Background
The laparoscopic magnified visual effects and evolution of the laparoscopic camera system have recently enabled us to observe details in the deep pelvic floor. Indications of laparoscopic ...surgery for colorectal cancer have been expanded, and laparoscopic (Lap) lateral pelvic node dissection (LLND) has been introduced in some institutions. We investigated the feasibility of Lap LLND in patients with locally advanced rectal cancer (LARC).
Methods
Lap LLND was performed in 38 patients diagnosed with cT3-4 or cN1-2 cancer during 2014–2018. We retrospectively analyzed their surgical and short-term outcomes.
Results
Laparoscopic surgery was performed in all patients. cStages II/III/IV were found in 6/31/1 patients, respectively. Among them, 25 patients underwent neoadjuvant chemotherapy without radiotherapy. Lap unilateral LLND was performed in 6 patients and Lap bilateral LLND was performed 32 patients. The number of harvested lymph nodes (LNs) were 4 in the unilateral group and 15 in the bilateral group. Operation time was 531 min, and blood loss was 105 ml. Oral intake has started on postoperative day (POD) 3, and pelvic drain was removed on POD 7. Hospital stay was 18.5 days. Seven patients developed a neurogenic bladder (all Clavien–Dindo grade (CD) II and all occured in the bilateral LLND group), one patient developed abdominal bleeding (CD IIIb) and one patient developed anastomotic leakage (CD IIIb). Pathological results revealed 2/5/16/14/1 patients with pStages 0/I/II/III/IV, respectively. Four patients had histopathologically verified lateral pelvic lymph node metastases. There were no local recurrences after curative surgery (median follow-up 24.2 months).
Conclusion
Although the median follow-up period is relatively short and further follow-up is necessary, oncologically, especially in the point of local control rate, Lap LLND appears to have acceptable in the treatment of LARC without radiotherapy in experienced centers. Further investigations focusing on indications and the Lap LLND procedural technique are required.
Background
This study aimed to assess the safety and efficacy of carbon-ion radiotherapy (CIRT) for salvage of previously X-ray-irradiated (XRT) locally recurrent rectal cancer (LRRC).
Methods
...Between September 2005 and December 2017, 77 patients with LRRC were treated with CIRT re-irradiation. All the patients had received prior XRT with a median dose of 50.0 Gy (range 20–74 Gy), principally for neoadjuvant or adjuvant recurrence prophylaxis in 34 patients and for recurrence in 43 patients. The total CIRT dose of 70.4 Gy (RBE) (gray relative biologic effectiveness) was administered in 16 fixed fractions during 4 weeks (4.4 Gy RBE per fraction).
Results
All the patients completed the scheduled treatment course. None of the patients received resection after CIRT. Acute grade 3 toxicities occurred for eight patients (10 %), including five grade 3 pelvic infections (2 involving pain and 1 involving neuropathy). Late grade 3 toxicities occurred for 16 patients (21 %): 13 with late grade 3 pelvic infections, 9 with gastrointestinal toxicity, 1 with skin toxicity, 2 with pain, and 4 with neuropathy. No grade 4+ toxicity was noted. The overall local control rates (infield + out-of-field recurrence) were 69 % at 3 years and 62 % at 5 years. In the planning target volume (PTV), the infield recurrence rates were 90 % and 87 % respectively. The control rates for regional recurrence were 85 % at 3 years and 81 % at 5 years. The median overall survival time was 47 months. The survival rates were 61 % at 3 years and 38 % at 5 years.
Conclusion
Carbon-ion re-irradiation of previously X-ray-irradiated locally recurrent rectal cancer appears to be safe and effective, providing good local control and survival advantage without unacceptable morbidity.
Cancer-associated fibroblasts (CAFs) are some of the most abundant components of the tumour microenvironment. A recent study suggested that in some cancers, CAFs express programmed death ligand 1 ...(PD-L1), which can act as a prognostic marker. The aim of this study was to investigate the clinicopathological significance of CAF PD-L1 expression in patients with triple-negative breast cancer (TNBC) and to identify the most suitable primary antibody for immunostaining for CAF PD-L1.
Immunohistochemical staining (primary antibodies of 73-10, SP142, and E1L3N) and tissue microarrays were used to analyse the expression profiles of PD-L1 in CAF in 61 patients with TNBC who underwent surgery. Overall survival (OS) was compared based on CAF PD-L1 expression, and the risk factors for OS were analysed. The relationship between clinicopathological parameters and survival was also examined.
Thirty-four (55.7%) patients were positive for CAF PD-L1 (73-10) expression. Compared with CAF PD-L1 negativity, there was a significant correlation between CAF PD-L1 positivity and better OS (p = 0.029). CAF PD-L1 expression, evaluated using SP-142 or E1L3N, did not correlate with OS. CAF PD-L1-positivity (73-10) correlated significantly with better prognosis in multivariate analyses (hazard ratio: 0.198; 95% confidence interval: 0.044-0.891; p = 0.035).
CAF PD-L1 expression is a novel marker for a better prognosis of patients with TNBC, and the 73-10 assay may be suitable for immunostaining CAF PD-L1.
Background
Malnutrition is an independent risk factor for postoperative mortality and morbidity in major gastrointestinal surgery. The aim of this study was to investigate the prevalence of ...malnutrition and identify the optimal preoperative nutritional support for preventing postoperative surgical site infections (SSIs) in malnourished gastric cancer patients undergoing gastrectomy.
Methods
We analyzed 800 patients with gastric cancer who underwent gastrectomy. Nutritional risk factors included weight loss >10 % within 6 months, body mass index <18.5 kg/m
2
, Subjective Global Assessment Grade C, and serum albumin <3.0 g/dl. Adequate energy intake was defined as receiving ≥25 kcal/kg ideal body weight per day. Optimal nutritional support was examined in terms of both duration and calorie intake.
Results
Overall, 152 patients (19.0 %) were classified as malnourished. The incidence of SSIs was significantly higher in malnourished patients than in well-nourished patients (35.5 vs. 14.0 %;
p
< 0.0001). The incidence of SSIs in malnourished patients was significantly lower in the well-supported group receiving adequate energy support for at least 10 days than in the poorly-supported group, which received inadequate or no energy support or adequate energy support for <10 days (17.0 vs. 45.4 %;
p
= 0.0006). In multivariate analysis, well-managed nutritional support was identified as an independent factor associated with fewer SSIs (odds ratio 0.14; 95 % confidence interval 0.05–0.37;
p
= 0.0002).
Conclusions
Malnutrition, a risk factor for SSI, was prevalent in gastric cancer patients preoperatively. Well-managed preoperative nutritional support decreased the incidence of postoperative SSIs in malnourished patients.
We established a preoperative exercise and nutritional support program for elderly sarcopenic patients with gastric cancer. Twenty-two gastric cancer patients aged 65 years or older with a diagnosis ...of sarcopenia according to the algorithm proposed by the European Working Group on Sarcopenia in Older People received our preoperative program. The median duration of the program participation was 16 days. Total calorie and protein intakes were significantly higher after the program than before 29.4 ± 6.9 kcal/kg ideal body weight (IBW) vs 27.3 ± 5.6 kcal/kg IBW,
p
= 0.049, and 1.3 ± 0.4 g/kg IBW vs 1.1 ± 0.3 g/kg IBW,
p
= 0.0019, respectively. Handgrip strength significantly increased after the program (21.2 ± 5.2 kg vs 20.0 ± 5.3 kg,
p
= 0.022). Likewise, gait speed and skeletal muscle mass index increased, although the differences did not reach statistical significance. Four patients became nonsarcopenic after the program. Postoperative complications were observed in three patients (13.6%); however, none of these complications were severe (Clavien-Dindo grade III or lower). A preoperative exercise and nutritional support program has the potential to reduce sarcopenia and improve postoperative outcome in elderly sarcopenic patients with gastric cancer.
CD155 is an immune checkpoint protein. Its overexpression is an indicator of poor prognosis in some types of cancer. However, the significance of CD155 expression in patients with triple-negative ...breast cancer, and the relationship between CD155 and programmed death-ligand 1 (PD-L1) expression, have not yet been analyzed in detail. Using immunohistochemical staining and tissue microarrays, we analyzed the expression profiles of CD155 and PD-L1 in 61 patients with triple-negative breast cancer. Relapse-free survival and overall survival rates were compared according to CD155 expression. The correlation between CD155 expression and clinicopathological factors, including PD-L1 expression (using SP142 and 73-10 assays), was also examined. CD155 expression was noted in 25 patients (41.0%) in this cohort. CD155 expression did not correlate with pathological stage, histological grade, Ki-67 labeling index, or stromal tumor-infiltrating lymphocytes. Only PD-L1 expression in tumor cells by SP142 assay significantly correlated with CD155 expression (p = 0.035); however, PD-L1 expression in tumor cells by 73-10 assay did not show a correlation (p = 0.115). Using the 73-10 assay, 59% of patients showed CD155 and/or PD-L1 expression in tumor cells. Moreover, using the SP142 assay, 63.3% of patients showed CD155 and/or PD-L1 expression in immune cells. CD155 expression did not correlate with either relapse-free survival or overall survival (p = 0.485 and 0.843, respectively). CD155 may be a novel target for antitumor immunotherapy. The results of this study indicate that CD155 may expand the pool of candidates with triple-negative breast cancer who could benefit from antitumor immunotherapy.
Adipophilin is a lipid droplet-associated protein whose expression can act as a prognostic marker for specific cancers. Using immunohistochemical staining and tissue microarrays, we assayed the ...expression of adipophilin in 61 patients with triple-negative breast cancer (TNBC) who underwent surgery from January 2006-December 2018. Relapse-free survival (RFS) and its risk factors were analyzed based on adipophilin expression. Fourteen (23.0%) patients expressed adipophilin. As compared to the adipophilin-negative TNBC patients, adipophilin-positive patients exhibited poor RFS (p = 0.032). Among the TNBC patients with a high Ki-67 labeling index, patients negative for adipophilin exhibited better RFS than patients positive for adipophilin (p = 0.032). Moreover, among patients who did not undergo adjuvant chemotherapy, patients negative for adipophilin expression exhibited better RFS than adipophilin-positive patients (p = 0.080). Multivariate analysis showed that adipophilin expression correlated with a high rate of relapse (hazard ratio, 4.89; 95% confidence interval, 1.04-23.0; p = 0.044). Taken together, these results indicate that adipophilin is a novel marker for the poor prognosis of patients with TNBC.
Stromal reaction is an important prognostic factor in several cancers, and the presence of myxoid change was assessed as a poor prognostic factor in colorectal cancer. However, the prognostic ...significance of myxoid change in triple-negative breast cancer (TNBC) remains unknown. This study aimed to determine the prognostic significance of myxoid change and fibrotic focus (FF), which is a fibrotic area within the tumor and considered a poor prognostic indicator in patients with TNBC.
We enrolled 62 patients with TNBC and reviewed the surgically resected specimens to evaluate myxoid change and FF in the tumor using previously outlined criteria. We evaluated tumor-infiltrating lymphocytes (TILs) using hematoxylin and eosin slides. Overall survival (OS) and relapse-free survival (RFS) were compared based on the presence of myxoid change and/or FF, and the risk factors for RFS were analyzed.
Myxoid change and FF were observed in 25.8% and 33.9% of specimens, respectively. Based on stromal lymphocyte infiltration, 19 patients (30.6%) had high TILs, while the remaining 43 patients (69.4%) had low/intermediate TILs. Presence of myxoid change was significantly correlated with poor OS and RFS (p = 0.040 and 0.031, respectively). FF was also significantly correlated with poor OS and RFS (p = 0.012 and 0.028, respectively). The combination of myxoid change and FF was an independent and poor prognostic factor according to the multivariate analysis (HR 11.61; 95% CI 1.027-131.2; p = 0.048). Presence of myxoid change and FF were significantly associated with low/intermediate TILs in the stroma (p = 0.013).
Histopathological assessment of myxoid change and FF in TNBC may be a useful, practical, and easily assessable method for predicting prognosis in patients with TNBC, which should be confirmed in larger prospective studies. Diagnostic criteria for the establishment of myxoid change and FF in TNBC must be established, and their underlying molecular events must be clarified.
Induced pluripotent stem cells (iPSCs) can be generated from differentiated human and mouse somatic cells using transcription factors such as Oct4, Sox2, Klf4, and c-Myc. It is possible to augment ...the reprogramming process with chemical compounds, but issues related to low reprogramming efficiencies and, with a number of protocols, residual vector sequences, remain to be resolved. We show here that it is possible to reprogram mouse and human cells to pluripotency by direct transfection of mature double-stranded microRNAs (miRNAs). Our approaches use a combination of mir-200c plus mir-302 s and mir-369 s family miRNAs. Because this reprogramming method does not require vector-based gene transfer, it holds significant potential for biomedical research and regenerative medicine.
► Transfected mature miRNAs can reprogram mouse somatic cells to pluripotency ► A combination of mir-200c plus mir-302 s and mir-369 s family miRNAs is required ► miRNA-generated mi-iPSCs show all characteristics of pluripotency ► The same combination of miRNAs can also reprogram human somatic cells
Background
Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. A recent study demonstrated the efficacy of anti-PD-L1 (anti-programmed death ligand-1) immunotherapy in ...patients with TNBC. However, the identification of TNBC patients who may benefit from immunotherapy is a critical issue. Several assays have been used to evaluate PD-L1 expression, and a few studies comparing PD-L1 expression using various primary antibodies in TNBC tissues have been reported. However, the expression profiles of the PD-L1 using the 73–10 assay have not yet been analyzed in TNBC tissues.
Methods
We analyzed the PD-L1 immunohistochemical profiles of 62 women with TNBC using the 73–10, SP142 (companion diagnostic for atezolizumab), and E1L3N assays. PD-L1 expression on immune cells (ICs) and tumor cells (TCs) was also evaluated, and PD-L1 positivity was defined as a PD-L1-expressing ICs or TCs ≥ 1%.
Results
The expression rates of PD-L1 were 79.0%, 67.7%, and 46.8% on ICs, and 17.7%, 6.5%, and 12.9% on TCs using the 73–10, SP142, and E1L3N assays, respectively. The concordance rates between the 73–10 and SP142 assays were 85.5% (on ICs) and 88.7% (on TCs), respectively, and substantial agreement on ICs (coefficient 0.634) and moderate agreement (coefficient 0.485) on TCs were noted. Sample age and tumor diameter did not influence the ratio of PD-L1 expression among the assays.
Conclusions
The positive rate on ICs and TCs of the 73–10 assay was higher than that of the SP 142 and E1L3N assays. Although substantial agreement on ICs and moderate agreement on TCs between the 73–10 and SP142 assays was noted in the present cohort, further studies are needed to clarify the PD-L1 expression status using various primary antibodies in a larger patient population. This would lead to the establishment of an effective evaluation method to assess the predictive value of anti-PD-L1 immunotherapy.
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