Among recent advances in cancer treatment, the emergence of novel drugs targeting specific molecules has considerably modulated therapeutic strategies. Despite the efficacy of these agents, renal complications that are distinct from those of conventional chemotherapeutic drugs have been reported. Targeted therapy drugs include monoclonal antibodies and small-molecule agents. Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF) and blocks tumor angiogenesis. This anti-angiogenic effect causes endothelial injury, resulting in "thrombotic microangiopathy-like lesions" confined to the glomerulus. Segmental hyalinosis of the glomerular tuft is also observed. Small molecular agents, including tyrosine kinase inhibitors (TKIs) such as pazopanib, can cause endothelial injury and podocytopathy by blocking VEGF receptors and their downstream signaling. Minimal change nephrotic syndrome and focal segmental glomerulosclerosis are associated with TKI-induced renal complications. Immune checkpoint inhibitors (ICIs) such as PD-1, CTLA-4, and PD-L1 modulate immune checkpoints and are a novel form of immunotherapy against cancer. Owing to their unique function, ICIs cause inflammatory side effects referred to as immune-related adverse events (irAEs). irAEs in the kidney include acute tubulointerstitial nephritis and tubulitis, occasionally accompanied by granuloma formation. Vasculitis, thrombotic microangiopathy, and glomerulonephritis have also been reported. Renal toxicity associated with other molecular drugs, such as protease inhibitors and mammalian target of rapamycin inhibitors, has also been documented. In this article, we review the clinicohistopathological aspects of renal complications associated with molecular targeted therapies and focus on anti-VEGF agents and immune checkpoint inhibitors from a pathological perspective.

Kampo Medicine is a traditional Japanese medicine and is well integrated with modern medicine. Anticancer agents are highly developed, and evidence regarding standard treatment has accumulated. Kampo Medicine helps support patients with cancer who lack vital energy and feel cold. Cancer chemotherapy is associated with adverse reactions that are refractory to modern therapy, such as anorexia, general malaise/fatigue, and peripheral neuropathy. Recently, evidence of the effectiveness of Kampo Medicines for these symptoms has been reported in randomized controlled trials (RCTs). The Japan Society for Oriental Medicine celebrated the first 20 years of its evidence-based medicine (EBM) committee in June 2021. The activities of this committee include publication of the Evidence Reports of Kampo Treatment, which contains RCTs and meta-analyses, including RCTs on cancer supportive care. Evidence is accumulating for hangeshashinto for mucositis, rikkunshito for anorexia, goshajinkigan and ninjin'yoeito for peripheral neuropathy, hochuekkito for general malaise/fatigue, and shakuyakukanzoto for myalgia/arthralgia. However, additional evidence and further clinical trials are needed. Supportive care with Kampo Medicine increases the likelihood of completing standard treatment for cancer.

With recent advances in systemic therapy, an increasing number of patients with advanced hepatocellular carcinoma (HCC) are expected to benefit from surgery. However, given the complex background of the disease and frequent presence of underlying liver injury, treatment of advanced HCC is complex and the treatment principle applied to colorectal liver metastases, for which conversion surgery has been actively performed, is often not applicable to patients with HCC. To maximize the survival outcomes of patients with HCC, optimization of each step of treatment through a multidisciplinary approach is inevitable. As initial treatment, systematic removal of tumor-bearing portal territory is associated with improved survival in patients with solitary HCC, and radiofrequency ablation is also effective for small, oligo HCCs. Although the high incidence of recurrence even after curative-intent treatment is a major concern in HCC, aggressive treatment for recurrence is important, because a prolonged cancer-free interval is associated with improved overall survival. For patients with advanced disease, recently introduced molecular-targeted agents may be effective for successful conversion to surgery in initially unresectable cases, although the overall response rate of HCC to systemic therapies remains unsatisfactory as compared to that of colorectal liver metastases. This report revisits the theoretical bases for management of HCC and discusses current strategies for maximizing survival of patients with advanced HCC.

Liver cancer, including hepatocellular carcinoma (HCC), is the fifth most common cause of cancer deaths in Japan. The main treatment options for HCC are surgical resection, liver transplantation, radiofrequency ablation (RFA), transarterial chemoembolization (TACE), and systemic chemotherapy. Here, recent medical treatments for HCC, including surgery, percutaneous ablation, transcatheter arterial chemoembolization/transcatheter arterial embolization, and drug therapy, are reviewed with a focus on Japan.

Background: The coronavirus disease (COVID-19) poses an urgent threat to global public health and is characterized by rapid disease progression even in mild cases. In this study, we investigated whether machine learning can be used to predict which patients will have a deteriorated condition and require oxygenation in asymptomatic or mild cases of COVID-19. Methods: This single-center, retrospective, observational study included COVID-19 patients admitted to the hospital from February 1, 2020, to May 31, 2020, and who were either asymptomatic or presented with mild symptoms and did not require oxygen support on admission. Data on patient characteristics and vital signs were collected upon admission. We used seven machine learning algorithms, assessed their capability to predict exacerbation, and analyzed important influencing features using the best algorithm. Results: In total, 210 patients were included in the study. Among them, 43 (19%) required oxygen therapy. Of all the models, the logistic regression model had the highest accuracy and precision. Logistic regression analysis showed that the model had an accuracy of 0.900, precision of 0.893, and recall of 0.605. The most important parameter for predictive capability was SpO₂, followed by age, respiratory rate, and systolic blood pressure. Conclusion: In this study, we developed a machine learning model that can be used as a triage tool by clinicians to detect high-risk patients and disease progression earlier. Prospective validation studies are needed to verify the application of the tool in clinical practice.

Background: The da Vinci Si version robot lacks a vascular stapler that can be controlled by the operating surgeon at the surgical console when dividing pulmonary vessels. Therefore, to initiate and safely perform robotic anatomical lobectomy for lung cancer, it is important to develop a safe method for introducing a surgical stapler. Methods: We performed a retrospective study of the first 42 consecutive patients who underwent robotic lobectomy for lung cancer at Nippon Medical School Hospital between January 2019 and December 2020. Results: Up to case 18, we performed robot-assisted thoracoscopic surgery (RATS) lobectomy by using a four-arm approach with two assistant ports. For dividing pulmonary vessels, the surgical stapler was introduced through the assist ports. However, since this is not the port position usually used in video-assisted thoracoscopic surgery (VATS), there were many difficult situations. For RATS lobectomy case 19 and all subsequent cases, we utilized a total port approach that uses three robotic arms and two assistant ports. To resect the pulmonary vessels or bronchi with endoscopic staplers, the port for the robotic arm was removed and the endoscopic staplers were placed through a 12-mm Xcel bladeless port. This change reduced operation time, blood loss, and robotic arm interference. No patient developed intraoperative complications during RATS lobectomy. Conclusion: The present total port approach, with three robotic arms, appears to be feasible for introducing surgical staplers during RATS with the da Vinci Si robotic system.

Background: We aimed to classify metastatic pyloric/antral gastric cancer in terms of macroscopic morphology and metastatic form. Methods: Thirty-eight patients with pyloric/antral gastric cancer were included in the study. Patients were classified according to a combination of Borrmann classification type and metastatic type, and the clinicopathological characteristics of each group were compared. Result: Of the 38 patients, 33 (type II: 9 and type III: 24) (87%) had ulcerative gastric cancer. Ulcerative gastric cancer was classified into four groups: lymphatic only group (L+H−P−), lymphatic + hematogenous group (L+H+P−), disseminated ± lymphatic group (L±H−P+), and lymphatic + hematogenous + disseminated group (L+H+P+). In the L+H−P− group, all patients had bulky lymph nodes and serum levels of both carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were high; the condition of patients was good, and the therapeutic response was good. In the L+H+P− group, metastases other than liver metastases were rare, and serum CEA levels were high. In the L±H−P+ group, the predominant histological type was signet ring cell carcinoma; both serum CEA and CA19-9 levels were low. Patients in the L+H+P+ group had higher serum CA19-9 levels and were more prone to hematogenous metastasis to various organs; these patients had worse patient status and lower treatment response. Gastric cancer other than ulcerative type was only detected in five patients (type V: 3, type IV: 1, type I: 1). Conclusion: Classification by a combination of macroscopic and metastatic form in pyloric/antral metastatic gastric cancer might be useful for diagnosis and treatment.

Background: We previously reported that pre-irradiation with infrared radiation A (IRA) eliminated ultraviolet B (UVB) -induced cyclobutane pyrimidine dimers (CPDs). Accelerated elimination of CPDs could have resulted from enhanced DNA repair and/or enhanced induction of apoptosis. Using Xpa knockout (KO) mice, which are deficient in DNA repair, we examined whether IRA accelerated elimination of CPDs by enhancing DNA repair. Methods: We have already generated mice harboring epidermal melanocytes that produce only eumelanin and dominant pheomelanin, and no melanin. To obtain such mice with impaired DNA repair ability, we backcrossed them with Xpa KO mice. Three hours before UVB irradiation, the mice were irradiated with IRA, and CPDs and apoptotic cells were examined. Results: Pre-irradiation of Xpa KO mice with IRA before UVB irradiation accelerated removal of CPDs and enhanced apoptotic changes. Conclusion: These results indicate that enhancement of UVB-induced apoptosis and acceleration of removal of CPDs by pre-irradiation with IRA does not depend on DNA damage repair.

Background: Determining when caregivers should take their children to a hospital is crucial in ensuring the health and safety of children. Because children cannot make these decisions on their own, caregivers bear the core responsibility for the wellness of their children. The aim of this study was to determine how disease, disability, and child behavior affect when and how often caregivers take their children to a hospital. Methods: A structured anonymous online survey was circulated to pediatricians in Japan. Pediatricians were queried about the characteristics of their patients, including reactivity to pain, expression of pain, behavior at the hospital, and the timing of presentation. Patients were school-aged children and included those with autism spectrum disorder, attention-deficit hyperactivity disorder, Down syndrome, mental retardation, epilepsy, premature birth, and allergies. Results: Sixty-eight of 80 pediatricians responded to the survey (85% response rate). The results indicated that caregivers of children with autism spectrum disorder, attention-deficit hyperactivity disorder, and mental retardation took them to the hospital later than was optimal. Conversely, children born prematurely and those with allergies were taken to hospitals even when symptoms were mild. Conclusions: Caregivers make decisions on when to present to hospital on the basis of their child's expression of pain and behavior. Guidelines should be developed to assist caregivers in determining when to present for treatment at a hospital.

Background: The number of people diagnosed with dementia worldwide is set to increase significantly. Patients with dementia often have comorbidities, particularly diabetes, and patients with type 2 diabetes mellitus (T2DM) have a high risk of cognitive decline. This study investigated whether older people with T2DM have disease-specific cognitive deficits. Methods: The Montreal Cognitive Assessment is a well-known tool for examining mild cognitive impairment, and the modified Japanese version (MoCA-J) has been confirmed as effective. Using the MoCA-J, we assessed the cognitive function of Japanese adults aged ≥75 years with and without T2DM and analyzed the results. Results: Thirty-three patients with T2DM and 23 non-DM patients completed the examination, and MoCA-J total scores differed between these groups (T2DM mean, 21.4 ± 3.5; non-DM mean, 23.5 ± 3.6). Only 9% of patients with T2DM and 39% of those with non-DM had scores ≥26, which is the cutoff point for mild cognitive impairment, although all patients were capable of self-care. Additionally, delayed recall scores were significantly lower for the older patients with T2DM had for the non-DM group. Conclusions: Patients aged ≥75 years with T2DM might have worse cognition than those without T2DM; the inability to perform delayed recall in T2DM patients suggests a decline in cognitive function. Therefore, patients aged ≥75 years with T2DM should receive explanations of their care that are individualized in relation to their cognitive status.

Background: Although some studies have described the association between serum ferritin levels and specific disorders in child and adolescent psychiatry, few have focused on mental status per se with low serum ferritin levels in children and adolescents. This study examined the effects of iron administration on psychological status of children and adolescents with reduced serum ferritin concentration. Methods: This prospective study evaluated 19 participants aged 6-15 years with serum ferritin levels <30 ng/mL who visited a mental health clinic and received oral iron administration for 12 weeks. The participants were assessed using the Clinical Global Impression Severity (CGI-S), Profile of Mood States 2nd Edition Youth-Short (POMS), Center for Epidemiologic Studies Depression Scale (CES-D), and Pittsburgh Sleep Quality Index (PSQI). In addition to serum ferritin, blood biochemical values such as hemoglobin (Hb) and mean corpuscular volume (MCV) were examined. School attendance was recorded. Results: The most prevalent physical symptoms were fatigability and insomnia. The CGI-S, PSQI, and CES-D scores decreased significantly following iron supplementation, whereas the scores of almost all POMS subscales improved significantly at week 12. No participant had hemoglobin levels <12 g/dL. Serum ferritin concentration increased significantly, whereas Hb and MCV remained unchanged. At baseline, 74% of the participants did not attend school regularly; this number improved to varying degrees by week 12. Conclusions: Serum ferritin levels would be preferable to be measured in children and adolescents with insomnia and/or fatigability regardless of psychiatric diagnoses or gender. Iron supplementation can improve the hypoferritinemia-related psychological symptoms of children and adolescents, such as poor concentration, anxiety, depression, low energy and/or irritability.

Background: The increasing age of patients with severe motor and intellectual disabilities (SMID) has become a serious concern. Few studies have investigated tumor treatment in this population. Methods: Tumor treatments for 12 SMID patients were examined. Results: Blood tests and ultrasonography were useful for screening. With regard to treatment, surgery for SMID patients was performed in the same manner as for patients without SMID, and the results were generally satisfactory, without major complications. Typically, cancer was diagnosed at an advanced stage, and many metachronous double cancers were observed. Conclusions: Treatment yielded satisfactory results for patients with SMID and their families. Future studies should examine the clinical significance of screening and tumor operative method for patients with SMID.

Background: A recent increase in the number of surgeries performed on obese patents has raised several issues. In this study, we examined the effects of obesity on laparoscopic and open distal gastrectomy. Methods: A total of 262 patients with gastric cancer (cStage I) who underwent distal gastrectomy were classified into open distal gastrectomy (ODG) (145 patients) and laparoscopic distal gastrectomy (LDG) (117 patients) groups. According to their body mass index (BMI), they were subdivided into obese (BMI ≥ 25) and non-obese patients (BMI < 25) to examine the duration of surgery, blood loss, the number of lymph node dissections, postoperative hospital stay, and incidence of postoperative complications. Results: The duration of surgery was longer and blood loss was higher for obese patients than for non-obese patients in both groups. The results for these two endpoints were significantly reduced in the LDG group than in the ODG group both in obese and non-obese patients. Furthermore, the number of lymph nodes dissected tended to be higher in the LDG group than in the ODG group in obese patients. Postoperative hospital stay was not significantly different between obese and non-obese patients in both groups, but was significantly shorter in the LDG group than in the ODG group regardless of the body weight. The incidence of postoperative complications was significantly higher in obese patients than in non-obese patients, although the difference between the groups was not significant. Conclusions: These findings indicate that LDG may be useful for obese patients with cStage I gastric cancer.

Background: Because of its low recurrence rate and safety, laparoscopic sacrocolpopexy (LSC) is an increasingly popular treatment for pelvic organ prolapse (POP). Although LSC may improve voiding function, it can also lead to de novo stress urinary incontinence. The exact effects of LSC on voiding function, and the mechanisms responsible, remain unclear. Therefore, in this study we prospectively evaluated the impact of LSC on voiding function by performing a pre- and postoperative urodynamic study of patients with stage 3 or worse POP. Methods: Urinary status was evaluated before and 3 months after LSC. Pre- and postoperative evaluations included medical history, clinical examination, urodynamic studies, chain cystography, and residual urine volume measurement. Urinary symptoms were assessed using the International Prostate Symptom Score (IPSS) and the Overactive Bladder Symptom Score (OABSS). Results: The nonrecurrence rate at 3 months was 82.3%. All recurrences involved bladder prolapse. In addition to the absence of a significant change in OABSS, the improvement in IPSS suggests that subjective voiding symptoms improved. Although the maximum urinary flow rate did not significantly change, bladder volume at first sensation increased, urinary storage function improved, and residual urine volume decreased. There were no perioperative complications, and no patient reported postoperative difficulty in urination or urinary retention. The retrovesical angle significantly decreased. Conclusions: The modified LSC in women with POP provides good functional outcomes in terms of IPSS, post-void residual volume (PVR), and urinary storage function.

Background: In the intensive care unit (ICU), multiple intravenous drugs are often administered through the same catheter line, greatly increasing the risk of drug incompatibility. We previously developed a compatibility chart including 27 drugs and have used it to avoid drug incompatibilities in the ICU. This retrospective study evaluated the utility of this chart by analyzing prescriptions and incidents of incompatibilities in an ICU. Methods: We analyzed 257 ICU prescriptions of two or more continuous infusions on the same day during the period between March 2016 and February 2017 and investigated the rate of compliance with the compatibility chart. Drug combinations were classified as "compatible," "tolerable compatible," "incompatible," and "no data." For all combinations, the compliance rate was defined as the ratio of compatible and tolerable compatible combinations. Additionally, using our hospital incident report database, we analyzed 27,117 injections administered in the ICU between March 2016 and February 2017 and investigated incidents related to incompatibility. Results: Three hundred infusion combinations were identified in the prescriptions. The compliance rate was 97% (n = 293). Of the 113 combinations judged to be tolerable compatible, 98% (n = 111) consisted of three or more continuous medications injected through the same intravenous line. Of the two incidents related to incompatibility in the incident report database, the combination "nicardipine and furosemide" was defined as incompatible in the compatibility chart. Conclusions: The high rate of compliance with the compatibility chart suggested it was useful in preventing drug incompatibility.

Clear-cell sarcoma of the kidney (CCSK) is a rare, aggressive pediatric renal tumor. Intratumoral hemorrhage and tumor rupture are oncologic emergencies requiring a rapid and appropriate response. An 11-year-old boy visited our hospital with abdominal distension of 1 month's duration. Computed tomography (CT) revealed a tumor in the left kidney (size: 200 mm), and analysis of a biopsy specimen confirmed a diagnosis of CCSK. Chemotherapy was initiated to shrink the large, densely vascularized tumor before surgical removal. Two days after starting chemotherapy, the patient developed abdominal and back pain, anemia, and hypotension. CT scanning showed intratumoral bleeding. Emergency transcatheter arterial embolization (TAE) was performed to control the bleeding. Three tumor feeding vessels were identified: an ascending branch from the celiac artery, an intermediate branch from the left renal artery, and a descending branch from the inferior mesenteric artery, of which the intermediate and descending branches were large and bleeding profusely. Therefore, the intermediate branch was injected with ethanol, and the descending branch was treated by gel-foam embolization. Chemotherapy was resumed, and the patient's condition gradually stabilized. The tumor began to shrink, and subsequent chemotherapy progressed well. In week 12 of chemotherapy, the patient underwent tumor resection and left nephrectomy. Postoperative chemotherapy was completed without complications, and there was no recurrence during a 6-year follow-up period. Therefore, TAE can effectively control intratumoral bleeding in pediatric solid tumors, thus preventing high-risk open surgery.

Hydrocephalus induced by low cerebrospinal fluid (CSF) pressure is extremely rare and sporadically reported. Subarachnoid hemorrhage, head trauma, and spinal drainage were reported to be causative factors for surgical treatment. A 33-year-old man with subarachnoid hemorrhage caused by right vertebral artery aneurysm rupture developed headache. Trapping surgery was performed, and a spinal drain was inserted from L4/5 for subarachnoid hemorrhage washout. On postoperative day 3, subdural fluid accumulation had increased at the posterior fossa craniotomy site and the cerebellar sulci had narrowed; the ventricles were slightly enlarged. The patient reported headache during head elevation. Low-pressure hydrocephalus (LPH) was suspected. After the spinal drain was removed, headache resolved, and cerebral ventriculomegaly disappeared. The subsequent clinical course was good. The patient was discharged 3 weeks after surgery. LPH is a rare disease caused by various factors and is treated by correcting liquorrhea or overdrainage, when present. Otherwise, drainage at negative CSF pressure is necessary. The symptoms and image findings for LPH are similar to those for intracranial hypertension and normal-pressure hydrocephalus. This report describes a suspected case of LPH caused by spinal drainage after subarachnoid hemorrhage and reviews the literature.