A Th1-like CD4+ T-cell Cluster That Predicts Disease-free Survival in Early-stage Lung Cancer.

Perioperative immune checkpoint inhibitors have been shown to improve prognosis in early-stage lung cancer. However, no biomarkers are known to indicate the requirement for treatment. This study aimed to identify T-cell clusters responsible for antitumor immunity in patients with early-stage lung cancer. Preoperative blood samples from 50 consecutive patients with lung cancer who were diagnosed as operable and underwent complete resection were analyzed by mass cytometry. Patients were divided into two groups: no recurrence at a minimum observation period of 851 days (median observation period: 1,031.5 days) and recurrence by the last observation date. Mass cytometry and single-cell RNA sequencing analysis of lymph nodes (LN) and tumor-infiltrating T cells were also performed. CCR4-CCR6+ Th7R showed discriminative ability between recurrence and non-recurrence patients with lung cancer. Patients with more than 3.04% Th7R showed significantly favorable disease-free survival. Th7R was a major component of CD4+ T cells in tumor microenvironments and LNs adjacent to lung cancer tissues and was the only cluster that decreased in peripheral blood after the removal of cancer tissues, suggesting that Th7R was primed and proliferated in tumor-draining LNs in the presence of cancer tissues. Th7R had the kinetics that antitumor T cells should have, as indicated by the cancer immunity cycle; thus, peripheral blood Th7R could represent the potency of tumor immunity by reflecting priming and proliferation in tumor-draining LNs and Th7R in the tumor microenvironment. Prediction using peripheral Th7R before surgery could allow the selection of patients who require perioperative drug therapy and optimize therapeutic interventions with clinical implications. Significance: Peripheral Th7R, a Th1-like CD4+ T-cell cluster reflecting priming status in draining LNs and immune status in the tumor microenvironment, predicts disease-free survival after complete resection and has significant clinical relevance in selecting appropriate therapeutic interventions in patients with early-stage lung cancer.

Prognostic significance of lymph node dissection for lung cancer surgery: a narrative review.

Background and Objective: Theoretically, systematic lymph node dissection (SLND) in lung cancer surgery is a technique that leaves less cancer cells behind and is speculated to improve the prognosis, but its prognostic significance still remains controversial. In addition, the social environment surrounding lymph node dissection has changed with the advent of limited surgery for peripheral small-sized lung cancer and emergence of immune check inhibitor (ICI). Therefore, we reconsidered the role of lymph node dissection. Methods: By referring to past reports, we reviewed the process leading up to the establishment of SLND in lung cancer surgery. We compared five randomized prospective comparative studies on SLND and lymph node sampling (LNS) in lung cancer surgery. Key Content and Findings: Of the five randomized prospective comparative studies, two reported an improvement in overall survival (OS) with SLND, but the remaining three reported no significant difference in OS between SLND and LNS. One out of the five reports revealed a significant increase in complications with SLND. For peripheral non-small cell lung cancer (NSCLC) cases with tumor diameter ≤2 cm and consolidation-to-tumor ratio >0.5 segmentectomy was found to significantly improve the hazard ratio of OS, when compared to a lobectomy. However, the proportion of SLND and lobe-specific lymph node dissection (L-SLND) in each group seems to be unclear. In segmentectomy, the dissection of intersegmental lymph nodes tends to be lenient, and therefore it seems necessary to examine the significance of lymph node dissection in segmentectomy. ICIs are already showing excellent effects, and it may be necessary to examine how they will be affected by removal of regional lymph nodes where cancer-specific cytotoxic T lymphocytes (CTLs) are concentrated. SLND is essential for accurate staging, but ideally-in a host with no cancer cells in the lymph node or a host with cancer cells having a high sensitivity to ICI-it might be better to leave the regional lymph node. Conclusions: SLND may not be the right choice in all cases. A time may come when the extent of lymph node dissection is determined individually for each case. Future verification results are awaited.

Tumor immunity is related to 18 F-FDG uptake in thymic epithelial tumor.

BACKGROUND: 2-deoxy-2-[fluorine-18] fluoro-d-glucose (18 F-FDG) positron emission tomography (18 F-FDG-PET) is a convenient modality to assess the metabolic activity within tumor cells. However, there is no consensus regarding the relationship between 18 F-FDG uptake and the immune environment in thymic epithelial tumors (TETs). We conducted a clinicopathological study to elucidate the relationship between 18 F-FDG uptake and programmed death ligands 1 and 2 (PD-L1/PD-L2) expression in patients with TETs. METHODS: A total of 108 patients with histologically confirmed TETs classified as thymomas or thymic carcinomas who underwent surgical resection or biopsy or needle biopsy and 18 F-FDG PET before any treatment between August 2007 and March 2020 were enrolled in this study. Tumor specimens underwent immunohistochemical staining for PD-L1, PD-L2, GLUT1, HIF-1α, VEGFR2, VEGF-C, and ß2 adrenergic receptor. RESULTS: High uptakes of SUVmax , SUVmean , MTV, and TLG were identified in 28 (25.9%), 61 (56.5%), 55 (50.9%), and 55 (50.9%) of 108 patients, respectively. High uptake of SUVmax significantly correlated with PS (performance status) of 1-2, thymic carcinoma, and advanced stage, and SUVmax on 18 F-FDG uptake displayed a close association with PD-L1 and PD-L2 expressions, but not with MTV and TLG. Our analysis revealed that SUVmax was identified as being significant relationship for positive PD-L1/PD-L2 expression. GLUT1, HIF-1α, and VEGFR2 were significantly associated with the expression of PD-L1/PD-L2 from the biological viewpoint. CONCLUSION: 18 F-FDG accumulation was closely associated with the expression of PD-L1/PD-L2, which, in turn, was correlated with glucose metabolism and hypoxia. PD-L1/PD-L2 could affect the glucose metabolism and hypoxia in thymic tumor cells.

Chylothorax associated with lymphatic reflux in a thoracic duct tributary after lung cancer surgery.

Chyle leaks are attributed to damage to the thoracic duct itself or its tributaries during surgery. Chylothorax after lung cancer surgery can occur due to damaged thoracic duct tributaries; however, little is known of the mechanism involved. A 71-year-old female underwent a left upper lobectomy with hilar and mediastinal lymphadenectomy for a 1.8-cm primary squamous cell carcinoma, and developed a chylothorax a day later. Catheter lymphangiography revealed high-flow chyle leaks from a damaged thoracic duct tributary, known as a bronchomediastinal lymph trunk, due to a lymphatic reflex from the thoracic duct. Subsequently, catheter embolization of the tributary repaired the chylothorax. The potential for persistent chylothorax after lung cancer surgery and successful lymphatic intervention should be noted.

Pulmonary high-grade fetal adenocarcinoma associated with cystic airspace: A case report.

Lung cancers associated with cystic airspaces have a life-threatening risk of a missed or delayed diagnosis. Here, we report a case of pulmonary high-grade fetal adenocarcinoma, a rare lung carcinoma associated with cystic airspaces, as confirmed by computed tomography (CT) scan. A 73-year-old asymptomatic male with a 52-pack a year smoking habit was referred to our hospital. Lung CT showed a thin-walled cystic space with exophytic and endophytic solid nodules along the cyst wall. After surgery, histological analysis of a resected lung specimen revealed a pure high-grade fetal adenocarcinoma probably associated with emphysematous bullae in pulmonary emphysema, suggesting smoking contributed to this pure form, as well as the emphysema. In conclusion, when treating elderly men with a smoking history, physicians need to carefully examine the walls of cystic airspaces on CT for fetal adenocarcinoma. KEY POINTS: Significant findings of the study •Pulmonary high-grade fetal adenocarcinoma may be associated with emphysematous bullae manifesting as cystic air spaces as shown by computed tomography. What this study adds •When scanning by computed tomography, physicians should carefully examine the pulmonary cystic airspace walls in elderly men with a smoking history.

Primary pulmonary synovial sarcoma with calcification: A case report.

The lung is the organ most commonly affected by primary synovial sarcoma. Intratumoral calcification is less common in this organ versus soft tissue. Meanwhile, the presence of calcification in a lung nodule reduces the risk of lung cancer. Here, we report a case of pulmonary synovial sarcoma which manifested as a nodule with calcification, depicted on computed tomography (CT). A 52-year-old asymptomatic male was referred to Saitama Medical University International Medical Center and CT revealed a well-defined nodule (1.8 cm), with punctate and eccentric calcification in the right lower lobe. Enhanced CT and 18F-fluorodeoxyglucose positron-emission tomography suggested a malignant tumor, and surgery was performed. Histology provided a preliminary diagnosis of monophasic spindle-cell synovial sarcoma with hyalinized collagen bands and calcifications. Genetically, the presence of the SYT-SSX2 fusion gene was consistent with the features of this disease. We conclude that primary pulmonary synovial sarcoma should be listed as a differential diagnosis for solitary pulmonary nodules with calcification.

Distinctive clinicopathological features of adenocarcinoma in situ and minimally invasive adenocarcinoma of the lung: A retrospective study.

OBJECTIVES: The aim of this study was to investigate distinguishing clinicopathological features, in addition to histological invasiveness, in adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) of the lung. MATERIALS AND METHODS: Patients with lung adenocarcinoma who underwent surgery at our hospital between 2007 and 2014 were reviewed, focusing on computed tomography (CT) images, operative procedures and clinical outcomes, histopathology, Ki-67 immunostaining, and EGFR-mutation status. EGFR mutations were examined using a peptide nucleic acid-locked nucleic acid PCR clamp method. Group comparisons were investigated by Mann-Whitney U or Fisher's exact tests. RESULTS: Of 629 patients with lung adenocarcinoma who underwent surgery, 91 (14%) of 103 AIS (n = 34) or MIA (n = 69) tumors were reviewed. The ratio of male to female patients with MIA compared to AIS was significantly higher (p < 0.02). Of 103 tumors, 99 (96%) were non-mucinous. By CT, 74% of AIS appeared as pure ground-glass nodules and 75% of MIAs as part-solid ground-glass nodules. Pathological tumor diameters and Ki-67 labeling index (LI) values were significantly greater for MIAs compared to AIS (p < 0.001 for both). A Ki-67 LI of ≥2.8% indicated the presence of an MIA rather than an AIS. EGFR mutations were more frequently detected in MIAs (33/69, 48%) than AIS (9/34, 26%; p = 0.055). The ratio of exon 19 deletions to exon 21 missense mutations in MIAs tended to be higher than those in AIS (p = 0.06). Patients did not experience a local recurrence or metastasis after AIS and MIAs were removed by wedge resection, segmentectomy or lobectomy. Five-year recurrence-free survival rates were 100%. CONCLUSION: Despite similar surgical outcomes for AIS and MIAs, we found differences in terms of gender, tumor diameters, CT findings, Ki-67 LI and a subset of EGFR mutations, highlighting the validity of classifying the two subtypes.

[Surgical Outcome of Sublobar Resection in High-risk Patients with Non-small Cell Lung Cancer].

OBJECTIVES: Pulmonary lobectomy is the standard surgical procedure for resectable non-small cell lung cancer (NSCLC), while sublobar resection is an important surgical alternative for high-risk patients with comorbidities. We evaluated the treatment outcome and prognostic factors of sublobar resection in high-risk patients with NSCLC. METHODS: Eighty three high-risk patients who underwent compromised sublobar resection for clinical-N0 NSCLC with a solid appearance were retrospectively reviewed. A total of 47 wedge resections and 36 segmentectomies performed. RESULTS: Poor pulmonary function and synchronous or metachronous multiple lung cancer were found in 56.7% and 20.5% of patients respectively, all requiring sublobar resection. There were 21 instances of tumor recurrence and 24 deaths during a mean follow-up of 1,500 days. There was no local recurrence in the segmentectomy group. The 3-year recurrence free survival (RFS) and overall survival (OS) were 72.6% and 73.8% respectively. A multivariate analysis indicated that resection type and lymphatic invasion were independent prognostic factors for RFS. In the wedge resection group, a ratio of surgical margin to clinical tumor size greater than 1 (MT ratio≥1) was an independent prognostic factor for RFS( 87.1%,p=0.001). CONCLUSION: Segmentectomy leads to a favorable prognosis. MT ratio was independently associated with a longer RFS in the wedge resection group.

[A Case of Malignant Phyllodes Tumor Effectively Treated by Radiation Therapy as a Palliative Medicine].

The current report presents the case of a 46-year-old woman with phyllodes tumor metastasis to the anterior chest wall treated by radiation therapy. Although the lesion was not controlled with surgery and chemotherapy, the tumor size markedly reduced after radiation therapy, and bleeding and foul odor from the tumor stopped. Radiation therapy for phyllodes tumor appears to be an effective treatment and should be recognized as one choice of palliative medicine.

[Clinical evaluation of eribulin mesylate for the treatment of metastatic breast cancer].

BACKGROUND: Eribulin mesylate, a novel non-taxane inhibitor of microtubule dynamics, results in a significant improvement in the overall survival of heavily pretreated patients with metastatic breast cancer(MBC). In the present study, we aimed to clarify the efficacy and safety of eribulin mesylate for the treatment of MBC. PATIENTS AND METHODS: We examined 18 patients with MBC who received eribulin mesylate in our hospital from October 2011 to May 2013. The patients were assessed for therapeutic response and adverse events with this treatment; in addition, these parameters were assessed in patients undergoing a combination treatment of eribulin mesylate and trastuzumab. RESULTS: The mean age of the patients in this study was 68.7 years(range, 60-85 years). All patients exhibited metastases to lymph nodes and distant sites. The mean number of prior regimens was 4.4(range, 2-9). The mean number of cycles of eribulin mesylate treatment administered was 7.2(range, 2- 17). The objective response rate and clinical benefit rate(PR+long SD)were 33.3%(6/18)and 50.0%(9/18), respectively, and the median progression-free survival was 6 months. The Grade 3/4 adverse events occurring in the patients included neutropenia in 13 patients(72.2%), anemia in 1 patient(5.6%), anorexia in 1 patient(5.6%), stomatitis in 1 patient(5.6%), and peripheral neuropathy in 1 patient(5.6%). However, 3 elderly patients who received the combination treatment of trastuzumab and eribulin mesylate experienced no adverse events. CONCLUSIONS: eribulin mesylate appears to demonstrate an acceptable tumor response in patients with MBC, and it can be safely administered to elderly patients if myelosuppression is carefully managed.

[A case of adenosquamous carcinoma of the sigmoid colon with inferior mesenteric vein thrombosis].

A 63-year-old man who had been admitted to another institute with sepsis and renal failure was referred to our hospital after computed tomography (CT) findings showed thickening of the walls in the sigmoid colon and a defect in contrast enhancement in the portal and inferior mesenteric veins. Emergency sigmoid colon resection with D2 lymphadenectomy was performed after detection of perforation due to sigmoid colon cancer. The histopathological diagnosis was adenosquamous carcinoma, pSS, int, INF b, ly1, v0, pN2, pStage IIIband inferior mesenteric vein thrombosis. He was discharged on day 12, and we administered anticoagulant warfarin therapy.

[A case of sigmoid colon cancer with abdominal wall abscess].

A 63-year-old man was admitted for an abdominal mass. Computed tomography revealed an abscess (21 × 20 cm) in the abdominal wall and a tumor in the sigmoid colon. Thus, cancer of the sigmoid colon complicated by an abscess of the abdominal wall was diagnosed. The abscess was drained and transverse colostomy was performed with curative intent. After the intervention, chemotherapy (XELOX×3) was administered. Three months later, sigmoidectomy was performed and the stoma was closed. Macroscopic and microscopic examination of the resected specimen detected no remnants of cancer. In patients with advanced colon cancer and abdominal wall involvement, a two-stage operation and preoperative chemotherapy may be considered essential when curative resection is performed.

[Long-term survival of a patient with esophageal cancer with brain metastasis after multidisciplinary therapy - a case report].

A 70-year-old woman was admitted for difficulty in swallowing. Esophageal cancer (MtLt, type 3, T4N3M0, cStage IVa) was diagnosed in May 2010. The cancer was unresectable, and chemoradiotherapy (CRT) with TS-1 was initiated in June 2010, and a partial response (PR) was observed. After CRT, TS-1 was continued, but a brain metastasis was detected owing to the development of right hemiplegia in April 2012. Craniotomy and tumorectomy were performed, and the right hemiplegia improved. Pathological examination of the brain tumor indicated squamous cell carcinoma. Because of a recurrence of brain metastasis, a gamma knife procedure was performed in May 2012. Subsequently, several recurrences of brain metastases were diagnosed, and a total of 7 gamma knife procedures were performed up to January 2014. Although systemic chemotherapy (5-fluorouracil and cisplatin [FP], 5 courses)was administered, the patient showed progressive lung metastases in February 2013. The chemotherapy regimen was changed from FP to docetaxel (TXT), but the lung metastases continued to progress up to June 2013. The patient died in March 2014. Patients with esophageal cancer and metastases to the brain have poor prognosis, but the present patient survived approximately 2 years after first diagnosis of metastases to the brain after multidisciplinary therapy.

Ductal branch-oriented pancreatic resection for an intraductal papillary mucinous neoplasm in the uncinate process that caused recurrent acute pancreatitis: a case report of successful treatment.

Acute pancreatitis reportedly occurs in about 15 % of cases of branch duct (BD)-intraductal papillary mucinous neoplasms (IPMNs), with two-thirds of BD-IPMNs being located in the head or uncinate process of the pancreas. However, the surgical indications and optimal treatment methods for BD-IPMNs have not been established. A 59-year-old Japanese male with epigastralgia was admitted to our hospital. A multidetector row computed tomography (MDCT) scan disclosed grade I acute pancreatitis. Magnetic resonance cholangiopancreatography disclosed a 1.5-cm BD-IPMN in the uncinate process. Two months after discharge, the epigastralgia recurred, and MDCT again revealed grade I pancreatitis. Due to the repeated episodes of pancreatitis, we performed ductal branch-oriented pancreatic resection. To detect the inferior branch of the Wirsung duct and avoid the development of a pancreatic fistula, we injected indigo carmine into the tumor which confirmed ligation of the inferior branch. Histopathologically, the tumor proved to be an adenoma. The postoperative course was uneventful in both the short- and long-term follow-up and, to date, there has been no recurrence of pancreatitis, or diabetes mellitus during the 6 years since pancreatectomy. This procedure is one of the methods that can be used for the successful resection of a BD-IPMN in the uncinate process that caused recurrent acute pancreatitis.

[A case of a patient with gastric cancer and liver metastasis -a long-term survival of 10 years].

We report a case of patient who is alive 10 years after total gastrectomy and partial liver resection for gastric cancer and liver metastasis, respectively. The patient is 69-year-old man who was examined in another hospital for nausea, tarry stool, and weight loss. Diagnosis by stomach fluoroscopy revealed gastric cancer and he was admitted to our hospital in September 2002. Computed tomography (CT) scan and ultrasonography (US) revealed liver metastasis in S7. Distant metastases were not detected. The patient underwent distal gastrectomy, transverse colon partial resection, and a hepatic partial resection in October 2002. Pathological findings showed SI, N1, and M1. Though adjuvant chemotherapy was given, a local recurrence was detected in the liver in February 2003. Hepatic arterial infusion (HAI) was started in April 2003. After 8 courses, HAI was discontinued because of hepatic artery obstruction. No additional distant metastases were found. Therefore, transdiaphragmatic radiofrequency ablation (RFA) was performed by thoracotomy. Currently, the patient is treatment free and remains alive after 10 years with no recurrence.