Development and evaluation of an original phantom model of ultrasonography-guided thyroid gland biopsy for the training of surgical residents and students.

PURPOSES: Fine-needle aspiration cytology (FNAC) is a specific and important test used for the diagnosis of thyroid gland cancer. We developed a thyroid gland phantom using original manufacturing techniques and direct three-dimensional (3D) printing. The aim of this study was to confirm the effectiveness of this phantom by collecting data to evaluate puncture training. METHODS: Data from 45 ultrasonography-guided thyroid nodule FNAC procedures performed on our thyroid phantom were evaluated in our department. The first group comprised qualified physicians who specialized in thyroid gland treatment (group A; n = 10). The second and third groups comprised senior and junior residents (group B; n = 8 and group C; n = 12; respectively). The fourth group comprised students (group D; n = 15). We measured the times taken by these groups to complete each task. RESULTS: The skills of all participants in groups B, C, and D improved after using this phantom involving the major (parallel)- (0.47 ± 0.07) and short (orthogonal)-axes (0.52 ± 0.07) methods (P < 0.001). The number of erroneous punctures decreased from 53 to 3. CONCLUSIONS: Our original phantom improved the puncture skills of students and junior doctors and was suitable as a tailored training model for practicing thyroid gland transfixion.

Prognosis of asymptomatic versus symptomatic metastatic breast cancer: a multicenter retrospective study.

In Japan, asymptomatic metastatic breast cancer (MBC) is often detected using tumor markers or imaging tests. We aimed to investigate differences in clinicopathological features, prognosis, and treatment between asymptomatic and symptomatic MBCs. Patients with MBC were retrospectively divided into asymptomatic and symptomatic groups to compare their prognosis by breast cancer subtype: luminal, human epidermal growth factor receptor 2 positive, and triple negative. Of 204 patients with MBC (114 asymptomatic, 90 symptomatic), the symptomatic group had a higher frequency of multiple metastatic sites and TN subtype. All cohorts in the asymptomatic group tended to or had longer post-recurrence survival (PRS) than those in the symptomatic group. In contrast, all cohorts and TN patients in the asymptomatic group tended to have or had longer overall survival (OS) than those in the symptomatic group, although no significant difference was observed in the luminal and HER2 subtypes. In the multivariate analysis, TN, recurrence-free survival, multiple metastatic sites, and symptomatic MBC were independently predictive of PRS. Regarding the luminal subtype, the asymptomatic group had longer chemotherapy duration than the symptomatic group, with no significant difference in OS between the groups. Asymptomatic and symptomatic MBCs differ in terms of subtypes and prognosis, and whether they require different treatment strategies for each subtype warrants further investigation.

Short- and long-term survival after curative resection for colorectal cancer in nonagenarian patients.

BACKGROUND/OBJECTIVE: With increased life expectancy, the incidence of colorectal cancer in oldest-old patients has been rising. Advanced age is a risk factor for adverse outcomes after surgery. This study aimed to evaluate the short- and long-term outcomes of curative resection for colorectal cancer in nonagenarians. METHODS: Patients who had undergone curative resection for colorectal cancer (CRC) at Stage I to III from January 2010 to December 2019 were included. Cases of emergent surgery were excluded. The clinical characteristics were documented retrospectively, and factors affecting the long-term outcome were analyzed using multivariate analysis. RESULTS: Fifty patients met the selection criteria. Most of them were women (58.0%), and the median age was 92 years. Among these patients, 29 (58.0%) had a poor performance status (ASA-PS≥3). Laparoscopic surgery was performed in 42.0% of the patients, and 50% of the patients had postoperative complications classified as Clavien-Dindo grade 2 or severer, including 3 patients (6.0%) with grade 3 disease. No postoperative mortality occurred. The 30-day, 180-day, 1-year, 3-year and 5-year survival rates were 100%, 80.4%, 71.0%, 46.3%, and 33.8%, respectively. Multivariate analysis showed that a preoperative poor performance status (ASA-PS≥3) (HR: 3.067; 95% CI: 1.220-7.709; p = 0.017) was an independent prognostic factor for OS. CONCLUSION: Curative elective resections for CRC in nonagenarians were performed safely without postoperative mortality. The preoperative performance status was significantly associated with OS after curative elective resection of colorectal cancer in nonagenarians. Our results suggest that excellent long-term outcomes can be achieved in a selected group with a good performance status.

Safe laparoscopic resection of a giant schwannoma in the retroperitoneum using a fluorescent ureteral stent: a case report.

Schwannomas that occur in the retroperitoneal cavity are rare. We herein report a patient who underwent safe laparoscopic resection by using a preoperative 3D computed tomography (CT) image and a fluorescent ureteral stent during the surgery. A 47-year-old man presented with left lower abdominal pain. CT showed a 10-cm continuous retroperitoneal tumor originating at the third lumbar nerve in the lower left abdomen. Schwannoma was suspected. We underwent laparoscopic resection of the tumor guided by 3D images obtained preoperatively. A fluorescent ureteral stent was implanted during the surgery to improve visibility and protect the left ureter. The resection was completed without injury of other organs and vessels. The patient was discharged on postoperative Day 5. By performing a preoperative simulation using 3D CT images, we could anticipate the anatomical findings and easily identify them intraoperatively. In addition, the fluorescent ureteral stent provided visual support, thereby contributing to safe surgery.

Long-Term Prognosis after Surgery for Locally Recurrent Rectal Cancer: A Retrospective Study.

OBJECTIVE: Resection is usually recommended for locally recurrent rectal cancer (LRRC) for which R0 resection is possible, but its suitability varies by individual patient risk. Here, we report outcomes of resected LRRC in our hospital. METHODS: We retrospectively evaluated short- and long-term results of 33 patients who underwent resections for LRRC from January 2003 to December 2019. RESULTS: At the initial surgeries for these 33 patients, their disease stages at that time were Stage I: n=2, Stage II: n=12, Stage III: n=11, Stage IV: n=6, and unknown: n=2. Patients with Stage IV disease at their initial surgeries underwent radical one-step or two-step procedures. Metastasis to other organs was observed in 5 patients at the their initial LRRC diagnoses. At the LRRC surgeries, 7 patients received palliative surgeries; 26 received intent-to-treat resections, of which 17 were R0 resections. All-grade postoperative complications were observed in 11 patients, including 1 surgery-related death. Five-year overall survival rates were all cases: 38.4%; R0 group: 52.3%, R1 or R2 group: 19.4%, and palliative surgery group: 0%. The R0 group thus had significantly better prognosis than other patients (P = 0.0012). Eleven patients in the R0 group (64.7%) suffered re-recurrences but some patients achieved long-term survival through chemotherapy, radiation therapy, and surgery for metastasis to other organs, even after re-recurrence. CONCLUSION: Long-term prognosis after surgery for LRRC was significantly better for patients with R0 margins. Multimodal treatments may greatly improve survival for patients who suffer re-recurrences after local recurrence resections.

Postoperative Complications Predict Long-term Outcome After Curative Resection for Perforated Colorectal Cancer.

BACKGROUND/AIM: Perforation and postoperative complications have a negative effect on long-term outcomes in patients with colorectal cancer (CRC). The aim of this study was to evaluate the clinical factors with special reference to postoperative complications predicting the long-term outcome in those for whom curative resection for perforated CRC was performed. PATIENTS AND METHODS: Patients who underwent curative resection for perforated CRC at stage II or III from April 2003 to March 2020 were included. Clinical factors were retrospectively analyzed. RESULTS: Forty-four patients met the selection criteria. The 30-day mortality rate was 4.5% and the complication rate was 47.7%. Excluding 30-day mortality, five-year recurrence-free survival (RFS) and overall survival (OS) were 62.3% and 73.6%, respectively. Multivariate analysis showed that postoperative complications (p=0.005) and pT4 pathological factor (p=0.009) were independent prognostic factors for RFS. Only postoperative complications (p=0.023) were an independent prognostic factor for OS. CONCLUSION: Postoperative complications were significantly associated with RFS and OS, and pT4 was associated with RFS. The prevention and management of postoperative adverse events may be important for perforated CRC.

Acute perforating appendicitis caused by metastatic squamous cell carcinoma from the lung: A case report.

INTRODUCTION: Lung cancer is one of the most common cancers. On the other hand, lung cancer metastasis to the appendix is extremely rare, and in many cases it has been diagnosed with the onset of acute perforating appendicitis. PRESENTATION OF CASE: An 85-year-old man with fever and abdominal pain visited our hospital. He had a history of squamous cell carcinoma of the left upper and lower lobes, metastasis to the ipsilateral lung and femur. CT showed that a finding of acute perforating appendicitis, emergency cecal resection was performed. Examination of the resected specimen showed that the appendix was thickened overall, with a white nodular structure at the root and a perforation in the middle. The final diagnosis was acute perforating appendicitis caused by metastatic squamous cell carcinoma from the lung. The patient had no particular problems during the postoperative course. DISCUSSION: A PubMed search was performed, this appears to be the first reported case of appendiceal metastasis of squamous cell carcinoma of the lung. Since squamous cell carcinoma of the lung has a stronger tendency for local extension than other histological types, perforating appendicitis due to distant metastasis to the abdominal organs and metastasis to the appendix was reported as a very valuable case. CONCLUSION: Because the progression of concomitant or secondary appendicitis is rapid, we recommend frequent imaging modalities, prophylactic appendectomy be considered for patients who also have lung cancer and imaging findings show suspected metastasis to the appendix.

[A case of polyradiculoneuritis associated with disseminated herpes zoster].

A 34-year-old man developed right-dominant lower limb paraplegia, and then upper limb paresis with radicular pain following disseminated herpes zoster (HZ) in his right forehead, back of the trunk, and lumbar and right lower limb regions. Cerebrospinal fluid (CSF) findings revealed an increase in lymphocytes (32 cells/µl) and protein content (50 mg/dl), and polymerase chain reaction (PCR) for varicella-zoster virus (VZV) DNA was negative in CSF, but VZV antigen was positive in the patient's vesicle smear. Lumbar root MRI using 3D Nerve VIEW (Philips) imaging showed high-intensity lesions on the L2-L5 spinal roots with contrast enhancements, and cervical MRI showed similar findings on both sides at the C4-Th1. Peripheral nerve conduction study revealed prolonged distal latency to 4.9 ms, decreased MCV to 38 m/s, and complete loss of F-wave was seen in the right peroneal nerve study. Minimal F-wave latency was prolonged in the right tibial nerve. Thus, the patient was diagnosed with VZV polyradiculoneuritis caused by disseminated HZ. Regarding the possible pathogenesis of polyradiculoneuritis in this patient with disseminated HZ, we speculate that VZV reached by retrograde transmission from the involved peripheral nerves to the spinal ganglia, which, then, produced polyradiculoneuritis.

Pathogenic POGZ mutation causes impaired cortical development and reversible autism-like phenotypes.

Pogo transposable element derived with ZNF domain (POGZ) has been identified as one of the most recurrently de novo mutated genes in patients with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), intellectual disability and White-Sutton syndrome; however, the neurobiological basis behind these disorders remains unknown. Here, we show that POGZ regulates neuronal development and that ASD-related de novo mutations impair neuronal development in the developing mouse brain and induced pluripotent cell lines from an ASD patient. We also develop the first mouse model heterozygous for a de novo POGZ mutation identified in a patient with ASD, and we identify ASD-like abnormalities in the mice. Importantly, social deficits can be treated by compensatory inhibition of elevated cell excitability in the mice. Our results provide insight into how de novo mutations on high-confidence ASD genes lead to impaired mature cortical network function, which underlies the cellular pathogenesis of NDDs, including ASD.

Subacute Sensory Ataxic Neuronopathy With Thymoma Presenting Marked Improvement After Steroid Therapy.

Subacute sensory ataxic neuronopathy is a well-known form of paraneoplastic syndrome. Most sensory neuronopathies are associated with small cell lung cancer and anti-Hu antibodies, and usually show only slight improvement with immunotherapy. To date, there have been few reports of neuropathy associated with thymoma and no treatment strategy has been established for thymoma-related neuropathy. Here, we provide the first report of a case of sensory ataxic neuronopathy with thymoma that showed marked improvement after steroid therapy, even though preceding intravenous immunoglobulin treatments and tumor resection were less effective. A 57-year-old Japanese man was referred to our hospital with a 6-week history of distal paresthesia in his four limbs and an unsteady gait. He presented with left-dominant ataxia in his four limbs due to reduced sensation in his extremities. He also complained of constipation, difficulty urinating, and erectile dysfunction. Upon investigation, including electrodiagnostic studies, the patient was diagnosed as having sensory ataxic neuronopathy with invasive thymoma. A first round of intravenous immunoglobulin therapy, a following thymectomy, and a second round of intravenous immunoglobulin therapy after the surgery were not effective in treating his neurological symptoms. Subsequently, oral steroid therapy was started, which brought about a remarkable improvement; 6 weeks after the beginning of the steroid therapy, his neurological symptoms were resolved, except for slight distal paresthesia in his feet. Although rarely reported, thymoma can underlie sensory neuronopathy, and the response of thymoma-associated sensory neuronopathy to immunotherapy might be better than that of anti-Hu antibody-related neuropathies. Even if the first immunotherapy is not effective in treating neuropathy with thymoma, further immunomodulatory treatment should be tried after treating the tumor.

Validation of a Novel Diagnostic Kit Using the Semidry Dot-Blot Method to Detect Metastatic Lymph Nodes in Breast Cancer: Distinguishing Macrometastases From Nonmacrometastases.

BACKGROUND: The semidry dot-blot method is a diagnostic procedure for detecting lymph node (LN) metastases using the presence of cytokeratin (CK) in lavage fluid from sectioned LNs. We evaluated 2 novel kits that use newly developed anti-CK-19 antibodies to diagnose LN metastases in breast cancer. PATIENTS AND METHODS: We examined 159 LNs dissected that we sliced at 2-mm intervals and washed with phosphate-buffered saline. The suspended cells in the lavage were centrifuged and lysed to extract protein. This extracted protein was used with a low-power and a high-power kit to diagnose LN metastasis. Diagnoses on the basis of the kits were compared with pathological diagnoses. RESULTS: Of the 159 LNs, 68 were assessed as positive and 91 as negative in permanent section examination. Sensitivity, specificity, and accuracy of the low-power kit for detecting LN metastases was 83.8%, 100%, and 93.1%, respectively. Those of the high-power kit were 92.6%, 92.3%, and 92.5%, respectively. Combining the low- and high-power kit results, those for distinguishing macrometastases were 94.5%, 95.2%, and 95.0%, respectively. Diagnosis was achieved in approximately 20 minutes, at a cost of less than $30 USD. CONCLUSION: The kits were accurate, fast, and cost-effective in diagnosing LN metastases without the loss of LN tissue.

Development of a Tailored Thyroid Gland Phantom for Fine-Needle Aspiration Cytology by Three-Dimensional Printing.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is a challenging and risky procedure for inexperienced clinicians to perform because of the proximity of the thyroid to the jugular veins, carotid arteries, and trachea. A phantom model for transfixion practice would help train clinicians in FNAC. OBJECTIVE: To fabricate a tailored phantom with consideration for authenticity of size, touch, feel, and ultrasonographic (US) characteristics. METHODS: A three-dimensional (3D) digital model of the human neck was reconstructed from computed tomography data of a subject. This model was used to create 3D-printed templates for various organs that require US visualization. The templates were injected with polymers that provided similar degrees of ultrasound permeability as the corresponding organs. For fabrication of each organ, the respective molds of organs, blood vessels, thyroid gland, and tumor were injected with the material. The fabricated components were then removed from the templates and colored. Individual components were then positioned in the neck mold, and agar gel was poured in. The complete phantom was then removed from the mold. Thereafter, 45 medical doctors and students performed ultrasound-guided FNAC using the phantom, following which they were queried regarding the value of the phantom. RESULTS: The structure, US characteristics, and elasticity of the phantom were similar to those of the human subject. In the survey, all 45 participants replied that they found the phantom useful for FNAC training, and 30 medical students professed increased interest in thyroid diseases after using the phantom. CONCLUSIONS: We successfully fabricated a tailored thyroid gland phantom for transfixion practice. As most of the phantom parts are injected in molds fabricated using a 3D printer, they can be easily reproduced once the molds are fabricated. This phantom is expected to serve as an effective and fully tailored training model for practicing thyroid gland transfixion.

Salvage surgery for local recurrence after carbon ion radiotherapy for patients with lung cancer.

OBJECTIVES: Carbon ion radiotherapy (CIRT) has been expected to be an alternative for surgery for early-stage non-small-cell lung cancer (NSCLC) and adopted as the second-best choice even in operable patients although local recurrence after CIRT is sometimes experienced. The purpose of this study was to investigate the demographic data, perioperative courses and therapeutic outcomes of patients who underwent salvage resection for local recurrence after CIRT. METHODS: From November 1994 to February 2012, CIRT was applied for 602 c-T1/T2/T3N0M0 NSCLC lesions of 599 patients at the National Institute of Radiological Science. A total of 95 (16%) patients were diagnosed as having local recurrence, of whom 12 underwent salvage surgeries. The medical records were retrospectively reviewed. RESULTS: There were 7 men and 5 women (mean age, 63 ± 7.4 years). The clinical stages upon initial presentation with NSCLC were as follows: 4 IA, 7 IB and 1 IIB. All the patients were operable, but refused surgery and underwent CIRT. The median progression-free survival time after CIRT was 20 months (range, 7.1-77 months), and salvage surgery was performed at a median of 24 months (range, 9-78 months) after CIRT. All surgeries were successfully performed without any significant CIRT-related adhesions during the surgery, resulting in no mortality or Clavien-Dindo grade 3-4 postoperative complications. However, the distribution of pathological stages was as follows: 4 IA, 3 IB, 2 IIB, 2 IIIA and 1 IV, which included 6 upstages from the clinical stages before CIRT. The Kaplan-Meier estimate of overall survival after the salvage surgery showed that the 3-year survival rate was 82%. CONCLUSIONS: The dose intensity of CIRT spared the hilum of the lungs and parietal pleura, none of the patients developed adhesions outside of the radiation field, such that the salvage surgeries for local recurrence after CIRT were safe and feasible.

Clinical Utility of Skin Biopsy in Differentiating between Parkinson's Disease and Multiple System Atrophy.

Background. It is often difficult to differentiate Parkinson's disease (PD) from multiple system atrophy (MSA), especially in their early stages. Objectives. To examine the clinical utility of histopathological analysis of biopsied skin from the chest wall and/or leg in differentiating between the two diseases. Methods. Skin biopsies from the lower leg and/or anterior chest wall were obtained from 38 patients with idiopathic PD (26 treated with levodopa and 12 levodopa-naïve) and 13 age-matched patients with MSA. We sought aggregates of phosphorylated α-synuclein on cutaneous nerve fibers using double fluorescence immunohistochemistry and confocal microscopy and measured intraepidermal nerve fiber density (IENFD). Results. Phosphorylated α-synuclein aggregates were identified on cutaneous nerves in two patients with PD (5.3%) but in none of the patients with MSA, and IENFD was significantly lower in patients with PD when compared to those with MSA. There was no difference in IENFD between levodopa-treated and levodopa-naïve patients with PD. Conclusions. Our findings suggest that an assessment of IENFD in biopsied skin could be a useful means of differentiating between PD and MSA but that detection of α-synuclein aggregates on cutaneous nerves in the distal sites of the body is insufficiently sensitive.

An autopsy case of meningeal carcinomatosis with parenchymal invasion through the cranial and spinal nerve roots.

Meningeal carcinomatosis is a well-known complication of malignant neoplasms. We report a case of meningeal carcinomatosis of 2 months' duration in a 22-year-old man, in whom the initial symptom was gradually worsening headache. Postmortem examination revealed infiltrating adenocarcinoma of the stomach. Carcinoma cells showed diffuse spread to the subarachnoid space of the brain and spinal cord. In many places, subarachnoid tumor cells had infiltrated to the cranial and spinal nerves. Moreover, carcinoma cells in the nerve roots extended to the parenchyma of the brain and spinal cord beyond the CNS-peripheral nervous system junction. These findings suggest that cranial and spinal nerve roots can be a possible route of parenchymal invasion in meningeal carcinomatosis.