5-Methoxytryptophan enhances the sensitivity of sorafenib on the inhibition of proliferation and metastasis for lung cancer cells.

BACKGROUND: Lung cancer is a leading cause of cancer-related mortality worldwide, and effective therapies are limited. Lung cancer is a leading cause of cancer-related mortality worldwide with limited effective therapy. Sorafenib is a multi-tyrosine kinase inhibitor frequently used to treat numerous types of malignant tumors. However, it has been demonstrated that sorafenib showed moderate antitumor activity and is associated with several side effects in lung cancer, which restricted its clinical application. This study aimed to examine the antitumor effect of the combination treatment of sorafenib and 5-methoxytryptophan (5-MTP) on cell growth and metastasis of Lewis lung carcinoma (LLC) cells. METHOD: The anticancer effect of the combination treatment of sorafenib and 5-MTP was determined through cytotoxicity assay and colony forming assays. The mechanism was elucidated using flow cytometry and western blotting. Wound healing and Transwell assays were conducted to evaluate the impact of the combination treatment on migration and invasion abilities. An in vivo model was employed to analyze the effect of the combination treatment on the tumorigenic ability of LLC cells. RESULT: Our results demonstrated that the sorafenib and 5-MTP combination synergistically reduced viability and proliferation compared to sorafenib or 5-MTP treatment alone. Reduction of cyclin D1 expression was observed in the sorafenib alone or combination treatments, leading to cell cycle arrest. Furthermore, the sorafenib-5-MTP combination significantly increased the inhibitory effect on migration and invasion of LLC cells compared to the single treatments. The combination also significantly downregulated vimentin and MMP9 levels, contributing to the inhibition of metastasis. The reduction of phosphorylated Akt and STAT3 expression may further contribute to the inhibitory effect on proliferation and metastasis. In vivo, the sorafenib-5-MTP combination further reduced tumor growth and metastasis compared to the treatment of sorafenib alone. CONCLUSIONS: In conclusion, our data indicate that 5-MTP sensitizes the antitumor activity of sorafenib in LLC cells in vitro and in vivo, suggesting that sorafenib-5-MTP has the potential to serve as a therapeutic option for patients with lung cancer.

Comparison of therapeutic outcomes in esophageal squamous cell carcinoma following neoadjuvant chemoradiotherapy: A prospective observational cohort study.

BACKGROUND: Patients with locally advanced esophageal squamous cell carcinoma (ESCC) following neoadjuvant chemoradiotherapy (nCRT) may not always receive resection despite the possible achievement of a pathologic complete response (pCR) being associated with superior survival benefit. We aimed to compare outcomes among ESCC patients with or without pCR and those refusing surgery. METHODS: In total, 111 medically operable, non-cervical ESCC patients after the same protocol of nCRT (platinum/5-fluorouracil plus radiation 50Gy) were prospectively enrolled between 2011 and 2021. Eighty-three of them underwent esophagectomy comprising pCR (n = 32) and non-pCR (n = 51), while 28 operable patients declined surgery (refusal-of-surgery group). Predictors and survival data were analyzed. RESULTS: In terms of esophagectomy, 38.5% (32/83) patients achieved pCR. The pCR group exhibited better pretreatment performance status than the non-pCR group (adjusted odds ratio: 0.11, 95% confidence interval: 0.03-0.58; p = 0.01). Among pCR, non-pCR, and refusal-of-surgery groups, the 5-year overall survival (OS) rates were 56%, 29% and 50% (p = 0.08) and progression-free survival (PFS) rates were 52%, 28% and 36% (p = 0.07) respectively. The pCR group had significantly better OS and PFS than the non-PCR group (adjusted hazard ratio: 2.33 and 1.93, p = 0.02 and 0.049 respectively) but not the refusal-of-surgery group. CONCLUSION: Better pretreatment performance status is associated with higher chance of pCR. Consistent with previous studies, we found attainment of pCR confers the best OS and PFS. Suboptimal OS in the refusal-of-surgery group reflects some of them would have residual disease in addition to complete remission. Further studies are needed to identify prognostic factors of pCR to select candidates who could validly decline esophagectomy.

Risk factors of stent migration in esophageal cancer patients who underwent fully-covered self-expanding metal stents for malignant dysphagia or tracheoesophageal fistula.

BACKGROUND: More than 50% of esophageal cancer patients are diagnosed with advanced diseases and commonly experience dysphagia, some of whom even have tracheoesophageal fistula. Self-expandable metal stent (SEMS) is one of the recommended palliative methods, although complications such as chest pain and stent migration are not uncommon. The goal of this study was to examine the predictors of stent migration. METHODS: We conducted a retrospective cohort study to include patients with esophageal cancer and dysphagia/tracheoesophageal fistula. Clinicopathological information, stent characteristics and patient outcomes were collected for analysis, while side-effects of SEMS were recorded, potential predictors were examined, and patients' nutritional outcomes were compared in the migration and non-migration groups. RESULTS: A total of 54 patients with esophageal cancer who received fully covered SEMS between 2013 and 2022 were included. We found tumor across the esophagogastric junction (adjusted odds ratio (OR) = 32.64, P = 0.01) and the female sex (adjusted OR = 12.5, P = 0.02) were significant predictors for stent migration. There was a decreasing tendency in body mass index/body weight in migration and non-migration groups, but the former had a steeper downslope. CONCLUSION: Fully covered SEMS is a safe and effective strategy to palliate dysphagia or fistula. Tumor across esophagogastric junction and the female sex were higher risk predictors of stent migration. A careful patient selection would optimize the effects of SEMS placement, especially in those with short-expected lifespan.

Lobectomy Versus Sublobar Resection in Simultaneous Bilateral Thoracoscopic Lung Resection.

BACKGROUND: Simultaneous bilateral thoracoscopic lung resection (SBTLR) has been shown to be a feasible and efficacious approach for a wide range of pulmonary conditions. Our aim was to evaluate the impact of different procedures on surgical outcomes in patients receiving SBTLR. METHODS: Between 2012 and 2021, 207 patients with bilateral lung neoplasms who underwent SBTLR were retrospectively reviewed. Fifty-one patients received ipsilateral plus contralateral lobectomy or sublobectomy (lobar group), whilst 156 patients received bilateral sublobectomy (sublobar group). Propensity scores were calculated and matched. Perioperative and clinicopathologic outcomes were compared. RESULTS: The lobar group had a greater mean age (64.5 vs. 60.0 years, p = 0.008), longer operative time (254 vs. 205 min, p < 0.001), and more blood loss (74 vs. 46 ml, p < 0.001). The sublobar group had fewer complications (6.4 vs. 19.6%, p = 0.006), shorter hospital stay (4.8 vs. 7.4 days, p < 0.001), and lower hospital costs (p = 0.03). Among 50 pairs of matched groups, significant differences were found only in operative time, hospital stay, and costs. Maximum tumor size and pathological features differed significantly before and after matching (all p < 0.05), with the lobar group consistently demonstrating a larger main tumor (median, 2.5 cm) and a higher percentage of primary lung cancer (84%). Multivariate logistic regression analysis showed that a longer operative time was the factor associated with more complications (OR: 1.01; 95% CI 1.00-1.02, p = 0.002). CONCLUSIONS: With regard to SBTLR, our data suggests that sublobectomy may reduce the prolonged recovery, hospital costs, and complications incurred by lobectomy, without compromising oncological outcomes.

Higher pre-treatment skin sympathetic nerve activity and elevated resting heart rate after chemoradiotherapy predict worse esophageal cancer outcomes.

BACKGROUND: Chemoradiotherapy (CRT), which might affect the autonomic system, is the mainstay therapy for advanced esophageal squamous cell carcinoma (ESCC). Autonomic dysfunction has been found to possibly lead to cancer mortality in those with elevated resting heart rates (RHR). Skin sympathetic nerve activity (SKNA) is a new method of stimulating electrical signals in skin to evaluate autonomic function from sympathetic tone. In this study, we investigated the association between changes in RHR and autonomic function and ESCC mortality. METHODS: Thirty-nine stage II-IV ESCC patients receiving CRT between March 2019 and November 2020 were prospectively enrolled and carefully selected, followed up and received the same meticulous supportive care. Serial RHR was recorded every two weeks from before CRT to eight weeks after CRT and average SKNA were recorded before and four weeks after CRT. All-cause mortality was defined as primary outcome. RESULTS: We found the RHR of ESCC patients to be significantly elevated and peaking at four weeks after CRT (p < 0.001) and then to gradually decrease. Those with an elevated RHR above the cutoff level (18 beat-per-minute) at eight weeks after CRT had worse overall survival. In addition, those with higher baseline sympathetic tone (average SKNA ≥ 0.86 µV) also had poor outcome. CONCLUSIONS: Increased pre-treatment sympathetic tone and elevated RHR after CRT are alarm signs of poor ESCC outcome. Further exploration of the mechanisms underlying these associations could potentially lead to intervention strategies for reducing mortality. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, identifier: NCT03243448.

Is a Chest Tube Necessary after Video-Assisted Thoracoscopic Mediastinal Tumor Resection?

BACKGROUND: The omission of chest tubes after thoracoscopic procedures such as sympathectomy, lung biopsy, and lung resection has proven efficacious in decreasing pain and length of hospital stay in some cases. However, its safety for mediastinal diseases remains unclear. This study evaluated the feasibility and outcome of eliminating chest drains after video-assisted thoracoscopic surgery (VATS) for mediastinal tumor resection. METHODS: We retrospectively investigated 70 patients receiving VATS mediastinal tumor resection in a single institution between January 2016 and November 2018. A total of 39 patients (drain group) received postoperative chest drains and 31 patients (no-drain group) did not. Group clinical outcomes and operation data were compared. A propensity score matching analysis was further performed to yield a fairer comparison. RESULTS: Before propensity score matching, the no-drain group had a higher prevalence of cystic lesions, a shorter operative time, and less blood loss compared with the drain group (p = 0.015, p = 0.018, and p < 0.001, respectively). After matching, the group differences in these perioperative variables lost significance (p = 0.095, 0.4, and 0.2, respectively). The no-drain group had lower postoperative day 2 pain scores and shorter postoperative hospital stays than the drain group, regardless of whether they were matched (pain: p = 0.028; hospital stay < 0.001) or not (pain: p = 0.003; hospital stay < 0.001). No major adverse events occurred in either group during hospitalization or follow-up period. CONCLUSION: Eliminating chest drain placement after VATS mediastinal tumor resection may benefit some patients and decrease postoperative pain and hospital stay without increasing complications or compromising patient safety.

Risk of two common glandular cell-type cancers (breast and colorectal cancers) in Chinese occupational chefs: a nationwide ecological study in Taiwan.

OBJECTIVES: Cooking oil fumes (COFs) contain many carcinogens. We investigated the association between COFs and incidence risk of colorectal cancer and female breast in chefs. METHODS: We identified Chinese food chefs and non-Chinese food chefs from Taiwan's national database of certified chefs in 1984-2007. In total, 379,275 overall and 259,450 females had not been diagnosed as having any cancer before chef certification. We followed these chefs in Taiwan's Cancer Registry Database (1979-2010) and Taiwan's National Death Statistics Database (1985-2011) for newly diagnosed colorectal cancer and female breast cancer. RESULTS: A total of 4,218,135 and 2,873,515 person-years were included in our analysis of colorectal cancer and female breast cancer incidence, respectively. Compared to non-Chinese food chefs, the Chinese food chefs had an adjusted IRR for colorectal cancer of 1.65 (95% CI 1.17-2.33). The risk of colorectal cancer was even higher among female Chinese food chefs certified for more than 5 years (adjusted incident rate ratio (IRR) = 2.39, 95% CI 1.38-4.12). For female breast cancer, the risk was also significant (adjusted IRR = 1.40, 95% CI 1.10-1.78) and the risks were even higher in female Chinese food chefs certified for more than 5 years (adjusted IRR = 1.74, 95% CI 1.37-2.22). CONCLUSIONS: This study found that Chinese food chefs had an increased risk of colorectal cancer and female breast cancer, particularly female chefs who had worked for more than 5 years. Future human and animal studies are necessary to re-confirm these findings.

Enteral nutrition and quality of life in patients undergoing chemoradiotherapy for esophageal carcinoma: a comparison of nasogastric tube, esophageal stent, and ostomy tube feeding.

BACKGROUND AND AIMS: This study prospectively recruited esophageal squamous cell carcinoma patients who received esophageal stent, nasogastric tube (NGT), or jejunostomy/gastrostomy feeding to compare the changes in nutritional status and quality of life during chemoradiation therapy (CRT). METHODS: In total, 81 patients were analyzed (stent, 7; surgical ostomy, 26; NGT, 19; oral intake, 29). An NGT was inserted when, despite medication, dysphagia or pain worsened with oral feeding during CRT. Serial body weight and daily narcotic demand were recorded. Changes in serum albumin level and quality of life were also assessed. In subgroup analysis comparing NGT and prophylactic surgical ostomy feeding, 5 patients with total occlusion in the ostomy group were excluded. RESULTS: Patients in all groups had similar decreases in mean body weight with an overall change of -6.41% ± 5.21% at the end of CRT. The stent group had significantly worse pain, decreased albumin (-1.03 ± .9 mg/dL), and decreased quality of life across CRT compared with the other groups. In subgroup analysis the stent group had significantly higher weight loss, whereas the NGT group had higher narcotic demand and slightly worse quality of life. Two patients (7.7%) had ileus days after jejunostomy creation. Five patients (23.8%) among those received prophylactic ostomy creation and scarcely used it. CONCLUSIONS: These preliminary results raise concerns that use of esophageal stents may be less suitable in patients undergoing CRT. Tube feeding by means of transnasal or percutaneous routes appear to be comparably effective during CRT, but both have advantages and disadvantages. We suggest a careful endoscopic evaluation to select the population more appropriate for NGT feeding on an as-needed basis during CRT.

Methylation status of retinoic acid receptor beta2 promoter and global DNA in esophageal squamous cell carcinoma.

BACKGROUND: Focal hypermethylation in promoter regions of tumor suppressor genes against the background of global hypomethylation is a landmark of carcinogenesis. This study aimed to investigate the methylation status of retinoic acid receptor beta2 (RARß2) and long interspersed nuclear elements (LINE-1) in different stages of esophageal squamous cell carcinoma (ESCC). METHOD: The tumor and adjacent normal esophageal tissues from 125 male ESCC patients who underwent primary surgery were analyzed for the methylation status of RARß2 promoter and LINE-1 through methylation-specific polymerase chain reaction and pyrosequencing. RESULTS: RARß2 hypermethylation was detected in 20% of the tumor samples, but not in the normal counterparts. The methylation frequency of LINE-1 was significantly lower in the tumor than in the normal parts (median: 67.7% vs. 80%, P < 0.0005). Ninety-eight patients (78.4%) had both RARß2 hypermethylation and LINE-1 hypomethylation or either one. There was a trend toward higher risk of advanced T stage (P for trend = 0.05) or lymph node metastasis (P for trend = 0.02) when more adverse gene methylation profiles were present. CONCLUSION: Methylation status of RARß2 and LINE-1 was related to the development and possibly the severity of ESCC.

Robot-assisted surgery outperforms video-assisted thoracoscopic surgery for anterior mediastinal disease: a multi-institutional study.

Anterior mediastinal procedures are increasingly being performed using robot-assisted thoracic surgery (RATS) or video-assisted thoracoscopic surgery (VATS). While both approaches have shown superior outcomes compared to open surgery, their comparative benefits are not as distinct. The aim of this retrospective study was to bridge this knowledge gap using a multicenter dataset. Patients who underwent elective minimally invasive surgery for anterior mediastinal disease between 2015 and 2022 were deemed eligible. The study participants were grouped based on whether a robot was used or not, and perioperative outcomes were compared. To mitigate selection bias, inverse probability of treatment weighting (ITPW) was applied using the propensity score. The final analysis included 312 patients (RATS = 120; VATS = 192). Following the application of IPTW, RATS was found to be associated with a longer operating time (215.3 versus 139.31 min, P < 0.001), fewer days with a chest tube (1.96 versus 2.61 days, P = 0.047), and a shorter hospital stay (3.03 versus 3.91 days, P = 0.041) compared to VATS. Subgroup analyses indicated that the benefit of RATS in reducing the length of hospital stay was particularly pronounced in patients with tumors larger than 6 cm (mean difference [MD] = - 2.28 days, P = 0.033), those diagnosed with myasthenia gravis (MD = - 3.84 days, P = 0.002), and those who underwent a trans-subxiphoid surgical approach (MD = - 0.81 days, P = 0.04). Both VATS and RATS are safe and effective approaches for treating anterior mediastinal disease. However, RATS holds distinct advantages over VATS including shorter hospital stays and reduced chest tube drainage periods.

Pneumorrhachis with spontaneous pneumomediastinum in pediatric patients: An 11-year retrospective study in Southern Taiwan.

BACKGROUND: Although uncommon, available evidence suggests that pneumorrhachis (PR) with spontaneous pneumomediastinum (SPM) in adulthood is usually benign and self-limiting. This study aimed to review our experience and identify the risk factors of PR in pediatric patients with SPM. METHODS: Between September 2007 and September 2017, SPM in patients aged ≤18 years was retrospectively reviewed and clinical features and outcomes between SPM patients with and without PR were analyzed. RESULTS: In total, thirty consecutive occurrences of SPM in 29 patients were finally identified and classified into SPM (n = 24) and SPM plus PR (n = 6) groups. No significant differences in received interventional exams, prophylactic antibiotic administration or restriction of oral intake between the two groups were found. Both groups were treated with hospitalization predominantly; but the SPM plus PR group tended to have longer length of hospital stay (median 5.5 vs. 3 days, p = 0.08). PR was observed more frequently in patients with abnormal serum C-reactive protein (CRP) levels (>5 mg/L), identified predisposing factors, and those with more severe grade of SPM (p = 0.005, 0.001 and < 0.001, respectively). On multivariable regression analysis, the SPM plus PR group exhibited more predisposing factors than did the SPM group (coefficient: 0.514, standard error: 0.136, p < 0.001). All patients were successfully treated without morbidity and mortality. CONCLUSION: Although patients with pneumorrhachis retained a higher CRP level, more identified predisposing factors and prolonged inpatient care, conservative management without an extensive work-up would be an appropriate and favorable strategy in pediatrics with concurrent SPM and PR.

Feasibility of emergency laparoscopic colectomy for children with acute colonic perforations and fibropurulent peritonitis.

BACKGROUND: Several studies have demonstrated that laparoscopic surgery is safe and effective for urgent and emergent colectomy in adulthood. The aim of the present study was to evaluate the feasibility of laparoscopic colectomy for children in emergent settings. METHODS: Between March 2008 and August 2011, 10 consecutive children with acute colonic perforations and fibropurulent peritonitis secondary to infectious colitis underwent emergency laparoscopic colectomy. Simultaneously, we reviewed and recorded the same data from another consecutive 10 patients who underwent standard laparotomy between November 2004 and February 2008. The two groups were compared with regard to operative time, length of hospital stay (LOS), and complications. RESULTS: The gender, age, body weight, serum C-reactive protein, number of involved bowel segments, operative time, and LOS were not significantly different (P = 0.36, 0.50, 0.33, 0.62, 0.81, 0.14 and 0.23, respectively). In the laparoscopy group, one patient required conversion to open surgery because of extensive bowel involvement, and another patient with solitary colonic perforation required reoperation for anastomostic leakage. However, patients who underwent laparotomy had a higher incidence of later complications, including wound infection, incisional hernia, and adhesion ileus (P = 0.03, 0.06, and 0.03, respectively) and thus required more additional unplanned operations (P = 0.05). CONCLUSIONS: Emergency laparoscopic surgery is technically feasible in most children with acute colonic perforations and fibropurulent peritonitis. However, extensive intestinal involvement with multiple perforations should be an indication for converting to open surgery.

Comparison of needlescopic and conventional video-assisted thoracic surgery for primary spontaneous pneumothorax.

Whether the outcome of primary spontaneous pneumothorax (PSP) when treated with needlescopic video-assisted thoracic surgery is positive is still under scrutiny. The present study was conducted to compare the needlescopic approach with the conventional approach. One-hundred and six patients with primary spontaneous pneumothorax who had undergone needlescopic video-assisted thoracic surgery (NVATS) between May 2006 and August 2008 were reviewed. Their age, gender, smoking status, BMI, side of attack, operative indications, operative time, intraoperative blood loss, postoperative length of stay, postoperative pain in visual analog scale (VAS), postoperative recurrence and follow-up period were recorded. These data were compared with those of 89 patients with PSP who had undergone conventional video-assisted thoracic surgery (CVATS) between June 2002 and April 2006. The operative time was shorter (NVATS: 82.36 ± 35.58 min, CVATS: 99.78 ± 35.74 min; p = 0.008) and intraoperative blood loss was less (NVATS: 16.67 ± 25.90 ml, CVATS: 24.36 ± 26.86 ml; p = 0.04) for the NVATS group. The postoperative pain in VAS was significantly less in NVATS. No major complication or mortality was found in either group. For treatment of primary spontaneous pneumothorax, NVATS is a safe and effective option. Further, it has the added benefit of less pain and improved cosmetics.

Pulmonary completion lobectomy after segmentectomy: An integrated analysis of perioperative outcomes.

BACKGROUND: Completion lobectomy (CL) after anatomical segmentectomy is technically challenging and rarely performed. Here, we aimed to report perioperative outcomes of a single center real-world CL data. METHODS: Seven patients who underwent CL after segmentectomy were retrospectively evaluated between 2015-2021. Additionally, 34 patients were included in the review based on relevant studies in the literature until March 2022. A total of 41 patients were finally analyzed and classified into groups, according to surgical approach (video-assisted thoracic surgery [VATS] and thoracotomy; 12 and 29 patients, respectively) or interval-to-CL following initial segmentectomy (≤8 weeks [short] and >8 weeks [long]; 11 and 30 patients, respectively). RESULTS: There were no significant differences in estimated blood loss, postoperative hospital stay, or complications between the predefined groups. However, a longer operative time was observed in the long interval-to-CL group than in the short interval-to-CL group (267 vs. 226 min, p = 0.02). The rate of severe hilar adhesions was higher in the thoracotomy versus VATS groups (72 vs. 42%, p = 0.06) and in the long versus short interval-to-CL groups (70 vs. 45%, p = 0.15). On multivariable logistic regression analysis of a subgroup (n = 30), completion lobectomy of upper lobes may be associated with severe hilar adhesions (p = 0.02, odds ratio: 13.98; 95% confidence interval [CI]: 1.36-143.71). CONCLUSION: Completion lobectomy after segmentectomy can be performed securely by either VATS or thoracotomy. Although the thoracotomy and long interval-to-CL groups retained a greater percentage of severe hilar adhesions, the perioperative outcomes were similar to those of VATS and short interval-to-CL groups, respectively.

Change in PD-L1 and CD8 Expression after Chemoradiotherapy for Esophageal Squamous Cell Carcinoma.

Esophageal cancer has a dismal prognosis with a five-year survival rate below 20%. Recently, immunotherapy has become a new standard of care for this cancer; therefore, we aimed to examine the programmed death ligand 1 (PD-L1) expression in esophageal squamous cell carcinoma (ESCC) tissues before and after concurrent chemoradiation therapy (CCRT). In total, 64 patients with pre-CCRT ESCC specimens were examined for PD-L1 expression, with twenty-three of them having a partial response (N = 23) or stable disease (N = 1) after CCRT while post-CCRT tissue specimens were collected. All of them were tested for PD-L1 and 15 of them also had CD8 expression in the paired ESCC samples. The prevalence of PD-L1 positivity was 54.7% and we found a trend of decreased PD-L1 expression and increased CD8 positive signal after CCRT. High pre-CCRT PD-L1 H-score in tumors was related to poor prognosis (adjusted hazard ratio = 2.81; p = 0.02), although CD8 signal was not associated with overall survival either in pre- or post-CCRT treatment. In conclusion, we found that PD-L1 expression tended to decrease in CCRT responders and our result supports PD-L1 expression in tumor as a predictor of ESCC prognosis.

Systematic Review and Network Meta-Analysis of Anaplastic Lymphoma Kinase (ALK) Inhibitors for Treatment-Naïve ALK-Positive Lung Cancer.

Several anaplastic lymphoma kinase inhibitors (ALKIs) have demonstrated excellent efficacy on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and also better adverse effect (AE) profiles compared to cytotoxic chemotherapy in advanced stage anaplastic lymphoma kinase (ALK) rearrangement-positive non-small cell lung cancer (NSCLC) in phase III randomized clinical trials (RCTs). We conducted this systematic review and network meta-analysis to provide a ranking of ALKIs for treatment-naïve ALK-positive patients in terms of PFS, ORR, and AEs. In addition, a sub-group analysis of treatment benefits in patients with baseline brain metastasis was also conducted. Contrast-based analysis was performed for multiple treatment comparisons with the restricted maximum likelihood approach. Treatment rank was estimated using the surface under the cumulative ranking curve (SUCRA), as well as the probability of being the best (Prbest) reference. All next-generation ALKIs were superior to crizotinib in PFS but lorlatinib and brigatinib had increased AEs. The probability of lorlatinib being ranked first among all treatment arms was highest (SUCRA = 93.3%, Prbest = 71.8%), although there were no significant differences in pairwise comparisons with high- (600 mg twice daily) and low- (300 mg twice daily) dose alectinib. In subgroup analysis of patients with baseline brain metastasis, low-dose alectinib had the best PFS (SUCRA = 87.3%, Prbest = 74.9%). Lorlatinib was associated with the best ranking for ORR (SUCRA = 90.3%, Prbest = 71.3%), although there were no significant differences in pairwise comparisons with the other ALKIs. In addition, low-dose alectinib had the best safety performance (SUCRA = 99.4%, Prbest = 97.9%). Lorlatinib and low-dose alectinib had the best PFS and ORR in the overall population and baseline brain metastasis subgroup, respectively. Low-dose alectinib had the lowest AE risk among the available ALKIs. Further head-to-head large-scale phase III RCTs are needed to verify our conclusions.

Radical resection or chemoradiotherapy for cervical esophageal cancer?

BACKGROUND: The prognosis and quality of life (QOL) for those with cervical esophageal cancer is extremely poor, and chemoradiotherapy remains the mainstay treatment. During the past few years, our surgical teams has implemented a more aggressive and radical resection: total laryngopharyngectomy with neck dissection, total esophagectomy, and reconstruction with stomach. This study compares the results of chemoradiotherapy and that of the aforementioned surgical approach. METHODS: This is a retrospective study of 15 patients who underwent radical resection and 14 patients who received chemoradiation. Their age, sex, tumor stage and grade, pre- and posttreatment dysphagia scores, operating time, blood loss, length of intensive care and postoperative stay, days to resume oral intake, complications, Eastern Cooperative Oncology Group (ECOG) status, QOL score, and disease-specific survival were recorded and compared. RESULTS: There were no significant differences in age, sex, pretreatment dysphagia score, cancer stage and grade, ECOG status (posttreatment), associate diseases, preoperative QOL, or follow-up period between the two groups. However, the posttreatment dysphagia score was significantly better for the operative group (P < 0.001). QOL improved in both groups, and the operative group seemed better although the difference was not significant. In addition, the survival between the two groups was statistically insignificant (P = 0.97, log-rank test). CONCLUSIONS: Our experience showed that radical surgery that includes total laryngopharyngectomy with neck dissection, total esophagectomy, and reconstruction with stomach for cervical esophageal cancer is beneficial to patients in terms of better eating.

Salvage surgery using simultaneous clamshell thoracotomy with median sternotomy for mediastinal growing teratoma syndrome.

This report describes the case of a 17-year-old man who developed mediastinal growing teratoma syndrome following two cycles of chemotherapy, after an initial diagnosis of primary mediastinal nonseminomatous germ cell tumor. The large, rapidly-growing mediastinal tumor was completely resected in conjunction with right pneumonectomy, using simultaneous clamshell thoracotomy and median sternotomy. The salvage surgery with perioperative management involved in mediastinal growing teratoma syndrome is presented here. KEY POINTS: Significant findings of the study The diagnosis and surgical management are challenging for patients with mediastinal growing teratoma syndrome. Nevertheless, with proper operative planning, favorable outcomes can be attained with complete resection despite the characteristic rapid growth and massive size of these neoplasms. What this study adds In spite of postoperative sternal dehiscence, we believe that a simultaneous clamshell thoracotomy with median sternotomy approach remains a viable option for an extremely large mediastinal growing teratoma, when tumor size prevents safe resection using other approaches due to limited visualization.

Early laparoscopy for ileocolic intussusception with multiple recurrences in children.

BACKGROUND: The risks of subsequent episodes and a lead point are common problems in ileocolic intussusception with more than two recurrences. To decrease subsequent recurrence and to detect a lead point, an early laparoscopy was performed for children with ileocolic intussusception. METHODS: This study enrolled six children with multiple recurrences of ileocolic intussusception from January 2004 to August 2007. Using a 5-mm laparoscope and two additional transabdominal wall stab incisions, an appendectomy and an ileocolonic pixie with nonabsorbable sutures were performed simultaneously for all the children after the last successful hydrostatic reduction. RESULTS: The mean operating time was 68.8 +/- 12.6 min (range, 55-86 min). There was no operative morbidity, and no lead point was found in any child. The mean follow-up period was 10.8 +/- 6.7 months (range, 2-20 months). No recurrence was observed during this period. CONCLUSION: The authors suggest that early intervention should be undertaken for ileocolic intussusception with multiple recurrences in children after the last nonsurgical reduction has been attempted successfully. Under this strategy, laparoscopy is an acceptable approach. It allows differentiation of a specific etiologic lesion, the possibility of incomplete reduction, and additional proximal invaginations. Later complications, such as repeat recurrence and associated surgical morbidity, also can be avoided.