Clinicopathological features of cholangiolocarcinoma and impact of tumor heterogeneity on prognosis: A single institution retrospective study.

Cholangiolocarcinoma (CLC) is an extremely rare tumor classified as a subtype of small duct-type intrahepatic cholangiocarcinoma (iCCA). There are few detailed reports on CLC and the prognostic impact of tumor heterogeneity is not clear. Between April 2006 and June 2022, of the 774 primary liver cancer resection cases who presented at Kanazawa University Hospital, 14 patients were pathologically diagnosed with CLC through immunohistochemical analysis of their molecular and biological features. Clinicopathological features and prognoses were evaluated retrospectively. Additionally, tumor heterogeneity was assessed and tumors were classified into pure and partial types according to the CLC component proportion in a single tumor. Chronic liver disease was observed in nine patients (64.3%). All tumors were mass-forming, and pathological R0 resection was achieved in 11 patients (78.6%). Tumor heterogeneity was classified as pure in 11 (78.6%) and partial in three (21.4%) patients. The median follow-up was 59.5 months (12-114 months). There was no difference in the 5-year disease-specific survival rates between the pure and partial (90.0% vs. 100.0%; P=0.200) types, but rates were significantly higher in the R0 resection group compared with those in the R1 resection group (100.0% vs. 50.0%; P=0.025). In conclusion, these results suggest that it is important for CLC patients to achieve curative resection, and CLC may have a good prognosis regardless of the proportion of CLC components in a single tumor.

Morphology of the Dorsal Pancreatic Artery and Its Oncological Significance in Pancreatic Cancer.

OBJECTIVES: Although the dorsal pancreatic artery (DPA) is an important artery that supplies the pancreas, its morphology has not been sufficiently studied. We investigated the morphology of the DPA and the progression of pancreatic cancer along this vessel. MATERIALS AND METHODS: Overall, 142 patients with pancreatic cancer who underwent surgical resection at Kanazawa University Hospital between 2004 and 2015 were enrolled. We examined the morphology of the DPA using preoperative computed tomography and cancer progression along the DPA using resected specimens. We investigated the anatomical structures surrounding the DPA through cadaveric examination. RESULTS: The analysis of computed tomography images revealed the presence of the DPA in 141 patients. In typical cases, the DPA divides into a head and a body branch. Histopathological examination revealed cancer progression along the DPA in 32 patients. Cancer progression along the DPA was identified as a factor associated with a poor prognosis in pancreatic head or body cancer. Cadaveric examination showed the presence of abundant nerve and lymphatic tissues along the DPA. CONCLUSIONS: It is important to remove the soft tissue surrounding the DPA during surgery for pancreatic head or body cancer because it may serve as an important route for cancer progression.

[Two Cases of Portal Vein Stent Placement for Portal Vein Stenosis Due to Recurrence of Pancreatic Cancer].

We report 2 cases of portal vein stent placement for malignant portal stenosis due to recurrence of pancreatic cancer with symptoms of portal hypertension. Case 1: The patient was a 68-year-old female. Five years ago, a mass was found around the aorta on a computerized tomography(CT)scan taken after a residual pancreatectomy for pancreatic cancer. It was diagnosed as lymph node recurrence and S-1 therapy was started. As further tumor enlargement led to portal vein compression, venostasis around the ascending jejunum, anemia, and black stools, a portal vein stent was placed. The portal vein blood flow was improved, the collateral vessels disappeared, and the patient no longer experienced anemia or black stool. Case 2: A 75-year-old female patient underwent a subtotal gastric-sparing pancreaticoduodenectomy and combined resection of the portal vein for pancreas head cancer. On a postoperative CT scan taken 6 months later, a mass compressing the portal vein appeared, which was diagnosed as a local recurrence. As thrombocytopenia was observed, a portal vein stent was placed before starting chemotherapy. The portal vein blood flow and the platelet count improved. Portal vein stenting is an effective procedure for malignant portal stenosis, improving portal blood flow and clinical symptoms.

Clinical impacts of positive intraepithelial neoplasia at pancreatic transection margin in pancreatic cancer surgery.

BACKGROUND/OBJECTIVES: The outcomes of patients with intraepithelial neoplasia at the pancreatic transection margin after pancreatic cancer surgery remain unclear. We evaluated the clinical impact of pancreatic transection margin status. METHODS: This retrospective observational study included 171 patients who underwent surgery for pancreatic ductal adenocarcinoma between January 2008 and December 2019. Patients were classified into three groups: negative pancreatic transection margin (group N), positive low-grade (group L), and positive high-grade (group H) intraepithelial neoplasia. The clinicopathological findings and prognoses were analyzed for each group. RESULTS: There were 140, 14, and 9 patients in groups N, L, and H, respectively. The median age was significantly higher in group H (p = 0.035). There were no significant differences in male ratio, preoperative chemotherapy administration rate, pretreatment tumor markers, operative procedure, operative time, or blood loss. Overall survival and recurrence-free survival were not significantly different; however, the cumulative risk of recurrence in the remnant pancreas was significantly higher in group H (p = 0.018). CONCLUSIONS: Intraepithelial neoplasia at the pancreatic transection margin did not affect overall/recurrence-free survival. As patients with high-grade intraepithelial neoplasia at the pancreatic transection margin have an increased risk of recurrence in the remnant pancreas, careful postoperative follow-up is required.

Cilostazol improves the prognosis after hepatectomy in rats with sinusoidal obstruction syndrome.

BACKGROUND AND AIM: Safe radical hepatectomy is important for patients with colorectal liver metastases complicated by sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy. This study aimed to investigate the impact of preoperative administration of cilostazol (CZ), an oral selective phosphodiesterase III inhibitor, on hepatectomy in rat SOS model. MATERIAL AND METHODS: Rats were divided into NL (normal liver), SOS (monocrotaline [MCT]-treated), and SOS + CZ (MCT + CZ-treated) groups. MCT or CZ was administered orally, and a 30% partial hepatectomy was performed 48 h after MCT administration. Postoperative survival rates were evaluated (n = 9, for each). Other rats were sacrificed on postoperative days (POD) 1 and 3 and evaluated histologically, immunohistochemically, biochemically, and using transmission electron microscopy (TEM), focusing particularly on SOS findings, liver damage, and liver sinusoidal endothelial cell (LSEC) injury. RESULTS: The cumulative 10-day postoperative survival rate was significantly higher in the SOS + CZ group than in the SOS group (88.9% vs 33.3%, P = 0.001). Total SOS scores were significantly lower in the SOS + CZ group than in the SOS group on both POD 1 and 3. Serum biochemistry and immunohistochemistry showed that CZ reduced liver damage after hepatectomy. TEM revealed that LSECs were significantly preserved morphologically in the SOS + CZ group than in the SOS group on POD 1 (86.1 ± 8.2% vs 63.8 ± 9.3%, P = 0.003). CONCLUSION: Preoperative CZ administration reduced liver injury by protecting LSECs and improved the prognosis after hepatectomy in rats with SOS.

Assaying ADAMTS13 Activity as a Potential Prognostic Biomarker for Sinusoidal Obstruction Syndrome in Mice.

Sinusoidal obstruction syndrome (SOS) is a serious liver disorder that occurs after liver transplantation, hematopoietic stem cell transplantation, and the administration of anticancer drugs. Since SOS is a life-threatening condition that can progress to liver failure, early detection and prompt treatment are required for the survival of patients with this condition. In this study, female CD1 mice were divided into treatment and control groups after the induction of an SOS model using monocrotaline (MCT, 270 mg/kg body weight intraperitoneally). The mice were analyzed at 0, 12, 24, and 48 h after MCT administration, and blood and liver samples were collected for assays and histopathology tests. SOS was observed in the livers 12 h after MCT injection. In addition, immunohistochemical findings demonstrated CD42b-positive platelet aggregations, positive signals for von Willebrand factor (VWF), and a disintegrin-like metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) in the MCT-exposed liver sinusoid. Although ADAMTS13's plasma concentrations peaked at 12 h, its enzyme activity continuously decreased by 75% at 48 h and, inversely and proportionally, concentrations in the VWF-A2 domain, in which the cleavage site of ADAMTS13 is located, increased after MCT injection. These findings suggest that the plasma concentration and activity of ADAMTS13 could be useful biomarkers for early detection and therapeutic intervention in patients with SOS.

Do standardization of the procedure reduce measurement variability of the sonographic anterior drawer test of the ankle?

BACKGROUND: In quantitative ankle stress sonography, different examiners use different techniques, which may cause measurement variability. This study aimed to clarify whether standardizing stress sonography techniques reduces variability in the quantitative measurement of anterior talofibular ligament length change. METHODS: Fourteen examiners with a mean ultrasound experience of 8.7 years participated in this study. Each examiner performed stress ultrasonography of the ankle using their preferred method on one patient with an intact anterior talofibular ligament (Patient 1) and on two patients with chronic ankle instability (Patient 2 and 3). Changes in the ligament length between the resting and stressed positions were determined. A consensus meeting was then conducted to standardize the sonographic technique, which was used by the examiners during a repeat stress sonography on the same patients. The variance and measured values were compared between the preferred and standardized techniques using F-tests and paired t-tests, respectively. RESULTS: At a consensus meeting, a sonographic technique in which the examiner pushed the lower leg posteriorly against the fixed foot was adopted as the standardized technique. In Patient 1, the change in the anterior talofibular ligament length was 0.4 (range, -2.3-1.3) mm and 0.6 (-0.6-1.7) mm using the preferred and standardized techniques, respectively, with no significant difference in the variance (P = 0.51) or the measured value (P = 0.52). The length changes in Patient 2 were 2.0 (0.3-4.4) mm and 1.7 (-0.9-3.8) mm using the preferred and standardized techniques, respectively. In Patient 3, the length changes were 1.4 (-2.7-7.1) mm and 0.7 (-2.0-2.3) mm. There were no significant differences between the techniques in either patient group. CONCLUSION: Variability in the quantitative measurement of ankle stress sonography was not reduced despite the standardization of the technique among examiners. Hence, comparing the measured values between different examiners should be avoided.

Anterior fusion surgery with overcorrection in the treatment of adolescent idiopathic scoliosis with Lenke 1 AR curve type: how to achieve overcorrection and its effect on postoperative spinal alignment.

BACKGROUND: The efficacy of anterior fusion with overcorrection in the instrumented vertebra for Lenke 1 AR type curves has been reported, but how to achieve overcorrection and how overcorrection affects spinal alignment are unclear. The purpose of this study was to identify the factors that cause overcorrection, and to investigate how overcorrection affects postoperative spinal alignment in the surgical treatment of Lenke 1 AR type curves. METHODS: Patients who had anterior surgery for a Lenke type 1 or 2 and lumbar modifier AR (L4 vertebral tilt to the right) type scoliosis and minimum 2-year follow-up were included. The radiographic data were measured at preoperative, postoperative 1 month, and final follow-up. The UIV-LIV Cobb angle was determined as the Cobb angle between the upper instrumented vertebra (UIV) and the lower instrumented vertebra (LIV), and a negative number for this angle was considered overcorrection. The screw angle was determined to be the sum of the angle formed by the screw axis and the lower and upper endplates in the LIV and UIV, respectively. The change (Δ) in the parameters from postoperative to final follow-up was calculated. The relationships between the UIV-LIV Cobb angle and other radiographic parameters were evaluated by linear regression analyses. RESULTS: Fourteen patients met the inclusion criteria. Their median age was 15.5 years, and the median follow-up period was 53.6 months. The median UIV-LIV Cobb angle was -1.4° at postoperative 1 month. The median screw angle was 4.7°, and overcorrection was achieved in 11 (79%) cases at postoperative 1 month. The screw angle (r2 = 0.42, p = 0.012) and Δ FDUV-CSVL (the deviation of the first distal uninstrumented vertebra from the central sacral vertical line, r2 = 0.53, p = 0.003) were significantly correlated with the UIV-LIV Cobb angle. CONCLUSIONS: Screw placement in the UIV and LIV not parallel to the endplate, but angled, was an effective method to facilitate overcorrection in the instrumented vertebrae. The results of the present study suggest that overcorrection could bring spontaneous improvement of coronal balance below the instrumented segment during the postoperative period.

Quantum Mpemba Effect in a Quantum Dot with Reservoirs.

We demonstrate the quantum Mpemba effect in a quantum dot coupled to two reservoirs, described by the Anderson model. We show that the system temperatures starting from two different initial values (hot and cold) cross each other at finite time (and thereby reverse their identities; i.e., hot becomes cold and vice versa) to generate thermal quantum Mpemba effect. The slowest relaxation mode believed to play the dominating role in Mpemba effect in Markovian systems does not contribute to such anomalous relaxation in the present model. In this connection, our analytical result provides necessary condition for producing quantum Mpemba effect in the density matrix elements of the quantum dot, as a combined effect of the remaining relaxation modes.

Hemophagocytic Lymphohistiocytosis With Elevated Cytokines Related to Macrophage Activation After Liver Transplantation for Autoimmune Hepatitis: A Case Report.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but lethal complication of liver transplantation (LT). HLH is characterized by pathologic macrophage activation with hypercytokinemia, excessive inflammation, and tissue destruction, resulting in progressive organ dysfunction. HLH is also known as macrophage activation syndrome (MAS) when complicated by rheumatic or autoinflammatory diseases. Measuring several serum cytokines could be helpful in diagnosing HLH and MAS. Cytokines related to macrophage activation: neopterin, interleukin-18 (IL-18), and soluble tumor necrosis factor receptors (sTNF-R) I and II have not been assessed in patients with HLH complicated by LT. In this case, these cytokines were evaluated in the perioperative period of LT. The patient was a 24-year-old woman who underwent living-donor LT for acute worsening of autoimmune hepatitis. On postoperative day 12, the patient was diagnosed with HLH on the basis of the criteria. Plasma exchange, steroid pulse therapy, intravenous immunoglobulin and granulocyte-colony stimulating factor effectively inhibited progression to lethal HLH. When HLH occurred after LT, cytokine analysis showed that neopterin, IL-18, sTNFR-I, and II were elevated: cytokine storm. Of note, cytokine analysis on hospital admission also revealed elevated cytokine levels. Particularly, IL-18 levels were markedly elevated, suggesting that activation of the innate immune system was involved. These results revealed that a cytokine storm and macrophage activation developed before LT. Based on these findings, cytokine analysis related to macrophage activation may be useful for diagnosing and predicting HLH and MAS in patients with LT.

Early progression of a pancreatic metastasis of synovial sarcoma after pancreatectomy.

BACKGROUND: Synovial sarcoma is a malignant tumor that constitutes up to 10% of all soft-tissue sarcomas. The most frequent metastatic sites of synovial sarcoma are the lungs, lymph nodes, and bone, whereas pancreatic metastasis is extremely rare. Here, we report a case of pancreatic metastasis of synovial sarcoma. CASE PRESENTATION: Nine years before presentation, a 31-year-old woman underwent extensive resection of the primary tumor after chemotherapy for left upper extremity synovial sarcoma. Six months before presentation, interscapulothoracic amputation was performed for an enlarged mass in the left upper extremity; the patient was treated with pazopanib. Three months before presentation, chest computed tomography showed multiple lung metastases; during subsequent follow-up, abdominal computed tomography revealed a pancreatic metastasis of synovial sarcoma. The doubling time of the pancreatic tumor was 14 days, and it grew rapidly. Furthermore, treatment-resistant pancreatitis symptoms were detected; thus, we performed distal pancreatectomy and administered one course of a 70% dose of trabectedin. However, the patient died of rapid progression of lung metastasis and respiratory failure within 2 months after surgery. CONCLUSIONS: Pancreatectomy may be carefully performed in cases of isolated pancreatic metastasis. However, the presence of other distant extrapancreatic metastases (e.g., uncontrolled lung metastases) may rule out pancreatectomy treatment.

Assessing the effectiveness of a comprehensive menstrual health education program for preadolescent girls with intellectual disability and high support needs in Japan.

The menarche age in girls with intellectual disability and high support needs (HSN) is approximately the same as in girls with typical development. However, there is no clear teaching procedure for menstrual hygiene management (MHM) skills before menarche. This study examined whether a menstrual education program that focuses on visual support affects the MHM skills of girls with intellectual disability/HSN. The study comprised 11 preadolescent girls with intellectual disability/HSN in their pre-menarche age. They were asked to change napkins on a doll three times: before, immediately following, and one month after attending the program. Fifteen MHM items were measured. The participants' scores were significantly higher after attending the program. There was no significant difference in the mean scores for each of the 15 items among the levels of intellectual disability. The program that utilized visual materials was effective, and the effect was not influenced by age or intellectual level.

Dynamic switch of immunity and antitumor effects of metformin in rat spontaneous esophageal carcinogenesis.

Chronic inflammation contributes to tumor development by creating a local microenvironment that facilitates neoplastic transformation and potentiates the progression of cancer. Esophageal cancer (EC) is an inflammation-associated malignancy with a poor prognosis. The nature of the switch between chronic inflammation of the esophagus and EC-related immunological changes remains unclear. Here, we examined the dynamic alterations of immune cells at different stages of chronic esophagitis, Barrett's esophagus (BE) and EC using an esophageal spontaneous carcinogenesis rat model. We also investigated the anticancer effects of metformin. To stimulate EC carcinogenesis, chronic gastroduodenal reflux esophagitis via esophagojejunostomy was induced in 120 rats in metformin-treated and non-treated (control) groups. After 40 weeks, BE and EC developed in 96.7% and 63.3% of the control group, and in 66.7% and 23.3% of the metformin-treated group, respectively. Flow cytometric analysis demonstrated that the balance of M1/M2-polarized or phospho-Stat3-positive macrophages, regulatory T, cytotoxic T, natural killer (NK), NK T cells, and Th17 T cells was dynamically changed at each stage of the disease and were resolved by metformin treatment. These findings clarify the immunity in esophageal carcinogenesis and suggest that metformin could suppress this disease by improving the immunosuppressive tumor microenvironment and immune evasion.

Laparoscopic repair for primary epigastric hernia containing falciform ligament: A case report and review of literature.

Falciform ligament herniation is a rare type of epigastric hernia. We report a case of a primary epigastric hernia containing a falciform ligament repaired using nonabsorbable barbed suture under laparoscopic surgery. A 74-year-old woman presented with discomfort in the upper abdomen. Physical examination revealed a 3-cm non-tender mass, and abdominal computed tomography revealed epigastric hernia with an incarcerated falciform ligament. By observation with a laparoscope, the fascial defect was single and 1.0 cm in diameter, thus sutured repair was selected. At 4 months follow-up, she had no complications or recurrence. The laparoscopic approach is useful for diagnosis and deciding a repair method of an epigastric hernia. The barbed suture closure system is convenient and effective for intracorporeal hernial defect closing. Both primary and incisional falciform ligament herniation have been reported in the past, and we reviewed six cases, including our case.

Genetic Analysis of UGT1A1 Polymorphisms Using Preserved Dried Umbilical Cord for Assessing the Potential of Neonatal Jaundice as a Risk Factor for Autism Spectrum Disorder in Children.

Neonatal jaundice has been suggested as a perinatal risk factor for autism spectrum disorder (ASD). We examined UGT1A1 polymorphisms to assess the potential of neonatal jaundice as a risk factor for ASD in children by using DNA extracted from preserved umbilical cord. In total, 79 children with ASD were genotyped for UGT1A1*28 (c.-41-40dup), UGT1A1*6 (c.211 G > A), and UGT1A1*27 (c.686 C > A). The allele frequency of UGT1A1*6 (OR = 1.34, p = 0.26) and UGT1A1*28 (OR = 0.80, p = 0.54) and the prevalence of UGT1A1*28/*6 diplotypes did not differ significantly from those in the control population. No UGT1A1*27 allele was detected in the subjects. ASD symptom assessment scores were not associated with UGT1A1*28/*6/*27 genotypes or UGT1A1*28/*6 diplotypes. These results suggest that neonatal jaundice is not significantly associated with ASD.

Longitudinal Changes and Features of Sleep Patterns of Mothers with Preterm Infants during the Early Postpartum Period.

This study comprised 13 mothers of preterm infants and 21 mothers of term infants. Sleep assessment was conducted using an actigraph for three consecutive days. The participants were asked to record their sleep behaviors and activities over these 3 days, and complete two questionnaires (Edinburgh Postnatal Depression Scale [EPDS] and Pittsburgh Sleep Quality Index [PSQI]). As compared to the mothers of term infants, the sleep efficiency in the preterm mothers was significantly lower than that in the term mothers. The total sleep time was shorter and nighttime awakenings were more frequent in the preterm mothers at 2 weeks after childbirth, but without a significant difference. We analyzed the changes in the sleep data of the mothers of preterm infants longitudinally, including sleep behaviors and the EPDS and PSQI scores. The total sleep time at 1 month postpartum was shorter than that at other periods, and significantly shorter than that at 2 weeks and 6 months postpartum. Our results suggested that sleep problems tended to last longer in mothers of preterm infants than in mothers of term infants, as the problems occurred twice, immediately after childbirth and immediately after discharge.

Alcohol Metabolism Enriches Squamous Cell Carcinoma Cancer Stem Cells That Survive Oxidative Stress via Autophagy.

BACKGROUND: Alcohol (ethanol) consumption is a major risk factor for head and neck and esophageal squamous cell carcinomas (SCCs). However, how ethanol (EtOH) affects SCC homeostasis is incompletely understood. METHODS: We utilized three-dimensional (3D) organoids and xenograft tumor transplantation models to investigate how EtOH exposure influences intratumoral SCC cell populations including putative cancer stem cells defined by high CD44 expression (CD44H cells). RESULTS: Using 3D organoids generated from SCC cell lines, patient-derived xenograft tumors, and patient biopsies, we found that EtOH is metabolized via alcohol dehydrogenases to induce oxidative stress associated with mitochondrial superoxide generation and mitochondrial depolarization, resulting in apoptosis of the majority of SCC cells within organoids. However, CD44H cells underwent autophagy to negate EtOH-induced mitochondrial dysfunction and apoptosis and were subsequently enriched in organoids and xenograft tumors when exposed to EtOH. Importantly, inhibition of autophagy increased EtOH-mediated apoptosis and reduced CD44H cell enrichment, xenograft tumor growth, and organoid formation rate. CONCLUSIONS: This study provides mechanistic insights into how EtOH may influence SCC cells and establishes autophagy as a potential therapeutic target for the treatment of EtOH-associated SCC.