Impact of radiological and pathological splenic vein involvement in patients with resectable pancreatic body or tail cancer.

PURPOSE: Several studies have reported a negative impact on survival associated with splenic vessel involvement, especially splenic artery (SpA) involvement, in patients diagnosed with pancreatic body or tail cancer. However, there is limited research on splenic vein (SpV) involvement. Therefore, we aimed to elucidate the significance of splenic vessel involvement, especially SpV involvement, in patients with resectable pancreatic body or tail cancer. METHODS: Between January 2007 and December 2021, 116 consecutive patients underwent distal pancreatectomies for pancreatic body or tail cancer. Among them, this study specifically examined 88 patients with resectable pancreatic body or tail cancer to elucidate prognostic factors using a multivariable Cox proportional analysis. The Kaplan-Meier method evaluated the impact of SpV involvement in terms of both radiological and pathological aspects and the efficacy of neoadjuvant therapy. RESULTS: Higher pre-operative carcinoembryonic antigen levels, larger tumour size, pathological SpV invasion, and non-completion of adjuvant therapy were identified as independent poor prognostic factors for overall survival (OS) and recurrence-free survival (RFS). Additionally, patients with radiological SpV encasement had significantly worse prognoses in terms of OS (p = 0.039) and RFS (p < 0.001). The sensitivity and specificity of multidetector-row computed tomography for detecting pathological SpV invasion were 81.0% and 61.2%, respectively. However, the prognostic impact of neoadjuvant therapy could not be determined, regardless of radiological SpV involvement. CONCLUSION: Radiological and pathological SpV involvement is a poor prognostic factor for patients with resectable pancreatic body or tail cancer. New innovative treatments and effective neoadjuvant therapy regimens are required for patients with SpV involvement.

A field study on the effects of inactivated bacteria vaccine for respiratory diseases in Japanese Black calves.

This study evaluated the effects of vaccination for Pasteurella multocida, Mannheimia haemolytica, and Histophilus somni in young Japanese Black calves at an ordinal farm, where respiratory diseases frequently occur at a young age. In total, 105 calves were divided into the vaccination group (n = 52), which received inactivated combined vaccine at 0 and 2 weeks of age, and the control group (n = 53), which received no vaccine. From both groups, eight calves each were randomly selected to determine the antibody titers. And, the incidence of respiratory disease and medical costs (treatment plus vaccination costs) were recorded for each group from birth to 16 weeks of age. In the vaccination group, the antibody titers against P. multocida, M. haemolytica, and H. somni were significantly higher than those in the control group after 8, 12, and 4 weeks of age, respectively (p < 0.05). The incidence of respiratory disease was significantly lower in the vaccination group compared to the control group (p < 0.01), and the medical costs per calf in the vaccination group were 46.4% lower than in the control group. These results might contribute to establishing an effective vaccination program against respiratory diseases in calves at each farm.

A case of bullous pemphigoid developing under treatment with benralizumab for bronchial asthma.

Bullous pemphigoid (BP) is an autoimmune disease characterized by itchy erythema and tense blisters on the whole body. Recent reports have unveiled the pathogenic roles of eosinophils in BP (e.g., dermal-epidermal separation, generation of pruritus). Thus, eosinophils are considered a therapeutic target. Benralizumab is an anti-IL-5 receptor alpha (IL-5Rα) monoclonal antibody (mAb) that is widely used to treat severe eosinophilic asthma. By affecting IL-5Rα, benralizumab depletes eosinophils and basophils due to apoptosis through antibody-dependent cell-mediated cytotoxicity. The efficacies of benralizumab and other biologics, including bertilimumab (anti-eotaxin-1 mAb) and mepolizumab (anti-IL-5 mAb), were evaluated in several clinical trials. Also, reslizumab, an anti-IL-5 mAb, was reported as a successful treatment option in a case of BP. We present a case of severe asthma treated with benralizumab at 8-week intervals for 3 years before BP developed. Histologically, subepidermal blisters without eosinophilic infiltration were observed. Methylprednisolone pulse therapy followed by 40 mg/day (1 mg/kg/day) of oral prednisolone (PSL) was initiated, but the skin lesions worsened. Additional intravenous immunoglobulin and oral azathioprine enabled the oral PSL to be tapered. The benralizumab was discontinued after the onset of BP because the asthma did not worsen. To the best of our knowledge, there have been no reports of BP developing during anti-eosinophil therapy. BP may occur paradoxically via various pathways during treatment with drugs that are typically effective against BP.

Collagen XVII deficiency alters epidermal patterning.

Vertebrates exhibit patterned epidermis, exemplified by scales/interscales in mice tails and grooves/ridges on the human skin surface (microtopography). Although the role of spatiotemporal regulation of stem cells (SCs) has been implicated in this process, the mechanism underlying the development of such epidermal patterns is poorly understood. Here, we show that collagen XVII (COL17), a niche for epidermal SCs, helps stabilize epidermal patterns. Gene knockout and rescue experiments revealed that COL17 maintains the width of the murine tail scale epidermis independently of epidermal cell polarity. Skin regeneration after wounding was associated with slender scale epidermis, which was alleviated by overexpression of human COL17. COL17-negative skin in human junctional epidermolysis bullosa showed a distinct epidermal pattern from COL17-positive skin that resulted from revertant mosaicism. These results demonstrate that COL17 contributes to defining mouse tail scale shapes and human skin microtopography. Our study sheds light on the role of the SC niche in tissue pattern formation.

Wnt/ß-Catenin Signaling Stabilizes Hemidesmosomes in Keratinocytes.

Hemidesmosomes (HDs) are adhesion complexes that promote epithelial-stromal attachment in stratified and complex epithelia, including the epidermis. In various biological processes, such as differentiation and migration of epidermal keratinocytes during wound healing or carcinoma invasion, quick assembly and disassembly of HDs are prerequisites. In this study, we show that inhibition of Wnt/ß-catenin signaling disturbs HD organization in keratinocytes. Screening with inhibitors identified the depletion of HD components and HD-like structures through Wnt inhibition, but keratinocyte differentiation was not affected. Wnt inhibition significantly diminished plectin and type XVII collagen expression in the basal side of Wnt-inhibited cells and the dermo-epidermal junction of the Wnt-inactive murine basal epidermis. Similar to Wnt inhibition, PLEC-knockout cells or cells with plectin-type XVII collagen binding defects showed type XVII collagen reduction in the basal side of the cells, implying the possible involvement of Wnt/ß-catenin signaling in HD assembly. Atypical protein kinase C inhibition ameliorated the phenotypes of Wnt-inhibited cells. These findings show that Wnt/ß-catenin signaling regulates the localization of HD components in keratinocytes and that the atypical protein kinase C pathway is involved in Wnt inhibition‒induced HD disarrangement. Our study suggests that the Wnt signaling pathway could be a potential therapeutic target for treating HD-defective diseases, such as epidermolysis bullosa.

Molecular dynamics study on the elucidation of polyamide membrane fouling by nonionic surfactants and disaccharides.

Reverse osmosis (RO) is a widely used energy-efficient separation technology for water treatment. Polyamide (PA) membranes are the conventional choice for this process. Fouling is a serious problem for RO separation. This issue leads to significant decreases in the water permeability of PA membranes, and it has yet to be fully elucidated. In particular, the fouling behavior of a nonionic substance on the negatively charged surface of a PA membrane in an aqueous environment has not been previously studied. In this work, the mechanisms of nonionic substances such as polyoxyethylene octyl ether (PE5) and maltose (Mal) were investigated using molecular dynamics (MD) simulations. In a PA membrane in which the carboxyl group was not dissociated, the hydrophobic portion of the membrane was exposed due to the localization of water molecules around the carboxyl groups in the PA membrane. This caused hydrophobic interaction with the hydrophobic groups of PE5. In the case of an amine-modified PA membrane containing no carboxyl groups, water was not localized around the functional group, and the water orientation of the polyamide surface was also low. Due to this membrane property, the presence of stabilized water around PE5 reduced the number of hydrophobic interactions. In similar manner, a PA membrane with a slightly dissociated carboxyl group was hydrophilic, which reduced the PE5 adsorption. The presence of many dissociated carboxyl groups, however, enhanced the adsorption of PE5 due to the increase in interactions between the dissociated carboxyl groups and the hydrophilic groups of PE5. Therefore, PE5 exhibited an amphipathic adsorption wherein both hydrophilic and hydrophobic groups contributed to adsorption onto the PA membrane. Mal, on the other hand, was highly stable in every aqueous environment independent of the state of the functional groups of the PA membrane, and was not easily affected by the properties of the PA membrane.

Hair follicle stem cell progeny heal blisters while pausing skin development.

Injury in adult tissue generally reactivates developmental programs to foster regeneration, but it is not known whether this paradigm applies to growing tissue. Here, by employing blisters, we show that epidermal wounds heal at the expense of skin development. The regenerated epidermis suppresses the expression of tissue morphogenesis genes accompanied by delayed hair follicle (HF) growth. Lineage tracing experiments, cell proliferation dynamics, and mathematical modeling reveal that the progeny of HF junctional zone stem cells, which undergo a morphological transformation, repair the blisters while not promoting HF development. In contrast, the contribution of interfollicular stem cell progeny to blister healing is small. These findings demonstrate that HF development can be sacrificed for the sake of epidermal wound regeneration. Our study elucidates the key cellular mechanism of wound healing in skin blistering diseases.

Effects of Vitamin C Supplementation on The Blood Oxidative Stress and Antibody Titre Against Histophilus Somni Vaccination in Calves.

INTRODUCTION: The purpose of this study was to determine the effects of vitamin C supplementation on blood oxidative stress biomarkers and antibody response to vaccination in calves. MATERIAL AND METHODS: Thirty-four clinically healthy 2 week old Japanese Black calves were randomly assigned to two groups. Seventeen calves formed the VC group which received 1,000 mg of vitamin C daily from 2 to 8 weeks of age, and the other 17 calves of the control group did not receive supplementation. All calves received an inactivated Histophilus somni vaccine at 4 and 8 weeks of age. Blood samples were taken at 2, 4, 8 and 12 weeks of age. RESULTS: The concentration of the serum reactive oxygen metabolites (d-ROMs), and the oxidative stress index (OSI), which is calculated from the d-ROMs and biological antioxidant potential, were significantly lower at 8 weeks of age in the VC group than in the control group (P < 0.05). The antibody titres to H. somni in the VC group were significantly higher than those in the control group at 12 weeks of age after the second vaccination (P < 0.05). CONCLUSION: Vitamin C supplementation to calves may reduce oxidative stress and enhance the antibody production after vaccination with H. somni.

[A Resected Case of Intussusception Due to Undifferentiated Carcinoma of the Colon].

An 89-year-old woman was pointed out to have anemia for a routine blood examination by her family doctor and was referred to our gastroenterological department for further examination. Colonoscopy showed a type Ⅰ tumor in the transverse colon and insertion of fiber across the tumor was difficult. On contrast enema using gastrographin, a crab's claw-like appearance was found. CT after contrast enema revealed a tumor, 5 cm in diameter with pseudokidney sign near the hepatic flexure of the transverse colon. Pathological examination of biopsy specimen proved the tumor to be a poorly differentiated adenocarcinoma. Thus, she was diagnosed with intussusception due to transverse colon cancer and we performed partial resection of the transverse colon without regional lymphadenectomy. Final pathological diagnosis of the tumor was undifferentiated carcinoma and tumor stage was pT3pN0cM0, pStage Ⅱa. She was discharged 13 days after surgery and alive without tumor recurrence at 7 months after surgery, not undergoing adjuvant chemotherapy.

[A Case of Conversion Surgery following Chemotherapy for HER2-Positive Advanced Gastric Cancer].

A 73-year-old female was referred to the gastroenterological department of our hospital for examination because of anemia. CA19-9 increased to 1,392 U/mL, and upper endoscopy revealed type 2 gastric cancer extending from the anterior wall to the lesser curvature in the lower part of the gastric body. Biopsy specimens revealed well-differentiated tubular adenocarcinoma, and HER2 was positive immunohistologically. Contrast-enhanced CT revealed wall thickness of the lower part of the gastric body with marked lymph node swelling beside the lesser curvature and a low-density nodule measuring 10 mm in diameter with rim enhancement in segment 5 of the liver, indicative of liver metastasis. Thus, she was diagnosed with unresectable advanced gastric cancer(cT3cN2M1, HEP, cStage ⅣB), and combined chemotherapy with capecitabine, cisplatin, and trastuzumab was administered. After 7 courses, CA19-9 normalized, and upper endoscopy revealed a scar of the primary tumor, and cancer was not detected in the biopsy specimen. On contrast-enhanced CT, lymph nodes beside the lesser curvature shrank significantly, and liver nodules disappeared. She was referred to our department for conversion surgery, and distal gastrectomy with D2 lymph node dissection was performed 7 months after her first visit to our hospital. Pathologically, tumor invasion was restricted to the lamina propria, and lymph node metastasis was not observed(ypT1aN0M0, ypStage Ⅰ A). She was discharged on postoperative day 13 and is alive without tumor recurrence at 7 months after surgery. She is not currently undergoing adjuvant chemotherapy.

[Case of Resected Retroperitoneal Dedifferentiated Liposarcoma Extending to the Posterior Mediastinum].

A 71-year-old woman visited our hospital for the examination and treatment of retroperitoneal tumor. CT showed a retroperitoneal tumor extending to the posterior mediastinum; the tumor pressed the IVC and widely abutted the aorta. On MRI, the tumor showed low intensity on T1WI and high intensity on T2WI and DWI. However, the tumor did not show signal reduction on an ADC map. PET-CT showed high accumulation at the tumor. The patient was diagnosed with sarcoma arising from the retroperitoneum. The tumor located on a part of the diaphragm was resected. Histological examination revealed spindle cells with atypical nuclear and multinuclear cells. There were no lesions of well-differentiated liposarcoma. Both CDK4 and MDM2 tested positive on immunohistological staining. Histopathologically, the tumor was diagnosed as dedifferentiated liposarcoma without any well-differentiated liposarcoma component. The postoperative course was uneventful, and she was discharged on the 13th day after surgery. Two months after surgery, no recurrence has been detected.

Cholecystohepatic duct detected during laparoscopic cholecystectomy: a case report.

BACKGROUND: The cholecystohepatic duct is a rare form of an aberrant hepatic duct that connects to the gallbladder. Although cholecystohepatic duct is reported to be a very rare anomaly, injury of cholecystohepatic duct during cholecystectomy may result in serious complications. Herein, we present a case of cholecystohepatic duct in the ventral branch of the right posterior inferior segmental bile duct detected during laparoscopic cholecystectomy. CASE PRESENTATION: A 77-year-old woman with cholecystolithiasis had been referred to our hospital for surgery. Drip infusion cholecystocholangiography-computed tomography revealed a bile duct branch without communication between the intra- and extrabiliary systems, although the existence of this aberrant hepatic duct was not suspected preoperatively. A 4-port laparoscopic cholecystectomy was performed. After critical view of safety was confirmed, the cystic artery and duct were divided after double clipping. During antegrade mobilization of the gallbladder from the gallbladder bed, a thin, white cord-like material connecting the gallbladder neck and bed was detected. After clipping and dividing it, a cholecystohepatic duct injury was recognized through rechecking the results of the preoperative examinations. Biliary reconstruction was considered unnecessary because of the lesion's small drainage area. The postoperative course was uneventful, and an enhanced computed tomography performed 6 months after the surgery revealed a dilation in the ventral branch of the right posterior inferior segmental bile duct. The patient's liver function remained normal, and she had no symptoms of cholangitis 42 months after the surgery. CONCLUSIONS: Although cholecystohepatic duct is a rare anomaly compared to other aberrant hepatic ducts, surgeons performing cholecystectomy should always keep its existence in mind to avoid serious postoperative complications. Ideally, preoperative detection of cholecystohepatic duct is preferable, but even if it is detected during surgery, the appropriate management according to the drainage area is also important.

[Two Cases of Gastric Cancer Diagnosed after Omental Patch Repair for Gastric Perforation].

Case 1: A 62-year-old man was urgently admitted to our hospital because of left lower abdominal pain. Abdominal CT showed gastric perforation and we performed omental patch repair emergently. Postoperative upper gastrointestinal endoscope revealed an ulcerative lesion in the lesser curve of upper area of gastric body, which proved to be a poorly differentiated adenocarcinoma by biopsy. Thus, we performed total gastrectomy with D2 lymph node dissection. Resected specimen revealed type 2 gastric cancer in the perforated area. Pathological stage was pT3pN0M0, pStage ⅡA. Adjuvant chemotherapy by S-1 was performed and he is alive without tumor recurrence 12 months after the first operation. Case 2: A 71-year- old man was urgently admitted to our hospital because of upper abdominal pain after dinner. Abdominal CT suggested gastric perforation and we performed emergent laparoscopic operation. Perforated lesion about 8 mm in diameter was found in the anterior wall of gastric body. After debridement, perforated lesion was closed with a running suture and additionally omental patch repair was performed. Pathologically, well-differentiated adenocarcinoma was detected in the debridement tissue, and he was diagnosed with perforated gastric cancer. Thus, we performed total gastrectomy with D2 lymph node dissection 28 days after surgery. Pathological stage was pT3pN0M0, pStage ⅡA. Adjuvant chemotherapy by CapeOX was performed and he is alive without tumor recurrence 12 months after the first operation.

[Resected Cases of Primary Duodenal Carcinoma-A Ten-Year Experience].

Primary duodenal carcinoma excluding tumors of the ampulla of Vaterare are rare, thus, therapeutic strategy has not been established. In this study, we investigated the treatment outcome of 7 cases of duodenal carcinoma resected in our hospital between January 2010 and December 2019. The tumor locations were the duodenal bulb in 5(71%), the descending part and the transverse part in 1, respectively. Distal gastrectomy was performed in 4 out of 5 bulbous cases, and pancreatoduodenectomy was performed in the other 3 cases. The pathological stage by the 8th edition of the UICC TNM classification was Stage Ⅰ(T1a/T2, N0)in 3 cases, ⅡA(T3, N0)in 1, ⅢA(N1)in 2, and ⅢB(N2)in 1. R0 resection was achieved in all cases. Adjuvant chemotherapy with S-1 was performed in 3 of 4 patients with Stage Ⅱ or more advanced Stage. There were no tumor recurrences in 4 patients with Stage Ⅰ and Stage ⅡA, but recurrence was occurred in 2 of 3 patients with Stage ⅢA or more. The surgical outcome for duodenal carcinoma without lymph node metastasis were good. On the other hand, the prognosis for advanced cases with lymph node metastasis were poor. Thus, the development of effective adjuvant chemotherapy is strongly expected.

Isolated pancreatic metastasis from malignant melanoma: a case report and literature review.

Isolated pancreatic metastasis from malignant melanoma is rare. Pancreatic metastasis is difficult to diagnose in patients with unknown primary malignant melanoma. Endoscopic ultrasound-guided fine-needle aspiration plays an important role in confirming the diagnosis. A 67-year-old woman was referred to our institution because of a mass in her pancreas. Computed tomography and magnetic resonance imaging revealed a 35-mm mass localized on the pancreatic tail, with low attenuation, surrounded by a high-attenuation rim. Endoscopic ultrasonography revealed a hypoechoic mass with central anechoic areas. Endoscopic ultrasound-guided fine-needle aspiration of the mass was performed, and the pathological diagnosis was malignant melanoma. Intense fluorodeoxyglucose uptake was observed in the pancreatic tail on positron emission tomography-computed tomography. No other malignant melanoma was found. Distal pancreatectomy was performed. Six months postoperatively, positron emission tomography-computed tomography revealed high uptake in the left nasal cavity, and biopsy revealed the mass to be a malignant melanoma, indicating that the primary site of the malignant melanoma was the left nasal cavity and that the pancreatic mass and peritoneal lesion were metastases. The patient had survived > 2 years after the distal pancreatectomy. Pancreatic resection of isolated pancreatic metastasis can possibly prolong survival; however, metastatic melanoma usually has poor prognosis.