine was performed after 6 weeks of drug withdrawal. Although direct closure with fascia incision was performed for the repair of wound dehiscence after surgery, re-dehiscence occurred because of paralytic ileus. Wound lavage and nutritional intervention were performed, followed by negative pressure wound therapy. Excellent wound healing was achieved by this therapeutic approach for 3 months.

[The Influence of Immunity, Nutrition, and Physical Function on the Onset of Pneumonia after Colorectal Cancer Resection].

PATIENTS AND METHODS: Four hundred and nineteen patients with colorectal cancer who underwent laparotomy were included in this study. Indicators that reflected immunity, nutrition, and physical function were selected, and risks associated with the presence of postoperative pneumonia were investigated. Cut-off values of factors affecting the occurrence of pneumonia were determined using the receiver-operating characteristic curve approach. RESULTS: Pneumonia was observed in 2.9%of the patients, and PNI(C40.0), CONUT(B2), BMI(<18.5 kg/m2), PS(B1), %VC(<80.0%), and FEV1.0%(<70.0%)were identified as risk factors in multivariate analysis(p<0.05). %VC(<80.0%)was extracted as an independent factor. The cutoff value of %VC was determined to be 80.0%based on the incidence of postoperative pneumonia. CONCLUSION: Low volume in %VC(<80.0%)may be a risk factor for pneumonia after resection of colorectal cancer.

[Prognostic Relevance of Palliative Tumor Resection and Chemotherapy in Stage â £Unresectable Colorectal Cancer].

This study was conducted to evaluate the prognostic factors in patients with unresectable Stage Ⅳ colorectal cancer. One hundred and twenty-five patients who underwent either primary resection or chemotherapy for unresectable Stage Ⅳ colorectal cancer and were treated at our hospital between April 2004 and March 2014 were enrolled this study. In multiple univariate analysis, the overall survival(OS)was significantly longer in the palliative resection and chemotherapy groups. Upon dividing the 125 patients in 3 groups(the intensive chemotherapy group[L-OHP or CPT-11 regimen], extensive chemotherapy group[other regimen], and non-chemotherapy group), the intensive chemotherapy group showed significantly longer OS. Next, upon comparing the patients based on the treatment they received(surgery plus chemotherapy, surgery alone, and chemotherapy alone), the surgery plus chemotherapy group showed longer OS. With both studies combined as 5 groups, only the surgery plus intensive chemotherapy group showed longer OS. This is shown in unresectable Stage Ⅳ cancer patients, wherein resection of the primary lesion in addition to intensive chemotherapy contributes to longer OS.

[A Case of Ascending Colon Cancer with Hepatic Metastases Showing Remarkable Efficacy of CapeOX plus Bevacizumab].

We report a case of ascending colon cancer with hepatic metastases that was treated by CapeOX plus bevacizumab with remarkable efficacy. A 40-year-old female patient presented with a medical history of surgery for resection of right breast cancer4 years ago, left-sided transverse colon 2 years ago, and right ovarian cancer 6 months ago. Follow-up computed tomography(CT)found wall thickening from the ascending colon to cecum. She was diagnosed with an ascending colon cancer by colonoscopy, and underwent right hemicolectomy. One month after the surgery, her serum marker carcinoembryonic antigen(CEA)and carbohydrate antigen 19-9(CA19-9)levels were high. She was diagnosed with unresectable multiple hepatic metastases by CT 2 months after the surgery. Her tumor was epidermal growth factor receptor(EGFR)- positive and wild-type for RAS; she received 4 courses of CapeOX plus bevacizumab. Thereafter, liver metastases were remarkably decreased in size, and she could undergo central bisegmentectomy. Pathology examination revealed no tumor and that the center of the tumor was changed to necrotic tissue and the surrounding area was changed to fibrous tissue and lymphocyte infiltration. The patient is disease-free since the last operation.

[A Case of Surgery after Chemotherapy for Cecal Cancer with Onset of the Stenosis of the Colostomy].

The patient was 55-year-old woman, undergoing Hartmann operation by the sigmoid colon diverticulum perforation, 2 years later visited our hospital with abdominal pain. Although lower endoscopy and histological examination could not be performed due to stoma stenosis, we diagnosed cecal carcinoma, liver metastasis, distant lymph node metastasis from CT and PET-CT, CapeOX plus Bmabtherapy and IRIS plus Bmabtherapy were performed. After that, repeated intestinal obstruction due to exacerbated stoma stenosis, metastatic lesion increased in CT examination, furthermore the patient had hope of stoma closure, we decided to resect the primacy tumor, performed subtotal colonectomy and stoma closure. Pathological diagnosis revealed RAS wild type. After surgery, Pmabplus CPT-11 therapy was performed and the metastatic lesion was temporarily shrunk but re-exacerbated, the patient died 2 years 2 months after the first treatment started, 7 months after the primary tumor resection. In the treatment of colorectal cancer, when metastatic lesion is unresectable, chemotherapy is often carried out except when the primary tumor is symptomatic. In our case, although the primary tumor was asymptomatic, an intestinal obstruction due to stoma stenosis was developed and it was necessary to examine whether to use anti-EGFR antibody drugs, therefore we performed operation.