Robotic versus laparoscopic right colectomy for nonmetastatic pT4 colon cancer: A European multicentre propensity score-matched analysis.

AIM: Minimally invasive surgery has been increasingly adopted for locally advanced colon cancer. However, evidence comparing robotic (RRC) versus laparoscopic right colectomy (LRC) for nonmetastatic pT4 cancers is lacking. METHODS: This was a multicentre propensity score-matched (PSM) study of a cohort of consecutive patients with pT4 right colon cancer treated with RRC or LRC. The two surgical approaches were compared in terms of R0, number of lymph nodes harvested, intra- and postoperative complication rates, overall (OS), and disease-free survival (DFS). RESULTS: Among a total of 200 patients, 39 RRC were compared with 78 PS-matched LRC patients. The R0 rate was similar between RRC and LRC (92.3% vs. 96.2%, respectively; p = 0.399), as was the odds of retrieving 12 or more lymph nodes (97.4% vs. 96.2%; p = 1). No significant difference was noted for the mean operating time (192.9 min vs. 198.3 min; p = 0.750). However, RRC was associated with fewer conversions to laparotomy (5.1% vs. 20.5%; p = 0.032), less blood loss (36.9 vs. 95.2 mL; p < 0.0001), fewer postoperative complications (17.9% vs. 41%; p = 0.013), a shorter time to flatus (2 vs. 2.8 days; p = 0.009), and a shorter hospital stay (6.4 vs. 9.5 days; p < 0.0001) compared with LRC. These results were confirmed even when converted procedures were excluded from the analysis. The 1-, 3- and 5-year OS (p = 0.757) and DFS (p = 0.321) did not significantly differ between RRC and LRC. CONCLUSION: Adequate oncological outcomes are observed for RRC and LRC performed for pT4 right colon cancer. However, RRC is associated with lower conversion rates and improved short-term postoperative outcomes.

The use of laparoscopy for T4a and T4b colon cancer: are we playing with fire?

BACKGROUND: The laparoscopic approach for colon cancer has become widely accepted. However, its safety for T4 tumors, and particularly for T4b tumors when local invasion to adjacent structures occurs, remains controversial. This study aimed to compare short and long-term outcomes in patients undergoing laparoscopic vs. open resection for T4a and T4b colon cancers. METHODS: A prospectively maintained, single-institution database was queried to identify patients with pathological stage T4a and T4b colon adenocarcinomas electively operated on between 2000 and 2012. Patients were divided into two groups based on the use of laparoscopy. Patient characteristics, perioperative, and oncologic outcomes were compared. RESULTS: One hundred and nineteen patients [41 laparoscopic (L), 78 open surgeries (O)] met the inclusion criteria. No difference was observed in age, gender, BMI, ASA, and procedure between groups. Tumors treated by L were smaller than O (p = 0.003). No difference was observed in morbidity, mortality, reoperation, or readmission between the groups. Length of hospital stay was shorter in L than O (6 vs. 9 days, p = 0.005). Conversion to open was necessary in 22% of all T4 tumors laparoscopic cases. However, when tumors were subdivided by pT4 classification, conversion was necessary for 4 of 34 (12%) pT4a patients vs. 5 of 7 (71%) pT4b patients (p = 0.003). In the pT4b cohort (n = 37), more tumors were treated by the open approach (30 vs. 7). For pT4b tumors, the R0 resection rate was 94% (86% in L vs. 97% in O, p = 0.249). The use of laparoscopy did not impact overall survival, disease-free survival, cancer-specific survival, or tumor recurrence overall in all T4 or T4a and T4b tumors. CONCLUSIONS: Laparoscopic surgery can be safely performed in pT4 tumors with similar oncologic outcomes as compared to open surgery. However, for pT4b tumors, the conversion rate is very high. The open approach may be preferable.

Favorable short-term oncologic outcomes following laparoscopic surgery for small T4 colon cancer: a multicenter comparative study.

BACKGROUND: Laparoscopic surgery for T4 colon cancer may be safe in selected patients. We hypothesized that small tumor size might preoperatively predict a good laparoscopic surgery outcome. Herein, we compared the clinicopathologic and oncologic outcomes of laparoscopic and open surgery in small T4 colon cancer. METHODS: In a retrospective multicenter study, we reviewed the data of 449 patients, including 117 patients with tumors ≤ 4.0 cm who underwent surgery for T4 colon cancer between January 2014 and December 2017. We compared the clinicopathologic and 3-year oncologic outcomes between the laparoscopic and open groups. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate analyses were performed using the Cox proportional hazards model. A p < 0.05 was considered statistically significant. RESULTS: Blood loss, length of hospital stay, and postoperative morbidity were lower in the laparoscopic group than in the open group (median [range], 50 [0-700] vs. 100 [0-4000] mL, p < 0.001; 8 vs. 10 days, p < 0.001; and 18.0 vs. 29.5%, p = 0.005, respectively). There were no intergroup differences in 3-year overall survival or disease-free survival (86.6 vs. 83.2%, p = 0.180, and 71.7 vs. 75.1%, p = 0.720, respectively). Among patients with tumor size ≤ 4.0 cm, blood loss was significantly lower in the laparoscopic group than in the open group (median [range], 50 [0-530] vs. 50 [0-1000] mL, p = 0.003). Despite no statistical difference observed in the 3-year overall survival rate (83.3 vs. 78.7%, p = 0.538), the laparoscopic group had a significantly higher 3-year disease-free survival rate (79.2 vs. 53.2%, p = 0.012). CONCLUSIONS: Laparoscopic surgery showed similar outcomes to open surgery in T4 colon cancer patients and may have favorable short-term oncologic outcomes in patients with tumors ≤ 4.0 cm.

Molecular Functions of Thyroid Hormone Signaling in Regulation of Cancer Progression and Anti-Apoptosis.

Several physiological processes, including cellular growth, embryonic development, differentiation, metabolism and proliferation, are modulated by genomic and nongenomic actions of thyroid hormones (TH). Several intracellular and extracellular candidate proteins are regulated by THs. 3,3,5-Triiodo-L-thyronine (T3) can interact with nuclear thyroid hormone receptors (TR) to modulate transcriptional activities via thyroid hormone response elements (TRE) in the regulatory regions of target genes or bind receptor molecules showing no structural homology to TRs, such as the cell surface receptor site on integrin αvß3. Additionally, L-thyroxine (T4) binding to integrin αvß3 is reported to induce gene expression through initiating non-genomic actions, further influencing angiogenesis and cell proliferation. Notably, thyroid hormones not only regulate the physiological processes of normal cells but also stimulate cancer cell proliferation via dysregulation of molecular and signaling pathways. Clinical hypothyroidism is associated with delayed cancer growth. Conversely, hyperthyroidism is correlated with cancer prevalence in various tumor types, including breast, thyroid, lung, brain, liver and colorectal cancer. In specific types of cancer, both nuclear thyroid hormone receptor isoforms and those on the extracellular domain of integrin αvß3 are high risk factors and considered potential therapeutic targets. In addition, thyroid hormone analogs showing substantial thyromimetic activity, including triiodothyroacetic acid (Triac), an acetic acid metabolite of T3, and tetraiodothyroacetic acid (Tetrac), a derivative of T4, have been shown to reduce risk of cancer progression, enhance therapeutic effects and suppress cancer recurrence. Here, we have reviewed recent studies focusing on the roles of THs and TRs in five cancer types and further discussed the potential therapeutic applications and underlying molecular mechanisms of THs.

Evaluating vertebral artery dominancy before T4 lung cancer surgery requiring subclavian artery reconstruction.

PURPOSES: To evaluate vertebral artery (VA) dominancy and the risk of brain infarction in T4 lung cancer patients with tumor invasion into the subclavian artery. METHODS: We reconstructed the subclavian artery in 10 patients with T4 non-small cell lung cancer. The histological stages were IIIA in eight patients and IIIB in two patients. We evaluated the VA dominancy by performing a four-vessel study preoperatively and investigated the relationship between the methods of VA treatment and postoperative brain complications, retrospectively. RESULTS: Seven patients had a superior sulcus tumor (SST) and three had direct invasion into the mediastinum. Based on the tumor location, a transmanublial approach was used in five patients and a posterolateral hook incision was used in the other five. All subclavian artery (SA) reconstructions were done using an artificial woven graft. Preoperative angiography of the VA revealed poor development of the contralateral side in two patients. One of these patients suffered a severe brain infarction on postoperative day 2, which proved fatal. In the other patient, the VA was connected to the left SA graft by a side-to-end anastomosis and there was no postoperative brain complication. CONCLUSIONS: Preoperative SA and VA angiography is mandatory for identifying the need for VA reconstruction in lung cancer patients with major arterial invasion.

Individualizing surgical treatment based on tumour response following neoadjuvant therapy in T4 primary rectal cancer.

BACKGROUND: Rectal cancer involving at least one adjacent organ (mrT4b) requires multi-visceral resection to achieve clear resection margin (R0). Performing pelvic compartment preservation according to the tumour response has not been considered. This study assesses the impact of changing the surgical strategy according to tumour response in rectal cancer mrT4b. METHODS: Patients with non-metastatic T4b rectal cancer at two tertiary referral centres between 2008 and 2013 were grouped as "Responders" ypT0-3abNx versus "Non-responders" ypT3cd-4Nx and divided into three surgical procedures: total mesorectal excision (TME), extended-TME (eTME) and beyond-TME (b-TME). End-points were circumferential resection margin, postoperative morbidity, definitive stoma formation, 3-years local recurrence (3y-LR) and 3-years disease-free survival (3y-DFS) according to both tumours' response and surgical procedures. RESULTS: Among 883 patients with rectal cancer, 101 were included. Responders had a higher rate of induction chemotherapy (59.7% vs. 38.2%; p = 0.04). Morbidity and definitive stoma formation were significantly higher in Non-responders. R0 was not impacted by either the tumour response or the surgical procedures. The 3y-LR was lower in Responders (14%) compared to Non Responders (32%) (HR 1.6; 95% CI: 1.02-2.59; p = 0.041), and was two-fold higher in e-TME compared to b-TME in Non-responders, whereas no difference was found in Responders. The 3y-DFS was higher in Responders irrespective to the surgery (71% vs. 47%; p = 0.07). CONCLUSION: In Responders, TME or e-TME are technically and oncollogically feasible and should be considered in preferrence to b-TME. In Non-responders, allowing for high rates of morbidity and local recurrence in patients with e-TME, b-TME procedures should be preferred.