Rectum necrosis in a patient with severe COVID19 infection after CAR-T therapy: a case report.

BACKGROUND: Coronavirus disease 2019 (COVID19) can cause gastrointestinal complications as well as respiratory tract disease. Coagulation abnormalities and thrombosis frequently occur in COVID19, especially in cases with severe clinical outcome. The relationship between gastrointestinal perforation and coagulopathy due to COVID19 remains unclear. CASE PRESENTATION: A 49-year-old female received Chimeric antigen receptor T (CAR-T) therapy for an early recurrence of diffuse large B-cell lymphoma (DLBCL) that was refractory to chemotherapy. She was diagnosed with cytokine release syndrome (CRS) because of a fever and oxygen desaturation, and administered tocilizumab. Forty days after completing CAR-T therapy, she was infected with COVID19 and transferred to our hospital. Her general condition worsened and she developed COVID19 pneumonia, and then steroid pulse therapy was started. While her respiratory condition improved, she experienced pain in the anal region and computed tomography (CT) revealed a rectal perforation. An emergency surgery was undertaken, and the lower rectum wall was found to be completely necrotic. Removal of the necrotic part of the rectum tissue, and drainage and lavage of necrotic tissue in the pelvic cavity were performed. The remaining rectum was resected with partial sigmoidectomy, but we could not make the anal stump closed. In addition, an end colostomy in the sigmoid colon was performed. Histopathological findings showed thromboses in the rectal mesentery veins. After the first surgery, the pelvic abscess cavity persisted and her high-grade fever continued. Reoperation was laparoscopically performed, and she underwent a resection of anal canal with residual necrotic rectal and mesorectal tissue, and a drainage of the pelvic abscess. After the reoperation, her general condition improved and CT showed that the abscess cavity had significantly improved. CONCLUSIONS: Gastrointestinal perforation, especially rectal necrosis due to coagulopathy caused by severe COVID19 infection, is a rare but life-threatening complication. Physicians should have a high degree of clinical suspicion for timely diagnosis and management, and surgical intervention is necessary in cases of rectal necrosis.

Risk Factors for Residual Back Pain After Balloon Kyphoplasty for Osteoporotic Vertebral Fracture.

Background: Balloon kyphoplasty (BKP) is a method for the management of osteoporotic vertebral body fracture (OVF). However, improvement in back pain (BP) is poor in some patients, also previous reports have not elucidated the exact incidence and risk factors for residual BP after BKP. We clarified the characteristics of residual BP after BKP in patients with OVF. Hypothesis: In this study, we hypothesize that some risk factors may exist for residual BP 2 years after the treatment of OVF with BKP. Patients and Methods: A multicenter cohort study was performed where patients who received BKP within 2 months of OVF injury were followed-up for 2 years. BP at 6 months after surgery and final observation was evaluated by Visual Analog Scale (VAS) score. Patients with a score of 40 mm or more were allocated to the residual BP group, and comparisons between the residual back pain group and the improved group were made for bone density, kyphosis, mobility of the fractured vertebral body, total spinal column alignment, and fracture type (fracture of the posterior element, pedicle fracture, presence or absence of posterior wall damage, etc.). Also, Short Form 36 (SF-36) for physical component summary (PCS) and mental component summary (MCS) at the final follow-up was evaluated in each radiological finding. Results: Of 116 cases, 79 (68%) were followed-up for 2 years. Two years after the BKP, 26 patients (33%) experienced residual BP. Neither age nor sex differed between the groups. In addition, there was no difference in bone mineral density, BKP intervention period (period from onset to BKP), and osteoporosis drug use. However, the preoperative height ratio of the vertebral body was significantly worse in the residual BP group (39.8% vs. 52.1%; p = 0.007). Two years after the operation, the vertebral body wedge angle was significantly greater in the residual BP group (15.7° vs. 11.9°; p = 0.042). In the multiple logistic regression model with a preoperative vertebral body height ratio of 50% or less [calculated by receiver operating characteristic (ROC) curve], the adjusted odds ratio for residual BP was 6.58 (95% confidence interval 1.64-26.30; p = 0.007); similarly, patients with vertebral body height ratio less than 50% had a lower score of SF-36 PCS 24.6 vs. 32.2 p = 0.08. Conclusion: The incidence of residual BP 2 years after BKP was 33% in the current study. The risk factor for residual BP after BKP was a preoperative vertebral body height ratio of 50% or less, which should be attentively assessed for the selection of a proper treatment scheme and to provide adequate stabilization. Level of Evidence: III.

Rikkunshito increases peripheral incretin-hormone levels in humans and rats.

BACKGROUND: It was reported that rikkunshito (TJ-43) improved the cisplatin-induced decreases in the active form of ghrelin in plasma; however, other effects on gastrointestinal hormones have not been investigated. AIM: To investigate the effects of TJ-43 on peripheral levels of incretin hormones, including gastric inhibitory polypeptide (GIP) and glucagon-like polypeptide-1 (GLP-1), in humans and rats. METHODS: Patients were divided into two groups, namely patients who received TJ-43 immediately following surgery [TJ-43(+) group] and those who received TJ-43 on postoperative day 21 [TJ-43(-) group], and the plasma levels of active GIP and active GLP-1 were assessed. In animal experiments, rats were treated with TJ-43 [rat (r)TJ-43(+) group] or without [rTJ-43(-) group] by gavage for 4 wk, and the plasma active GIP and active GLP-1 levels were measured. The expression of incretin hormones in the gastrointestinal tract and insulin in the pancreas were investigated by immunohistochemistry. Furthermore, the cyclic adenosine monophosphate activities were assessed in pancreatic tissues from rats treated with or without TJ-43 in vivo, and the blood glucose levels and plasma insulin levels were measured in rats treated with or without TJ-43 in oral glucose tolerance tests. RESULTS: In humans, the active incretin hormone levels increased, and values were significantly greater in the TJ-43(+) group compared those in the TJ-43(-) group. In rats, the plasma active incretin levels significantly increased in the rTJ-43(+) group compared with those in the rTJ-43(-) group. GIP and GLP-1 expressions were enhanced by TJ-43 treatment. Moreover, plasma insulin levels increased and blood glucose levels were blunted in the rTJ-43(+) group. CONCLUSION: The results show that TJ-43 may be beneficial for patients who undergo pancreatic surgery.

PaCS-Toolkit: Optimized Software Utilities for Parallel Cascade Selection Molecular Dynamics (PaCS-MD) Simulations and Subsequent Analyses.

Parallel cascade selection molecular dynamics (PaCS-MD) is an enhanced conformational sampling method conducted as a "repetition of time leaps in parallel worlds", comprising cycles of multiple molecular dynamics (MD) simulations performed in parallel and selection of the initial structures of MDs for the next cycle. We developed PaCS-Toolkit, an optimized software utility enabling the use of different MD software and trajectory analysis tools to facilitate the execution of the PaCS-MD simulation and analyze the obtained trajectories, including the preparation for the subsequent construction of the Markov state model. PaCS-Toolkit is coded with Python, is compatible with various computing environments, and allows for easy customization by editing the configuration file and specifying the MD software and analysis tools to be used. We present the software design of PaCS-Toolkit and demonstrate applications of PaCS-MD variations: original targeted PaCS-MD to peptide folding; rmsdPaCS-MD to protein domain motion; and dissociation PaCS-MD to ligand dissociation from adenosine A2A receptor.

Investigating Cytoglobin Expression in Colon Cancer: Clinicopathological Insights from Immunohistochemical Analysis.

BACKGROUND/AIM: Cytoglobin (Cygb), a protein involved in cellular oxygen metabolism and protection, has garnered attention owing to its potential role in the initiation and progression of cancer, particularly colon cancer (CC). This study investigated the expression and significance of Cygb in CC. PATIENTS AND METHODS: This study included 145 patients who underwent R0 surgery for CC (clinical stage II/III) at our institution between January 2007 and December 2014. Immunohistochemical analysis was performed to evaluate the Cygb expression patterns in CC tissues. Additionally, the correlation between Cygb expression levels and the clinicopathological characteristics of patients with CC was investigated. RESULTS: Colon cancer tissues were categorized into high-expression (95 cases) and low-expression (50 cases) groups. Cygb was highly expressed in well-differentiated cases, whereas its expression decreased in poorly differentiated cases. No significant differences in other clinicopathological factors were observed between the two groups. Cygb expression had no significant effect on recurrence-free survival or overall survival. CONCLUSION: This study contributes to the growing understanding of Cygb expression and its significance in CC. The expression of Cygb in CC was found to be unrelated to the recurrence rate and prognosis, but showed a correlation with differentiation status.

Postoperative Remission of Diabetes Mellitus After Gastrectomy in Patients With Diabetes Mellitus and Gastric Cancer.

BACKGROUND/AIM: We investigated the postoperative treatment status for diabetes mellitus and perioperative HbA1c levels in patients with diabetes mellitus and examined the effects of clinical factors on the remission of diabetes mellitus. PATIENTS AND METHODS: In this study, 126 patients with gastric cancer were considered to have diabetes mellitus preoperatively, of whom 79 were treated with oral antidiabetic drugs and/or insulin treatment. We compared diabetic treatment status and HbA1c values between the preoperative and postoperative periods in patients who underwent gastrectomy and examined the effects of clinical factors on improving diabetes mellitus. RESULTS: Of the 79 patients treated preoperatively for diabetes mellitus, 34 (43%) discontinued all medications for diabetes mellitus and for 37 (47%) the therapeutic dose was reduced or switched from insulin to oral antidiabetic drugs. Total gastrectomy was an independent factor for remission of antidiabetic treatments after gastrectomy. Concerning HbA1c levels, only the absence of preoperative insulin use was an independent factor for improvement. However, reconstruction was not a significantly correlated factor for the improvement of postoperative HbA1c levels and reduction of antidiabetic medications after distal gastrectomy. CONCLUSION: Almost all patients discontinued or had their dose of antidiabetic medications reduced after gastrectomy in clinical practice, and special attention should be paid in the management methods for diabetes mellitus in patients who underwent total gastrectomy for gastric cancer.

Detection of Abdominal Lymph Node Metastasis from Pancreatic Neuroendocrine Tumor by Somatostatin Receptor Scintigraphy: Comparison with Somatostatin Receptor Type 2 Immunostaining.

We report a 58-year-old male with a histopathologically proven grade 2 (G2) pancreatic neuroendocrine neoplasm and multiple abdominal node metastases by use of a laparoscopic pancreatic body and tail resection procedure, plus abdominal lymph node dissection. A primary pancreatic tail neuroendocrine tumor sized 20 × 25 mm was detected by contrast-enhanced computed tomography, somatostatin receptor scintigraphy (SRS), and fluorodeoxyglucose positron emission tomography (FDG-PET) examinations and pathologically diagnosed as a pancreatic neuroendocrine tumor (PNET, G2) based on positive immunostaining for somatostatin receptor (SSTR) type 2. Of three metastatic histopathological lymph nodes, two measured 18 × 21 and 10 × 12 mm, respectively, with whole strong SSTR immunostaining showing moderate uptake in SRS findings, whereas the other node, sized 8 × 10 mm, had strong SSTR immunostaining only in a small 6 × 6-mm-sized portion and showed no uptake in SRS findings, likely because of the limited spatial resolution of scintigraphy. On the other hand, only the largest node (18 × 21 mm) was visualized by FDG-PET. SRS may be useful for metastatic lymph node diagnosis based on SSTR immunostaining, though a disadvantage is the spatial resolution limitation.

Rikkunshito increases appetite by enhancing gastrointestinal and incretin hormone levels in patients who underwent pylorus-preserving pancreaticoduodenectomy: A retrospective study.

BACKGROUND: Rikkunshito (TJ-43) relieves gastrointestinal disturbance by increases in the levels of acylated ghrelin. AIM: To investigate the effects of TJ-43 in patients undergoing pancreatic surgery. METHODS: Forty-one patients undergoing pylorus-preserving pancreaticoduodenectomy (PpPD) were divided into two groups; patients took daily doses of TJ-43 after surgery or after postoperative day (POD) 21. The plasma levels of acylated and desacylated ghrelin, cholecystokinin (CCK), peptide YY (PYY), gastric inhibitory peptide (GIP), and active glucagon-like peptide (GLP)-1 were evaluated. Oral calorie intake was assessed at POD 21 in both groups. The primary endpoint of this study was the total food intake after PpPD. RESULTS: The levels of acylated ghrelin were significantly greater in patients treated with TJ-43 than those in patients without TJ-43 administration at POD 21, and oral intake was significantly increased in patients treated with TJ-43. The CCK and PYY levels were significantly greater in patients treated with TJ-43 than those in patients without TJ-43 treatment. Furthermore, the GIP and active GLP-1 levels increased and values at POD 21 were significantly greater in patients treated with TJ-43 than those in patients without TJ-43 administration. Insulin secretion tended to increase in patients treated with TJ-43. CONCLUSION: TJ-43 may have advantages for oral food intake in patients in the early phase after pancreatic surgery. Further investigation is needed to clarify the effects of TJ-43 on incretin hormones.

The Prognostic Implications of Perioperative Serum Cholesterol Levels in Patients With Gastric Cancer.

BACKGROUND/AIM: Although cholesterol is an important indicator of nutritional status, it is also involved in cancer progression. In this study, we investigated the clinical significance of the dynamics of perioperative total cholesterol (T-Cho) levels in patients with gastric cancer (GC). PATIENTS AND METHODS: A total of 212 patients with pathological stage II/III disease who underwent gastrectomy between 2004 and 2020 were enrolled in this retrospective study. The preoperative and postoperative serum T-Cho levels were measured in these patients. RESULTS: Increased serum T-Cho levels were significantly correlated with low preoperative serum albumin levels (p<0.001). Patients with increased serum T-Cho levels after surgery had significantly lower overall and recurrence-free survival rates (p=0.030 and p=0.013, respectively; log-rank test). Cox proportional hazards model revealed that increased serum T-Cho levels (p=0.040), advanced pathological stage (p<0.001), and the provision of adjuvant chemotherapy (p=0.006) were independent prognostic factors for recurrence-free survival in patients with GC. CONCLUSION: Increased serum T-Cho levels after gastrectomy may be an independent prognostic factor in patients with GC.

Metastasis of Hepatocellular Carcinoma in the Pouch of Douglas Successfully Treated by Radiation Therapy: A Case Report.

Metastasis of hepatocellular carcinoma (HCC) in the pouch of Douglas is relatively rare. A 65-year-old man with liver cirrhosis was admitted for detailed examination of a pelvic tumor. He had a previous history of ruptured HCC, and received emergent hemostasis with transcatheter arterial embolization followed by curative ablation. His blood tests showed an increase in des-gamma-carboxy prothrombin (DCP). Contrast-enhanced computed tomography (CE-CT) revealed a heterogeneously enhanced large pelvic tumor, but no additional tumorous lesions were detected in other organs, including the lungs, liver and abdominal lymph nodes. The colonoscopy showed compression by an extra-luminal/submucosal tumor, and computed tomography-guided percutaneous needle biopsy revealed that the pelvic tumor was metastasis of HCC. Because of the poor liver function, the solitary pelvic tumor was treated with three-dimensional conformal radiation therapy (3D-CRT). The tumor size and the DCP value were markedly decreased after radiation therapy. Nine months later, occasional mild bloody stool due to radiation proctitis was observed; however, no serious side effects occurred. Our case suggests that radiation therapy may be a therapeutic option for a solitary metastatic lesion of HCC in the pouch of Douglas.

Recombinant Human Thrombomodulin Reduces Mortality and Acute Lung Injury Caused by Septic Peritonitis in Rats.

This study aimed to investigate the therapeutic effects of recombinant human thrombomodulin (rhTM) on acute lung injury (ALI) caused by sepsis in rats. Rats that underwent cecal ligation and puncture (CLP) were treated with or without rhTM, and then mortality was analyzed. In another set of experiments, ALI was assessed. Furthermore, microthrombosis in the lungs was investigated by immunohistochemistry. Moreover, plasma inflammatory and anti-inflammatory cytokines, such as TNF-α, high-mobility group box chromosomal protein 1 (HMGB-1), and IL-10, were evaluated by ELISA. Production of TNF-α and HMGB-1 by isolated tissue macrophages (Mφs) was assessed in vitro. Mortality after CLP was significantly improved by rhTM treatment. In addition, rhTM treatment improved the wet/dry weight ratio of the lungs, the pulmonary microvascular permeability, and the lung injury scores in animals that underwent CLP. Microthrombosis was detected in the lungs after CLP. These pathophysiological changes were blunted by rhTM treatment. Increased plasma TNF-α and HMGB-1 levels were blunted by rhTM treatment; however, the anti-inflammatory cytokine IL-10 was significantly greater in the rhTM(+) group than in the rhTM(-) group. Increased TNF-α and HMGB-1 production by the tissue Mφs stimulated with LPS were significantly blunted by rhTM treatment in vitro, but the production of IL-10 by the tissue Mφs was not changed in the cells incubated with rhTM. Overall, rhTM improved the mortality caused by septic peritonitis. The possible mechanisms are most likely anti-inflammatory and anticoagulant effects, which lead to the prevention of ALI.

Periostin increased by mechanical stress upregulates interleukin-6 expression in the ligamentum flavum.

Ligamentum flavum (LF) hypertrophy is a major cause of lumbar spinal canal stenosis. Although mechanical stress is thought to be a major factor involved in LF hypertrophy, the exact mechanism by which it causes hypertrophy has not yet been fully elucidated. Here, changes in gene expression due to long-term mechanical stress were analyzed using RNA-seq in a rabbit LF hypertrophy model. In combination with previously reported analysis results, periostin was identified as a molecule whose expression fluctuates due to mechanical stress. The expression and function of periostin were further investigated using human LF tissues and primary LF cell cultures. Periostin was abundantly expressed in human hypertrophied LF tissues, and periostin gene expression was significantly correlated with LF thickness. In vitro, mechanical stress increased gene expressions of periostin, transforming growth factor-ß1, α-smooth muscle actin, collagen type 1 alpha 1, and interleukin-6 (IL-6) in LF cells. Periostin blockade suppressed the mechanical stress-induced gene expression of IL-6 while periostin treatment increased IL-6 gene expression. Our results suggest that periostin is upregulated by mechanical stress and promotes inflammation by upregulating IL-6 expression, which leads to LF degeneration and hypertrophy. Periostin may be a pivotal molecule for LF hypertrophy and a promising therapeutic target for lumbar spinal stenosis.

Carcinoembryonic antigen levels in pancreatic juice are associated with histological subtypes of intraductal papillary mucinous neoplasm of the pancreas.

Background: The present study aimed to examine the correlation between preoperative carcinoembryonic antigen levels in pancreatic juice (PJ-CEA) and the histological subtype of intraductal papillary mucinous neoplasm (IPMN). Methods: We enrolled IPMN patients who underwent endoscopic retrograde pancreatography between March 2002 and March 2018. Clinical factors associated with IPMN histological subtypes of 67 patients who underwent surgery were analyzed. Furthermore, the relationship between CEA immunohistochemistry findings and histological subtypes was investigated. Results: Median PJ-CEA were 15 ng/ml in the gastric type, 150 ng/ml in the intestinal type, and 175 ng/ml in the pancreatobiliary type. Both intestinal and pancreatobiliary types had significantly higher PJ-CEA than the gastric type (p = 0.001). In the analysis of histological subtype predictors, high PJ-CEA (≥63 ng/ml) only showed a significant difference in multivariate analyses (95% confidence interval 4.8-70.2; p < 0.001). Immunohistochemistry findings revealed significantly higher CEA expression in the non-gastric type than in the gastric type (p < 0.001). The non-gastric type showed a significantly worse prognosis than the gastric type (p = 0.017). Conclusion: PJ-CEA was an independent predictor of IPMN histological subtypes in a preoperative setting. High PJ-CEA predict the non-gastric type, while low PJ-CEA predict the gastric type.

[Long-Term Prognosis of Patients with Biliary Tract Cancer Undergoing Pancreaticoduodenectomy].

We divided the patients with biliary tract cancer who underwent pancreaticoduodenectomy(PD)at our hospital into the 5-year recurrence-free and recurrence groups and investigated the prognostic factors. Additionally, we investigated the efficacy of adjuvant chemotherapy in patients with and without lymph node (LN) metastasis. There was no significant difference between the two groups for patient characteristics and perioperative factors. However, patients with LN metastasis tended to have a higher recurrence rate. For patients without LN metastasis, the median overall survival(OS)was not significantly different between the patients who received and did not receive adjuvant chemotherapy. For patients with LN metastasis, although it was not significantly different(p=0.234), the OS of patients who received adjuvant therapy was more than 3 times than that of patients who did not(58.6 months and 18.4 months, respectively). For patients with biliary tract cancer who underwent PD, positive LN metastasis may be a poor prognostic factor, and adjuvant therapy may possibly improve prognosis.

Intended preoperative trans-arterial embolization for large hepatocellular carcinoma: a retrospective cohort study.

BACKGROUND: Generally, a large tumor size of hepatocellular carcinoma (HCC) is associated with poor visibility and uncertainty in the surgical field which results in increased surgical difficulty as well as unfavorable postoperative outcomes. We performed intended preoperative trans-arterial embolization (TAE) in patients with a large HCC. In this study, we investigated the oncological significance of intended preoperative TAE for a large HCC, using a comparison between patients with and without TAE, and detailed analyses for pre- and post-TAE status. METHODS: A total of 411 patients who underwent hepatectomy for primary HCC at the University of Yamanashi Hospital between January 2007 and December 2018 were included in this study. The patients were divided into two groups: patients with larger HCCs (≥50 mm, n=51) and those with smaller HCC (<50 mm, n=360) according to the size of their HCCs. Comparison of clinicopathological features between these groups and clinical outcomes between the TAE and non-TAE groups were compared. In addition, a detailed analysis of each case in the TAE group was conducted, comparing clinicopathological factors between pre- and post-TAE status. RESULTS: The clinical unfavorable short- and long-term outcomes of patients with large HCCs (≥50 mm) were revealed compared to those with small HCCs (<50 mm). The prognostic analyses showed that a large tumor size and increased tumor markers, multiple tumor numbers, and others were adverse prognostic factors, and vascular invasions and residual tumors were included in the multivariate analysis. Further detailed analyses revealed that the average rates of change in tumor size and tumor shrinkage after TAE were - 48.6±35.6 mm and - 30.7±17.0%, respectively. Pathological high necrotic changes in the tumor, after multiple-times TAE aiming to a better effect, were related to a better prognosis in patients with large HCC. Poor prognostic factors became less common in patients who underwent intended preoperative TAE, and these patients had better prognoses. CONCLUSIONS: The large tumor size of HCC is associated with unfavorable outcomes; the intended preoperative TAE for large HCC patients performed multiple times aiming to affect the tumor as much as possible might improve their prognoses.

Soluble podoplanin as a biomarker in diffuse­type gastric cancer.

Diffuse­type gastric cancer, also known as scirrhous gastric cancer, is characterized by a larger number of stromal cells, referred to as cancer­associated fibroblasts (CAFs), than the number of cancer cells in the tissue. The present study focused on CAFs in gastric cancer and examined their potential as a blood biomarker. A total of 46 and 84 patients with gastric cancer were respectively included in a development and an independent validation cohort to assess the clinicopathological characteristics of plasma podoplanin (PDPN) levels. The prognostic impact of plasma PDPN was also investigated in the validation cohort. The cut­off value of the plasma­PDPN concentration was set to the median plasma PDPN concentration in the development cohort that was then divided into the high­PDPN and low­PDPN groups. The high­PDPN group tended to have more diffuse­type disease (P=0.079), which was further confirmed through logistic regression analysis (P=0.008). Kaplan­Meier survival estimates indicated that the recurrence­free survival rate was significantly lower in the high­PDPN group (P=0.029). In conclusion, plasma soluble PDPN was demonstrated to be a marker for diffuse gastric cancer and may reflect the prognosis of this disease.

[Two Cases of Carcinoma en Cuirasse, as Cutaneous Metastasis of Breast Cancer].

We present 2 cases of carcinoma en cuirasse, an uncommon clinical manifestation of metastatic cutaneous breast cancer. Case 1, a 70-year-old woman, presented with diffuse erythematous, indurated skin lesions that covered her entire anterior chest wall. Skin biopsy revealed tumor cells in the dermis which were ER and PgR positive and HER2 negative. CT showed pleural and pericardial effusion which led to a final diagnosis of cutaneous metastasis from breast cancer. Fulvestrant monotherapy was initiated and maintained a good clinical effect for 40 months. She died of multiple liver metastasis after 53 months from her first visit. Case 2 was a 71-year-old woman, with a 24 month history of a left breast tumor that gradually accompanied erythematous skin indurations and erosion, which spread to her entire left chest wall and contralateral breast. Following skin biopsy and CT, she was diagnosed to have triple negative breast cancer with multiple lymph node and cutaneous metastasis. After 4 cycles of EC, capecitabine was administrated and her skin lesions improved rapidly, including the lymph nodes. She is currently alive after 12 months since her first visit and under chemotherapy against new cutaneous metastasis.

Role of podoplanin and Kupffer cells in liver injury after ischemia-reperfusion in mice.

AIM: To investigate the relationship between the intrahepatic expression of podoplanin (PDPN) and Kupffer cells (KCs) in ischemia-reperfusion (I/R) liver damage. METHODS: C57Bl/6 mice were injected with 200 µl of clodronate liposomes (macrophage depletion; MDP group) to deplete KCs or control liposomes (control group) via the ophthalmic vein plexus 24 h prior to ischemia. Animals were subjected to 90 min of partial hepatic ischemia (70%), followed by reperfusion, and were then killed at designated time points. Serum and liver tissues were harvested for further analyses. RESULTS: Serum ALT levels, mortality rates, and the percentage of necrotic area in liver sections were significantly higher in the MDP group than in the control group. PDPN was expressed in the lymphatic epithelium, interlobular bile duct epithelium, and in some hepatocytes in each group. Its expression in hepatocytes was down-regulated in the MDP group. The accumulation of platelets in the sinusoid was reduced 6 h after I/R in the MDP group. Tissue HGF and IGF-1 levels decreased in the MDP group. CONCLUSIONS: These results suggest that KCs play a key role in the activation of platelets through direct contact with PDPN-positive hepatocytes in I/R livers.

Prognostic impact of lymph node micrometastasis in patients with gastric cancer.

PURPOSE: The clinical significance of lymph node micrometastasis (LNMM) remains controversial in gastric cancer (GC). In this study, we investigated the prognostic impact of LNMM in patients with GC. METHODS: A total of 624 patients with pathologically lymph node metastasis-negative (pN0) and N1 status (pN1) who underwent gastrectomy between 2004 and 2018 were enrolled in this retrospective study. The diameter of tumor cell clusters in metastatic lymph nodes was measured in 120 patients with pN1 GC. RESULTS: Patients with lymph node tumors < 1500 µm in diameter (LNMM) had a significantly better prognosis than those with tumors ≥ 1500 µm in diameter (p = 0.012; log-rank test). Cox's proportional hazards model revealed that LNMM (p = 0.016), several dissected lymph nodes (p = 0.049), and the provision of adjuvant chemotherapy (p = 0.002) were independent prognostic factors for the overall survival of patients with pN1 GC. There was no significant difference in the overall survival between patients with LNMM who received chemotherapy and those who did not (p = 0.332). CONCLUSIONS: LNMM is associated with a favorable prognosis and maybe an independent prognostic marker in patients with pN1 GC. LNMM in GC may be considered a factor preventing adjuvant chemotherapy.

Is surgery the best treatment for elderly gastric cancer patients?

As the elderly population increases, the number of patients with gastric cancer has also been increasing. Elderly people have various preoperative problems such as malnutrition, high frequency of comorbidities, decreased performance status, and dementia. Furthermore, when surgery is performed, high postoperative complication rates and death from other diseases are also concerns. The goal of surgery in the elderly is that short-term outcomes are comparable to those in nonelderly, and long-term outcomes reach life expectancy. Perioperative problems in the elderly include: (1) Poor perioperative nutritional status; (2) Postoperative pneumonia; and (3) Psychological problems (dementia and postoperative delirium). Malnutrition in the elderly has been reported to be associated with increased postoperative complications and dementia, pointing out the importance of nutritional management. In addition, multidisciplinary team efforts, including perioperative respiratory rehabilitation, preoperative oral care, and early postoperative mobilization programs, are effective in preventing postoperative pneumonia. Furthermore, there are many reports on the usefulness of laparoscopic surgery for the elderly, and we considered that minimally invasive surgery would be the optimal treatment after assessing preoperative risk.