Ileal perforation induced by acute radiation injury under gefitinib treatment.

Enteritis is one of the side effects of radiotherapy to the abdominal cavity. Radiation enteritis involves damage to mucous membranes in the acute phase and to stromal tissues in the late phase. Perforation of the intestine tends to occur in the late phase, and rarely in the acute phase. However, we describe here a case of intestinal perforation occurring in the acute phase after irradiation in a patient who received gefitinib treatment. Gefitinib, one of the epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), is widely used to treat non-small cell lung cancer (NSCLC) patients, but is simultaneously known to inhibit wound healing. We suspect that gefitinib may affect regeneration of the small intestinal mucosa injured by irradiation. A 76-year-old woman had NSCLC with metastases to the 5th lumbar, sacral, and right iliac bones. To control the pain from bone metastasis, anterior-posterior opposing portal irradiation (total 35 Gy) was started, and was completed over 22 days. On day 25 after starting radiotherapy, the patient began to take gefitinib. On day 35, she presented with acute peritonitis, and an emergency laparotomy was performed. The terminal ileum was affected by radiation enteritis and there were two pin-hole perforations. In the surgical specimen, no cancerous lesions were detected, and immunohistochemical staining of phosphorylated EGFR (pEGFR) was negative. pEGFR has an important role in mucous membrane repair after irradiation. Intestinal perforation in the acute phase of radiation enteritis may be associated with impaired mucosal repair mechanisms due to the use of an EGFR-TKI such as gefitinib, as evidenced by the absence of pEGFR.

A neutrophil elastase inhibitor improves lung function during ex vivo lung perfusion.

OBJECTIVE: Ex vivo lung perfusion (EVLP) has been used not only for graft evaluation but also for graft reconditioning prior to lung transplantation. Inflammatory cells such as neutrophils may cause additional graft injury during EVLP. Neutrophil elastase inhibitors protect lungs against neutrophil-induced lung injury, such as acute respiratory distress syndrome. This study aimed to investigate the effect of a neutrophil elastase inhibitor during EVLP. METHODS: EVLP was performed for 4 h in bilateral pig lungs that had previously experienced warm ischemia for 2 h with or without a neutrophil elastase inhibitor (treated and control groups, respectively; n = 6). Following EVLP, the left lung was transplanted into a recipient pig, and this was followed by observation for 4 h. Pulmonary functions were observed both during EVLP and during the early post-transplant stage. RESULTS: During EVLP, decreases in neutrophil elastase levels (P < 0.001), the wet-dry weight ratio (P < 0.05), and pulmonary vascular resistance (P < 0.01) and increases in the PaO2/FiO2 ratio (P < 0.01) and pulmonary compliance (P < 0.05) were observed in the treated group. After transplantation, decreased pulmonary vascular resistance (P < 0.05) was observed in the treated group. CONCLUSIONS: A neutrophil elastase inhibitor attenuated the inflammatory response during EVLP and may decrease the incidence of lung reperfusion injury after transplantation.

Does sex difference influence the neuromuscular blocking potencies of vecuronium?

One hundred and fifty patients of ASA class I-II undergoing elective surgery were given vecuronium 0.1 mg·kg-1 under fentanyl- (NLA), halothane, enflurane, isoflurane, or sevoflurane anesthesia, and the spontaneous recovery was monitored to study the sex differences as to onset time, duration [(T1, train of four (TOF)], and recovery index (T1, TOF). The onset time was significantly shorter in women than in men under isoflurane and sevoflurane anesthesia. No significant differences were seen between the sexes in terms of duration and recovery index of both T1 and TOF. We suggest that the results regarding onset time were due to the differences in distribution volume and extracellular fluid volume influenced by the proportions of lean body mass, fat tissue, and the occasional menstruation in women. It remains unclear, however, whether or not the effects of volatile gases to the sensitivity of receptors may contribute to the observed sex difference. Similar durations and recovery indexes in any anesthetic method indicate that the drug's rate of elimination is similar between the sexes. In conclusion, female patients favor the rapid onset of vecuronium when used under isoflurane or sevoflurane, but the recovery from the paralysis seems to be the same between the sexes regardless of the type of general anesthesia used.

Detection of airway ischaemic damage after lung transplantation by using autofluorescence imaging bronchoscopy.

OBJECTIVES: Airway complications related to ischaemia are a major cause of morbidity after lung transplantation. Early detection of airway ischaemia and optimal management of the anastomotic site could reduce the risk of airway complications. Autofluorescence imaging (AFI) bronchoscopy has been increasingly recognized as an effective technique for detecting abnormal mucosal thickening. The aim of this study was to investigate whether AFI bronchoscopy can facilitate the detection of airway ischaemic damage in lung transplant patients. METHODS: Twenty Landrace pigs were used to create a tracheal autotransplantation model. A four-ring length of trachea was excised and implanted orthotopically. The tracheal autograft was observed on postoperative days 0, 2, 4 and 7 with AFI bronchoscopy. The extent and origin of graft autofluorescence were examined using histology and measured according to fluorescence intensity. RESULTS: The lesions on the tracheal autografts appeared as bright green fluorescence on AFI bronchoscopy. On confocal fluorescence microscopy, high-intensity green fluorescence was observed in the elastin fibre layer of the submucosa. The fluorescence intensity of elastin was significantly higher in the graft showing fluorescence than the graft that did not show fluorescence and that at the control site. CONCLUSIONS: Bright green fluorescence was seen in an elastin fibre layer in the submucosa, which was likely a result of epithelial sloughing. There is a close relationship between the bright green fluorescence pattern observed using AFI bronchoscopy and airway ischaemic damage. We conclude that AFI bronchoscopy may detect airway ischaemic damage after lung transplantation.

Unilateral lung transplantation using right and left upper lobes: an experimental study.

OBJECTIVE: The shortage of organ donors is a serious problem in Japan. The right and left upper lobes of rejected extended-criteria lungs have the potential to be used for downsized lung transplantation; however, the 2 upper lobes are too small for a size-matched recipient. The present study investigated the feasibility of unilateral transplantation using the right and left upper lobes. METHODS: After harvesting the heart-lung block from donor swine, a left lung graft was created using the right and left upper lobes and transplanted into the left thoracic space of the recipient swine (group A, n = 5). We then evaluated graft function for 6 hours and compared these results with those of a control group (group B, n = 5), in which orthotopic left lung transplantation had been performed. RESULTS: The mean partial pressure of oxygen in the arterial blood gas after reperfusion was 507 mm Hg in group A and 463 mm Hg in group B (P = .2). The mean pulmonary arterial pressure was 30.3 mm Hg in group A and 27.5 mm Hg in group B (P = .4). The mean airway pressure was 6.4 mm Hg in group A and 6.2 mm Hg in group B (P = .7). CONCLUSIONS: Our results suggest that unilateral left lung transplantation using the right and left upper lobes is technically and functionally feasible for size-matched recipients. In addition, this technique enables the use of rejected lungs if the upper lobes are still intact.

Effect of donor pre-mortem hypoxia and hypotension on graft function and start of warm ischemia in donation after cardiac death lung transplantation.

BACKGROUND: The start of warm ischemic time (WIT) of donor lungs in donation after cardiac death (DCD) is not clearly defined. We investigated the effect of donor pre-mortem hypotension and hypoxia to determine which physiologic factor is the determinant of WIT onset in controlled DCD lung transplantation. METHODS: Twenty mechanically-ventilated donor pigs were placed in 4 groups (n = 5 each) and exposed to each of the pseudo-agonal conditions for 60 minutes: (1) control group, no intervention and optimum ventilation, followed by cardiac arrest; (2) hypotension (HT) group, controlled cardiac tamponade reducing systolic blood pressure to <50 mm Hg, followed by cardiac arrest; (3) hypoventilation (HV) group, ventilation with room air at 5 breaths/min, followed by cardiac arrest; (4) non-circulation (NC) group, initial cardiac arrest, followed by a 60-minute standoff time. The lung graft was retrieved and the left lung was transplanted to the recipient. Graft function was evaluated for 4 hours after contralateral pulmonary artery ligation. The reperfusion injury was evaluated based on tissue cytokine expression, wet weight-to-dry weight ratio, and histology at the end of the reperfusion period. RESULTS: Impaired post-transplant graft function was seen in the HV group, which had significantly poorer oxygenation during the reperfusion period than the other groups (p < 0.001). The HV group also had higher tissue levels of interleukin-8 (p < 0.05), a higher wet weight-to-dry weight ratio (p < 0.05), and histologic findings of graft tissue injury than the control group. The difference in these parameters among the control, HT, and NC groups was not significant. CONCLUSIONS: Only pre-mortem hypoxia provoked by hypoventilation significantly impaired lung graft function in DCD lung transplantation. Ventilatory rather than circulatory deterioration can trigger the onset of warm ischemia.