Current research of idiopathic normal pressure hydrocephalus: Pathogenesis, diagnosis and treatment.

Idiopathic normal pressure hydrocephalus (iNPH) is caused by impaired cerebrospinal fluid absorption in the elderly; it is a surgically treatable form of dementia. Gait disturbance, dementia, and urinary incontinence are the triad of signs for iNPH. In addition to these clinical findings, imaging studies show characteristic ventricular enlargement. High Evans Index and 'disproportionately enlarged subarachnoid hydrocephalus' are other well-known imaging findings of iNPH. If the tap test shows improved symptoms, shunt surgery is performed. The disease was first described by Hakim and Adams in 1965, followed by the publication of the first, second, and third editions of the guidelines in 2004, 2012, and 2020, respectively. Recent studies signal the glymphatic system and classical cerebrospinal fluid (CSF) absorption from the dural lymphatics as aetiological mechanisms of CSF retention. Research is also underway on imaging test and biomarker developments for more precise diagnosis, shunting technique options with fewer sequelae and complications, and the influence of genetics. Particularly, the newly introduced 'suspected iNPH' in the third edition of the guidelines may be useful for earlier diagnosis. However, less well-studied areas remain, such as pharmacotherapy in non-operative indications and neurological findings other than the triadic signs. This review briefly presents previous research on these and future issues.

A case report of an alcoholic with delirium tremens diagnosed with hypopharyngeal cancer: Psychiatrists played important roles in the smooth diagnosis and treatments.

Background: Alcohol use increases the risk of developing several types of cancer. Of these, hypopharyngeal cancer has one of the worst prognoses. Moreover, treating an alcoholic patient with hypopharyngeal cancer is often difficult. There are various treatments for hypopharyngeal cancer, including surgery, chemotherapy, and radiotherapy, depending on the state of the cancer and the patient's quality of life. Patients need physical, psychological, and social support in decision-making and post-treatment follow-up. This is especially true for alcoholic patients. Case Presentation: A 59-year-old man was admitted to our hospital with complaints of fatigue, loss of appetite, and tremor of the upper limbs. He was single, alcoholic, and had no family. After treatment for delirium tremens, he complained of throat pain. After endoscopy, magnetic resonance imaging, and examination with 18F-fluorodeoxyglucose positron emission tomography/computed tomography, he was diagnosed with Stage 4 A (T2 N2c M0) hypopharyngeal cancer. The psychiatrist and otolaryngologist discussed the patient's decision-making capacity and the various risks associated with treatment. Shared decision-making with the patient was considered most important in determining the treatment strategy. As a result, the patient decided to receive endoscopic laryngopharyngeal surgery in combination with lymphadenectomy, a challenging surgical treatment. The operation was successful, and the patient is now ready for a new life after discharge. Conclusion: Psychiatrists have a significant role to play in the oncological treatment of patients with alcoholism and other psychiatric disorders.

A case report of nonsurgical idiopathic normal pressure hydrocephalus differentiated from Alzheimer's dementia: Levetiracetam was effective in symptomatic epilepsy.

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a common form of dementia that causes gait disturbance, cognitive impairment, and urinary incontinence. iNPH is a "treatable dementia" that can be treated with shunt surgery, but this can be ineffective in some cases and can be accompanied by complications. As a result, many patients with iNPH do not undergo surgery. However, there is insufficient evidence on effective treatments other than surgical therapy. Case Presentation: A 75-year-old woman presented to our hospital with a chief complaint of cognitive decline. She showed reduced motivation and inactivity. Brain magnetic resonance imaging showed a high score on the Evans Index (maximum width between bilateral lateral ventricular anterior horns/maximum intracranial cavity in the same slice). The subarachnoid space was enlarged at and below the Sylvian fissure, and narrowed at the higher arcuate region. She was diagnosed with iNPH. However, no shunt surgery was performed; 11 months later, she had a generalized convulsive seizure with loss of consciousness. An electroencephalogram showed generalized epileptic discharges. The possibility of surgery for her iNPH was ruled out. Levetiracetam prevented seizure recurrence and cognitive functions such as spontaneity and motivation were improved. Conclusion: It is often assumed that surgery is the only effective treatment for patients with iNPH. However, as in the present case, symptomatic epileptic seizures may be a factor in dementia. Even in the absence of surgical treatment, we should examine the cause of dementia in patients with iNPH and consider pharmacological treatment, including antiepileptic drugs.

Concepts and techniques: how to determine and identify the appropriate target segment in anatomical pulmonary segmentectomy?

Anatomical segmentectomy is gathering increasing interest among thoracic surgeons because of increased detection of pulmonary nodules with ground-glass opacity (GGO) as well as an increase in the number of compromised patients. Accurate determination of intersegmental planes is a challenge in anatomical segmentectomy, and multiple methods have been proposed including developing inflation/deflation lines and injecting indocyanine green either intravenously or intrabronchially. Considering resection margins, adding a localization technique to conventional methods, or conducting virtual-assisted lung mapping (bronchoscopic multi-spot dye marking) may be an optional approach for optimal anatomical segmentectomy to identify intersegmental planes and obtain adequate resection margins. To determine optimal resection lines in anatomical segmentectomy, surgeons must also consider oncological validity such as venous and lymph drainage, resection margins, and lung anatomy to avoid complications such as venous congestion, infarction, and air leakage. Although anatomical segmentectomy is an attractive approach to resect small early-stage lung cancer and some metastatic lung tumors, caution is needed to optimally perform this technically demanding surgery.

The AMAGAMI technique: an easy technique to achieve precise stapling in thoracoscopic segmentectomy.

The "AMAGAMI" or "incomplete grasping" technique is used to adjust the location of the lung while gently grasping the lung tissue with a stapler. Thoracoscopic segmentectomy requires precise but complex stapling, while the surgical view and the number of available instruments are limited. In the AMAGAMI technique, instead of moving the stapler to the targeted position of the lung tissue, an unlocked stapler is used to hold the lung tissue at an easily accessible position, and the lung tissue can then be slid to the ideal resection line using forceps. To use the AMAGAMI technique effectively, "standing stitches" are very helpful in enabling visualization of the ideal resection lines. Standing stitches are placed along intersegmental lines that have been determined based on the information provided by virtual-assisted lung mapping (VAL-MAP) or other marking techniques; these stiches are usually placed at the corner of the targeted segment and in-between if necessary. Monofilament suture is used for standing stitches, and about 1 cm lengths are left to enable later visualization. As these stitches stick out of the lung surface even when viewed from a tangential angle, the direction of stapling is easily visualized in thoracoscopic surgery. These techniques are particularly useful in challenging segmentectomy requiring complex staple lines, such as S10 segmentectomy, and in surgery with limited instrumental access, such as uniportal thoracoscopic surgery.

Thoracoscopic stapler-based "bidirectional" segmentectomy for posterior basal segment (S10) and its variants.

Thoracoscopic segmentectomy for the posterior basal segment (S10) and its variant (e.g., S9+10 and S10b+c combined subsegmentectomy) is one of the most challenging anatomical segmentectomies. Stapler-based segmentectomy is attractive to simplify the operation and to prevent post-operative air leakage. However, this approach makes thoracoscopic S10 segmentectomy even more tricky. The challenges are caused mostly from the following three reasons: first, similar to other basal segments, "three-dimensional" stapling is needed to fold a cuboidal segment; second, the belonging pulmonary artery is not directly facing the interlobar fissure or the hilum, making identification of target artery difficult; third, the anatomy of S10 and adjacent segments such as superior (S6) and medial basal (S7) is variable. To overcome these challenges, this article summarizes the "bidirectional approach" that allows for solid confirmation of anatomy while avoiding separation of S6 and the basal segment. To assist this approach under limited thoracoscopic view, we also show stapling techniques to fold the cuboidal segment with the aid of "standing stiches". Attention should also be paid to the anatomy of adjacent segments particularly that of S7, which tends to be congested after stapling. The use of virtual-assisted lung mapping (VAL-MAP) is also recommended to demark resection lines because it flexibly allows for complex procedures such as combined subsegmentectomy such as S10b+c, extended segmentectomy such as S10+S9b, and non-anatomically extended segmentectomy.

Identification of Individual Cancer-Specific Somatic Mutations for Neoantigen-Based Immunotherapy of Lung Cancer.

INTRODUCTION: Two strategies for selecting neoantigens as targets for non-small cell lung cancer vaccines were compared: (1) an "off-the-shelf" approach starting with shared mutations extracted from global databases and (2) a personalized pipeline using whole-exome sequencing data on each patient's tumor. METHODS: The Catalogue of Somatic Mutations in Cancer database was used to create a list of shared missense mutations occurring in more than 1% of patients. These mutations were then assessed for predicted binding affinity to HLA alleles of 15 lung cancer patients, and potential neoantigens (pNeoAgs) for each patient were selected on this basis. In the personalized approach, pNeoAgs were selected from missense mutations detected by whole-exome sequencing of the patient's own samples. RESULTS: The list of shared mutations included 22 missense mutations for adenocarcinoma and 18 for squamous cell carcinoma (SCC), resulting in a median of 10 off-the-shelf pNeoAgs for each adenocarcinoma (range 5-13) and 9 (range 5-12) for each SCC. In contrast, a median of 59 missense mutations were identified by whole-exome sequencing (range 33-899) in adenocarcinoma and 164.5 (range 26-232) in SCC. This resulted in a median of 46 pNeoAgs (range 13-659) for adenocarcinoma and 95.5 (range 10-145) for SCC in the personalized set. We found that only one or two off-the-shelf pNeoAgs were included in the set of personalized pNeoAgs-and then in only three patients, with no overlap seen in the remaining 12 patients. CONCLUSIONS: Use of an off-the-shelf pipeline is feasible but may not be satisfactory for most patients with non-small cell lung cancer. We recommend identifying personal mutations by comprehensive genome sequencing for developing neoantigen-targeted cancer immunotherapies.

Techniques of stapler-based navigational thoracoscopic segmentectomy using virtual assisted lung mapping (VAL-MAP).

Anatomical segmentectomies play an important role in oncological lung resection, particularly for ground-glass types of primary lung cancers. This operation can also be applied to metastatic lung tumors deep in the lung. Virtual assisted lung mapping (VAL-MAP) is a novel technique that allows for bronchoscopic multi-spot dye markings to provide "geometric information" to the lung surface, using three-dimensional virtual images. In addition to wedge resections, VAL-MAP has been found to be useful in thoracoscopic segmentectomies, particularly complex segmentectomies, such as combined subsegmentectomies or extended segmentectomies. There are five steps in VAL-MAP-assisted segmentectomies: (I) "standing" stitches along the resection lines; (II) cleaning hilar anatomy; (III) confirming hilar anatomy; (IV) going 1 cm deeper; (V) step-by-step stapling technique. Depending on the anatomy, segmentectomies can be classified into linear (lingular, S6, S2), V- or U-shaped (right S1, left S3, S2b + S3a), and three dimensional (S7, S8, S9, S10) segmentectomies. Particularly three dimensional segmentectomies are challenging in the complexity of stapling techniques. This review focuses on how VAL-MAP can be utilized in segmentectomy, and how this technique can assist the stapling process in even the most challenging ones.

Gender Differences in Long-Term Survival after Surgery for Non-Small Cell Lung Cancer.

Background This retrospective study examined gender differences in non-small cell lung cancer (NSCLC) by analyzing surgical cases at a single institution. Patients and Methods In this study, 735 NSCLC patients who underwent surgery from 1995 to 2010 were included. Clinical and pathological characteristics were retrieved by reviewing charts retrospectively, and variables between genders were compared. Results There were 489 males and 246 females in the study. The percentage of screening-detected lung cancers (83.7%), never smokers (82.9%), adenocarcinoma histology (90.7%), and pathological stage IA (42.7%) was higher in females than that in males (71.2, 8.2, 51.3, and 23.1%, respectively). Female patients had fewer cases of coronary artery disease (2.8%) and fewer pneumonectomy cases (2.0%) than the male patients (7.4 and 5.3%, respectively). The median follow-up period after surgery was 5.9 years. The overall survival rates at 5 years were 57.3% for males and 76.2% for females (p < 0.001, log-rank test). Based on univariate analysis, we report that histology, smoking history, and pathological stage were significant prognostic factors in addition to gender. Based on multivariate analysis, pathological stage III/IV (hazard ratio, 3.60; 95% confidence interval [CI], 2.84-4.54) and female gender (hazard ratio, 0.55; 95% CI, 0.37-0.82) were significant prognostic factors. Subgroup analysis demonstrated that female gender and adenocarcinoma histology were significant positive prognostic factors only in pathological stages I and II (n = 557). Conclusion Female gender as well as pathological stage was favorable prognostic factors. The survival advantage observed in female NSCLC patients was limited to those with cancer at stages I and II.

Significance of the Glasgow Prognostic Score as a prognostic indicator for lung cancer surgery.

OBJECTIVES: The Glasgow Prognostic Score (GPS), which is calculated with C-reactive protein (CRP) and albumin (Alb) values, is a prognostic indicator for various types of cancers. However, its role in lung cancer still remains unclear, and its optimal cut-off values are controversial. Here, we evaluated the significance of the GPS and adjusted GPS (a-GPS) using our institution's cut-off values in patients undergoing resection for primary lung cancer. METHODS: We analysed 1043 lung cancer patients who underwent resection between 1998 and 2012. The overall survival (OS) probabilities of the GPS subgroups were estimated using the Kaplan-Meier method and were compared using the log-rank test. The prognostic significance of the GPS and the a-GPS was assessed by the Cox proportional hazards model with clinicopathological variables and inflammation markers, such as the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR). The GPS was calculated based on cut-off values of 1.0 mg/dl for CRP and 3.5 g/dl for Alb, as previously reported. The a-GPS was calculated based on cut-off values 0.3 mg/dl for CRP and 3.9 g/dl for Alb, which are the standard thresholds used by our institution. RESULTS: The GPS and the a-GPS were correlated with preoperative factors, such as age, sex, smoking status, the NLR and the PLR, and oncological factors, including the pathological stage, histological type and level of lymphovascular invasion. The 5-year OS rates were 82, 55 and 55% with GPS 0, 1 and 2 (1 vs 0: P < 0.01; 2 vs 1: P = 0.66), respectively, and 88, 67 and 59% with a-GPS 0, 1 and 2 (1 vs 0: P < 0.01; 2 vs 1: P = 0.04), respectively. Multivariable analysis revealed that the GPS [1 vs 0, hazard ratio (HR): 1.63, 2 vs 0, HR: 1.44] and the a-GPS (1 vs 0, HR: 2.00, 2 vs 0, HR: 2.10) were independent prognostic factors. The a-GPS classification showed a clearer prognostic distribution than the GPS classification. CONCLUSIONS: The GPS is a useful prognostic indicator of the OS in lung cancer surgery. The optimal cut-off values for GPS estimation may need to be re-evaluated.

[Tracheal Resection and Reconstruction for a Squamous Cell Carcinoma of the Trachea;Report of a Case].

We report a case of tracheal resection and reconstruction for a squamous cell carcinoma of the trachea that was found in an 82-year-old male patient who had underwent right lower lobectomy for an adenosquamous cell carcinoma 3.5 years before. He noticed bloody sputum. Chest computed tomography (CT) revealed a 15 mm tumor in the anterior wall of the trachea. A transbronchial biopsy for the tracheal tumor showed a squamous cell carcinoma. Under right thoracotomy, we resected the tumor with 3 tracheal rings. Histologically a squamous cell carcinoma was diagnozed. As there was intraepithelial spread of cancer cells in the oral margin, the tracheal tumor was suspected to be a primary tracheal tumor rather than a metastasis from lung cancer. After the surgery, combination therapies of an external radiation therapy for 50 Gy and brachytherapy 2 times for totally 8 Gy were performed as a postoperative adjuvant therapy. He does not have any signs of recurrence in 1 year and 6 months after the surgery.

Outcomes of combined modality therapy for patients with stage III or IV mediastinal malignant germ cell tumors.

PURPOSE: The treatment of primary mediastinal germ cell tumors with cisplatin-based chemotherapy followed by surgery is an established practice; however, the prognosis has remained poor. This study reviews the survival outcomes of patients with primary mediastinal germ cell tumors to evaluate the efficacy of our treatment. METHODS: We retrospectively reviewed 11 consecutive patients with primary mediastinal germ cell tumors. RESULTS: We had treated four patients with seminomas and seven patients with non-seminomas. Ten patients had undergone cisplatin-based chemotherapy. All patients underwent complete resection. Two patients showed a failure of first-line chemotherapy and thus received salvage chemotherapies, including paclitaxel plus ifosfamide followed by high-dose carboplatin plus etoposide (TI-CE) with stem cell transplantation. One of them died of relapse 29 months later; while the other patient remained disease-free for 56 months postoperatively. The postoperative overall 3-year survival rates of the patients with non-seminomas and seminomas were 83 and 100%, respectively. CONCLUSION: Complete resection after establishing normalized or decreased at a low-level serum tumor markers plateau plays a crucial role in the management of patients with primary mediastinal malignant germ cell tumors.

Validation of 7th TNM staging system for lung cancer, based on surgical outcomes.

BACKGROUND: Validation of the clinical classification for lung cancer of the 7th edition of the TNM staging system among surgical cases has not been reported previously. METHODS: Data of 489 males and 246 females, with a mean age of 67.6 years, who underwent surgical resection for non-small-cell lung cancer were analyzed retrospectively. RESULTS: The 5-year survival rate of these patients was 72.2% for clinical stage IA (n = 365), 58.4% for IB (n = 158), 51.2% for IIA (n = 77), 49.1% for IIB (n = 42), 36.8% for IIIA (n = 86), 80% for IIIB (n = 5) and 50% for IV (n = 2). The 5-year survival rate of patients was 100% for pathological stage 0 (n = 2), 86.1% for IA (n = 216), 73.8% for IB (n = 173), 46.1% for IIA (n = 97), 47.2% for IIB (n = 69), 33.3% for IIIA (n = 155), 33.3% for IIIB (n = 3) and 30.9% for IV (n = 20). Prognostic factors included female sex and 70 years of age or younger, as well as adenocarcinoma histology. CONCLUSIONS: Deterioration in patient survival was indicated with the exception of stages IIIB and IV, each of which included only a small number of patients. Our study validated the current TNM staging system in surgical cases with regard to both clinical and pathological classifications.

Outcome and survival analysis of pulmonary metastasectomy for hepatocellular carcinoma.

OBJECTIVE: The lung is the most common site for extrahepatic metastasis from hepatocellular carcinoma (HCC). We previously reported in a series of 20 patients that pulmonary metastasectomy for HCC is feasible in selected patients. The objective of this study was to re-evaluate the long-term outcomes and prognostic factors with an additional 25 patients. METHODS: We retrospectively analyzed the records of 45 consecutive patients who underwent pulmonary metastasectomy due to HCC at our institution between 1990 and 2010. RESULTS: Thirty-nine patients underwent hepatectomy or liver transplantation, whereas six patients underwent locoregional therapy for primary liver lesions. Twenty-seven patients died during a median 17.6-month follow-up period. The 2-year disease-free survival (DFS) was 19.5%. The 5-year overall survival (OS) was 40.9%. History of recurrence and serum des-gamma-carboxy prothrombin (DCP) level >40 mAU ml(-1) at initial pulmonary resection were unfavorably associated with OS in univariate analysis. CONCLUSIONS: Pulmonary metastasectomy for HCC in selected patients resulted in relatively good outcomes with regard to OS. History of recurrence and serum DCP levels were shown to be candidates of prognostic factors for OS.

Lung lobectomy in a patient with an implantable left ventricular assist device.

Non-cardiac surgical procedures in patients with left ventricular assist devices (LVADs) pose a special challenge given the hemodynamic and hematologic considerations in these patients. During pulmonary procedures in patients with LVADs, special attention should be paid to hemodynamics because lung resection surgery requires a lateral decubitus position, single-lung ventilation and postoperative decrease in the pulmonary vascular bed, all of which may lead to inadequate preload to the LVAD. We present a case of lower lobectomy of the left lung for an adenocarcinoma found in a patient with an implantable continuous-flow LVAD.

Adoptive immunotherapy for advanced non-small cell lung cancer using zoledronate-expanded γδTcells: a phase I clinical study.

Human γδ T cells can recognize and kill non-small cell lung cancer (NSCLC) cells using the Vγ9Vδ2 T-cell receptor and/or NKG2D. We have established clinical grade large-scale ex vivo expansion of γδ T cells from peripheral blood mononuclear cells by culturing with zoledronate and interleukin-2 (IL-2). A phase I study was conducted to evaluate safety and potential antitumor effects of re-infusing ex vivo expanded γδ T cells in patients with recurrent or advanced NSCLC. Patient's peripheral blood mononuclear cells were stimulated with zoledronate (5 µM) and IL-2 (1000 IU/mL) for 14 days. Harvested cells, mostly γδ T cells, were given intravenously every 2 weeks without additional IL-2, a total of 6 times. The cumulative number of transferred γδ T cells ranged from 2.6 to 45.1 x 109 (median, 15.7×109). Fifteen patients underwent adoptive immunotherapy with these γδ T cells. There were no severe adverse events related to the therapy. Immunomonitoring data showed that with increasing numbers of infusions, the number of peripheral γδ T cells gradually increased. All patients remained alive during the study period with a median survival of 589 days and median progression-free survival of 126 days. According to the Response Evaluation Criteria In Solid Tumors, there were no objective responses. Six patients had stable disease, whereas the remaining 6 evaluable patients experienced progressive disease 4 weeks after the sixth transfer. We conclude that adoptive transfer of zoledronate-expanded γδ T cells is safe and feasible in patients with NSCLC, refractory to other treatments.

Resection of solitary pulmonary lesion is beneficial to patients with a history of malignancy.

BACKGROUND: Solitary pulmonary lesion poses a diagnostic challenge, especially in patients with a history of malignancy. The purpose of this study was to evaluate the characteristics of solitary pulmonary lesions and the outcome of surgical resection. METHODS: We retrospectively analyzed 243 patients with a history of cancer who underwent surgery for new-found solitary pulmonary lesion between January 1998 and December 2007. RESULTS: The diagnosis was primary lung cancer in 92 patients, metastasis in 133, and benign lesions in 18. The 5-year survival rate was 67.9% in all patients, 74.6% in those with primary lung cancer, 62.8% in those with metastasis, and 79.9% in those with benign lesions (p = 0.56). In metastasis patients, history of extrapulmonary recurrence and larger diameter lesion were risk factors for recurrence by multivariate analysis. History of cancers other than colorectal and bone and soft tissue sarcoma and shorter disease-free interval were indicators of poor prognosis. Pathologic stage was the only indicator of prognosis for primary lung cancer, and none of the factors concerning antecedent cancer influenced prognosis. CONCLUSIONS: Surgical resection of solitary pulmonary lesion is essential in patients with a history of cancer because substantial numbers of benign lesions are included. In the case of malignancy, metastasectomy had a life-prolonging effect for selected patients, and prognosis of primary lung cancer was no worse than for the general population if treated appropriately. It is important not to hesitate to take a surgical approach for a diagnosis and to treat with standard therapy for primary lung cancer.