Kinematic and hydrodynamic analyses of turning manoeuvres in penguins: body banking and wing upstroke generate centripetal force.

Penguins perform lift-based swimming by flapping their wings. Previous kinematic and hydrodynamic studies have revealed the basics of wing motion and force generation in penguins. Although these studies have focused on steady forward swimming, the mechanism of turning manoeuvres is not well understood. In this study, we examined the horizontal turning of penguins via 3D motion analysis and quasi-steady hydrodynamic analysis. Free swimming of gentoo penguins (Pygoscelis papua) at an aquarium was recorded, and body and wing kinematics were analysed. In addition, quasi-steady calculations of the forces generated by the wings were performed. Among the selected horizontal swimming manoeuvres, turning was distinguished from straight swimming by the body trajectory for each wingbeat. During the turns, the penguins maintained outward banking through a wingbeat cycle and utilized a ventral force during the upstroke as a centripetal force to turn. Within a single wingbeat during the turns, changes in the body heading and bearing also mainly occurred during the upstroke, while the subsequent downstroke accelerated the body forward. We also found contralateral differences in the wing motion, i.e. the inside wing of the turn became more elevated and pronated. Quasi-steady calculations of the wing force confirmed that the asymmetry of the wing motion contributes to the generation of the centripetal force during the upstroke and the forward force during the downstroke. The results of this study demonstrate that the hydrodynamic force of flapping wings, in conjunction with body banking, is actively involved in the mechanism of turning manoeuvres in penguins.

Contribution of pre-existing neoantigen-specific T cells to a durable complete response after tumor-pulsed dendritic cell vaccine plus nivolumab therapy in a patient with metastatic salivary duct carcinoma.

Although immune checkpoint inhibitors (ICIs) have emerged as new therapeutic options for refractory cancer, they are only effective in select patients. Tumor antigen-pulsed dendritic cell (DC) vaccine therapy activates tumor-specific cytotoxic T lymphocytes, making it an important immunotherapeutic strategy. Salivary ductal carcinoma (SDC) carries a poor prognosis, including poor long-term survival after metastasis or recurrence. In this study, we reported a case of refractory metastatic SDC that was treated with a tumor lysate-pulsed DC vaccine followed by a single injection of low-dose nivolumab, and a durable complete response was achieved. We retrospectively analyzed the immunological factors that contributed to these long-lasting clinical effects. First, we performed neoantigen analysis using resected metastatic tumor specimens obtained before treatment. We found that the tumor had 256 non-synonymous mutations and 669 class I high-affinity binding neoantigen peptides. Using synthetic neoantigen peptides and ELISpot analysis, we found that peripheral blood mononuclear leukocytes cryopreserved before treatment contained pre-existing neoantigen-specific T cells, and the cells obtained after treatment exhibited greater reactivity to neoantigens than those obtained before treatment. Our results collectively suggest that the rapid and long-lasting effect of this combination therapy in our patient may have resulted from the presence of pre-existing neoantigen-specific T cells and stimulation and expansion of those cells following tumor lysate-pulsed DC vaccine and ICI therapy.

[A Case of Delayed Anastomotic Leakage after Ileocecal Resection in a Hemodialysis Patient].

A 66-year-old man was referred to our department with the diagnosis of ascending colon cancer. He was undergoing dialysis for chronic renal failure due to diabetic nephropathy. Laparoscopic ileocecal resection was planned for the ascending colon cancer, but the procedure was converted to laparotomy owing to intraoperative bleeding. The patient was discharged from the hospital after 7 days. On the 14th postoperative day, the patient presented with purulent drainage from the wound and fever and was diagnosed to have a minor anastomotic leak. The suture of the anterior sheath was exposed in part of the wound. The patient's general condition was stable, and conservative treatment was planned. However, when he coughed, the wound separated and the intestine prolapsed, and emergency surgery was performed. Intraoperative findings showed leakage of intestinal fluid from the anastomotic border, and we diagnosed delayed suture failure. We present a rare case of delayed anastomotic leakage in a hemodialysis patient.

Kinematics and hydrodynamics analyses of swimming penguins: wing bending improves propulsion performance.

Penguins are adapted to underwater life and have excellent swimming abilities. Although previous motion analyses revealed their basic swimming characteristics, the details of the 3D wing kinematics, wing deformation and thrust generation mechanism of penguins are still largely unknown. In this study, we recorded the forward and horizontal swimming of gentoo penguins (Pygoscelis papua) at an aquarium with multiple underwater action cameras and then performed a 3D motion analysis. We also conducted a series of water tunnel experiments with a 3D printed rigid wing to obtain lift and drag coefficients in the gliding configuration. Using these coefficients, the thrust force during flapping was calculated in a quasi-steady manner, where the following two wing models were considered: (1) an 'original' wing model reconstructed from 3D motion analysis including bending deformation and (2) a 'flat' wing model obtained by flattening the original wing model. The resultant body trajectory showed that the penguin accelerated forward during both upstroke and downstroke. The motion analysis of the two wing models revealed that considerable bending occurred in the original wing, which reduced its angle of attack during the upstroke in particular. Consequently, the calculated stroke-averaged thrust was larger for the original wing than for the flat wing during the upstroke. In addition, the propulsive efficiency for the original wing was estimated to be 1.8 times higher than that for the flat wing. Our results unveil a detailed mechanism of lift-based propulsion in penguins and underscore the importance of wing bending.

[A Case of Anastomotic Recurrence 10 Years after Excision of Sigmoid Colon Cancer with Submucosal Invasion].

A 72-year-old woman underwent sigmoid colon resection plus D2 lymph node dissection in 2008, with additional resection after endoscopic mucosal resection(EMR). Histopathological examination revealed only atypical ducts in the EMR scar, with no invasion below the submucosa. No lymphatic, venous, or nerve invasions were confirmed, and oral and anal stumps and lymph node metastases were negative. She was followed up for 5 years after the surgery, and no recurrence was detected. In 2018, she visited our hospital with the chief complaint of diarrhea and constipation. Colonoscopy revealed a circumferential lesion around the anastomosis. She underwent laparoscopic low anterior resection for suspected anastomotic recurrence, which was confirmed by histopathological diagnosis. The anastomotic recurrence 10 years after surgery for SM cancer of the colon with negative lymph node metastasis and vascular factor was extremely rare. We recognized the importance of surveillance 5 years after surgery.

[A Case of Sarcoid‒Like Reaction with Multiple Lymphadenopathy by Rectal Cancer after an Operation].

We are reporting on a case of lymphadenopathy after surgery for rectal cancer. The case was a 66‒year‒old female. Laparoscopic high anterior resection(D3 dissection)was performed for rectal cancer(pT1bpN0M0, pStage Ⅰ)in April 2018, and she was followed up with on an outpatient basis. In July of the same year, a painless mass had formed in the right groin. An abdominal contrast‒enhanced CT showed lymph node swelling around the right groin and external iliac artery, but the tumor markers, CEA 2.3 ng/mL and CA19‒9 <2 U/mL, were within the standard values. An inguinal lymph node biopsy was performed during the same month. Pathological examination revealed no cancer cells and formation of epithelioid granuloma with giant cells. There was no suspicion of systemic sarcoidosis based on the test results and clinical findings. From the above, the patient was diagnosed with sarcoid reaction due to the tumor. Abdominal contrast‒enhanced CT scan 2 months after the biopsy showed lymph node shrinkage and there was no recurrence 2 years after the biopsy.

[Hemorrhage of Peritoneal Dissemination of the Ascending Colon Cancer Successfully Controlled by Palliative Radiotherapy-A Case Report].

An 81-year-old man underwent laparoscopic right hemicolectomy for ascending colon cancer. The postoperative diagnosis was tub1>tub2, pT4apN1bM0, pStage Ⅲb, ascending colon cancer. At 1 year 4 months after operation, abdominal CT showed dissemination around anastomosis. The patient has been treated with first-line systematic chemotherapy(capecitabine, oxaliplatin and bevacizumab). Epigastralgia and grade 4 anemia were observed at 5 years 7 months after initiation of chemotherapy when he was treated with second-line chemotherapy(capecitabine, irinotecan and bevacizumab). As abdominal CT showed that the dissemination progressed rapidly in size 30 mm to 100 mm, we diagnosed tumor bleeding in the dissemination. Palliative radiotherapy(30 Gy/10 Fr)for the dissemination was performed. Hemostasis and tumor shrinkage were achieved, and epigastralgia improved after receiving the radiation therapy. The patient discharged our hospital on 31 days form admission. We believe that palliative radiotherapy is effective to recurrent colon cancer with tumor bleeding.

[A Case of Intra-Abdominal Desmoid Tumors Occuring Four Years after Open Radical Prostatectomy].

Desmoid tumor is one kind of fibromatosis, and much occurs the abdominal wall and outside the abdominal wall. Intra- abdominal desmoid tumor is rare at about 8%. We experienced a case of intra-abdominal desmoid tumors occurring 4 years after open radical prostatectomy with some literature review. A 72-year-old man had undergone open radical prostatectomy for prostate cancer. Four years after that resection, multiple intra-abdominal tumors measuring 56 mm in maximum diameter was identified on follow-up computed tomography, and he was referred to our department for management. We performed laparotomy and investigation of the biopsy. Immunohistochemistry of the resected specimen indicated the tumor cells were positive for vimentin and ß-catenin, and the diagnosis was desmoid. We performed partial resection of the small intestine and ileocecal resection. His postoperative course was uneventful and he was discharged on the 12th postoperative day. He has shown no sign of recurrence in the 4 months follow-up since surgery. In the past, an operation was the best treatment for intra-abdominal desmoid tumor. But it is reported that watchful waiting is also possible by the case which has no symptom and dysfunction in NCCN guidelines 2019. Further research is needed.

[Hyperammonemia with Disturbance of Consciousness during 5-FU plus Nedaplatin Therapy for Esophageal Cancer-A Case Report].

Hyperammonemia is a rare adverse event of 5-FU. Here, we report a case of hyperammonemia with disturbance of consciousness during 5-FU plus nedaplatin therapy for esophageal cancer and present a literature review. A 69-year-old man was diagnosed with cT2N2M0, cStage Ⅲ esophageal cancer. He was administered with DCF therapy as the first-line neoadjuvant chemotherapy. After the first course, he showed renal dysfunction. Therefore, as the second-line neoadjuvant chemotherapy, he was administered with 5-FU plus nedaplatin. He vomited on treatment day 5 and suddenly presented with disturbance of consciousness on treatment day 6. Blood tests showed hyperammonemia(114 µg/dL). He was treated with rehydration and branched-chain amino acid solutions, resulting in a gradual improvement of symptoms. Hyperammonemia has been reported in patients with colorectal cancer but rarely in patients with esophageal cancer. A case of hyperammonemia during the 5-FU plus nedaplatin therapy has never been reported in Japan. We should be aware that 5-FU may cause hyperammonemia and resultant disturbance of consciousness during chemotherapy with 5-FU.

[A Case of Obstructing Rectal Cancer with Obstructive Colitis Resected after Neoadjuvant Chemotherapy to Avoid Anastomotic Leakage].

A 61-year-old male was referred to our department after decompression of the transanal ileus tube due to a rectal cancer obstruction. Colonoscopy revealed a circumferential type 2 tumor, 4 cm from the anal verge. The tumor was diagnosed as rectal cancer tub1-2, Group 5 on biopsy analysis. Longitudinal ulcers descending to the sigmoid colon were present and obstructive colitis was suspected. Enhanced computed tomography showed wall thickness in the Ra, Rb rectum and swelling of the mesorectum lymph node, but distant metastases were not identified. We diagnosed the patient with Ra, Rb rectal cancer cT4aN1aM0, cStage Ⅲb. Because of the risk of anastomotic leakage with obstructive colitis, we planned neoadjuvant chemotherapy(SOX therapy)after laparoscopic transverse colostomy. After neoadjuvant chemotherapy, colonoscopy revealed improvements in the obstructive colitis. The tumor was reduced in size and the chemotherapy appeared effective. We performed laparoscopic rectal super low anterior resection with resection of the D3 lymph node. Histopathological examination revealed tub1, ypT3, ypN0, and the chemotherapeutic outcome was rated as Grade 1a. The final diagnosis was Ra, Rb rectal cancer with ypT3ypN0M0, ypStage Ⅱa.

[A Case of Disseminated Carcinomatosis of the Bone Marrow with Carcinoma of the Rectum Diagnosed by Disseminated Intravascular Coagulation].

A 77-year-old man with rectal cancer was admitted to our hospital. After neoadjuvant chemotherapy, laparoscopic abdominoperineal resection of rectum with D3 dissection was performed. The pathological diagnosis was poorly differentiated carcinoma, pT3, N1a, M0, pStage Ⅲa. Adjuvant chemotherapy was not performed. Fifteen months after operation, his chief complaint was fatigue. Thrombocytopenia and elevation of tumor maker was detected by blood test and disseminated intravascular coagulation(DIC)was suspected. He was admitted to our hospital and we started anti DIC therapy immediately. Bone scintigraphy revealed multiple bone metastases, then we diagnosed disseminated carcinomatosis of the bone marrow. He died 10 days after hospitalization. Disseminated carcinomatosis of the bone marrow with colon cancer is rare and prognosis is very poor. It is important to diagnose and start treatment as early as possible.

[Effective Palliative Radiation for Hemostasis of Recurrent Colon Cancer in the Lymph Node with Gastric Wall Invasion].

A 76-year-old man underwent laparoscopic left hemicolectomy D3(pStage Ⅱb)for sigmoid colon cancer in 2015. Later, partial transverse colectomy D2(pStage Ⅱb)was performed because transverse cancer was also detected. Recurrent peritoneal dissemination was found in 2018. In 2019, hematemesis/black stool, as well as prominent anemia(Hb 3.1 g/dL)and bleeding from recurrent gastric wall invasion of the lymph nodes on the lesser curvature side of the stomach, was observed. Although hemostasis was performed endoscopically, palliative irradiation(30 Gy in 10 fractions)was performed to control bleeding because the risk of rebleeding was high. After irradiation, endoscopy showed that the ulcer in the infiltrated area of the gastric wall had a tendency to improve. No bleeding or progression of anemia was observed, and oral intake became possible. However, the patient's general condition deteriorated, and he died 80 days after palliative irradiation. For palliative radiation therapy, alleviation of pain owing to bone metastasis, as well as alleviation of the narrowed airway and esophagus, is known. Palliative radiation therapy has recently been performed for symptom relief and prognosis extension against tumor bleeding. Palliative radiation therapy for controlling bleeding has limited hemostatic effect compared with surgical resection, and it takes some time before hemostasis is achieved, but it is less invasive and less adverse event and may be an effective treatment option.

[A three-week regimen of S-1 monotherapy reduced gastrointestinal toxicity and maintained efficacy in patients with gemcitabine-refractory advanced pancreatic cancer].

S-1 administration for 28 consecutive days followed by 14 days of rest (6-week cycle) is often chosen as second-line chemotherapy for advanced pancreatic cancer (PC), but it causes gastrointestinal toxicity. In comparison, in gastric cancer or head and neck cancer, S-1 administration for 14 consecutive days followed by a 7-day rest period (3-week cycle) reduced gastrointestinal toxicity. This study retrospectively evaluated the efficacy and safety of a 3-week S-1 schedule compared to a 6-week schedule in patients with gemcitabine (GEM)-refractory advanced PC. Fifty-seven patients were treated with the 6- week S-1 schedule and 68 patients were treated with the 3-week S-1 schedule. There were no statistical differences in overall survival (p=0.13) and progression-free survival (p=0.190). With regard to adverse events, the rates of nausea (p<0.01) and vomiting (p=0.04) were lower with the 3-week schedule than with the 6-week schedule. Thus, S-1 therapy with a 3- week schedule as second-line chemotherapy in patients with GEM-refractory advanced PC was associated with reduced gastrointestinal toxicity and similar efficacy, when compared to a 6-week schedule.

UV laser-processed microstructure for building biohybrid actuators with anisotropic movement.

Fabrication of a biohybrid actuator requires muscle cells anisotropically aligned in a line, curve, or combination of lines and curves (similar to the microstructure of living muscle tissue) to replicate lifelike movements, in addition to considering the arrangement of skeletal structure or muscular structure with anisotropic straight patterns. Here, we report a UV laser-processed microstructure for freely directing cellular alignment to engineer a biohybrid actuator composed of poly(styrene-block-butadiene-block-styrene triblock copolymer) (SBS) thin film with tailor-made microgrooves (MGs) and skeletal myotubes aligned along these MGs. Specifically, straight, circular, or curved MGs were transferred to SBS thin films from a UV laser-processed template, allowing for the successful alignment of myotubes along MGs. The biohybrid actuator, composed of anisotropically aligned myotubes on a curved microgrooved SBS thin film, was contracted by electrical stimulation. Contraction of biohybrid actuators with curved aligned myotubes permits twisted-like behavior, unlike straight microgrooved films. Therefore, the UV laser-ablation system is a unique maskless and rapid microfabrication technique that provides intriguing opportunities for omni-directional microgrooved structures to achieve the complex motion of living organisms.

Focal coagulative necrosis of the liver in a patient with sustained virologic response to anti-hepatitis C virus therapy.

A 69-year-old woman with chronic hepatitis C virus (HCV) infection was referred to our hospital due to liver enzyme abnormalities. Four years after anti-HCV therapy, the patient with sustained virologic response and no clinical symptoms developed an oval hepatic mass with mixed high and low internal echoes near the portal vein on ultrasound. Magnetic resonance imaging (MRI) of the liver lesion showed a slightly hypo intense pattern on T1-weighted images, a hyper intense pattern both on T2- and diffusion-weighted images, a slight rim enhancement pattern with no intra-lesional enhancement up to the late phase, and a very low intense pattern on hepatobiliary phase images. Positron emission tomography/computed tomography (PET / CT) showed no areas of avid radiotracer uptake in the liver. No tumor markers showed abnormally high values. All these images and laboratory findings led us to the assessment of the liver lesion as a non-neoplastic disorder. However, due to the patient's strong preference to get both definitive diagnosis and cure of the lesion, the patient underwent laparoscopic partial hepatectomy. Pathological study showed 2 necrotic areas surrounded by multiple lymph follicles, epithelioid cells, lymphocytes, collagen fibers, and plasma cells, leading to the diagnosis of focal coagulative necrosis of the liver (FCNL). Physicians should note that FCNL can occur without any symptoms and can be diagnosed at least as a non-neoplastic disorder with combined MRI and PET/CT analysis.

Single-port laparoscopic surgery for cecum cancer with intussusception: a case report.

BACKGROUND: Most adult cases of intussusception are caused by colorectal cancer, and emergency surgery is performed when symptoms such as abdominal pain and vomiting are present. The patient must customarily undergo both bowel decompression and radical surgery for colorectal cancer at the same time, and laparotomy is generally the procedure of choice. CASE PRESENTATION: An 86-year-old woman presented to our hospital with diarrhea and bloody stools. Preoperative examination revealed the presence of a cancerous tumor in the advanced part of the transverse colon and bowel intussusception. Radical surgery was successfully performed using the laparoscopic single-port technique through a small incision at the umbilical site to treat intussusception caused by cecum cancer. CONCLUSIONS: With only one wound site at the umbilicus, this single-port laparoscopic approach is much less invasive than endoscopic surgery that requires four to five incision wounds to perform the procedure. Furthermore, the patient was discharged without major complications and this surgical technique could be of great benefit if established as a standard procedure in the future.

The Hedgehog inhibitor suppresses the function of monocyte-derived dendritic cells from patients with advanced cancer under hypoxia.

Immunotherapy using monocyte derived dendritic cells (Mo-DCs) from cancer patients has been developed; however, the Mo-DCs regularly studied have been derived from non-cancer bearing donors or mice, and evaluated in normoxic conditions. In the present study, we investigated the effects of Hedgehog (Hh) inhibitors which are being developed as molecular target drugs for cancer on the functions of Mo-DCs derived from patients with advanced cancer when cultured in a tumor-like hypoxic environment. Mo-DC induction, migration, chemotaxis, phagocytosis, maturation, IL-12 p40 or p70 secretion and the allogeneic lymphocyte stimulation activity of Mo-DCs from patients with advanced cancer were all significantly inhibited by the Hh inhibitor, cyclopamine under hypoxic conditions. Our results suggest that Hh signaling plays an important role in the maintenance and function of Mo-DCs derived from patients with advanced cancer when cultured under hypoxic conditions.

The Hedgehog inhibitor cyclopamine impairs the benefits of immunotherapy with activated T and NK lymphocytes derived from patients with advanced cancer.

Hedgehog (Hh) signaling is activated in various types of cancer and contributes to the progression, proliferation, and invasiveness of cancer cells. Many Hh inhibitors are undergoing clinical trial and show promise as anticancer drugs. Hh signaling is also induced in the activated T and NK (TNK) lymphocytes that are used in immunotherapy. Activated TNK lymphocyte therapy is anticipated to work well within a tumor's hypoxic environment. However, most studies on the immunobiological functions of activated TNK lymphocytes have been conducted on healthy donor samples, under normoxic conditions. In the present study, we evaluated the effects of Hh inhibition and oxygen concentrations on the function of activated TNK lymphocytes derived from patients with advanced cancer. Proliferation, migration, surface NKG2D expression, and cytotoxicity were all significantly inhibited, and IFN-γ secretion was significantly increased upon Hh inhibitor treatment of activated TNK lymphocytes under hypoxic conditions in vitro. Tumors from mice injected with cyclopamine-treated activated TNK lymphocytes showed a significant increase in tumor size and had fewer apoptotic cells compared with the tumors in mice injected with control activated TNK lymphocytes. These results suggest that Hh signaling plays a pivotal role in activated TNK lymphocyte cell function. Combination therapy using Hh inhibitors and activated TNK lymphocytes derived from patients with advanced cancer may not be advantageous.

Nutritional management contributes to improvement in minimal hepatic encephalopathy and quality of life in patients with liver cirrhosis: A preliminary, prospective, open-label study.

AIM: Problems in patients with minimal hepatic encephalopathy (MHE) include episodes such as falls and deficient driving skills, without any recognition of neurophysiological dysfunction. Patients with MHE are also more likely to develop overt hepatic encephalopathy. However, there is not yet any interventional strategy for MHE involving nutritional management. We conducted a preliminary study to investigate the proportion of positive MHE and the effects of nutritional management on MHE. METHODS: Patients with viral liver cirrhosis and abnormal neuropsychological tests were included. Nutritional consultations were conducted periodically by a dietitian, who recommended 30-35 kcal with 1.0-1.5 g of protein/kg of ideal bodyweight/day. The primary end-point was to evaluate the proportion of patients who recovered from MHE. The secondary end-point was to evaluate the improvement in the patients' quality of life (QOL). RESULTS: Thirty-two (30.1%) of 106 patients were diagnosed with MHE. Nineteen patients were enrolled in the study. Eleven of 19 patients became non-MHE after 4 weeks, and 13 of 19 patients (68.4%, P < 0.001) after 8 weeks. The mental summary scores were significantly improved at 8 weeks (P = 0.0413). Changes in albumin levels from week 0 to week 8 were 0.15 ± 0.16 g/dL in the improved MHE group and -0.28 ± 0.33 g/dL in the non-improved MHE group, which differ significantly (P = 0.0130). CONCLUSION: Periodical nutritional management improved MHE and QOL. Improving the patient's nutritional condition may be one approach to treating MHE.

Experimental analysis of the sweepback angle effect on the thrust generation of a robotic penguin wing.

Penguins have evolved excellent swimming skills as diving birds, benefiting from their agile wings. This paper experimentally analyzes the effects of the wing sweepback angle on thrust generation using a robotic penguin wing. A developed wing mechanism that can realize penguin-like flapping and feathering motion was used for actuating five alternative wing models, with different sweepback angles ranging from 0° to 50°. Force measurements under a steady water flow were conducted for both fixed and flapping states for all wing models. The results showed that small sweepback angles of 30° or less in the fixed state caused a steep lift curve and a moderate sweepback angle of 30° produced the largest lift-to-drag ratio. In the flapping state, the smaller sweepback wings generated a larger net thrust for the same wing motion, whereas the larger-sweepback wings produced more thrust under the same Strouhal number. The findings also revealed that larger sweepback wings more easily achieve the maximum net thrust in terms of less angle-of-attack control. In contrast, the hydrodynamic efficiency was not greatly affected by the sweepback. Regardless of the sweepback, the trend of the efficiency increasing with increasing flow speed indicates that the penguin wings can be more suitable for high-speed locomotion for higher hydrodynamic efficiency.