Use of 3D-CT-derived psoas major muscle volume in defining sarcopenia in colorectal cancer.

BACKGROUND: Sarcopenia is characterized by reduced skeletal muscle volume and is a condition that is prevalent among elderly patients and associated with poor prognosis as a comorbidity in malignancies. Given the aging population over 80 years old in Japan, an understanding of malignancies, including colorectal cancer (CRC), complicated by sarcopenia is increasingly important. Therefore, the focus of this study is on a novel and practical diagnostic approach of assessment of psoas major muscle volume (PV) using 3-dimensional computed tomography (3D-CT) in diagnosis of sarcopenia in patients with CRC. METHODS: The subjects were 150 patients aged ≥ 80 years with CRC who underwent primary tumor resection at Juntendo University Hospital between 2004 and 2017. 3D-CT measurement of PV and conventional CT measurement of the psoas major muscle cross-sectional area (PA) were used to identify sarcopenia (group S) and non-sarcopenia (group nS) cases. Clinicopathological characteristics, operative results, postoperative complications, and prognosis were compared between these groups. RESULTS: The S:nS ratios were 15:135 for the PV method and 52:98 for the PA method. There was a strong positive correlation (r = 0.66, p < 0.01) between PVI (psoas major muscle volume index) and PAI (psoas major muscle cross-sectional area index), which were calculated by dividing PV or PA by the square of height. Surgical results and postoperative complications did not differ significantly in the S and nS groups defined using each method. Overall survival was worse in group S compared to group nS identified by PV (p < 0.01), but not significantly different in groups S and nS identified by PA (p = 0.77). A Cox proportional hazards model for OS identified group S by PV as an independent predictor of a poor prognosis (p < 0.05), whereas group S by PA was not a predictor of prognosis (p = 0.60). CONCLUSIONS: The PV method for identifying sarcopenia in elderly patients with CRC is more practical and sensitive for prediction of a poor prognosis compared to the conventional method.

Analysis of Factors Related to Variation in Dissolution Profiles Estimated from Continuously Conducted Dissolution Tests of Generic Products.

The development of generic pharmaceuticals involves a bioequivalence study to ensure the therapeutic equivalence of the test formulation to the original innovative product. The formulation characteristics of generic products are expected to be maintained in the long term after approval. This study analyzed the factors contributing to the changes in the dissolution profiles of approved products during their life cycles. Cumulative data on the dissolution similarity of 1675 products of 127 ingredients tested by official laboratories in Japan were assessed according to Japanese bioequivalence guidelines with slight modifications. The products showing dissimilarities in dissolution profiles were analyzed for reporting year, therapeutic category, co-development, physical properties of the active pharmaceutical ingredient (API), and suspected reasons for dissolution change. The increase in the number of dissimilar products is related to the co-development of generic products. Although the solubility of the API was not associated with the dissolution change in the analysis of the total dissolution data, control of the API particle size is suggested to be important for drugs with poorly soluble APIs. Additionally, a risk factor for dissolution changes in the test solutions at a certain pH was the presence of acidic or basic residues. These results indicate the importance of proper development through a thorough evaluation of the formulation and process factors affecting the dissolution properties throughout the product lifecycle.

Impact of the Covid-19 pandemic and ensuing online teaching on pre-clinical medical education.

BACKGROUND: Major disruptions and changes in education have occurred worldwide as a result of the coronavirus disease (COVID-19) pandemic and the ensuing shift from in-person to online education. However, the effect of such changes on medical education, its magnitude, and the learning domains impacted by such rapid changes have not been adequately addressed, particularly with regard to objective assessment approaches. METHODS: Second-year medical students enrolled in our Medical English Course between 2019 and 2021 were recruited from Hokkaido University, Japan (N = 321) to participate in this study. We evaluated the potential impact of teaching styles on the academic performance of students before (2019; face-to-face) and during (2020; online; 2021; in-person and online) the pandemic. We examined the potential effect of three teaching styles--in-person (2019), online (2020), and a combination of these (2021) on the academic performance of medical students using: (i) subjective assessment of self-reported general English skills, including reading, writing, listening, and speaking; and (ii) objective assessment of medical terminology scores, evidence-based medicine (EBM) skills, and final written exam scores. RESULTS: In-person education significantly improved listening and speaking skills in 2019 (p < 0.001). This trend was observed for writing skills in an online course in 2020 (p = 0.001). With the combined teaching method, students reported significant improvements in all four English skills. In our objective assessments, medical terminology improved significantly post-test versus pre-test for all three teaching styles, and we found that the online course did not adversely affect the gain in medical terminology knowledge during the course. Additionally, we did not find any significant differences across the three applied teaching styles regarding EBM skill levels. It is noteworthy that the students taking online courses had a significantly higher final exam score (mean ± SD; 82.8 ± 8.2) than in in-person (78.6 ± 8.8) and combined (79.7 ± 12.1) teaching styles. CONCLUSIONS: In our study, the online/combined courses showed better academic outcomes compared to the face-to-face course in the preclinical clerkship. Although the current results need to be replicated on a larger scale, online/combined courses can continue and evolve in the post-pandemic education of medical students. Medical schools and institutions should consider incorporating such courses, especially combined courses, into their curricula in the future to improve the effectiveness, accessibility, and flexibility of medical education.

Tyrosine kinase alterations in colorectal cancer with emphasis on the distinct clinicopathological characteristics.

AIMS: Tyrosine kinase (TK) alterations, such as anaplastic lymphoma kinase (ALK) fusion, neurotrophic tyrosine receptor kinase (NTRK) fusion, c-ros oncogene 1 (ROS1) fusion and mesenchymal-epithelial transition factor (MET) exon 14 skipping, have been reported in colorectal cancers (CRC). We have previously reported CRCs with NTRK fusion among our cohort. However, their clinicopathological features have not been fully elucidated. METHODS AND RESULTS: Tissue microarray (TMA)-based immunohistochemistry (IHC) was performed on 951 CRC lesions from 944 patients. IHC was evaluated as positive or negative for ALK and ROS1 and 0 to 3+ for c-MET. For ALK and ROS1 IHC-positive cases, RNA-based imbalanced gene expression assays, Archer FusionPlex assays and reverse transcription-polymerase chain reaction (RT-PCR) followed by Sanger sequencing were performed. For c-MET IHC 3+ cases, RT-PCR followed by Sanger sequencing were performed. ALK IHC was positive in three cases (0.2%) and all showed imbalanced ALK gene expression. The following ALK fusions were confirmed: EML4 (exon 21)::ALK (exon 20), EML4 (exon 6)::ALK (exon 19) and HMBOX1 (exon 6)::ALK (exon 20). Two showed microsatellite instability-high/mismatch repair (MMR)-deficient, and all were located in the right colon. ROS1 IHC was positive in one case; however, imbalanced expression and ROS1 fusion was negative. Forty-two cases (4.4%) showed c-MET IHC3+. MET exon 14 skipping was confirmed in nine cases. All cases were microsatellite stable/MMR-proficient, and eight were located in the left colon and rectum. CONCLUSIONS: CRCs with these TK alterations had distinct clinicopathological features. Together with our previous study, 15 cases (1.6%) harboured targetable TK alterations (three NTRK fusion, three ALK fusion, nine MET exon 14 skipping).

Analysis of Circulating DNA to Assess Prognoses for Metastatic Colorectal Cancer Patients Treated with Regorafenib Dose-Escalation Therapy: A Retrospective, Exploratory Analysis of the RECC Trial.

INTRODUCTION: Regorafenib is a multi-kinase inhibitor approved for patients with metastatic colorectal cancer (mCRC) who were previously treated with standard therapies. A few reports showed the impact of KRAS mutation on therapeutic efficacy of regorafenib. Only one study reported poor prognoses for patients treated with regorafenib who had large amounts of circulating cell-free DNA (cfDNA). In the present study, we evaluated the impact of KRAS mutations in tissue or plasma and amounts of cfDNA on prognoses of mCRC patients treated with regorafenib. METHOD: This is a biomarker investigation of the RECC study, which evaluated efficacy of regorafenib dose-escalation therapy. Plasma samples were obtained just before initiation of treatment with regorafenib. KRAS mutations were evaluated using tissue and plasma samples. cfDNA was extracted from plasma samples and quantified. RESULTS: Forty-five patients were enrolled in this biomarker study. Median progression-free survival (PFS) and overall survival (OS) of patients without KRAS mutations in tissues were 1.9 months (95% confidence interval [CI] 1.7-2.0) and 8.9 months (95% CI: 6.5-11.2), and those of patients with KRAS mutations were 1.4 months (95% CI: 1.3-1.5) and 6.8 months (95% CI: 5.0-8.5). Median PFS and OS of patients with plasma KRAS mutations were 1.9 months (95% CI: 1.8-1.9) and 7.0 months (95% CI: 5.3-8.7), respectively. Median PFS and OS of patients without plasma KRAS mutations were 1.7 months (95% CI: 1.1-2.3) and 8.9 months (95% CI: 6.7-11.2), respectively. Prior to administration of regorafenib, KRAS mutations were detected in 6 of 16 (37.5%) patients who had no tissue KRAS mutations. Median OS of patients with high cfDNA concentration (>median) was significantly poorer than that of patients with low cfDNA. CONCLUSION: KRAS mutations in the tissue or plasma have no impact on efficacy of regorafenib. KRAS emerging mutations were observed in quite a few patients. Large amounts of cfDNA may indicate poorer prognoses for patients receiving late-line regorafenib chemotherapy.

Intramuscular and intermuscular coherence analysis while obstacle crossing during treadmill gait.

PURPOSE: This study aimed to identify the contribution of the common synaptic drives to motor units during obstacle avoidance, using coherence analysis between a-pair electromyography (EMG) signals (EMG-EMG coherence). MATERIALS AND METHODS: Fourteen healthy volunteers walked on a treadmill with and without obstacle avoidance. During obstacle gait, subjects were instructed to step over an obstacle with their right leg while walking that would randomly and unpredictably appear. Surface EMG signals were recorded from the following muscles of the right leg: the proximal and distal ends of tibialis anterior (TAp and TAd), biceps femoris (BF), semitendinosus (ST), lateral gastrocnemius (LG), and medial gastrocnemius (MG). Beta-band (13-30 Hz) EMG-EMG coherence was analysed. RESULTS: Beta-band EMG-EMG coherence of TAp-TAd during swing phase and BF-ST during pre and initial swing phase when stepping over an obstacle were significantly higher compared to normal gait (both p < 0.05). Beta-band EMG-EMG coherence of TAp-TAd, BF-ST, and LG-MG during stance phase were not significantly different between the two gait conditions (all p > 0.05). CONCLUSIONS: The present findings suggest increased common synaptic drives to motor units in ankle dorsiflexor and knee flexor muscles during obstacle avoidance. It also may reflect an increased cortical contribution to modify the gait patterns to avoid an obstacle.

Dynamic ultrasound reveals the specific behavior of the medial meniscus extrusion in patients with knee osteoarthritis.

BACKGROUND: In the dynamic condition, knee osteoarthritis (OA) usually presents with pain. In the weight-bearing condition, a medial meniscus extrusion (MME) may cause severe symptoms and pathological progression. However, the correlation between a dynamic MME and pain has not been elucidated. Now, an MME can be evaluated under dynamic conditions and reflect the characteristics of symptomatic knee OA. This study investigated MMEs during walking and their correlation with knee pain. METHODS: Thirty-two symptomatic patients with knee OA (mean age, 60.5 ± 9.9 years) were enrolled in this study. The medial meniscus was evaluated using ultrasonograms during walking, and in the static supine and unipedal standing positions, as dynamic and static conditions, respectively. The ΔMME (the difference between the maximum and minimum MMEs) was obtained in each condition. The intensity of the knee pain during walking was measured by the visual analog scale (VAS). RESULTS: The ΔMME in the dynamic condition was significantly higher than that in the static condition (P < 0.01). There was a significant correlation between VAS and ΔMME only in the dynamic condition. CONCLUSIONS: The dynamic evaluation is a valid tool for understanding the mechanisms of knee pain and the behavior of the medial meniscus in symptomatic knee OA.

Risk factors for small-bowel obstruction after colectomy for colorectal cancer: a retrospective study.

PURPOSE: Postoperative adhesions are a concerning complication of abdominal surgery with major implications on quality of life. This study aimed to investigate the risk factors for postoperative small-bowel obstruction (SBO) after colectomy for colorectal cancer. METHODS: We reviewed the clinicopathological variables of 1646 patients who underwent colectomy for colorectal cancer between 2009 and 2018. RESULTS: SBO occurred following primary tumor resection for colorectal cancer in 67 (4.1%) of the 1646 patients. The median observation period was 7.5 (range: 3.0-12.0) years. Multivariate analysis revealed that rectal tumors, anastomotic leakages, previous abdominal surgeries, and longer operating times were all correlated with postoperative SBO, but there were no differences in the incidence of SBO between laparoscopic vs. open surgery. The use of adhesion prevention material had no effect on SBO. Our data showed that the onset of SBO tended to be relatively early, within a year after surgery (89.5%). CONCLUSIONS: Tumor localization in the rectum is associated with several problems, including a wide resection area, prolonged operative duration, and high risk of anastomotic leakage, which may increase the risk of SBO. Laparoscopic surgery and adhesion prevention material did not demonstrate a clear preventive effect against SBO.

Examination of colorectal cancer cases with metal allergy.

PURPOSE: To report our initiatives and treatment results for patients with colorectal cancer with metal allergy. METHODS: A total of 27 patients (2.6%) with a history of metal contact dermatitis were identified among 1027 patients who underwent curative resection of colorectal cancer from 2014 to 2020. The results of the patch test, perioperative results, and postoperative colonoscopy findings were also investigated. RESULTS: The patch test for metal allergens and staples was performed in 21 patients (77.8%), and 13 of them (61.9%) tested positive for at least one metal allergen. Ni (38.1%), Co (28.6%), and Pd (19.0%) showed higher positive rates than other metals, and 1 patient (4.8%) tested positive for staples. Stapled anastomosis/suturing was performed as planned in 15 of 27 patients. In 10 patients, the anastomosis method was changed from stapled to hand-sewn according to the no-patch test results (60%), positivity for multiple metals (20%), positivity for staples (10%), and surgeon's judgment (10%). No complications and abnormal colonoscopy findings were found to be associated with stapled anastomosis/suturing. CONCLUSION: The patch test is useful for selecting an optimal anastomosis method for patients with suspected metal allergy.

Association of combined hip-pelvic-lumbar mobility with hip muscle strength and clinical outcomes in patients treated for femoroacetabular impingement syndrome: A case-control study.

BACKGROUND: It is unclear whether hip and pelvic mobility in the sagittal plane are associated with hip function in FAIS. This study aimed to determine whether hip-pelvis-lumbar mobility is associated with preoperative hip function and postoperative outcomes in FAIS. METHODS: This was a level 3 case-control study. This study included 111 patients who underwent arthroscopic FAI correction and labral preservation between 2015 and 2019. The Hip-Pelvic-Lumbar Mobility Test (HPLMT) was performed preoperatively; hip flexion with the hip adducted and internally rotated was examined in the lateral decubitus position, and a total hip flexion angle of less than 120° was diagnosed as positive. HPLMT-positive patients were classified as cases, and HPLMT-negative patients were classified as controls. Hip muscle strength was measured preoperatively using a hand-held dynamometer. The modified Harris hip score (mHHS), Nonarthritic Hip Score (NAHS), and International Hip Outcome Tool-12 score were obtained preoperatively and postoperatively. The rates of patient acceptable symptomatic state (PASS) achievement for patient-reported outcome scores (PROSs) were compared between groups. RESULTS: The preoperative PROSs for the HPLMT-positive patients were significantly lower than those for the HPLMT-negative patients. HPLMT-positive patients had significantly weaker hip strength on the affected side than HPLMT-negative patients (flexion; p < 0.001, abduction; p = 0.001). HPLMT-positive patients had significantly lower postoperative mHHS than HPLMT-negative patients. HPLMT-positive patients were significantly less likely to achieve a PASS for the mHHS (62% versus 85%) and NAHS (48% versus 71%) than HPLMT-negative patients. CONCLUSION: Hip-pelvis-lumbar mobility is associated with hip function and clinical outcomes in FAIS patients. The HPLMT is an efficient tool for assessing FAIS patients.

[A Case of Cecum Cancer with Lymph Node Metastasis and Invasion in the Superior Mesenteric Vein Treated with Combined SMV Resection and Reconstruction].

The patient was a 77-year-old woman. She visited her family doctor with a complaint of bloody stools, and was pointed out a Type 3 colon cancer in the cecum with a colonoscopy. In addition, an enlarged lymph node(#203)was found on the right side of the superior mesenteric vein(SMV). Laparoscopic surgery was initiated, and when the patient was moved to vascular processing, a firm adhesion of the lymph node(#203)was observed on the right side of the SMV. A small laparotomy was added, and a partial combined resection of the SMV was performed en bloc to complete the ileal resection. Histopathological findings showed T4b(transverse colon)N3M0, pStage Ⅲc, and metastatic lymph node(#203)showed evidence of invasion to the SMV. Adjuvant chemotherapy was administered, but lung metastases appeared 4 months and liver metastasis appeared 29 months after surgery. The patient was transferred to a different hospital for best supportive care(BSC)at 34 months after surgery.

Comprehensive collection of genes and comparative analysis of full-length transcriptome sequences from Japanese larch (Larix kaempferi) and Kuril larch (Larix gmelinii var. japonica).

BACKGROUND: Japanese larch (Larix kaempferi) is an economically important deciduous conifer species that grows in cool-temperate forests and is endemic to Japan. Kuril larch (L. gmelinii var. japonica) is a variety of Dahurian larch that is naturally distributed in the Kuril Islands and Sakhalin. The hybrid larch (L. gmelinii var. japonica × L. kaempferi) exhibits heterosis, which manifests as rapid juvenile growth and high resistance to vole grazing. Since these superior characteristics have been valued by forestry managers, the hybrid larch is one of the most important plantation species in Hokkaido. To accelerate molecular breeding in these species, we collected and compared full-length cDNA isoforms (Iso-Seq) and RNA-Seq short-read, and merged them to construct candidate gene as reference for both Larix species. To validate the results, candidate protein-coding genes (ORFs) related to some flowering signal-related genes ​were screened from the reference sequences, and the phylogenetic relationship with closely related species was elucidated. RESULTS: Using the isoform sequencing of PacBio RS ll and the de novo assembly of RNA-Seq short-read sequences, we identified 50,690 and 38,684 ORFs in Japanese larch and Kuril larch, respectively. BUSCO completeness values were 90.5% and 92.1% in the Japanese and Kuril larches, respectively. After comparing the collected ORFs from the two larch species, a total of 19,813 clusters, comprising 22,571 Japanese larch ORFs and 22,667 Kuril larch ORFs, were contained in the intersection of the Venn diagram. In addition, we screened several ORFs related to flowering signals (SUPPRESSER OF OVEREXPRESSION OF CO1: SOC1, LEAFY: LFY, FLOWERING Locus T: FT, CONSTANCE: CO) from both reference sequences, and very similar found in other species. CONCLUSIONS: The collected ORFs will be useful as reference sequences for molecular breeding of Japanese and Kuril larches, and also for clarifying the evolution of the conifer genome and investigating functional genomics.

Elderly patients with suspected Charcot-Marie-Tooth disease should be tested for the TTR gene for effective treatments.

BACKGROUND AND AIMS: Some hereditary transthyretin (ATTRv) amyloidosis patients are misdiagnosed as Charcot-Marie-Tooth disease (CMT) at onset. We assess the findings to identify ATTRv amyloidosis among patients with suspected CMT to screen transthyretin gene variants for treatments. METHODS: We assessed clinical, cerebrospinal fluid, and electrophysiological findings by comparing ATTRv amyloidosis patients with suspected CMT (n = 10) and CMT patients (n = 489). RESULTS: The median (interquartile range) age at onset of neurological symptoms was 69 (64.2-70) years in the ATTRv amyloidosis vs 12 (5-37.2) years in CMT group (Mann-Whitney U, p < 0.01). The proportion of patients with initial sensory symptoms was 70% in the ATTRv amyloidosis group vs 7.1% in CMT group (Fisher's exact, p < 0.01). The proportion of patients with histories of suspected chronic inflammatory demyelinating polyneuropathy (CIDP) were 50% in the ATTRv amyloidosis group vs 8.7% in CMT group (Fisher's exact, p < .01). Other measures and outcomes were not different between the two groups. Five of the six patients with ATTRv amyloidosis received treatment and survived. INTERPRETATION: For effective treatments, the transthyretin gene should be screened in patients with suspected CMT with old age at onset of neurological symptoms, initial sensory symptoms, and histories of suspected CIDP.

The regulation of glucose and lipid homeostasis via PLTP as a mediator of BAT-liver communication.

While brown adipose tissue (BAT) is well-recognized for its ability to dissipate energy in the form of heat, recent studies suggest multifaced roles of BAT in the regulation of glucose and lipid homeostasis beyond stimulating thermogenesis. One of the functions involves interorgan communication with metabolic organs, such as the liver, through BAT-derived secretory factors, a.k.a., batokine. However, the identity and the roles of such mediators remain insufficiently understood. Here, we employed proteomics and transcriptomics in human thermogenic adipocytes and identified previously unappreciated batokines, including phospholipid transfer protein (PLTP). We found that increased circulating levels of PLTP, via systemic or BAT-specific overexpression, significantly improve glucose tolerance and insulin sensitivity, increased energy expenditure, and decrease the circulating levels of cholesterol, phospholipids, and sphingolipids. Such changes were accompanied by increased bile acids in the circulation, which in turn enhances glucose uptake and thermogenesis in BAT. Our data suggest that PLTP is a batokine that contributes to the regulation of systemic glucose and lipid homeostasis as a mediator of BAT-liver interorgan communication.

A case of Miller Fisher syndrome with delayed onset peripheral facial nerve palsy after COVID-19 vaccination: a case report.

BACKGROUND: To prevent the spread of the novel coronavirus disease 2019 (COVID-19) infection, various vaccines have been developed and used in a large number of people worldwide. One of the most commonly used vaccines is the mRNA vaccine developed by Moderna. Although several studies have shown this vaccine to be safe, the full extent of its side effects has not yet been known. Miller-Fisher syndrome (MFS) is a rare condition that manifests ophthalmoplegia, ataxia, and loss of tendon reflexes. It is a subtype of Guillain-Barré syndrome and an immune-mediated disease related to serum IgG anti-GQ1b antibodies. Several vaccines including those for COVID-19 have been reported to induce MFS. However, there have been no reports of MFS following Moderna COVID-19 vaccine administration. CASE PRESENTATION: A 70-year-old man was referred to our hospital due to diplopia that manifested 1 week after receiving the second Moderna vaccine dose. The patient presented with restricted abduction of both eyes, mild ataxia, and loss of tendon reflexes. He was diagnosed with MFS based on his neurological findings and detection of serum anti-GQ1b antibodies. The patient was administered intravenous immunoglobulin, and his symptoms gradually improved. Five days after admission, the patient showed peripheral facial paralysis on the right side. This symptom was suggested to be a delayed onset of peripheral facial nerve palsy following MFS that gradually improved by administration of steroids and antiviral drugs. CONCLUSION: There have been no previous reports of MFS after Moderna COVID-19 vaccination. This case may provide new information about the possible neurological side effects of COVID-19 vaccines.

Pharmacokinetics and metabolism of mirogabalin, a novel α2δ ligand, in rats and monkeys.

The purpose of this study was to investigate the pharmacokinetic behaviour of mirogabalin in rats and monkeys.Pharmacokinetic parameters of mirogabalin after its oral and intravenous administration were determined. Distribution study, mass balance study, and metabolite identification were also conducted after the oral administration of [14C]mirogabalin.Plasma exposure (Cmax and AUCinf) increased dose-proportionally after the oral administration of mirogabalin at 1, 3, and 10 mg/kg to rats and monkeys. Mean total body clearance (CLtot) after intravenous administration at 3 mg/kg was 13.5 mL/min/kg in rats and 9.02 mL/min/kg in monkeys, and absolute bioavailability at 3 mg/kg was 97.6% in rats and 85.2% in monkeys. There was a greater recovery of radioactivity in urine than that in faeces after the oral administration of [14C]mirogabalin. The main radioactive component in the plasma, urine, and faeces was mirogabalin. A204-4455 (lactam form), an oxidised metabolite of mirogabalin, mirogabalin N-glucuronide and O-glucuronide of oxidised A204-4455 were detected as minor components in monkeys and rats.Mirogabalin administered orally was almost completely eliminated via urinary excretion. A small part of the orally administered dose of mirogabalin was metabolised via glucuronidation at the amine and carboxylic acid moiety and oxidation as the primary metabolic pathway.

Biweekly TAS-102 and bevacizumab as third-line chemotherapy for advanced or recurrent colorectal cancer: a phase II, multicenter, clinical trial (TAS-CC4 study).

BACKGROUND: TAS-102 improves overall survival (OS) of patients with refractory colorectal cancer (CRC), resulting in median progression-free survival (PFS) of 2.0 months (RECOURSE trial). Subsequently, a combination of TAS-102 and bevacizumab was shown to extend median PFS by 3.7 months. However, approximately half of these patients experience grade 3/4 neutropenia. In this study, we evaluated whether biweekly TAS-102 and bevacizumab therapy has efficacy equal to that of conventional TAS-102 and bevacizumab therapy and whether it reduces adverse hematological effects. METHODS: This phase II, investigator-initiated, open-label, single-arm, multicenter study was conducted in Japan. Eligible patients had previously received first- and second-line chemotherapy for metastatic CRC. TAS-102 (35 mg/m2) was given twice daily on days 1-5 and days 15-19 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion for 30 min every 2 weeks. The primary end point was progression-free survival (PFS), and secondary end points were time-to-treatment failure (TTF), response rate (RR), OS, and safety. RESULTS: 44 patients with metastatic colorectal cancer were enrolled in this study. Median PFS was 4.6 months (95% confidence interval [95% CI] 3.6-5.3) and median OS was 10.5 months (95% CI 9.6-11.4). A partial response was observed in 2 patients (4.5%, 95% CI 0.4-16.0%). The most common adverse event above grade 3 was neutropenia (7 patients, 15.9%, 95% CI 7.6-29.7%). CONCLUSIONS: Biweekly TAS-102 and bevacizumab therapy as third-line chemotherapy appears as effective as conventional TAS-102 and bevacizumab therapy, and this approach reduces adverse hematological effects.

Covering reinforced staples with polyethylene glycolic acid felt-covered fibrin sealant to prevent pancreatic fistula after distal pancreatomy: a retrospective comparative study.

BACKGROUND: In accordance with previous reports on the utility of polyethylene glycolic acid (PGA) felt and fibrin glue for postoperative pancreatic fistula (POPF), we usually perform distal pancreatectomy (DP) with a PGA felt reinforcement stapler when dissecting the pancreas and cover the stump with PGA felt and fibrin glue (the PPF method). In this study, we retrospectively analyzed our DP cases to compare the risk factors for POPF and the postoperative course of patients receiving the PPF method of treatment versus that of those receiving conventional treatment. METHODS: A total of 127 DP procedures performed in our department between January 2008 and June 2021 were retrospectively analysed. RESULTS: In the PPF method, grade B/C POPF rate tended to decrease, and POPF rate showed a significant decrease. The duration of drainage and the length of postoperative hospitalisation were also significantly shorter with the PPF method. The risk of grade B/C POPF significantly decreased with the PPF method if the pancreas was thick (> 13.5 mm) or the patients were obese. CONCLUSIONS: The PPF method is useful for POPF in DP and is particularly effective when a thick pancreas or obese patient is involved. Removing the drainage tube early in the PPF method may lead to early discharge.

Hepatobiliary-pancreatic surgery for patients with a prepancreatic postduodenal portal vein: a case report and literature review.

BACKGROUND: Prepancreatic portal vein (PPV) is a congenital anatomical variant of the portal vein (PV). PPVs are extremely rare and generally classified into two categories, prepancreatic preduodenal portal vein and prepancreatic postduodenal portal vein (PPPV). Prepancreatic preduodenal portal veins are rare, with approximately 100 reported cases globally; PPPVs are even more atypical, with less than 20 documented cases globally. Despite the extremely low occurrence, PPPV knowledge and recognition are important, especially for hepatobiliary-pancreatic (HBP) surgeries, such as pancreaticoduodenectomy (PD) for patients of a PPPV. Here, we report a case of PPPV and a literature review. CASE PRESENTATION: A 73-year-old-male with ampullary carcinoma underwent PD at our hospital. Preoperative enhanced CT revealed an abnormal L-shaped PV, identified as a PPPV. Both the PPPV and the postpancreatic "normal" superior mesenteric vein (SMV) divaricated from the SMV at the caudal side of the pancreas. A splenic vein and inferior mesenchymal vein flowed into the postpancreatic "normal" PV, which encircled the common bile duct and potentially flowed into the liver, forming a cavernous transformation at the hilar plate. During surgery, we attempted to isolate the PV from the pancreas and common bile duct. However, it was difficult to isolate from the pancreas. The PPPV was so fragile that bleeding from the PPPV became uncontrollable. To remove the tumor, we resected the PPPV and reconstructed a "normal" PV as an autogenous graft. To maintain intraoperative hepatic blood flow and avoid small bowel congestion, an antithrombogenic bypass catheter was placed between the SMV and umbilical vein during reconstruction. After surgery, several complications occurred, such as PV thrombosis and hyperammonemia. The patient was discharged on postoperative day 45. CONCLUSIONS: PPPV is a rare vascular variant but is easily diagnosed preoperatively due to its distinct shape on CT imaging. However, isolating the PPPV from the pancreas and bile duct is incredibly difficult and potentially associated with increased operative risks and postoperative complications. PV resection rather than isolation is a potential solution to reduce the risk of hemorrhage, even in the absence of invasion.

[A Case of Recurrence in the Abdominal Wall and Perineal Region of Rectal Cancer Successfully Treated with Minimally Invasive Surgery and Radiation Therapy].

Local recurrence after rectal cancer surgery is often difficult to treat because there are few effective treatments. In this study, we report a case of parastomal and perineal recurrence after Miles' surgery in an elderly patient who had a favorable outcome after laparoscopic surgery and radiation therapy. Our results suggest that a combination of minimally invasive treatment may be effective in elderly patients and after polysurgery.