The critical roles of heat shock protein 90 (HSP90) in immune reactions associated with viral infection and autoimmune disease are well known. To date, however, its roles in the alloimmune response ...and the immunosuppressive effect of HSP90 inhibitors in allotransplantation have remained unknown. The purpose of this study was to examine the therapeutic efficacy of the HSP90 inhibitor 17-DMAG in allotransplantation models. C57BL/6 (H-2b) and BALB/c (H-2d) mice were used as donors for and recipients of skin and heart transplantation, respectively. Treatment with 17-DMAG (daily i.p.) or a vehicle was initiated 3 days before transplantation. Immunological outcomes were assessed by histopathological examinations, flow cytometric analysis, quantitative RT-PCR, ELISA, ELISPOT assay, and MLR. 17-DMAG treatment significantly prolonged the survival of both skin and heart allografts. In 17-DMAG-treated mice, donor-reactive splenocytes producing IFN-γ were significantly reduced along with the intragraft mRNA expression level and serum concentration of IFN-γ. Intragraft mRNA expression of cytokines and chemokines associated with both innate and adaptive immunity was suppressed in 17-DMAGtreated group. MLR showed suppression of the donor-specific proliferation of CD4 + T and CD19 + B cells in the spleens of 17-DMAG-treated mice. 17-DMAG treatment also reduced the number of activated NK cells. Furthermore, the treatment lowered the titers of donor-specific antibodies in the serum and prolonged a second skin allograft in mice sensitized by previous skin transplantation. HSP90 inhibition by 17-DMAG can affect various immune responses, including innate immunity, adaptive immunity, and humoral immunity, suggesting its therapeutic potential against acute rejection in allotransplantation.
Purpose
Postoperative complications have a significant impact on perioperative outcomes; however, their association with the long-term prognosis remains unclear. We evaluated the impact of ...postoperative complications on the long-term outcomes after curative surgery in lung cancer patients.
Methods
This study included 1129 patients with primary lung cancer who underwent lobectomy between April 2011 and March 2017. Univariate and multivariate analyses were performed to assess the association of postoperative complications with the overall and recurrence-free survival.
Results
Postoperative complications were observed in 147 (13.0%) patients over a median follow-up period of 5-years. Compared to patients without complications, those with complications showed had worse long-term outcomes, including the 5-year overall survival (75.3% vs. 86.1%,
p
< 0.001) and 5-year recurrence-free survival (64.2% vs. 74.4%,
p
= 0.004). A multivariate analysis revealed that the incidence of postoperative complications was significantly associated with the overall survival (hazard ratio = 1.665,
p
= 0.006) and recurrence-free survival (hazard ratio = 1.416,
p
= 0.025) in all patients. The prognostic influence was greater in patients with pathological stages II and III cancer (overall survival: hazard ratio = 2.019,
p
= 0.005; recurrence-free survival: hazard ratio = 1.90,
p
= 0.001) than in those with pathological stage I cancer.
Conclusion
Postoperative complications are independent predictors of the overall and recurrence-free survival in lung cancer patients, especially advanced-stage cancer patients.
Metastatic burden is a critical factor for therapy decision‐making in metastatic hormone‐sensitive prostate cancer. The present study aimed to identify prognostic factors in men with high‐ or ...low‐metastatic burden treated with primary androgen‐deprivation therapy. The study included 2450 men with de novo metastatic prostate cancer who were treated with primary androgen‐deprivation therapy at 30 institutions across Japan between 2008 and 2017. We investigated the prognostic value of various clinicopathological parameters for progression‐free survival (PFS) and overall survival (OS) in patients stratified by low‐ or high‐metastatic burden. Among the 2450 men, 841 (34.3%) and 1609 (65.7%) were classified as having low‐ and high‐metastatic burden, respectively. Median PFS of the low‐ and high‐burden groups were 44.5 and 16.1 months, respectively, and the median OS was 103.2 and 62.7 months, respectively. Percentage of biopsy‐positive core, biopsy Gleason grade group, T‐stage, and N‐stage were identified to be differentially prognostic. M1a was associated with worse PFS than was M1b in the low‐burden group, whereas lung metastasis was associated with better PFS and OS than was M1b in the high‐burden group. Differential prognostic factors were identified for patients with low‐ and high‐burden metastatic prostate cancer. These results may assist in decision‐making to select the optimal therapeutic strategies for patients with different metastatic burdens.
This study investigated prognostic factors according to metastatic burden, and found that prognostic impact of some factors was different. This finding may be valuable in decision‐making to select the optimal therapeutic strategies for patients with different metastatic burdens.
We describe the case of a patient who underwent tracheal resection for post-tracheostomy stenosis following T-tube stenting for 10 years. A 32-year-old female patient with a T-tube in the trachea was ...referred to us. She had brain surgery for intracranial hemorrhage 10 years ago and developed a post-tracheostomy tracheal stenosis, for which she had been treated with a T-tube. At the time of referral, she was ambulatory with a cane and otherwise independent in her daily life. We assessed her stenosis and determined that it was amenable to tracheal resection as a definitive treatment. We resected the tracheal stenosis including the stoma site and performed an end-to-end tracheal anastomosis. The anastomosis was widely patent at 6 months follow-up. Long-term treatment of tracheal stenosis with T-tube does not preclude tracheal resection as a definitive treatment. A careful review of airway stenosis for resectability on a case-by-case basis is imperative.
Objectives
To clarify the incidence of postoperative hydronephrosis and verify the validity of diagnostic and therapeutic approaches for hydronephrosis after cystectomy and urinary diversion for ...bladder cancer.
Methods
Totally, 290 patients receiving urinary diversion from 2005 through 2017 with complete data were enrolled, including 258 (89.0%) with an ileal conduit and 32 (11.0%) with an ileal neobladder. Postoperative radiographic images were reviewed. In patients with postoperative hydronephrosis, antegrade pyelography and ureteroscopy were performed to exclude malignant etiology. Balloon dilation and open surgical revision were performed according to the conditions.
Results
Forty‐six patients (58 renal units) developed postoperative hydronephrosis. The cumulative incidence was 11.4% by a median follow‐up of 59.5 months. Ureteral recurrence was detected by antegrade examinations in two patients, whereas malignant strictures were subsequently revealed in three patients. Thus, malignant etiology was found in hydronephrosis in five renal units (12.8%) of five patients (16.1%). The median times to diagnosis of hydronephrosis were 0 (interquartile range IQR 0–4) and 14 months (IQR 9–12) for benign and malignant strictures, respectively (p = 0.003). Of them, 31 patients (39 renal units) received interventions. Balloon dilation was performed in 13 renal units with benign strictures, and was successful in two (15.4%). Open surgical revision was performed in eight patients (11 renal units), including two with failed balloon dilation, all of which was successful.
Conclusions
Postoperative hydronephrosis is potentially associated with recurrent disease. Accurate differential diagnosis is challenging although antegrade procedures may be helpful in some cases. Open surgical revision is highly effective to treat benign strictures.
Background and purpose: Several recent randomized controlled trials
(RCTs) in non-metastatic castration resistant prostate cancer
(nmCRPC) have demonstrated a significant improvement in ...metastasis-free survival
(MFS); however, an improvement in overall survival (OS) is not
reported yet. Since the surrogacy of MFS to OS has not been formally investigated in nmCRPC in
Japan, this study evaluated the correlation between MFS and OS among a nmCRPC population in
Japan.
Methods: This is a retrospective longitudinal observational cohort study in
patients with nmCRPC using the Japanese Medical Data Vision (MDV) database
covering over 20 million patients. A total of 1236 patients with CRPC who had no prior medical
history of cancer except prostate cancer and no distant metastasis, and who fulfilled PCWG2
criteria, were identified. Following the identification of nmCRPC, patients' medical
records were investigated for subsequent events of metastasis and death.
Results: The median follow-up time was 24 months. Median MFS was
28 months (95% CI: 24.0 to 33.0 months) and median OS could
not be estimated (95% CI: not estimated). There was a statistically
significant correlation between MFS and OS (Pearson's correlation
coefficient = 0.62; 95% CI: 0.58-0.65;
p < .0001, Spearman's correlation
coefficient = 0.62; 95% CI: 0.58-0.65;
p < .0001 and Kendall's τ
statistic = 0.53; 95% CI: 0.49-0.56;
p < .0001).
Conclusions: The results of this study indicate a significant correlation
between MFS and OS. It may justify the usefulness of MFS as surrogate for OS in nmCRPC.
Trial registration:
ClinicalTrials.gov identifier: NCT01946204.
Trial registration:
ClinicalTrials.gov identifier: NCT02200614.
Purpose
Most robot-assisted thoracoscopic surgery (RATS) is performed from the vertical view. This study evaluates the initial outcomes of our novel confronting RATS technique, in which the patient ...was viewed horizontally, as in open thoracotomy.
Methods
We reviewed data on patients who underwent thoracoscopic lobectomy between January, 2019 and April, 2022. Perioperative outcomes were compared between RATS and video-assisted thoracoscopic surgery (VATS), using propensity-score matching.
Results
RATS and VATS were performed for 83 and 571 patients, respectively. After propensity-score matching, data on 81 patients from each of the two groups were retrieved. The operative time was significantly longer for RATS than for VATS (199 ± 44 min vs. 173 ± 37 min,
p
< 0.001). There was no mortality or conversion to thoracotomy in either of the groups. The rates of overall complications and prolonged air leak did not differ significantly between the groups. The serum creatine phosphokinase level on postoperative day 4 was higher after RATS than after VATS. The number of resected lymph nodes and the rates of nodal upstaging did not differ significantly between the groups.
Conclusion
The initial perioperative outcomes of RATS using the confronting settings were comparable to those of VATS.
Smoking has a major role in the risk of postoperative pulmonary complications. This study aimed to elucidate the correlation between smoking status and pulmonary complications after thoracoscopic ...surgery for lung cancer.
A total of 1751 patients who underwent thoracoscopic lobectomy or segmentectomy for lung cancer between April 2011 and March 2020 were assessed. The rate of pulmonary complications was evaluated according to smoking status and preoperative duration of smoking cessation. Univariate and multivariate logistic regression analyses were performed.
Pulmonary complications were observed in 50 patients (2.9%), whereas 3 (0.2%) died within 90 days of surgery. The rate of pulmonary complications was higher in smokers than in nonsmokers (4.6% vs 0.9%; P < .001), and smoking history was an independent risk factor for pulmonary complications (odds ratio, 3.31; P = .007). The complication rate in patients with a cessation period of more than 2 months was significantly lower than that in patients who ceased smoking within 2 months (4.0% vs 8.5%; P = .043), but it was still higher than that in nonsmokers (4.0% vs 0.9%; P < .001). In the multivariable analysis for smokers, preoperative short-term smoking cessation within 2 months, male sex, histologic type, tumor size, and cardiopulmonary comorbidities were associated with pulmonary complications instead of pack-year smoking history.
Smoking habits and preoperative smoking cessation were independently associated with pulmonary complications after thoracoscopic surgery for lung cancer. A preoperative smoking cessation period of 2 months or more is preferable for reducing the risk of such complications.
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Postoperative pneumatocele is a rare complication of lung surgery. Here we describe 2 cases of pneumatoceles arising from the unaltered bottom part of the lower lobe a month or more after upper ...lobectomy. Based on histopathologic findings, we speculated that (1) negative pressure created by the volumetric gap between the thoracic cavity and the remnant lung and (2) increased positive pressure by the check valve mechanism from kinking or flexion of the airway after an upward movement of the remnant lung play crucial roles in the pathogenesis of postoperative pneumatoceles.
Background
Liver-type fatty acid-binding protein (L-FABP) in urine is one of the early diagnostic biomarkers for acute and chronic kidney injuries. Although this protein is also identified in the ...intestine, there is no verified reference value for patients with intestinal urinary diversion (UD). The aim of the present study was to measure L-FABP values in such patients and compare them with the results for patients without UD.
Methods
Spot urine specimens were collected from 41 patients with UD and 50 subjects without UD with estimated glomerular filtration rates of over 60 ml/min/1.73 m
2
, and the L-FABP values were measured. The normal upper cutoff value in healthy subjects without UD is considered to be 7.24 μg/g Cr. First, the median values of the two groups were compared. Next, the subjects with negative proteinuria and without comorbidities associated with renal function were further selected and the median values of the groups were compared.
Results
The mean age was significantly higher in the UD group. The types of UD were ileal conduit (38 patients) and ileal neobladder (three patients). The median L-FABP value in the UD group was significantly higher than that in the non-diversion group (89.1 μg/g Cr vs. 2.0 μg/g Cr,
p
< 0.0001). After adjustment for their backgrounds, the median value remained higher in the UD group.
Conclusions
L-FABP values in subjects with UD are higher than in those without UD. By this result, to develop a reference value in patients with intestinal UD population, further studies are required.
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