Neutralization against Omicron sublineages (BA.2/BA.5/BQ.1.1/XBB/XBB.1.5) in bivalent BNT162b2-vaccinated HCWs with or without risk factors, or following BT infection with Omicron.

SARS-CoV-2-BA.4/5-adapted-bivalent-BNT162b2-vaccine (bvBNT), developed in response to the recent emergence of immune-evasive Omicron-variants, has been given to individuals who completed at least 2-doses of the monovalent-BNT162b2-vaccine (mvBNT). In the present cohort study, we evaluated neutralization-titers (NT50s) against Wuhan-strain (SCoV2Wuhan) and Omicron-sublineages including BA.2/BA.5/BQ.1.1/XBB/XBB.1.5, and vaccine-elicited S1-binding-IgG in sera from participants-vaccinated with 5th-bvBNT following 4th-mvBNT. The 5th-bvBNT-dose elicited good protective-activity against SCoV2Wuhan with geometric-mean (gMean)-NT50 of 1966-2091, higher than the peak-values post-4th-mvBNT with no statistical significance, and favorable neutralization-activity against not only BA.5 but also BA.2, with ~ 3.2-/~ 2.2-fold greater gMean-NT50 compared to the peak-values post-4th-mvBNT-dose, in participants with or without risk factors. However, neutralization-activity of sera post-5th-bvBNT-dose was low against BQ.1.1/XBB/XBB.1.5. Interestingly, participants receiving bvBNT following breakthrough (BT) infection during Omicron-wave had significantly enhanced neutralization-activity against SCoV2Wuhan/BA.2/BA.5 with ~ 4.6-/~ 6.3-/~ 8.1-fold greater gMean-NT50, respectively, compared to uninfected participants receiving bvBNT. Sera from BT-infected-participants receiving bvBNT had enhanced neutralization-activity against BQ.1.1/XBB/XBB.1.5 by ~ 3.8-fold compared to those from the same participants post-4th-mvBNT-dose, and had enhanced gMean-NT50 ~ 5.4-fold greater compared to those of uninfected-participants' sera post-bvBNT. These results suggest that repeated stimulation brought about by exposure to BA.5's-Spike elicit favorable cross-neutralization-activity against various SARS-CoV-2-variants.

t6A and ms2t6A Modified Nucleosides in Serum and Urine as Strong Candidate Biomarkers of COVID-19 Infection and Severity.

SARS-CoV-2 infection alters cellular RNA content. Cellular RNAs are chemically modified and eventually degraded, depositing modified nucleosides into extracellular fluids such as serum and urine. Here we searched for COVID-19-specific changes in modified nucleoside levels contained in serum and urine of 308 COVID-19 patients using liquid chromatography-mass spectrometry (LC-MS). We found that two modified nucleosides, N6-threonylcarbamoyladenosine (t6A) and 2-methylthio-N6-threonylcarbamoyladenosine (ms2t6A), were elevated in serum and urine of COVID-19 patients. Moreover, these levels were associated with symptom severity and decreased upon recovery from COVID-19. In addition, the elevation of similarly modified nucleosides was observed regardless of COVID-19 variants. These findings illuminate specific modified RNA nucleosides in the extracellular fluids as biomarkers for COVID-19 infection and severity.

Neutralization activity of sera/IgG preparations from fully BNT162b2 vaccinated individuals against SARS-CoV-2 Alpha, Beta, Gamma, Delta, and Kappa variants.

In the present prospective study, 225 individuals in Kumamoto General Hospital, Japan, who received two-doses of BNT162b2 vaccine were enrolled/followed up over 150 days and neutralizing activity (NT50) of their sera and antiviral activity (EC50) of IgG purified from sera on day-60 post-1st-dose were determined against wild-type SARS-CoV-2 (SARS-CoV-2Wuhan) (n = 211) and 9 variants (Alpha, Beta, Gamma, Delta, and Kappa) (n = 45). Time-dependent changes of IgG-activity (n = 25) against SARS-CoV-2Wuhan and variants were also examined. Day-60 sera showed reduced NT50 by more than 50% against all variants examined, and greatest reduction was seen with Beta. IgG fractions of high-responders and moderate-responders showed similar fold-changes in EC50 against each variant compared to SARS-CoV-2Wuhan. Evaluation of EC50 of IgG obtained at different time-points (day-28 to -150) revealed time-dependent reduction of activity against all variants. However, against Delta, relatively long-lasting favorable antiviral activity (at least 150 days) was observed. Our data strongly suggest that the successful antecedent scale-up of mRNA-based vaccine administrations in Japan was the primary contributor to the lessening of the otherwise more devastating SARS-CoV-2 pandemic wave caused by the Delta variant. The present data that the effectiveness of vaccine against the then-dominant SARS-CoV-2 variant was likely associated with the moderation of the COVID-19 pandemic wave suggest that as in the case of influenza vaccines, the development of multivalent mRNA-based vaccines represent a generalizable approach to pre-emptively respond pandemic with mutable pathogens.

Clinical impact of perirenal thickness on short- and long-term outcomes of gastric cancer after curative surgery.

Background: A variety of factors for short- and long-term outcomes have been reported after radical resection for gastric cancer (GC). Obesity and emaciation had been reported to be a cause of poor short- and long-term outcomes with gastrointestinal cancer. However, the indicators are still controversial. The purpose of this study was to evaluate the relationship between perirenal thickness (PT) and short- and long-term outcomes after radical surgery for GC. Methods: We analyzed the data of 364 patients with GC who underwent radical surgery. We evaluated the distance from the anterior margin of the quadratus lumborum muscle to the dorsal margin of the left renal pole using computed tomography (CT) as an indicator of PT. The association between PT and clinicopathological factors and short- and long-term outcomes was evaluated. Results: The PT data were divided into low, normal, and high groups by gender using the tertile value. We found that the PT low group was 121 patients, normal group was 121 patients, and high group was 122 patients. Multivariate analyses showed that the high PT group was an independent risk factor for a short-outcome after curative surgery in GC patients (odds ratio 2.163; 95% confidence interval [CI] 1.156-4.046; P = .016). And the low PT group was an independent risk factor for overall survival (hazard ratio 2.488; 95% CI 1.400-4.421; P = .0019) and relapse-free survival (hazard ratio 2.342; 95% CI 1.349-4.064; P = .0025) after curative surgery in GC patients. Conclusion: Perirenal thickness is a simple and useful factor for predicting short- and long-term outcomes after radical surgery for GC.

Correlates of neutralizing/SARS-CoV-2-S1-binding antibody response with adverse effects and immune kinetics in BNT162b2-vaccinated individuals.

While mRNA vaccines against SARS-CoV-2 are exceedingly effective in preventing symptomatic infection, their immune response features remain to be clarified. In the present prospective study, 225 healthy individuals in Japan, who received two BNT162b2 doses, were enrolled. Correlates of BNT162b2-elicited SARS-CoV-2-neutralizing activity (50% neutralization titer: NT50; assessed using infectious virions) with various determinants were examined and the potency of sera against variants of concerns was determined. Significant rise in NT50s was seen in sera on day 28 post-1st dose. A moderate inverse correlation was seen between NT50s and ages, but no correlation seen between NT50s and adverse effects. NT50s and SARS-CoV-2-S1-binding-IgG levels on day 28 post-1st dose and pain scores following the 2nd dose were greater in women than in men. The average half-life of NT50s was ~ 68 days, and 23.6% (49 out of 208 individuals) failed to show detectable neutralizing activity on day 150. While sera from elite-responders (NT50s > 1,500: the top 4% among the participants) potently to moderately blocked all variants of concerns examined, some sera with low NT50s failed to block the B.1.351-beta strain. Since BNT162b2-elicited immunity against SARS-CoV-2 is short, an additional vaccine or other protective measures are needed.

Pancreaticoduodenectomy at a Non-high-volume Center and Efforts to Perform Safe Surgery.

AIM: The aim of the current study was to investigate whether the artery-first approach (AFA) improved surgical outcomes of pancreaticoduodenectomy (PD) at our non-high-volume center. PATIENTS AND METHODS: We retrospectively reviewed data on 121 consecutive patients who underwent PD between January 2009 and December 2018. The perioperative data of 49 patients who underwent conventional PD (conventional group) and 72 patients who underwent PD via artery-first approach were analyzed and compared to assess the effectiveness of the AFA. RESULTS: Although no significant difference was observed between the two groups overall, in those with pancreatic cancer, the duration of surgery, intraoperative blood loss and transfusion rate in the AFA group (n=33) were significantly lower than those for the conventional group (n=11) (p=0.011, p=0.021 and p=0.038 respectively). CONCLUSION: AFA can be used to reduce the operative time, intraoperative blood loss, and transfusion rate in patients with pancreatic cancer.

Correlates of Neutralizing/SARS-CoV-2-S1-binding Antibody Response with Adverse Effects and Immune Kinetics in BNT162b2-Vaccinated Individuals.

BACKGROUND: While mRNA vaccines against SARS-CoV-2 have been exceedingly effective in preventing symptomatic viral infection, the features of immune response remain to be clarified. METHODS: In the present prospective observational study, 225 healthy individuals in Kumamoto General Hospital, Japan, who received two BNT162b2 doses in February 2021, were enrolled. Correlates of BNT162b2-elicited SARS-CoV-2-neutralizing activity (50% neutralization titer: NT 50 ; assessed using infectious virions and live target cells) with SARS-CoV-2-S1-binding-IgG and -IgM levels, adverse effects (AEs), ages, and genders were examined. The average half-life of neutralizing activity and the average time length for the loss of detectable neutralizing activity were determined and the potency of serums against variants of concerns was also determined. FINDINGS: Significant rise in NT 50 s was seen in serums on day 28 post-1st dose. A moderate inverse correlation was seen between NT 50 s and ages, but no correlation was seen between NT 50 s and AEs. NT 50 s and IgG levels on day 28 post-1st dose and pain scores following the 2nd shot were greater in women than in men. The average half-life of neutralizing activity in the vaccinees was approximately 67.8 days and the average time length for their serums to lose the detectable neutralizing activity was 198.3 days. While serums from elite-responders (NT 50 s>1,500-fold: the top 4% among all participants' NT 50 s) potently to moderately blocked the infectivity of variants of concerns, some serums with moderate NT 50 s failed to block the infectivity of a beta strain. INTERPRETATION: BNT162b2-elicited immune response has no significant association with AEs. BNT162b2-efficacy is likely diminished to under detection limit by 6-7 months post-1st shot. High-level neutralizing antibody-containing serums potently to moderately block the infection of SARS-CoV-2 variants; however, a few moderate-level neutralizing antibody-containing serums failed to do so. If BNT162b2-elicited immunity memory is short, an additional vaccine or other protective measures would be needed. RESEARCH IN CONTEXT: Evidence before this study: While mRNA vaccines against SARS-CoV-2 have been exceedingly effective in preventing symptomatic viral infection, the salient features of immune response including the persistence of protection remain to be clarified. There is a report that anti-SARS-CoV-2 antibodies persist through 6 months after the second dose of mRNA-1273 vaccine (Doria-Rose et al. N Engl J Med . 2021;384:2259-2261); however, more definite immune kinetics following mRNA-vaccine-elicited protection have to be clarified. The mRNA-vaccine-elicited protection against SARS-CoV-2 variants are also to be determined. Added value of this study: In the present prospective study, 225 twice-BNT162b2-dose-receiving individuals in Japan were enrolled. No significant correlation was seen between 50% neutralizing titers (NT 50 s), determined by using infectious SARS-CoV-2 virions and live target cells, and adverse effects. Largely, NT 50 s and IgG levels were greater in women than in men. Following 28 days post-2 nd shot, significant reduction was seen in NT 50 s, IgG, and IgM levels. The average half-life of NT 50 s was ∼68 days and the average time-length for participants' serums to lose the detectable activity was ∼198 days. Although serums from elite-responders potently to moderately blocked the infectivity of variants of concerns, some serums with moderate NT 50 s failed to block the infectivity of a beta strain. Implications of all the available evidence: BNT162b2 efficacy is likely to be diminished to under detection limit by 6-7 months post-1 st shot on average. Individuals with moderate NT 50 s may fail to block beta variants. If BNT162b2-elicited immune memory is lost soon, additional vaccine(s) or other protective means would be needed.

Retroperitoneal fibrous tumor recurring as lung metastases after 10 years: a case report.

BACKGROUND: Solitary fibrous tumor (SFT) is a relatively rare mesenchymal tumor that mainly affects adults. Its prognosis is good after curative resection, but distant recurrences after 10 years or longer have been reported. Recurrent SFT usually arises as a local lesion; distant metastasis is rarely reported. Here, we report lung metastases that recurred a decade after excising a retroperitoneal primary SFT. CASE PRESENTATION: A 44-year-old woman had an SFT resected from her right retroperitoneum at our hospital. Ten years later, at age 54, she underwent a lung resection after CT showed three suspected metastases in her left lung. All three were histologically diagnosed as lung metastases from the retroperitoneal SFT. However, whereas the primary SFT had 1-2 mitotic cells/10 high power fields (HPF), the metastatic lesion increased malignancy, at 50/10 HPF. CONCLUSION: Patients who have had resected SFTs should be carefully followed up, as malignancy may change in distant metastasis, as in this case.

A case of repeat hepatectomy for liver metastasis from solid pseudopapillary neoplasm of the pancreas: a case report.

BACKGROUND: Solid pseudopapillary neoplasm of the pancreas is a rare tumor in young women, metastasizing in only 5-15% of cases, and most commonly to the liver. Although treatment guidelines have not been established, surgical resection is usually performed. We report a rare case of repeat hepatectomy for liver metastases after distal pancreatectomy with solid pseudopapillary neoplasm. CASE PRESENTATION: The patient was a 71-year-old woman who underwent distal pancreatectomy for solid pseudopapillary neoplasm, and liver metastasis occurred 4 years after the first surgery. Partial liver resection was performed for four liver metastases, and histopathological examination revealed a diagnosis of liver metastasis from solid pseudopapillary neoplasm. However, 18 months later, liver metastases were detected again; three tumors were identified, and partial resection was performed, which has provided 18 months' recurrence-free survival. CONCLUSIONS: Long-term prognosis can be expected following R0 resection for resectable liver metastasis from solid pseudopapillary neoplasm.

A rare anastomosis between the root of common hepatic artery and proper hepatic artery: implications for pancreaticoduodenectomy.

BACKGROUND: Hepatic artery anomalies are often observed, and the variations are wide-ranging. We herein report a case of pancreatic cancer involving the common hepatic artery (CHA) that was successfully treated with pancreaticoduodenectomy (PD) without arterial reconstruction, thanks to anastomosis between the root of CHA and proper hepatic artery (PHA), which is a very rare anastomotic site. CASE PRESENTATION: A 78-year-old woman was referred to our department for the examination of a tumor in the pancreatic head. Contrast-enhanced computed tomography (CT) revealed a low-density tumor of 40 mm in diameter located in the pancreatic head. The involvement of the common hepatic artery (CHA), the root of the gastroduodenal artery (GDA), and portal vein was noted. Although such cases would usually require PD with arterial reconstruction of the CHA, it was thought that the hepatic arterial flow would be preserved by the anastomotic site between the root of the CHA and the PHA, even if the CHA was dissected without arterial reconstruction. PD with dissection of the CHA and PHA was safely completed without arterial reconstruction, and sufficient hepatic arterial flow was preserved through the anastomotic site between the CHA and PHA. CONCLUSION: We presented an extremely rare case of an anastomosis between the CHA and PHA in a patient with pancreatic cancer involving the CHA. Thanks to this anastomosis, surgical resection was successfully performed with sufficient hepatic arterial flow without arterial reconstruction.

Ascending colon cancer with synchronous external iliac and inguinal lymph node metastases but without regional lymph node metastasis: a case report and brief literature review.

Lymph node metastasis to the iliac or inguinal region of colon cancer is extremely rare. We experienced a case of ascending colon cancer with synchronous isolated right external iliac and inguinal lymph node metastases but without any regional lymph node metastasis. An 83-year-old woman was admitted to our hospital due to anemia. Colonoscopy and computed tomography revealed an ascending colon cancer and also right external iliac and inguinal lymph node swelling. Further examination by F-deoxyglucose positron emission tomography strongly suggested that these lymph nodes were metastatic. Right hemicolectomy with lymph node dissection along the superior mesenteric artery, and right external iliac and inguinal lymph node dissection were performed. Histological examination revealed that both lymph nodes were metastasized from colon cancer, and there was no evidence of regional lymph node metastasis. The patient has shown no sign of recurrence at 27 months after surgery.

The intentional oblique transection double stapling technique in anterior resection for rectal cancer.

The double stapling technique (DST) is an intestinal reconstruction technique that has been widely adopted in anterior resection (AR) for rectal cancer. However, anastomotic leakage (AL) after the operation remains a major concern for colorectal surgeons. The sharp-angled corner of the remnant rectum that is often created by the ordinary DST can be a risk factor for AL. We have developed a new method of performing intentional oblique transection DST (IOT-DST). Using this technique, the anal side of the rectum is intentionally obliquely transected with linear staplers, and the area of the sharp-angled edge is totally punched out with a circular stapler. Between September 2015 and March 2016, we used the IOT-DST technique in the treatment of 15 consecutive rectal cancer patients and experienced no anastomosis-related complications, including leakage and stenosis. IOT-DST is easy to use and less stressful to perform than other techniques. IOT-DST has the potential to become the standard technique for AR in rectal cancer surgery.

Intraoperative baseline oxygen consumption as a prognostic factor in emergency open abdominal surgery.

BACKGROUND: A new anesthesia system, the E-CAIOVX (GE Healthcare) enables the continuous monitoring of oxygen consumption (VO2) and carbon dioxide elimination (VCO2) during the surgical operation. The aim of this study was to evaluate the prognostic role of intraoperative baseline VO2 and VCO2 in an emergency open abdominal operation. METHODS: A total of 103 patients who had an emergency open abdominal operation were enrolled in the study. VO2 and VCO2 were continuously measured from the induction of anesthesia to the end of the operation. RESULTS: There were significant correlations between intraoperative baseline VO2 and body surface area (BSA; P < .001, r = 0.68), VO2 and tidal volume (P < .001, r = 0.59), and VO2 and baseline body temperature (P < .0001, r = 0.49). Also, there were significant correlations between intraoperative baseline VCO2 and BSA (P < .001, r = 0.70), VCO2 and tidal volume (P < .001, r = 0.70), and VCO2 and body temperature (P < .001, r = 0.41). Fifteen (14.6%) of the 103 patients died within 4 months after the operation without having been discharged from hospital. Baseline VO2/BSA was higher in surviving patients (123.7 ± 23.6 mL/min ∙ m(2)) than the deceased (103.8 ± 15.6 mL/min ∙ m(2); P = .002). There was no significant difference in baseline VCO2/BSA levels between surviving (106.2 ± 20.1 mL/min ∙ m(2)) and deceased patients (99.4 ± 21.4 mL/min ∙ m(2)). In multivariate analysis, baseline body temperature lower than 36.2°C (P = .02), serum albumin less than 3.0 g/dL (P = .002), and baseline VO2/BSA less than 111.9 mL/min ∙ m(2) (P = .03) were independent factors. CONCLUSION: Baseline low VO2/BSA less than 111.9 mL/min ∙ m(2) was one of the poor predictors for the prognosis of an emergency open abdominal surgery.

Predictive factors of pathological vascular invasion in hepatocellular carcinoma within 3 cm and three nodules without radiological vascular invasion.

AIM: The aim of this study was to determine the predictive factors of pathological vascular invasion as contra-indicators for ablation therapy in patients with hepatocellular carcinoma (HCC) within 3 cm and three nodules without radiological vascular invasion. METHODS: Two hundred and seventeen patients with HCC within 3 cm and three nodules without radiological vascular invasion who underwent hepatic resection were retrospectively investigated. RESULTS: Pathological vascular invasion was positive in 46 patients, consisting of 38 portal vein invasions, three hepatic vein invasions, two hepatic artery invasions, one hepatic duct invasion and two with portal and hepatic vein invasions. In univariate analysis, patients with α-fetoprotein (AFP) of more than 100 ng/mL had higher rates of pathological vascular invasion than those without. In addition, patients with protein induced by vitamin K absence (PIVKA-II) of more than 100 mAU/mL had higher rates of pathological vascular invasion than those without. Multivariate analysis revealed that AFP of more than 100 ng/mL and PIVKA-II of more than 100 mAU/mL were independent predictive factors for pathological vascular invasion. As these patients were treated with hepatic resection, cumulative 5-year recurrence-free and overall survivals were not significantly different between the pathological vascular invasion negative and positive cases. CONCLUSION: AFP of more than 100 ng/mL and PIVKA-II of more than 100 mAU/mL can predict pathological vascular invasion in patients with HCC within 3 cm and three nodules without radiological vascular invasion. In treating such cases, hepatic resection rather than local ablation therapy is recommended.

The effect of extensive intraoperative peritoneal lavage therapy (EIPL) on stage III B + C and cytology-positive gastric cancer patients.

BACKGROUND: The aim of this study was to investigate the effects of extensive intraoperative peritoneal lavage (EIPL) therapy on stage III B + C and CY1/P0 gastric cancer patients after potentially curative surgery. METHODS: The study included 37 patients with CY1/P0 and 23 patients with stage III B + C gastric cancer who were treated with potentially curative gastrectomy and EIPL therapy between March 1995 and May 2013. D2 lymphadenectomy, R0 resection, and EIPL therapy were performed for all cases. RESULTS: Multivariate analysis revealed that male gender (P = 0.01) and lymph node metastasis (P = 0.03) were independent prognostic factors, while positive cytology was not (P = 0.21). There was no significant difference in overall survival rates between the CY1/P0 and stage III B + C groups (P = 0.93). There was also no significant difference in peritoneal recurrence rates, i.e., 13 (35.1%) in the CY1/P0 group and 5 (21.7%) in the stage III B + C group (P = 0.39). CONCLUSIONS: EIPL therapy combined with complete resection and sufficient (D2) lymphadenectomy could improve the prognosis of CY1/P0 gastric cancer and, to a similar extent, that of stage III B + C.