Insight into the significance of Foxp3 + tumor-infiltrating lymphocytes in squamous cell lung cancer.

PURPOSE: Although developing a better understanding of tumor-infiltrating Foxp3 + lymphocytes (Foxp3 + TILs) might provide essential knowledge to predict response to immunotherapy and prognosis, our current knowledge about Foxp3 + TILs is inadequate. This study investigated the prognostic significance of tumor-infiltrating Foxp3 + lymphocytes (Foxp3 + TILs) in squamous cell lung cancer (SQ-LC) objectively. METHODS: Among patients with SQ-LC surgically resected in our institution between 2011 and 2017, those with pathological stage IA3-IIIA were immunohistochemically studied to evaluate Foxp3 + TILs in their tumor stroma. The impact of Foxp3 + TILs on relapse-free survival (RFS) was analyzed with Kaplan-Meier survival analysis and multivariate analysis using a Cox proportional hazards model/Fine-Gray model. RESULTS: This study analyzed 100 patients. Multivariate analysis showed that a large number of Foxp3 + TILs in the stroma does not associate with a poor prognosis, rather that a large number of Foxp3 + TILs (≥ 64 cells) tend to be associated with a more favorable prognosis than a small number of Foxp3 + TILs (< 64 cells) (large vs small number: HR, 0.56; 95% CI, 0.17-1.83; P = 0.34). Exploratory analysis also showed that in the two populations divided by a difference in Foxp3 expression levels, similar trends to the main analysis were observed. CONCLUSION: Our results showed that a large number of Foxp3 + TILs in the stroma may not associate with a poor prognosis in SQ-LC. To use the seemingly complicated information of Foxp3 + TILs as biomarkers, better understanding the diversity and heterogeneity of Foxp3 + TILs and analyzing their subpopulations that increase in the TME may be needed.

Insight into the significance of CD8+ tumor-infiltrating lymphocytes in squamous cell lung cancer.

BACKGROUND: Although there are great expectations regarding the use of tumor-infiltrating lymphocytes (TILs) to predict effects of immunotherapies and prognosis, knowledge about TILs remains insufficient for clinical application. METHODS: We objectively investigated the prognostic significance of tumor-infiltrating CD8 + lymphocytes (CD8 + TILs) in squamous cell lung cancer (SQ-LC). Among patients who underwent surgical resection of SQ-LC in 2011-2017, 100 patients with pathological stage IA3-III were immunohistochemically studied to evaluate CD8 + TILs in the tumor stroma and parenchyma. The impact of CD8 + TILs on relapse-free survival was analyzed using a Kaplan-Meier survival analysis and multivariate analyses using Fine-Gray and Cox proportional hazards models. RESULTS: The multivariate analysis showed that large and small numbers, but not intermediate numbers, of CD8 + TILs in the tumor stroma may be related to a more favorable prognosis (small vs. intermediate: HR, 0.64; 95% CI: 0.29-1.41, p = 0.27; large vs. intermediate: HR, 0.48; 95% CI: 0.21-1.09, p = 0.08). In contrast, a large number of CD8 + TILs in the tumor parenchyma was associated with a poor prognosis (HR, 2.60; 95% CI: 0.91-7.42, p = 0.075). An exploratory analysis showed a potentially strong association between an extremely large number of CD8 + TILs in the tumor parenchyma and a poor prognosis, even with a large number of CD8 + TILs in the tumor stroma. CONCLUSION: Our study provided partial but important information on the significance of CD8 + TILs in SQ-LC. To use CD8 + TILs as biomarkers, a better understanding of CD8 + TILs as well as other important components in the tumor microenvironment and the inflammatory phenotypes they form may be needed.

Micropapillary and solid components as high-grade patterns in IASLC grading system of lung adenocarcinoma: Clinical implications and management.

OBJECTIVES: The grading system proposed by the International Association for the Study of Lung Cancer is based on a combination of predominant histologic subtypes and the proportion of high-grade components with a cutoff of 20%. We aimed to examine the clinical implications of the grading system beyond the discrimination of patient prognosis, while assessing the biological differences among high-grade subtypes. METHODS: We retrospectively reviewed 648 consecutive patients with resected lung adenocarcinomas and examined their clinicopathologic, genotypic, and immunophenotypic features and treatment outcomes. Besides the differences among grades, the clinical impact of different high-grade components: micropapillary (MIP) and solid (SOL) patterns, was individually evaluated. RESULTS: Survival outcomes were well-stratified according to the grading system. Grade 3 tumors exhibited aggressive clinicopathologic features, while being an independent prognostic factor in multivariable analysis. A small proportion (<20 %) of high-grade components in grade 2 had a negative prognostic impact. The prognostic difference bordering on the 20 % cutoff of the MIP proportion was validated; however, the proportion of SOL component did not affect prognosis. A survival benefit from adjuvant chemotherapy was observed in grade 3 tumors regardless of histologic subtype, but not in grade 1-2 tumors. The molecular and immunophenotypic features were different among grades, but still heterogeneous in grade 3, with MIP harboring frequent EGFR mutation and SOL exhibiting high PD-L1 expression. The treatment outcome after recurrence was worse in grade 3, but tumors with MIP pattern had an equivalent prognosis to that of grade 1-2 tumors, reflecting the high frequency of molecular targeted therapy. CONCLUSIONS: In addition to stratifying patient prognosis, the current grading system could discriminate clinical course, therapeutic effects of adjuvant chemotherapy, and molecular and immunophenotypic features. Further stratification based on biological heterogeneity in grade 3 remains necessary to enhance the role of the grading system in guiding patient management.

Prognostic implications of prostaglandin E-major urinary metabolite in resected non-small-cell lung cancer.

OBJECTIVES: Cyclooxygenase-2-derived prostaglandin E2 (PGE2) is highly involved in the promotion of cancer progression. The end product of this pathway, PGE-major urinary metabolite (PGE-MUM), is a stable metabolite of PGE2 that can be assessed non-invasively and repeatedly in urine samples. The aim of this study was to assess the dynamic changes in perioperative PGE-MUM levels and their prognostic significance in non-small-cell lung cancer (NSCLC). METHODS: Between December 2012 and March 2017, 211 patients who underwent complete resection for NSCLC were analysed prospectively. PGE-MUM levels in 2 spot urine samples taken 1 or 2 days preoperatively and 3-6 weeks postoperatively were measured using a radioimmunoassay kit. RESULTS: Elevated preoperative PGE-MUM levels were associated with tumour size, pleural invasion and advanced stage. Multivariable analysis revealed that age, pleural invasion, lymph node metastasis and postoperative PGE-MUM levels were independent prognostic factors. In matched pre- and postoperative urine samples obtained from patients who are eligible for adjuvant chemotherapy, an increase in PGE-MUM levels following resection was an independent prognostic factor (hazard ratio 3.017, P = 0.005). Adjuvant chemotherapy improved survival in patients with increased PGE-MUM levels after resection (5-year overall survival, 79.0 vs 50.4%, P = 0.027), whereas survival benefit was not observed in those with decreased PGE-MUM levels (5-year overall survival, 82.1 vs 82.3%, P = 0.442). CONCLUSIONS: Increased preoperative PGE-MUM levels can reflect tumour progression and postoperative PGE-MUM levels are a promising biomarker for survival after complete resection in patients with NSCLC. Perioperative changes in PGE-MUM levels may aid in determining the optimal eligibility for adjuvant chemotherapy.

Examination of the effectiveness of local therapy for oligo-recurrence of EGFR-mutated NSCLC.

BACKGROUND: The effectiveness of local therapy has been reported in patients with oligo-recurrence of non-small cell lung cancer (NSCLC), a metachronous recurrence with a limited number of recurrences, which can be treated with local therapy. Conversely, remarkable progress has been made in systemic therapy for NSCLC with the advent of molecular targeted therapy. In particular, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are very effective in the treatment of EGFR-mutated NSCLC. There is currently no consensus on treatment for oligo-recurrence of EGFR-mutated NSCLC. METHODS: From 2004 to 2014, 811 patients underwent complete resection for NSCLC at Kitasato University Hospital and, of these, 244 patients developed recurrence. Oligo-recurrence was defined as the presence of two or less recurrent lesions, and 34 patients presented with EGFR-mutated oligo-recurrence. RESULTS: We retrospectively examined and compared the effects of EGFR-TKIs with those of radical local therapy in patients with oligo-recurrent EGFR-mutated NSCLC. The five-year post-recurrence survival (PRS) rates of patients with EGFR-mutated oligo-recurrence who received radical local therapy (n = 23) and those who did not (n = 11) were 59.4 and 45.5%, respectively (p = 0.777). Multivariate analysis revealed no favorable prognostic factors associated with prolonged PRS, and radical local therapies did not improve PRS in patients with oligo-recurrence (p = 0.551). CONCLUSION: Radical local therapy did not affect PRS in patients with oligo-recurrent EGFR-mutated NSCLC. Even in cases of oligo-recurrence, the administration of local therapy in patients with EGFR-mutated NSCLC might be carefully considered.

Factors associated with lymph node metastasis upstage after resection for patients with micropapillary lung adenocarcinoma.

BACKGROUND: Micropapillary adenocarcinoma has a poor prognostic histological pattern. Additionally, preoperative detection of lymph node metastases by preoperative examination is difficult in some patients with micropapillary adenocarcinoma, and postoperative upstage may occur. However, clinicopathological features of patients with micropapillary adenocarcinoma with nodal upstage have not been established, therefore this study aimed to identify the factors associated with potential lymph node metastases during preoperative examination to ensure effective surgical procedures. METHODS: Between January 2011 and December 2020, 1029 patients received complete resection for primary non-small-cell lung cancer by lobectomy or more extensive resection with systematic lymph node dissection at this institution. One hundred and thirty-one patients diagnosed with adenocarcinoma with micropapillary component were included in this study. The clinicopathological features of patients with nodal upstage whose postoperative N stage was more advanced than the preoperative N stage were examined. RESULTS: Forty patients had nodal upstage after resection. 18 F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) revealed that a maximum standardized uptake value (SUVmax) ≥5 for the primary lesion was significantly associated with postoperative nodal upstage. There were no significant differences in terms of sex, age, smoking history, surgical procedure, and diabetes. Among 38 patients with nodal upstage, 23 patients had no significant preoperative lymphadenopathy and showed no abnormal FDG uptake in the lymph nodes on 18 F-FDG-PET-CT, respectively. CONCLUSIONS: Lymph node metastases were suspected in patients preoperatively diagnosed with micropapillary adenocarcinoma with FDG SUVmax ≥5 for the primary tumor. Therefore, standard surgical resection and careful lymph node dissection should be performed for such patients.

Selection of preoperative stress electrocardiography test for appropriate patients with non-small cell lung cancer.

OBJECTIVE: Lobectomy is an established surgical procedure for treating non-small cell lung cancer; however, it significantly impacts postoperative cardiac function. The stress electrocardiography test is relatively easy to perform and is used to confirm the presence of coronary artery stenotic lesions. However, it has a low pre-test probability and may yield many false positives. We examined the factors that would enable the appropriate selection of patients for stress electrocardiography as a preoperative cardiovascular examination preceding lobectomy for non-small cell lung cancer. METHODS: From June 2016 to July 2018, 240 patients at our institution who underwent stress electrocardiography before lobectomy for primary lung cancer were included in this study. Clinical information was extracted from electronic medical records and evaluated retrospectively. Smoking history, diabetes, hypertension, dyslipidemia, and ischemic heart disease were considered risk factors for coronary artery stenosis. We determined the coronary risk factors that were applicable to each participant and calculated the total number of coronary risk factors as a risk score. RESULTS: Patients with coronary risk factor scores of ≥ 3 were significantly more likely to have abnormal stress electrocardiography results. In addition, these patients also underwent more comprehensive examinations to identify coronary diseases. There were no patients with complications that could be attributed to ischemic heart disease. CONCLUSION: Stress electrocardiography may be more useful before lobectomy in non-small cell lung cancer patients if the patients are appropriately selected, with the test utilized mainly in patients with coronary risk factor scores of ≥ 3.

A Japan nationwide web-based survey of patient preference for renal denervation for hypertension treatment.

Renal denervation is a potential alternative to antihypertensive drug therapy. However, data on patient preference for this treatment option are limited and there are no data specifically from Asian patients. This study evaluated patient preference for renal denervation in patients with hypertension from Japan. Patients were a subset of those who participated in a March 2020 online electronic survey of patients with hypertension who had regularly visited medical institutions for treatment, were receiving antihypertensive drug therapy and had home blood pressure recordings available. The survey included a question about patient preference for treatment with renal denervation. A total of 2,392 patients were included (66% male, mean age 59.8 ± 11.6 years, mean duration of hypertension 11.4 ± 9.5 years). Preference for renal denervation was expressed by 755 patients (31.6%), and was higher in males than in females, in younger compared with older patients, in those with higher versus lower blood pressure, in patients who were less adherent versus more adherent to antihypertensive drug therapy, and in those who did rather than did not have antihypertensive drug-related side effects. Significant predictors of preference for renal denervation on logistic regression analysis were younger patient age, male sex, higher home or office systolic blood pressure, poor antihypertensive drug adherence, the presence of heart failure, and the presence of side effects during treatment with antihypertensive drugs. Overall, a relevant proportion of Japanese patients with hypertension expressed a preference for renal denervation. This should be taken into account when making shared decisions about antihypertensive drug therapy.

A Japan nationwide web-based survey of estimation on patients for renal denervation based on blood pressure level and the number of antihypertensives (J-NEEDs survey).

Catheter-based renal denervation (RDN) is currently being developed as a new complementary treatment option for hypertension. RDN has not yet received approval in Japan and so the number of possible candidates for RDN in Japan also remains unknown. A total of 10 756 hypertensive patients who regularly visit medical institutions and reported their latest home blood pressure (BP) values were identified from registrants at an online research company. They filled out a survey regarding their prescribed antihypertensives and latest BP values in March 2020 in Japan. The mean age of the patients was 61.3 years old (83.5% male). According to JSH 2019, the prevalence of resistant hypertension (RHT) was estimated to be 1.4% (0.52% having an office BP of 140/90 mm Hg or more while taking three antihypertensives, including diuretics; 0.84% taking four or more antihypertensives regardless of BP level). Assuming the indication for RDN was RHT with morning home systolic BP (HSBP) ≥ 135 mm Hg and office systolic BP (OSBP) ≥ 140 mm Hg, the number of candidates for RDN was estimated to be approximately 340 000 and 372 000, respectively. When hypertensive patients prescribed three or more, two, one, and no antihypertensives were included, the estimated number based on uncontrolled HSBP and OSBP cumulatively increased 2.6, 14.2, 40.6, and 58.0-fold; 1.8, 8.6, 25.3, and 36.4-fold, respectively. These findings revealed that a substantial number of hypertensive patients are unable to adequately control their BP level with existing treatments, and new complemental therapies, such as RDN, would alleviate the burden of hypertension in this population.

Subxiphoid dual-port thymectomy for thymoma in a patient with post-aortic left brachiocephalic vein.

Post-aortic left brachiocephalic vein (PALBV) is one of the rare congenital vessel abnormalities associated with congenital heart disease. As only a few reports of surgical treatment for thymic tumor in patients with PALBV are available, this study reports the case of a patient with PALBV who underwent surgical treatment for thymoma. In a 60-year old woman, a nodule in the anterior mediastinum was detected on chest computed tomography (CT) during examination for arrhythmia. Thymoma was suspected, and surgical resection was considered. PALBV was detected on a contrast CT scan before surgery. Video-assisted thoracoscopic surgery was used to perform thymectomy using the subxiphoid dual-port approach. This method provided an appropriate view of the operative field and made it easy to confirm the presence of PALBV and identify the thymic veins branching off from the internal thoracic vein.

[Introduction of Minimally Invasive Thoracoscopic Surgery for the Anterior Mediastinum;Subxiphoid Video-assisted Thoracoscopic Thymectomy and Robot-assisted Thymectomy].

In Japan, robot-assisted surgery for malignant lung tumors, benign mediastinal tumors, and malignant mediastinal tumors has been covered by the national health insurance since 2018. Hence, the number of domestic robotic surgical procedures is increasing. Recently, we introduced endoscopic surgery such as video-assisted thoracoscopic surgery (VATS) via a subxiphoidal approach for thymectomy. Here, we compared VATS and robotic surgery via a subxiphoidal approach in terms of clinical factors. During the study period, 5 consecutive patients who underwent robotic thymectomy and 24 patients who underwent VATS were analyzed. Although the operative time was longer in the robotic group, the intraoperative blood loss, postoperative length of stay, and postoperative complications were favorable in the robotic group. The disadvantage of robotic surgery is the necessity for a reduction in operative time including console duration time. However, future developments in the field of robotic engineering will lead to the creation of systems that allow for more advanced surgical techniques. We must chose procedures in consideration of the best method for each patient, and it is necessary to perform robotic surgery based on the expense and therapeutic effect, social environment, and way of life of each patient.

Resection of intra-pulmonary endometriosis by video-assisted thoracoscopic surgery under pre-operative CT-guided marking synchronized with menstrual cycle.

A 37-year-old woman experienced repeated catamenial hemoptysis. She had a history of intrauterine curettage. Computed tomography (CT) showed ground glass opacity (GGO) in the right upper lung lobe. We suspected pulmonary endometriosis and scheduled surgery coincides with her menstrual cycle. Then she underwent surgical resection after pre-operative CT-guided marking of the pulmonary endometrial lesion. A yellowish change of the pleura was observed near the marking and the lesion was resected using video-assisted thoracoscopic surgery. Histopathologically, endometrial glands and intimal interstitium were evident. She has no symptoms 2.5 years after surgery. In this case, scheduling the surgery at the time of her menstrual period and video-assisted thoracoscopic surgery (VATS) after CT-guided marking facilitated effective resection.

Correlation between histological invasiveness and the computed tomography value in pure ground-glass nodules.

PURPOSE: The purpose of this study was to evaluate the correlation between histological invasiveness and the computed tomography (CT) value and size in pure ground-glass nodules (GGNs) to determine optimal "follow-up or resection" strategies. METHODS: Between 2001 and 2014, 78 resected, pure GGNs were retrospectively evaluated. The maximum diameter and CT value of pure GGNs were measured using a computer graphics support system. RESULTS: All GGNs with a maximum diameter ≤10 mm and CT value ≤-600 Hounsfield units (HU) were considered to be noninvasive lesions, while 21 of 26 (81 %) with a maximum diameter >10 mm and CT value >-600 HU were considered to be invasive lesions. With respect to the correlation between each histological type and pure GGN with a maximum diameter ≤10 mm and CT value ≤-600 HU, the specificity was 90 % and the sensitivity and negative predictive value were both 100 % in atypical adenomatous hyperplasia (AAH), while the specificity was 58 % and the sensitivity and positive predictive value were 0 % in minimally invasive and invasive adenocarcinoma. CONCLUSION: Pure GGNs with a maximum diameter of ≤10 mm and CT value of ≤-600 HU are nearly always pre-invasive lesions; therefore, surgery should be carefully selected in such patients.

A Surgical Case of Bronchial Artery Aneurysm Directory Connecting with Pulmonary Artery.

We present a surgical case of bronchial artery aneurysm (BAA) connecting pulmonary artery accompanied with racemose hemangioma. This is a third surgical case report of BAA directly connecting pulmonary artery in the English literature. A 63-year-old female was found a BAA, 2 cm in diameter, connecting right A4 pulmonary artery. The patient underwent two attempts for embolization. However, due to extensive collaterals, there was persistent flow in the aneurysm. Standard lateral thoracotomy was performed. A BAA was located between A4 and A5 PA. A small branch of A4 PA was separated, and the small vessel connecting to the BAA could be ligated. A5 PA was separated similarly, however BAA was ruptured not to identify the other small vessel connecting to the BAA. After a clamp of the BAA, middle lobe lobectomy was performed. We removed the aneurysm with dilated bronchial artery connecting to the aneurysm. The postoperative course was uneventful.

[Ultra powered stapling system for general lung surgery].

OBJECTIVE: Stapling systems can significantly improve lung tissue approximation during open and video-assisted thoracic surgery. We here evaluated an iDrive Ultra powered stapling system for lung resection. MATERIALS AND METHODS: The iDrive Ultra powered stapling system( Covidien) is the powered version of the EndoGIA stapling system. It comprises hand-held control unit combined with a loading unit,which is a powered EndoGIA- cartridges, for use in open and minimally invasive thoracic surgery. The mounted control unit has uses as follows:controlling the accurate placement of the cartridge by orientating the tip of the rigid shaft;and controlling the closure of the stapler and the firing. From April to July 2013, the system was used for a consecutive series of 15 patients during thoracic lung surgery. RESULTS: There were 6 women and 9 men, with a mean age of 62 years. The following procedures were performed:lobectomies, segmentectomies, and wedge resections. The system was used for stapling lung parenchyma for wedge resection(5 patients), segmentectomy( 2 patients), or fissure division (9 patients). There were no stapling failures and no complications related to use of the staplers. CONCLUSIONS: The new powered and handy stapling system is safe and efficient for lung resection.

Variants in the flavin-containing monooxygenase 3 (FMO3) gene responsible for trimethylaminuria in a Japanese population.

Loss-of-function mutations of flavin-containing monooxygenase 3 (FMO3), the enzyme responsible for trimethylamine N-oxygenation, cause the inherited disorder trimethylaminuria, or fish odor syndrome. The aim of this study was to further investigate the inter-individual variations of FMO3 activity in a Japanese cohort that we had studied previously. The subjects were 640 Japanese volunteers with self-reported trimethylaminuria; genomic DNA was sequenced in those that had 10-70% FMO3 metabolic capacity in urine tests. A heterozygote for the novel single nucleotide substitution p.Ile441Thr (proband 1) and a heterozygote for the novel single nucleotide substitution p.Ser195Leu (proband 2) were identified. The biological parents of probands 1 and 2 were heterozygous and had >90% trimethylamine N-oxygenation metabolic capacity. In addition, single nucleotide substitutions p.Val58Ile, p.Pro70Leu, and p.Gly421Val in FMO3 were found in probands 3-7. In the course of DNA sequencing, another FMO3 variant, p.Thr488Ala, was found in two unrelated heterozygous subjects. Variant FMO3 proteins recombinantly expressed in Escherichia coli membranes exhibited decreased activity toward typical FMO3 substrates. Although the allele frequencies of these six novel variants were low (<1%), the present results suggest that individuals homozygous or heterozygous for any of the six novel missense FMO3 variants or known nonsense mutations such as p.Cys197stop or p.Arg500stop may possess abnormal trimethylamine N-oxygenation.

One-dimensional mean computed tomography value evaluation of ground-glass opacity on high-resolution images.

OBJECTIVE: Differentiation of atypical adenomatous hyperplasia (AAH), bronchioloalveolar carcinoma (BAC), and invasive carcinoma on computed tomography (CT) is useful for determining "follow-up or resection" strategies for lesions displaying ground-glass opacity (GGO). The purpose of this study is to evaluate one-dimensional quantitative CT values of GGO on high-resolution CT (HRCT) images using computer-aided diagnosis. METHODS: Between April 2001 and March 2010, a total of 44 nodules in 42 patients with pure or mixed GGOs ≤2 cm were retrospectively evaluated. Maximum diameter and one-dimensional mean CT (m-CT) value of the diameter were measured using a computer graphics support system (HOPE/DrABLE-EX, Fujitsu, Tokyo, Japan) that displays a CT density profile across the tumor. RESULTS: m-CT values were -682 ± 64 HU (range) for AAH lesions, -544 ± 179 (range) for Type A lesions, -496 ± 147 (range) for Type B lesions, and -371 ± 142 (range) for invasive lesions. AAH lesions had a significantly lower m-CT value than Type B lesions. AAH, Type A, and Type B lesions had significantly lower m-CT values than invasive lesions (p < 0.05). All seven GGO lesions with a maximum diameter ≤1 cm and m-CT value ≤-600 HU were pre-invasive lesions, while 16 of 22 (73 %) cases with maximum diameter >1 cm and m-CT value >-600 HU were invasive lesions. CONCLUSION: Observation may be indicated for GGO lesions with a maximum diameter ≤1 cm and m-CT value ≤-600 HU.

C(3)-symmetric chiral trisimidazoline: design and application to organocatalyst.

C(3)-symmetric chiral trisimidazoline was designed and synthesized as a new entry of organocatalyst with the concept of constructing C(3)-symmetric molecules with three C(2)-symmetric chiral components, and the application of this novel catalyst to asymmetric conjugate addition of beta-ketoesters to nitroolefins was described.

Tandem beta-enamino ester formation and cyclization with o-alkynyl anilines catalyzed by InBr3: efficient synthesis of beta-(N-indolyl)-alpha,beta-unsaturated esters.

A tandem reaction providing beta-(N-indolyl)-alpha,beta-unsaturated esters from beta-keto esters and o-alkynyl anilines was developed. Z-Alkenes were selectively formed due to the stability of the beta-enamino ester as an intermediate of the reaction. This reaction includes the intermolecular beta-enamino ester formation and intramolecular cyclization catalyzed by InBr(3).