Toru Bando

Pulmonary Resection for Metastases from Hepatocellular Carcinoma

BackgroundPulmonary metastasectomy has become the standard therapy for various metastatic malignancies to the lungs; however, few data have been available about lung metastasectomy for hepatocellular carcinoma. To confirm the role for resection of pulmonary metastases for such tumors, we reviewed our institutional experience.MethodsBetween 1993 and 2005, 12 patients with pulmonary metastases from hepatocellular carcinomas underwent complete pulmonary resection. All patients had undergone curative resection of their primary hepatocellular carcinomas and also had obtained or had obtainable locoregional control of their primaries. Various perioperative variables were investigated retrospectively to analyze the possible prognostic factors for overall survival and pulmonary metastases-free survival after pulmonary metastasectomy.ResultsNine patients were male and three were female (median age, 53 (range, 43-80) years). Overall survival rate after metastasectomy was 80.8%, 57.7%, and 28.9% at 1, 2, and 5xa0years, respectively. Pulmonary metastases-free survival rate was 64.2%, 32.1%, and 21.4% at 1, 2, and 5xa0years, respectively. Five patients presented recurrences in the remaining liver before pulmonary metastases, but hepatic recurrences at this interval did not affect an overall survival after pulmonary metastasectomies. Two patients had undergone living-related liver transplantation. The maximum tumor size of the pulmonary metastasisxa0<xa03xa0cm was the only favorable prognostic factor for overall survival (Pxa0=xa00.0006), whereas there was no significant prognostic factor for pulmonary metastases-free survival.ConclusionsPulmonary metastasectomy for hepatocellular carcinoma in selected patients was well justified when the maximum tumor size wasxa0<3xa0cm.

Repeat resection of pulmonary metastasis is beneficial for patients with colorectal carcinoma.

BackgroundThe role for repeat pulmonary metastasectomy for colorectal carcinoma has not been well defined. To identify the class of patients who benefit from pulmonary resection of recurrent pulmonary metastases, we herein reviewed our institutional experience.MethodsBetween 1990 and 2007, 84 patients with pulmonary metastases from colorectal carcinomas underwent complete pulmonary resection, and 22 of them (26%) later underwent complete resection for repeat pulmonary metastasis. Various perioperative variables were investigated retrospectively in these patients to confirm a role for repeat metastasectomy and analyze prognostic factors after repeat pulmonary metastasectomy.ResultsOverall survival and disease-free survival after repeat pulmonary metastasectomy were, respectively, 61 and 32% at 5xa0years. On univariate analysis, male gender and less than 1 year of disease-free status after the first pulmonary metastasectomy demonstrated significantly adverse overall survival (pxa0=xa00.01 and pxa0=xa00.009, respectively). Elevated preoperative serum carcinoembryonic antigen (CEA) level and maximum tumor size larger than 3xa0cm were also significantly adverse prognostic factors for disease-free survival (pxa0=xa00.03 and pxa0=xa00.04, respectively). The overall survival curve after repeat pulmonary metastasectomy was almost identical with that after complete resection of the first pulmonary metastasis.ConclusionsPatients with more than 1xa0year of disease-free status after the first pulmonary metastasectomy demonstrated a significantly better overall survival. Normal preoperative serum CEA level and maximum tumor size <3xa0cm were significantly adverse prognostic factors for disease-free survival. Our data imply that repeat pulmonary metastasectomy might be beneficial as it can salvage a subset of patients with colorectal carcinoma who retain favorable prognostic determinants.

Pulmonary resection for metastasis from esophageal carcinoma

Pulmonary metastasectomy has become the standard therapy for various metastatic malignancies to the lungs; however, few data have been available regarding lung metastasectomy for esophageal carcinoma. To confirm a role for resection of pulmonary metastases for such tumors, we reviewed our institutional experience. Between 2001 and 2007, five patients with pulmonary metastases from esophageal carcinoma underwent complete pulmonary resection. All patients had undergone curative resection of their primary esophageal carcinomas and also had obtained locoregional control of their primaries. Disease-free interval varied from 13 to 56 months, with a median of 21 months. In three patients, lung metastases were found to be unilateral and solitary. The other two patients presented several metastases in the unilateral or bilateral lungs. All patients underwent wedge resection or segmentectomy. Currently, four patients are alive without evidence of disease and one patient has died of disease. All patients undertook or were going to undertake chemotherapy after the pulmonary metastasectomy. Three patients with solitary metastasis are all alive without disease 13, 48, and 90 months after the first pulmonary metastasectomy, respectively. Pulmonary metastasectomy for esophageal carcinoma with postoperative chemotherapy was seemingly justified. Solitary pulmonary metastasis might be a good candidate for favorable prognostic factor.

Perioperative assessment of oversized lobar graft downsizing in living-donor lobar lung transplantation using three-dimensional computed tomographic volumetry

A 15‐year‐old boy with bronchiolitis obliterans after bone marrow transplantation successfully underwent bilateral living‐donor lobar lung transplantation (LDLLT) with segmentectomy of the superior segment of an oversized right lower lobe graft. As the recipient was small for his age, the predicted value of his functional vital capacity of the recipient was difficult to determine preoperatively. Three‐dimensional computed tomography (CT) volumetry revealed that the ratio of donor graft volume to recipient hemithorax volume was 159% on the right side and 82% on the left side. The patient is alive and well 7u2003months after transplantation, and three‐dimensional CT volumetry revealed that the right and left donor lungs were still compressed to 73% and 84% of the original size, respectively. In LDLLT, segmentectomy of the superior segment of the lower lobe is a useful option for downsizing an oversized graft and three‐dimensional CT volumetry can provide meaningful data for size matching.

Sirolimus treatment for recurrent lymphangioleiomyomatosis after lung transplantation.

Pulmonary lymphangioleiomyomatosis is a rare disease that generally progresses to respiratory failure. We experienced a patient who had recurring lymphangioleiomyomatosis in the transplanted lungs. A chest computed tomographic scan showed a progressing emphysematous change. The patient had a subclinical extent of pan-circumferential stricture at the distal site of the left bronchial anastomosis. We treated the patient with sirolimus for three years. Chest computed tomography showed no sign of exacerbation during the late 3 years, whereas pulmonary function test revealed a slight increase after the use of sirolimus. Bronchial stricture also disappeared almost completely. This is the first reported case with sirolimus treatment for post-transplant recurrent lymphangioleiomyomatosis.

Nebulized Phosphodiesterase III Inhibitor During Warm Ischemia Attenuates Pulmonary Ischemia–Reperfusion Injury

BACKGROUNDnThe control of warm ischemia-reperfusion injury is crucial in managing donors after cardiac death for lung transplantation. We focused on transalveolar administration as a drug-delivery route for such donors. Milrinone is a phosphodiesterase 3 inhibitor that inhibits the breakdown of cyclic adenosine monophosphate and selectively relaxes smooth muscle. We hypothesized that nebulized milrinone would mitigate warm ischemia-reperfusion injury of lung.nnnMETHODSnThis study was conducted with an isolated rat lung perfusion model. Lungs were excised, exposed to 55-minute ischemia at 37 degrees C, and reperfused for 60 minutes. During ischemia, nebulized milrinone (n = 6) or saline (n = 6) was inhaled. Lungs were continuously perfused without ischemia as a sham group (n = 6). Airway resistance, pulmonary vascular resistance, pulmonary compliance, weight gain and blood gas were measured. Adenine nucleotide levels and apoptosis were investigated in the reperfused lungs.nnnRESULTSnMilrinone nebulization decreased post-ischemic pulmonary vascular resistance (0.98 +/- 0.05 and 1.74 +/- 0.17 cm H(2)O/ml.min at 60 minutes of reperfusion in the milrinone and control groups, respectively [p < 0.01]). It did not alter cyclic adenosine monophosphate levels, but it did elevate adenosine triphosphate levels (9.87 +/- 0.38 and 6.91 +/- 0.45 in the milrinone and control groups, respectively [p < 0.01]) and suppressed apoptosis (3.83 +/- 0.91 and 46.17 +/- 3.39 of mean apoptotic cell numbers in the milrinone and control groups, respectively [p < 0.01]).nnnCONCLUSIONSnMilrinone nebulization decreased post-ischemic pulmonary vascular resistance, elevated adenosine triphosphate levels, and suppressed apoptosis. Nebulized milrinone has some protective effects against warm ischemia.

A follow-up report on a new method of segmental resection for small-sized early lung cancer

We previously reported a new method of segmentectomy, pulmonary artery-guided segmentectomy as a surgical alternative for small-sized early lung cancer with favorable results, but the follow-up time was too short for definitive conclusion. To examine the efficacy of the segmentectomy, and to determine the appropriate surgical procedure for early lung cancer, we conducted a retrospective follow-up study, and examined the influences of tumor size and preoperative serum tumor marker levels on the prognosis. We reviewed the records of 91 patients who underwent the segmentectomy for pathological T1N0M0 non-small cell lung cancer from 1993 to 2002. In 85 patients, carcinoembryonic antigen, squamous cell carcinoma-related antigen, and a fragment of cytokeratin were measured preoperatively. The overall 5-year survival rate was 83%. Indication (intentional, n=47; compromised, n=44) and tumor size (20mm or less, n=68; 21 to 30 mm, n=23) had no significant impact on survival. The 5-year survival rate for 49 patients with normal tumor marker levels was 93%, and significantly higher than 36 patients with at least one elevated tumor marker level (68%, p<0.01). Median follow-up time of 72.0 months revealed 11 locoregional recurrences. The incidence of locoregional recurrence was significantly higher in the patients with tumors of 21-30 mm, and elevated tumor marker (p<0.01). The follow-up study demonstrated that the segmentectomy could be an acceptable surgical treatment for early lung cancer patients with tumors of 20mm or smaller and normal tumor marker levels.

Value of FOXP3 expression in peripheral blood as rejection marker after miniature swine lung transplantation.

BACKGROUNDnOutcome for highly immunogenic lung transplantation remains unsatisfactory despite the development of potent immunosuppressants. The poor outcome may be the result of a lack of minimally invasive methods to detect early rejection. There is emerging clinical evidence that, paradoxically, expression of forkhead box P3 (FOXP3, a specific marker for the regulatory T cells) is upregulated within rejecting grafts.nnnMETHODSnOrthotopic lung transplantation was performed using miniature swine without immunosuppression. Rejection was monitored by chest radiography and open lung biopsy. Expressions levels of FOXP3, perforin, Fas-L and IP-10 mRNA were quantified in the peripheral blood. In addition, rescue immunosuppressive therapy (steroid plus tacrolimus) was administered on post-operative day (POD) 4 or 6.nnnRESULTSnEarly rejection was detected by open lung biopsy, but misdiagnosed by chest radiography on POD 4. Expression of FOXP3 in the peripheral blood reached its highest value as early as POD 4, followed by a decline. Such an increase of FOXP3 was not observed in recipients given high-dose tacrolimus. Neither perforin, Fas-L or IP-10 in the peripheral blood exhibited significant fluctuations in the early phase of rejection. Rescue immunosuppressive therapy from POD 4, when peak FOXP3 was seen, prolonged graft survival (27.2 days, versus 9.1 days without immunosuppression, p < 0.001), in contrast to POD 6, when rejection was suspected by chest radiography (11.5 days, p = not statistically significant [NS]).nnnCONCLUSIONSnIn a miniature swine lung transplantation model, the FOXP3 mRNA level in the peripheral blood was upregulated at an early phase of rejection. The clinical implication of this finding remains to be elucidated.

Forced Oscillation Technique as a Non-Invasive Assessment for Lung Transplant Recipients

We usually use spirometry for the medical follow-up of respiratory mechanics after lung transplantation. However, especially in the first few post-operative weeks, it is easily affected by postoperative pain and the patients co-operation during forced breathing effort. To avoid missing out on assessing pulmonary function, we perform non-invasive forced oscillation techniques on the patients who cannot perform forced breathing maneuvers. In this paper, we discuss the application of forced oscillation techniques on a patient with suspicion of acute lung rejection, whose spirometry could not be correctly performed and seemed to be unreliable. The respiratory impedance measurements had good correlation with the patients clinical symptoms before and after steroid therapy. Thus, postoperative pulmonary function follow-up using forced oscillation technique was useful in assessing peripheral airway condition in critically ill patients, and may be able to detect acute rejection.

Living-donor lobar lung transplantation with sparing of bilateral native upper lobes: a novel strategy.

A 44-year-old man became wheelchair-bound due to sever bronchiolitis obliterans caused by peripheral blood stem cell transplantation for acute myelogenous leukemia. His lung donors, his sister and his wife, were 17 cm shorter than him. He successfully underwent living-donor lobar lung transplantation with sparing of the bilateral native upper lobes to address the size mismatch. Ten months after the transplantation, the patient has returned to a normal lifestyle without supplemental oxygen.