Relationship between dyspnoea and related factors in patients with cancer: a cross-sectional study.

OBJECTIVES: Dyspnoea is a common and distressing symptom in patients with cancer. We aimed to analyse the association between dyspnoea and related factors and to estimate their causal relationship. METHODS: A cross-sectional study was conducted. Patients with cancer with dyspnoea and a mean Numerical Rating Scale (NRS) of ≥3 over 24 hours were enrolled at 10 institutions in Japan from December 2019 to February 2021. The outcomes included dyspnoea, cough and pain NRS over 24 hours, Eastern Cooperative Oncology Group Performance Status, Hospital Anxiety and Depression Scale, Somatosensory Amplification Scale, opioids for dyspnoea and respiratory failure. Path analyses were conducted to estimate the direct and indirect paths with reference to dyspnoea and related factors. RESULTS: A total of 209 patients were enrolled and 208 patients were included in the analysis. Cough worsened dyspnoea (ß=0.136), dyspnoea increased emotional distress (ß=1.104), emotional distress increased somatosensory amplification (ß=0.249) and somatosensory amplification worsened cough (ß=0.053) according to path analysis. CONCLUSION: There may be a vicious circle among dyspnoea and related factors: cough worsened dyspnoea, dyspnoea increased emotional distress, emotional distress increased somatosensory amplification and somatosensory amplification worsened cough. When treating dyspnoea in patients with cancer, managing these factors aimed at interrupting this vicious circle may be useful. TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (UMIN000038820).

Prevalence of Myofascial Pain Syndrome and Efficacy of Trigger Point Injection in Patients with Incurable Cancer: A Multicenter, Prospective Observational Study (MyCar Study).

OBJECTIVE: Myofascial pain syndrome (MPS) is caused by overload or disuse of skeletal muscles. Patients with cancer are often forced to restrict their movement or posture for several reasons. The study was conducted to investigate the prevalence and risks of MPS in patients with incurable cancer. The efficacy of trigger point injection (TPI) was also explored. METHODS: This was a multicenter, prospective observational study. Patients with incurable cancer who started receiving specialist palliative care were enrolled. We investigated the MPS in this population and accompanying risk factors for restricting body movement. Pre- and post-TPI pain was also evaluated using a Numerical Rating Scale (NRS) in patients who received TPI. The primary outcome was the prevalence of MPS. RESULTS: A total of 101 patients were enrolled from five institutions in Japan. Most of the patients (n = 94, 93.1%) had distant metastases, and half of the patients (50, 49.5%) received anticancer treatment. Thirty-nine (38.6%) patients had MPS lesions at 83 sites. Multivariate analysis revealed that the significant risk factor for MPS was poor Performance Status (PS) (odds ratio 3.26; 95% confidence interval [CI] 1.18-9.02, P = .023). We performed TPI for 40 out of 83 MPS lesions. Mean NRS for MPS before TPI was 7.95, which improved to 4.30 after TPI (P < .001). CONCLUSIONS: MPS was common in patients with incurable cancer and the risk factor identified in this study was poor performance status. TPI could be a treatment option.

Effects of molecular targeting agents and immune-checkpoint inhibitors in patients with advanced cancer who are near the end of life.

BACKGROUND: In recent years, the use of both molecular targeting agents (MTAs) and immune-checkpoint inhibitors (ICIs) tend to occupy important positions in systemic anticancer therapy (SACT). The objective of this study is to describe the predictors of SACT include both MTAs and ICIs near the end of life (EOL) and the effect on EOL care in patients with advanced cancer. METHODS: We analyzed all patients who died of advanced cancer from August 2016 to August 2019, and we analyzed the survival time of patients who underwent anticancer agents excluded due to the loss of information about the last administration of SACT. The primary endpoint of this study was to identify predictors during the last administration of SACT near EOL. RESULTS: In a multivariate analysis, the Eastern Cooperative Oncology Group performance status (ECOG-PS) (ORs 33.781) was significantly related factors within 14 days of death from the last administration of SACT. Age (ORs 0.412), ECOG-PS (ORs 11.533), primary cancer site of upper GI cancers (ORs 2.205), the number of comorbidities (ORs 0.207), MTAs (ORs 3.139), and ICIs (ORs 3.592) were significantly related factors within 30 days of death. The median survival time (MST) of patients with PS 3-4 was 29 days, while that of patients with both PS 0-2 was 76 days. The prevalence rate of delirium with MTAs was 17.5%, which was significantly lower than that of patients without it (31.8%). The prevalence rate of the mean dose of opioids in patients with ICIs was 97.9 mg/day, which was significantly higher than that of patients without it (44.9 mg/day). CONCLUSIONS: Age, ECOG-PS, primary cancer site, the number of comorbidities, MTAs, and ICIs use were significant associated with SACT near EOL. Information on these factors may aid clinical decision making in referral to palliative care institutes.

Prognostic factors in patients who received end-of-life chemotherapy for advanced cancer.

BACKGROUND: Clinical efficacy of aggressive end-of-life (EOL) chemotherapy remains unclear. METHOD: Medical records of patients with advanced cancer between August 2011 and August 2016 were retrospectively analyzed. The primary endpoint was to identify prognostic factors at the last administration of chemotherapy. The secondary endpoint was to analyze the relationship between EOL symptoms and EOL treatment details. RESULTS: Among 300 evaluated patients, the number of patients who died within 14 and 30 days from the last administration of chemotherapy were 16 (5.3%) and 50 (16.7%), respectively. Multivariate analysis revealed that ECOG-PS (OR 3.698, p < 0.001) and GPS2 (OR 3.791, p = 0.028) were significant prognostic factors. The MST of patients with both PS 2-4 and GPS2 (+) was 38 days, while that in patients with both PS 0-1 and GPS2 (-) was 134.5 days. The prevalence rate of nausea and vomiting (25.0%) and the mean hydration volume (0.50 L/day) in patients who died within 30 days from the chemotherapy was significantly higher than others (7.4%) (0.20 L/day). CONCLUSION: ECOG-PS and GPS were significant prognostic factors for aggressive EOL chemotherapy. Information on these factors may aid clinical decision-making in terms of risk-benefit balance, particularly in patients with poor prognosis.

A patient with peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and severe hypoganglionosis associated with a novel SOX10 mutation.

In this report, we present the case of a female infant with peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease (PCWH) associated with a novel frameshift mutation (c.842dupT) in exon 5, the last exon of SOX10. She had severe hypoganglionosis in the small intestine and entire colon, and suffered from frequent enterocolitis. The persistence of ganglion cells made both the diagnosis and treatment difficult in the neonatal period. She also showed hypopigmentation of the irises, hair and skin, bilateral sensorineural deafness with hypoplastic inner year, severe demyelinating neuropathy with hypotonia, and diffuse brain hypomyelination. The p.Ser282GlnfsTer12 mutation presumably escapes from nonsense-mediated decay and may generate a dominant-negative effect. We suggest that hypoganglionosis can be a variant intestinal manifestation associated with PCWH and that hypoganglionosis and aganglionosis may share the same pathoetiological mechanism mediated by SOX10 mutations.

The preoperative HbA1c level is an independent prognostic factor for the postoperative survival after resection of non-small cell lung cancer in elderly patients.

PURPOSE: The aim of this study was to investigate the influence of a history of diabetes mellitus (DM) and the glycated hemoglobin (HbA1c) level on the survival in patients who underwent complete resection for non-small cell lung cancer (NSCLC). METHODS: Of the patients who underwent complete resection for NSCLC between 2007 and 2015, 468 were classified into DM (who were currently taking medication for DM) and no DM groups as well as into high HbA1c (≥ 6.5) and normal HbA1c (< 6.5) groups. RESULTS: The overall survival (OS) did not differ significantly between either pair of groups. Among the elderly patients, the OS did not differ significantly between the DM and no DM groups, but was significantly higher in the normal-HbA1c group than in the high-HbA1c group (5-year survival rate: 84.7 versus 37.2%, respectively, p < 0.01). In the elderly patients, non-adenocarcinoma histology, advanced stage, a high Charlson comorbidity index, and a high preoperative HbA1c level were found to be independent risk factors for the OS. CONCLUSION: We revealed that a high preoperative HbA1c level was associated with a poor OS in elderly patients who underwent complete resection for NSCLC. This suggests that it is necessary to achieve diabetic control prior to complete resection in NSCLC patients.

Clinical outcome of posterior fixation surgery in patients with vertebral metastasis of lung cancer.

Vertebral metastasis of non-small-cell lung cancer (NSCLC) often leads to neurological paralysis, with deterioration of the patients' activities of daily living (ADL). Surgical treatments for the symptoms are unlikely to be recommended due to the poor prognosis of patients with advanced NSCLC. The aim of the present study was to retrospectively evaluate the clinical outcome of posterior spinal fixation surgery in patients with neurological paralysis resulting from vertebral metastasis of NSCLC. Between April, 2007 and March, 2012, 4 patients (3 men and 1 woman; median age, 56.5 years) underwent fixation surgery at the Shiga University of Medical Science Hospital (Otsu, Japan). The mean preoperative Tokuhashi and Tomita scores of the patients were high (8.25 and 7.0, respectively). However, the Frankel grade functional score and performance status of the patients improved following fixation surgery, after which all patients received chemoradiotherapy. Postoperatively, the median paralysis-free time was 41 months (range, 17-42 months) and the median survival time was 42.5 months (range, 22-43 months). According to the functional scores, the patients had a poor prognosis, which may have been a contraindication for fixation surgery. In these cases, however, surgical treatment improved the patients' ADL and increased the likelihood of receiving anticancer therapy, contributing to the prolongation of survival. Therefore, fixation surgery may be beneficial for patients with neurological paralysis following vertebral metastasis of advanced NSCLC.

Thymic papillo-tubular adenocarcinoma containing a cyst: report of a case.

We report a case of thymic papillo-tubular adenocarcinoma in a 55-year-old man, who had no symptoms. Sternotomy revealed a tumor in the anterior mediastinum, tightly adhered to the pericardium. It was resected completely. Interestingly, the tumor contained a unilocular cyst filled with mucinous fluid, suggesting that it originated from a pre-existing thymic cyst. Pathological examination of the tumor revealed a primary thymic papillo-tubular adenocarcinoma resembling a tumor of gut origin. Thymic adenocarcinomas, particularly of the tubular subtype, are extremely rare.

Difference in blood tacrolimus concentration between ACMIA and MEIA in samples with low haematocrit values.

OBJECTIVES: The aim was to compare blood tacrolimus concentrations in anaemic patients between affinity column-mediated immunoassay (ACMIA) and microparticle enzyme immunoassay (MEIA). METHODS: Blood concentrations of tacrolimus in 235 whole-blood samples from 64 patients treated with tacrolimus were determined by the two assay methods. Fifty-three samples had low haematocrit (Ht) values (<25%), whereas the other samples had normal Ht values. KEY FINDINGS: Measured tacrolimus concentrations in samples with normal Ht values did not differ between ACMIA and MEIA (median, range; 6.6, 0-29.1 vs 7.3, 0-27.4 ng/ml). On the other hand, MEIA determined significantly higher tacrolimus concentrations in samples with lower Ht values compared with ACMIA (14.0, 2.4-25.7 vs 11.5, 0-21.3 ng/ml; P < 0.05). This difference was caused by overestimated blood concentrations in MEIA derived from lower Ht values, which could be corrected using the Ht value for each sample (calculated MEIA (MEIAcalc)). The corrected concentrations (MEIAcalc; 10.8, 0-21.3 ng/ml) were comparable with those of ACMIA. It was confirmed that the difference in concentrations between ACMIA and MEIA was remarkable in routine monitoring of blood tacrolimus for a liver transplant recipient with anaemia. CONCLUSIONS: ACMIA can be applied to routine therapeutic drug monitoring of tacrolimus therapy in anaemic patients.

Closure of the larynx for intractable aspiration in neurologically impaired patients.

We present three patients with intractable aspiration pneumonia in the setting of permanent neurologic impairment, who had received a tracheostomy and showed a juxtaposition of the innominate artery against the trachea. Neurologically impaired patients often show a juxtaposition or compression of the innominate artery against the trachea by chest deformity in the setting of severe scoliosis, which could result in a trachea-innominate artery fistula. For intractable aspiration, laryngotracheal separation is safely performed and effective in controlling aspiration, but is occasionally complicated by trachea-innominate artery fistula. As an alternative procedure, we performed a closure of the larynx in these three cases, using double flaps of the vocal folds and false vocal folds, as a treatment for intractable aspiration. After operation, the patients did well without complication or clinical evidence of recurrent aspiration.

Omental pseudocyst formation associated with perforated gastric duplication: a case report.

We present a case of omental pseudocyst associated with a perforated gastric duplication. A boy (2.5 years old) with an abdominal mass was admitted because thick-walled and thin-walled double cysts were identified on computed tomography and magnetic resonance imaging. At laparotomy, the double cysts were interconnected and located in the omentum with no communication to the stomach. Microscopic examination showed a thick-walled cyst composed solely of gastric tissue with muscle layers divided at the stricture between the 2 cysts and a thin-walled cyst without a true endothelial lining. Gastric duplications can be complicated with perforation and malignancy, and primary surgery is the first choice of treatment.

A rare case of presacral cystic neuroblastoma in an infant.

Cystic neuroblastoma (CN) is an extremely rare entity, although neuroblastoma is the most common solid tumor in infants. The radiologic diagnosis of CN is very difficult because of both the rarity and minimum solid component of the lesion. We describe herein the case of a 2-month-old girl presenting with dysuria because of a large presacral mass. Imaging studies including ultrasonography, computed tomography, and magnetic resonance imaging demonstrated a large septated cystic tumor mimicking a cystic sacrococcygeal teratoma, which commonly occurs in the presacral region. The tumor was finally diagnosed as CN after surgical resection. This is the second case report of presacral CN in the English literature. Cystic neuroblastoma should be considered in the differential diagnosis of presacral cystic tumors in infants.

Use of sample hematocrit value to correct blood tacrolimus concentration derived by microparticle enzyme immunoassay.

The quality of microparticle enzyme immunoassay (MEIA) for blood tacrolimus is guaranteed in samples with hematocrit (Ht) values of 25 to 45%. Because MEIA provides inaccurate blood tacrolimus concentrations in samples with Ht out of this range (i.e. <25% or >45%), correction of the calibration is required for therapeutic drug monitoring. The authors demonstrated previously that overestimated MEIA tacrolimus concentration could be corrected by modified, calibrated MEIA (cMEIA) using the original calibrator. Here, an equation was established to more easily derive a corrected tacrolimus concentration by calculation (MEIAcalc) using the Ht of each sample. The tacrolimus concentrations of 99 whole-blood samples with low Ht (<25%) were then tested by the 3 assay methods: MEIA, cMEIA, and MEIAcalc. MEIA gave a significantly higher blood concentration of tacrolimus (median 12.9 ng/ml, range 3.6-26.4 ng/ml) than did cMEIA (median 10.0 ng/ml, range 0.2-21.1 ng/ml, p<0.05). This overestimation was eliminated by using MEIAcalc. There was no difference in blood tacrolimus concentration between cMEIA and MEIAcalc (median 10.0 ng/ml, range 1.7-21.4 ng/ml). MEIAcalc can be used to correct the tacrolimus concentration in samples obtained from patients with unstable Ht values.

Type I biliary atresia without extrahepatic biliary cyst.

Currently, magnetic resonance cholangiography (MRC) is used for the differentiation of biliary atresia (BA) from other causes of infantile cholestasis. The authors present a case of type I BA without an extrahepatic biliary cyst in a 2-month-old girl. MRC clearly visualized the patency of the gallbladder, cystic duct, and hepatic ducts with disappearance of the common bile duct. Intraoperative cholangiography demonstrated a cloudy appearance of the intrahepatic bile ducts, confirming the diagnosis of type I BA. We believe that this is the first reported case of type I BA without an extrahepatic biliary cyst diagnosed by MRC.

A new technique for treatment of tracheal compression by the innominate artery: external reinforcement with autologous cartilage graft and muscle flap suspension.

We report a new technique for treatment of tracheomalacia or tracheal compression caused by the innominate artery, utilized in two patients with neuromuscular disorders. Both cases developed a chest deformity in the setting of severe scoliosis. Computed chest tomography and fiberoptic bronchoscopy showed that the cervical trachea was compressed between the innominate artery and the cervical spine in the setting of deformity of the thoracic cavity. Both patients required prolonged mechanical ventilation prior to the operative procedure. To relieve compression by the innominate artery, the superior mediastinum was exposed by resection of part of the manubrium allowing a greater space, and external stenting of the cervical trachea with a reinforcing autologous cartilage graft and tracheopexy, as well as anterior suspension of the innominate artery with a sternohyoid muscle flap were carried out. Both patients were successfully weaned from prolonged mechanical ventilation. Resection of the manubrium sterni, tracheal stenting with rib segments and use of the strap muscle to elevate the innominate artery off of the trachea offer potential long-term release of airway obstruction.

Intrahepatic biliary cysts in children with biliary atresia who have had a Kasai operation.

PURPOSE: In patients with biliary atresia who had undergone a Kasai operation, treatment of intrahepatic biliary cysts (IBCs), particularly when complicated by cholangitis, is often difficult because the clinical implications and the course of IBCs are unclear. Thus, to determine the best treatment guideline, the morphology of IBCs, the clinical course, and the outcomes of such patients were evaluated. PATIENTS AND METHODS: A total of 44 patients with type III biliary atresia who underwent a Kasai operation from 1977 to 2005 were postoperatively examined for IBC by using ultrasonography and computed tomography. We classified the IBCs based on their number and shape. RESULTS: Intrahepatic biliary cysts developed in 12 of 54 patients. Three patients with solitary simple cysts and 1 patient with multiple simple cysts had no history of cholangitis. Two patients with multiple simple cysts had cholangitis at the time of IBC diagnosis and were treated with percutaneous transhepatic cholangiodrainage (PTCD). Patients with simple IBCs did not develop persistent cholangitis and their prognosis depended largely on their liver function; 3 of 6 patients remained healthy without cholangitis, whereas 3 patients required liver transplantation (LT) because of progressive liver failure or worsening hepatopulmonary syndrome, and not severe cholangitis. On the other hand, all 6 patients with multiple complicated IBCs had persistent cholangitis, eventually requiring LT. Even after bile flow to the intestine was reestablished after PTCD, both IBCs and cholangitis recurred. These patients required LT because of severe cholangitis. CONCLUSIONS: Intrahepatic biliary cysts without cholangitis are not a source of infection and require no treatment. Simple IBCs with cholangitis can be controlled by antibiotics and/or PTCD. Patients with multiple complicated IBCs have a poor prognosis, requiring LT to control cholangitis. Although PTCD can control cholangitis in these patients as they wait for LT, PTCD does not alleviate it--LT is the final solution.

Prolonged use of dexmedetomidine in an infant with respiratory failure following living donor liver transplantation.

We used dexmedetomidine for more than 2 months in a mechanically ventilated infant without serious adverse effects. An infant with liver cirrhosis of unknown cause underwent living donor liver transplantation at the age of 9 months. Long-term mechanical ventilation was required postoperatively, and midazolam with fentanyl had been used to sedate the patient. They required increase to 1.7 mg.kg(-1).h(-1) and 3.5 microg.kg(-1).h(-1), respectively, which were still inadequate. On postoperative day 29, dexmedetomidine was added. The rate of dexmedetomidine infusion was increased gradually to 1.4 microg.kg(-1).h(-1). It was discontinued temporarily to exclude drug-induced liver dysfunction. However, without dexmedetomidine, adequate sedation level was unattainable. Liver dysfunction was likely to be attributed to cytomegalovirus infection and after restarting dexmedetomidine, the respiratory condition improved. He was extubated 10 weeks after the operation. Dexmedetomidine was successfully tapered off over the following 2 weeks with no signs of withdrawal. Dexmedetomidine was a useful sedative for an infant who required mechanical ventilation for a prolonged period of time.

A pitfall in ligation of intrahepatic shunting after Fontan type operation.

An 8-year-old boy experienced progressive cyanosis after a Fontan type operation. Under the guidance of intraoperative color Doppler we performed a transabdominal ligation of the accessory hepatic veins which drained into a common atrium. Reoperation was needed through a median sternotomy to eliminate residual shunting. Although intraoperative Doppler is useful to aid in the ligation of accessory veins while portal hypertension is monitored, intraoperative angiogram serves better to ensure the elimination of intrahepatic shunting in a transabdominal approach.

Rare association of severe hypoplasia of the abdominal aorta with imperforate anus, colonic atresia, and choledochal cyst.

Hypoplasia of the abdominal aorta (HAA) is a rare condition that causes marked hypertension. Although multiple etiologies have been postulated for HAA, congenital structural anomalies are rarely observed except in cases associated with some hereditary syndromes. The authors describe a neonatal case with HAA complicated by multiple anomalies including colonic atresia (CA), imperforate anus, choledochal cyst, facial cleft, and brain defects. This patient showed CA in the descending colon and caliber change in the transverse colon mimicking Hirschsprung disease, both of which were thought to be caused by vascular insult to the mesentery due to HAA. Although multiple surgical corrections were successfully performed, the hypertension was uncontrollable.