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.

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.

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.

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.

[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.

[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.

[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.

[Two Cases of Complete Response to Trastuzumab Combined with Chemotherapy for Recurrence of HER2-Positive Gastric Cancer].

Case 1: A 67-year-old male underwent distal gastrectomy for advanced gastric cancer. Postoperative histopathological examination indicated pT2a, pN2, M0, pStage ⅢA. He received 4 courses of TS-1 with paclitaxel chemotherapy and TS-1 chemotherapy for 2 years. Three years and 5 months after surgery, computed tomography suggested lymph node metastasis of the mediastinum, so TS-1 with cisplatin(CDDP)therapy was administered. Five years and 10 months after surgery, recurrence occurred and docetaxel and CPT-11 were administered with no response. Since HER2 was overexpressed in the primary tumor, he was treated with capecitabine, CDDP, and trastuzumab(XPT)therapy. After 1 year and 6 months, the patient was considered to have achieved a complete response(CR), and after further trastuzumab therapy for half a year, CR was maintained for 12 years and 3 months after surgery. Case 2: A 59-year-old female underwent total gastrectomy for advanced gastric cancer. Postoperative histopathological examination indicated pT3, pN3a, M0, pStageⅢB. She received TS-1 chemotherapy for 1 year and 8 months. Computed tomography suggested paraaortic lymph node metastasis, and XPT therapy was administered. The patients responded well, and alternate administration of XPT and capecitabine and docetaxel(XT) was performed. Three years and 5 months after surgery, recurrence of lymphadenopathy occurred and intensity-modulated radiation therapy in addition to XPT/XT alternate therapy was introduced, leading to a CR 5 years and 8months after surgery. XT therapy was continued afterward, and CR was maintained for 9 years and 2 months after surgery.

[A Resected Case of UR-LA Pancreatic Tail Cancer with Aortic Invasion after Chemoradiotherapy].

A 70-year-old male was referred to our hospital because of weight loss and epigastric discomfort. CT showed an irregularshaped, low-density tumor, 12 cm in diameter in the tail of the pancreas. This tumor widely invaded to the left kidney and to the anterior and left lateral sides of the aorta in spite of no involvement of celiac and superior mesenteric arteries. Moreover, it closely contacted with the stomach and the spleen. EUS-fine-needle aspiration biopsy of the tumor detected adenocarcinoma. Thus, he was diagnosed with UR-LA pancreatic cancer with aortic invasion. He received combination chemotherapy(S-1 plus gemcitabine[GEM])and 50.4 Gy 3-dimensional conformal radiation therapy, but this therapy had no expected effect. We changed the regimen to GEM plus nab-PTX. After 1 course of changed regimen, the tumor ruptured into the stomach and endoscopic debridement of the necrotic tissue was performed. Twenty-six days later, We performed distal pancreatectomy with splenectomy, total gastrectomy, left nephrectomy, left adrenalectomy, and segmental resection of the colon. The tumor was detached from the aorta as much as possible. The final diagnosis was pT3N0M0, pStage II A. Fifty-nine days after operation, we restarted GEM plus nab-PTX therapy. However, a cerebral infarction suddenly occurred, and we discontinued the chemotherapy. Five months after the operation, he died of cancerous peritonitis.

[A Case of Small Intestinal Neuroendocrine Tumor Detected One Year after Resection of Liver Metastasis].

A 49-year-old woman received a detailed examination for a myoma uteri, and a hepatic tumor was detected incidentally. A CT scan showed a tumor 6 cm in diameter in the posterior segment, which was irregularly enhanced. The tumor showed a low signal intensity on T1WI MRI and a slightly high intensity with high-density spots on T2WI. The tumor showed a low signal intensity in the hepatobiliary phase of the EOB-enhanced MRI. Percutaneous liver biopsy proved that this tumor was a grade 1 neuroendocrine tumor(NET G1). We examined her whole body in detail but found no primary lesions. Therefore, we made a diagnosis of primary hepatic NET or hepatic metastasis of an unknown origin and performed right hepatectomy. A year after the operation, a tumor was found in the jejunum. We made a diagnosis of NET by using endoscopic biopsy and performed partial intestinal resection. Histological findings showed NET G2(Ki-67 labeling index: 3.5%), which had venous invasion and one lymph node metastasis, suggesting that the jejunum was a primary lesion of NET. Three years and 2 months after the first operation, multiple liver metastases were found, and bland TAE was performed three times. Four years and 6 months after the first operation, we started sustained-release somatostatin analogues for tumor progression. She is still alive 5 years and 6 months after the first operation.

[A Case of Primary Peritoneal Cancer Successfully Treated with Debulking Surgery and Postoperative Chemotherapy].

A 52-year-old woman with abdominal pain and a feeling of incomplete evacuation visited a local clinic. Enlargement of the right ovary was detected, and the patient was referred to the gynecological department of our hospital. CT and MRI revealed a round-shaped mass, 8 cm in diameter, with cystic and solid components in the Douglas pouch. The patient underwent a laparotomy under the diagnosis of ovarian cancer. Intraoperatively, both the ovaries appeared normal and the tumor strongly adhered to the rectum and uterus. An exploratory laparotomy was performed; the tumor was identified as unresectable, and the patient was referred to our department after the surgery. PET-CT revealed nodules in the liver and peritoneum, in addition to the main tumor. Gastrointestinal endoscopy and immunohistochemical examination of a needle biopsy of the main tumor did not lead to the identification of the primary lesion. Thus, debulking surgery was performed to alleviate the patient's complaints. Histologically, the tumor was diagnosed as a primary peritoneal clear cell carcinoma. One month after surgery, multiple liver metastases and swelling of the peritoneal lymph nodes occurred. Six courses of dose-dense TC therapy were administered, and the patient achieved a complete response. At 8 months after surgery, the patient is still alive without tumor recurrence.

Synthesis of Azepines via a [6 + 1] Annulation of Ynenitriles with Reformatsky Reagents.

A protocol for the direct synthesis of azepines using a hafnium(III)-catalyzed [6 + 1] annulation of N-tethered ynenitriles with Reformatsky reagents is reported. A broad range of 3-amino-2,7-dihydro-1H-azepine-4-carboxylates 4aa-4he were obtained in high yields and with excellent functional group tolerance. The copper-mediated reactions of isolable Blaise intermediates (enamino esters 3), uniquely underwent 5-endo cyclization to afford the ß-2,5-dihydropyrrolyl α,ß-unsaturated esters 5aa-5fc, which exhibit anticancer activity.

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.