[Video-assisted Thoracoscopic Surgery for Chest Trauma].

Video-assisted thoracoscopic surgery (VATS) is now commonly used in emergency surgery to confirm the site of injury and observe the thoracic cavity, especially in cases of chest trauma with stable vital signs. VATS was used in all 33 chest trauma surgeries performed at our department from October 2009 to July 2023. The common injury mechanisms were traffic trauma and falls, but there were also cases of trauma from a bullhorn, heavy machinery and farm equipment, and penetrating injury. The common surgical procedures were treatment of rib fractures and pulmonary suture or partial lung resection, followed by treatment of diaphragmatic injuries. Unusual surgical procedures included extrapleural hematoma drainage, pericardial drainage, hemostasis of intrathoracic bleeding from thoracic vertebral fracture, and lobectomy for airway bleeding. Here, we report our surgical policies and techniques for chest trauma. First, the thoracic cavity should be observed thoracoscopically to determine the site of injury. The key to repair is placement of a small thoracotomy directly above the rib fracture site, where dislocation is largest, followed by suture repair of the lung and diaphragm by combining direct and thoracoscopic views.

[Three-dimensional and 4K Three-dimensional Uniportal Video-assisted Thoracoscopic Surgery for Mediastinal and Chest Wall Disease During Respiratory Surgery].

Uniportal video-assisted thoracoscopic surgery (VATS) lobectomy has recently been used with increasing frequency by thoracoscopic surgeons, even in Japan. However, few reports have previously described uniportal VATS for mediastinal and chest wall disease. From April 2008 to December 2022, 159 patients were treated for mediastinal and chest wall disease. We divided the patients into three groups based on the type of surgery:robot-assisted thoracoscopic surgery( RATS), n=21;multi-portal surgery (using a two-dimensional [2D] system), n=55;and uniportal surgery, n=83. Of the 83 cases in the uniportal surgery group, 49 underwent surgery with a three-dimensional( 3D) or 4K-3D system. The operation duration, blood loss, and postoperative stay duration were compared among the groups. A p-value of <0.05 was considered statistically significant. The operation duration, intraoperative blood loss, and postoperative stay duration were significantly lower in the uniportal group (3D, 4K-3D) than in the multi-portal group (2D), with respective p-values of 0.001, 0.034, and 0.005. The RATS group showed a reduced blood loss trend, but not to a significant degree. In conclusion, our findings suggest that a 3D system can optimize surgical performance compared to a 2D system. In particular, using a 4K-3D system with high-definition imaging and stereoscopic vision enables surgeons to perform less-invasive thoracoscopic surgery than would otherwise be feasible.

[Palmar Hyperhidrosis Associated with the Azygos Lobe].

A 66-year-old man visited our department because of palmar hyperhidrosis. Computed tomography had revealed division of the right upper lobe by a fissure and the azygos vein, and the presence of an azygos lobe had been diagnosed. Endoscopic thoracic sympathectomy (resection of T3 ganglion) was performed. Adhesion between the azygos lobe and parietal pleura was dissected to pulling out the azygos lobe and the sympathectomy was safely performed.

Final report of KSCC0803: feasibility study of capecitabine as adjuvant chemotherapy for stage III colon cancer in Japan.

BACKGROUND: The impact of oral capecitabine as adjuvant chemotherapy for Japanese patients with resected colon cancer was unclear. We previously planned and conducted a prospective feasibility study (KSCC0803) and reported on the safety of oral capecitabine as adjuvant chemotherapy for Japanese patients with resected stage III colon cancer. The purpose of the current study was to assess the survival results from that study. METHODS: The study subjects were Japanese patients with resected stage III colon cancer. The protocol adjuvant regimen consisted of oral capecitabine 1250 mg/m2 twice daily on days 1-14 of a 3-week cycle for a total of eight cycles. The 3- and 5-year disease free survival (DFS) rates and overall survival (OS) rates were analyzed in the eligible cohort. RESULTS: Ninety-seven patients were registered between September 2008 and August 2009 and treated with the protocol regimen. The median follow-up time was 60.7 months. The 3- and 5-year DFS rates were 71.2% [95% confidence interval (CI): 61.7-79.8%] and 69.7% (95% CI: 59.4-77.8%), respectively. The 3- and 5-year OS rates were 92.6% (95% CI: 85.2-96.4%) and 84.5% (95% CI: 75.1-90.5%), respectively. CONCLUSIONS: The survival results in this study are in line with those of previously reported, reliable, studies. The safety and tolerability of the protocol regimen have already been confirmed. Oral capecitabine is acceptable as adjuvant chemotherapy for Japanese patients with resected stage III colon cancer.

UDP-glucuronosyltransferase 1A1*6 and *28 polymorphisms as indicators of initial dose level of irinotecan to reduce risk of neutropenia in patients receiving FOLFIRI for colorectal cancer.

BACKGROUND: Irinotecan (CPT-11)-induced neutropenia is associated with UDP-glucuronosyltransferase (UGT) 1A1*6 and *28 polymorphisms. This prospective study investigated whether using these polymorphisms to adjust the initial dose of CPT-11 as part of FOLFIRI treatment in colorectal cancer patients might improve safety. METHODS: All data were collected by a physician. The relationship between UGT1A1 polymorphisms and first-cycle neutropenia, reasons for treatment discontinuation, and time-to-treatment failure were evaluated. Multivariate analysis was used to assess the risk of neutropenia. RESULTS: A total of 795 patients were divided into wild-type (*1/*1) (50.1 %), heterozygous (*28/*1, *6/*1) (41.1 %), and homozygous (*28/*28, *6/*6, *28/*6) (8.8 %) groups, in which the median starting dose of CPT-11 was 143.0, 143.0, and 115.0 mg/m(2), respectively. First-cycle grade ≥3 neutropenia occurred in 17.3, 25.4, and 28.6 % of these patients, respectively. Multivariate analysis revealed that the incidence of grade ≥3 neutropenia was significantly greater in the heterozygous and homozygous groups than in the wild-type group [odds ratio (OR) 1.67; 95 % confidence interval (CI) 1.16-2.42; p = 0.0060, and OR 2.22; 95 % CI 1.22-4.02; p = 0.0088, respectively]. Age (OR 1.77; 95 % CI 1.24-2.53; p = 0.0017), coelomic fluid (OR 1.84; 95 % CI 1.05-3.25; p = 0.0343), and non-reduction in starting dose (OR 1.53; 95 % CI 1.08-2.18; p = 0.0176) were also identified as significant risk factors. CONCLUSION: The risk of neutropenia was higher in the heterozygous and homozygous groups at initiation of CPT-11 treatment. This suggests that when a reduction in dose is required in patients harboring two variant alleles, the decrease should be approximately 20 %.

Phase II trial of an alternating regimen consisting of first-line mFOLFOX6 plus bevacizumab and FOLFIRI plus bevacizumab for patients with metastatic colorectal cancer: FIREFOX plus bevacizumab trial (KSCC0801).

OBJECTIVES: The purpose of this phase II study was to explore the efficacy and safety of an alternating regimen consisting of folinic acid, 5-fluorouracil (5-FU) and oxaliplatin (mFOLFOX6) plus bevacizumab, and folinic acid, 5-FU and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer. METHODS: Fifty-two patients with metastatic colorectal cancer received an alternating regimen consisting of four cycles of mFOLFOX6 plus bevacizumab followed by four cycles of FOLFIRI plus bevacizumab until disease progression. The primary endpoint was progression-free survival. RESULTS: The median age was 60 years (range 37-75 years). Median progression-free survival was 14.2 months (95 % confidence interval [CI] 10.6-16.3) and median overall survival was 28.4 months (95 % CI 22.6-39.1). The overall response rate was 60.0 % (95 % CI 45.2-73.6). Regarding toxicity, the commonest grade 3-4 hematological adverse events were neutropenia (34.6 %) and leukopenia (7.7 %), and the commonest grade 3-4 non-hematological adverse events were anorexia (13.5 %), fatigue (9.6 %), nausea (9.6 %), and vomiting (9.6 %). Bevacizumab-related grade 3-4 adverse events included hypertension (1.9 %) and thrombosis (1.9 %). CONCLUSIONS: An alternating regimen consisting of mFOLFOX6 plus bevacizumab and FOLFIRI plus bevacizumab is an effective and well-tolerated first-line chemotherapy combination for patients with metastatic colorectal cancer.

A prospective study of XELOX plus bevacizumab as first-line therapy in Japanese patients with metastatic colorectal cancer (KSCC 0902).

BACKGROUND: This study was designed to evaluate the efficacy and safety of XELOX plus bevacizumab in a Japanese metastatic colorectal cancer population that included elderly patients. METHODS: This was a multicenter, single-arm, open-label prospective study. The major inclusion criteria were previously untreated metastatic colorectal cancer, presence of measurable lesions, age ≥ 20 years; Eastern Cooperative Oncology Group performance status of 0-2, and adequate organ function. Patients received bevacizumab (7.5 mg/kg on day 1) and XELOX (130 mg/m(2) oxaliplatin on day 1 plus 1,000 mg/m(2) capecitabine b.i.d. on days 1-14) every 3 weeks. The primary endpoint was confirmed objective response rate. RESULTS: The study included 47 patients (male/female 30/17; median age 69 years; age range 38-81 years with 10 patients ≥ 75 years; PS 0/1/2, 40/5/2) enrolled between May 2010 and March 2011. Responses were assessed in 46 eligible patients. The objective response rate was 52.2 % (95 % confidence interval [CI] 37.0-67.1). The median progression-free survival and overall survival were 10.0 months (95 % CI 7.8-12.3) and 34.6 months (95 % CI 19.9-not estimable), respectively. Frequently encountered grade 3 and 4 adverse events in this study were aspartate aminotransferase elevation (23.4 %), alanine aminotransferase elevation (21.3 %), anorexia (12.8 %), neutropenia (10.6 %), fatigue (8.5 %) and anemia (6.4 %). Grade 3 or 4 peripheral neuropathy was not observed. CONCLUSION: First-line treatment with XELOX plus bevacizumab showed a promising response rate and an acceptable tolerability profile in the clinical practice of Japanese metastatic colorectal cancer patients that included elderly patients. REGISTRY: UMIN-CTR, ID number: UMIN000003915, URL:https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000004706&language=E.

Poor association between dihydropyrimidine dehydrogenase (DPYD) genotype and fluoropyrimidine-induced toxicity in an Asian population.

OBJECTIVE: Dihydropyrimidine dehydrogenase (DPYD) genotype is closely associated with fluoropyrimidine (FP)-induced toxicities in Caucasian population and European Medicines Agency now recommends DPYD genotype-based FP dosing strategy. PATIENTS AND METHODS: The current study aimed to investigate their impact on FP-related toxicities in an Asian population using genome-wide association study (GWAS) data set from 1364 patients with colon cancer. RESULTS: Among 82 variants registered in the Clinical Pharmacogenetics Implementation Consortium, 74 DPYD variants were directly genotyped in GWAS cohort; however, only 7 nonsynonymous DPYD variants (CPIC variants) were identified and none of the four recurrent DPYD variants (DPYD*2A, c.2846A>T, c.1679T>G, c.1236G>A) were included. Seven CPIC variants were investigated for their association with the incidence of FP-related toxicities; however, none of these variants revealed a significant correlation with FP-related toxicities. CONCLUSION: These data suggested that the DPYD genotype registered in CPIC plays a minor role in FP-related toxicities in an Asian population.

[Single-incision thoracoscopic surgery( SITS) for mediastinal disease].

The use of single-incision laparoscopic surgery is spreading widely, even in Japan, however, in the field of thoracic surgery, there exist no previous reports on the use of the Wound retractor system in single-incision thoracoscopic surgery (SITS) for mediastinal disease. We herein describe the 1st cases of video-assisted SITS of the mediastinum. Fifteen patients (5 males, 10 females) with mediastinal disease underwent SITS. The average age of the patients was 66.8( 44 ~ 90) years. The mean operative time was 186.2 minutes. Chest drainage tubes were not placed in 12 cases. Chest tubes were removed after 2.5 days in three cases. The mean postoperative hospital stay was 3.3 (2 ~ 8) days. In this report, the use of an access instrument for SITS is presented. We performed extended thymectomy using Vein harvest during surgery in patients with myasthenia gravis. The device could be handled successfully, thereby avoiding interferences between the operator and assistants. In conclusion, we believe that SITS is a feasible and safe procedure that is beneficial in selected cases.

Partial breast reconstruction for an inferomedial breast carcinoma using an omental flap.

BACKGROUND: Various oncoplastic techniques are used for partial reconstruction after breast-conserving surgery (BCS), but treatment of an inferomedial breast carcinoma (IMBC) can be difficult, especially in a small breast. We review our experience with immediate partial breast reconstruction after BCS for an IMBC using a laparoscopically harvested omental flap (OF). METHODS: The subjects were 24 patients with an IMBC who underwent immediate partial breast reconstruction with the OF between April 2002 and June 2009. A wide excision (>20% of the breast tissue) was performed through a skin incision along the medial inframammary fold. The pedicled OF was harvested laparoscopically and used to fill the dead space in the inferomedial quadrant. RESULTS: The mean follow-up period was 35 months. The mean tumor size was 3.2 cm. The mean volume of resected breast tissue was 180 g and the mean extent of resection was 40%. The complication rate was 12.5% and all were minor and treated conservatively. Laparoscopy-associated complications did not occur, except for one minor injury of the gastroepiploic artery. The surgical margin was positive in only 1 patient (4.2%) and neither local nor systemic recurrence has occurred to date in any patients. Cosmetic outcomes were mostly satisfactory, with minimal donor-site scars in the abdominal wall. Cosmetic failure occurred in 1 patient (4.2%) due to an inadequate OF volume. CONCLUSIONS: Laparoscopic harvesting of the OF is a safe procedure with minimal donor-site morbidities and deformities. This approach is an option for immediate partial reconstruction after BCS for an IMBC.

JOIN trial: treatment outcome and recovery status of peripheral sensory neuropathy during a 3-year follow-up in patients receiving modified FOLFOX6 as adjuvant treatment for stage II/III colon cancer.

PURPOSE: Adjuvant FOLFOX therapy is an established standard-of-care for resected colon cancer. Peripheral sensory neuropathy (PSN) is regarded as the major toxicity issue related to FOLFOX therapy. There have been a few reports on the recovery status from PSN thereafter. JOIN trial investigated the tolerability and efficacy of adjuvant modified FOLFOX6 (mFOLFOX6) in Japanese patients with stage II/III colon cancer. METHODS: Twelve cycles of mFOLFOX6 were given to patients with stage II/III curatively resected colon cancer. Treatment outcomes, including disease-free survival (DFS), relapse-free survival (RFS), overall survival (OS), and recovery status of PSN during 3-year follow-up, were investigated. RESULTS: Of the 882 patients enrolled from 2010 to 2012, 864 were eligible for the efficacy analyses. Three-year DFS, RFS, and OS were favorable in 92.1, 92.8, and 97.4% of stage II patients; 76.4, 77.9, and 93.8% of stage IIIA/B; and 61.6, 62.7, and 85.9% of stage IIIC, respectively. The cumulative incidence of PSN during treatment was 47.8% in grade 1 (G1), 30.3% in G2, and 5.8% in G3. For those with G3 PSN during treatment, there was gradual recovery in 1.1% of patients at 12 months after enrollment, 0.5% at 24 months, and 0.2% at 36 months. However, G1 or G2 residual PSN after 3 years was observed in 21.0% (18.7%, G1; 2.3%, G2). CONCLUSIONS: Adjuvant mFOLFOX6 therapy was effective and well tolerated in patients with stage II/III colon cancer. Most patients recovered from G3 PSN related to oxaliplatin, but approximately 20% of patients had G1 or G2 PSN at 3-year follow-up.

A Multicenter Clinical Phase II Study of FOLFOXIRI Plus Bevacizumab as First-line Therapy in Patients With Metastatic Colorectal Cancer: QUATTRO Study.

BACKGROUND: FOLFOXIRI (Fluorouracil, folinate, oxaliplatin, and irinotecan) plus bevacizumab improved progression-free survival (PFS) and overall survival in patients with metastatic colorectal cancer (mCRC), compared with FOLFIRI (fluorouracil, folinate, and irinotecan) plus bevacizumab, but significantly increased the incidences of adverse events. The efficacy and safety profiles of FOLFOXIRI plus bevacizumab in ethnic Asian patients have not been established yet. PATIENTS AND METHODS: This study was an open-label, single-arm, multi-centered phase II prospective clinical trial in patients with mCRC who received FOLFOXIRI plus bevacizumab. The primary endpoint was the PFS rate at 10 months. Secondary endpoints included overall survival, response rate, and safety. RESULTS: A total of 69 patients received FOLFOXIRI plus bevacizumab as induction therapy and were assessed for efficacy and safety. The PFS rate at 10 months was 75.2% and the median PFS was 13.3 months. Complete response and partial response were achieved in 2 (2.9%) and 47 patients (69.1%), respectively. Grade 3 and 4 adverse events with incidence rates exceeding 20% were neutropenia (72.5%), hypertension (34.8%), leucopenia (33.3%), and febrile neutropenia (21.7%). Significantly more patients with grade 4 neutropenia had single-heterozygous UGT1A1*1/*6 or *1/*28 (46.2%) than UGT1A1 wild-type genotype (*1/*1) (13.3%) (P = .004). CONCLUSIONS: FOLFOXIRI plus bevacizumab is considered an effective first-line regimen that improves the outcome of patients with mCRC regardless of ethnicity. In Asian patients, utmost attention should be paid to the possible onset of severe neutropenia or febrile neutropenia attributed to different types of UGT1A1*6 and *28 polymorphism, when FOLFOXIRI plus bevacizumab is administered.

Initial safety report on the tolerability of modified FOLFOX6 as adjuvant therapy in patients with curatively resected stage II or III colon cancer (JFMC41-1001-C2: JOIN trial).

PURPOSE: Adjuvant FOLFOX is a widely accepted standard therapy for resected colon cancer. The incidence of grade 3-4 peripheral sensory neuropathy (PSN) was 12.4 and 5.7 % in the MOSAIC and Eastern MASCOT trials, while that of grade 3-4 allergic reactions (AR) was 2.9 and 3.1 %, respectively. The JFMC41-1001-C2 trial (JOIN trial) investigated the tolerability of modified FOLFOX6 (mFOLFOX6) in Japanese colon cancer patients. METHODS: Twelve cycles of mFOLFOX6 were given to patients with the same eligibility criteria as in the MOSAIC study: stage II or III curatively resected colon cancer, performance status of 0-1, aged 20 years or older, starting mFOLFOX6 within 7 weeks of surgery, and adequate organ function. The primary endpoints were the incidence of PSN persisting for ≥8 days that interfered with daily activities and the incidence of grade 3-4 AR. The target sample size was 800. RESULTS: From November 2010 to March 2012, 882 patients were enrolled at 198 institutions. Safety was analyzed in 828 patients with finalized data out of 848 patients receiving mFOLFOX6. The incidence of PSN persisting ≥8 days was 3.3 % [95 % confidence interval (CI) 2.2-4.7], while that of grade 3-4 AR was 1.7 % (95 % CI 0.9-2.8). The treatment completion rate was 67.0 %. The median total dosage of oxaliplatin was 811.1 mg/m(2). The overall incidence of grade 3-4 PSN was 5.8 %. Interstitial pneumonitis occurred in one patient. There were no treatment-related deaths. CONCLUSIONS: Adjuvant mFOLFOX6 is tolerable for Japanese patients with colon cancer.