Two thousand transhiatal esophagectomies: changing trends, lessons learned

OBJECTIVE: "Rediscovered" in 1976, transhiatal esophagectomy (THE) has been applicable in most situations requiring esophageal resection and reconstruction. The objective of this study was to review the authors' 30-year experience with THE and changing trends in its use. METHODS: Using the authors' prospective Esophagectomy Database, this single institution experience with THE was analyzed retrospectively. RESULTS: Two thousand and seven THEs were performed-1063 (previously reported) between 1976 and 1998 (group I) and 944 from 1998 to 2006 (group II), 24% for benign disease, 76%, cancer. THE was possible in 98%. Stomach was the esophageal substitute in 97%. Comparing outcomes between group I and group II, statistically significant differences (P < 0.001) were observed in hospital mortality (4% vs. 1%); adenocarcinoma histology (69% vs. 86%); use of neoadjuvant chemoradiation (28% vs. 52%); mean blood loss (677 vs. 368 mL); anastomotic leak (14% vs. 9%); and discharge within 10 days (52% vs. 78%). Major complications remain infrequent: wound infection/dehiscence, 3%, atelectasis/pneumonia, 2%, intrathoracic hemorrhage, recurrent laryngeal nerve paralysis, chylothorax, and tracheal laceration, <1% each. Late functional results have been good or excellent in 73%. Aggressive preoperative conditioning, avoiding the ICU, improved pain management, and early ambulation reduce length of stay, with 50% in group II discharged within 1 week. CONCLUSION: THE refinements have reduced the historic morbidity and mortality of esophageal resection. This largest reported THE experience reinforces the value of consistent technique and a clinical pathway in managing these high acuity esophageal patients.     

Myxoid solitary fibrous tumor: a clinicopathologic study of three cases

While focal myxoid areas are occasionally observed in solitary fibrous tumors, neoplasms of this type exhibiting extensive myxoid change are considered exceedingly uncommon. Due to their rarity, the biologic behavior of myxoid solitary fibrous tumor has not been determined. Three cases of myxoid solitary fibrous tumor are described in order to better characterize the clinical and pathologic features of this uncommon variant of solitary fibrous tumor. The tumors occurred in one man and two women, with ages of 37, 47, and 58 years, respectively. Sites of involvement included the retroperitoneum, pelvis, and soft tissue of the neck. Histologically, all cases were characterized predominantly by the presence of myxoid stroma comprising 70% to 100% of the tumor. The tumor cells were predominantly spindled in all cases, and arranged randomly, in loose fascicles, or in anastomosing strands imparting a microcystic/reticular appearance. The lesional cells had a bland cytologic appearance and low mitotic count. All tumors lacked necrosis and areas of increased cellularity. By immunohistochemistry, all cases were positive for CD34, CD99, and bcl-2, and negative for keratin, epithelial membrane antigen, desmin, actin, smooth muscle actin, and S-100 protein. To date, all cases have followed a benign course without evidence of recurrence or metastasis with a follow-up duration ranging from 50 to 87 months. The data suggest that myxoid solitary fibrous tumors are associated with an indolent clinical course and favorable prognosis.     

Longitudinal trends of total and allergen-specific IgE throughout childhood

Background:  The development and the quantitative relationship between allergen-specific IgE (S-IgE) responses and total IgE (T-IgE), during childhood and adolescence have not been described and understood in detail. The objective of this study was to describe and compare the longitudinal trends of serum levels of S-IgE and T-IgE during childhood.
Methods:  We analysed data from participants in the MAS birth cohort study at 2, 5, 7 and 10 years of age ( n  = 273) and at 1, 3, 5, 6, 7, 10 and 13 years ( n  = 84). Total-IgE and the overall level of specific-IgE against nine locally relevant airborne and food allergens were determined by FEIA (ImmunoCAP). Allergic rhino-conjunctivitis and asthma were ascertained by questionnaires.
Results:  Longitudinal patterns of T-IgE levels from age 1 to 13 years were highly heterogeneous (declining, flat or increasing with different profiles). From 5 years of age, logarithmic (log₁₀) transformed values of T-IgE and of S-IgE levels tend to follow a parallel trend, so that their relation remained constant throughout school age. A flat trend of T-IgE vs a constantly increasing trend of T-IgE was associated with a low or, respectively, high rate of wheezing at 13 years of age.
Conclusions:  Beginning at the age of 5 years, total serum IgE levels in children from an industrialized country evolved in parallel with overall S-IgE levels. Therefore, variations in T-IgE levels at school age closely reflect variations in overall S-IgE levels. Further studies are required to strengthen the biological and clinical implication of this novel finding.     

The Direction of Longitudinal Associations Between Sleep Problems and Depression Symptoms: A Study of Twins Aged 8 and 10 Years

Study Objectives:

To establish the direction and etiology of longitudinal associations between sleep problems and depression symptoms in children.

Design:

Data on twins aged 8 and 10 years were obtained. At assessments, parents completed the Child Sleep Habits Questionnaire, and twins completed the Children''s Depression Inventory.

Setting:

Participants were mainly interviewed at the Institute of Psychiatry, London.

Patients or Participants:

Three hundred twin pairs initially enrolled in the study.

Interventions:

N/A.

Measurements and Results:

A genetically informative cross-lagged model examined links between sleep and depression. Sleep problems at age 8 predicted depression at age 10 (partial regression coefficient [95% confidence intervals] = 0.10 [0.01-0.18]). The converse was not found. Stability of sleep problems across time was mainly due to genes (46% of the genetic influence on sleep at 10 was due to the same genetic influence on sleep aged 8). Stability of depression was mainly due to nonshared environmental influences (19% of the nonshared environmental influence on depression at 10 was due to the same nonshared environmental influence on depression at age 8). The cross-lagged association between sleep problems at 8 and depression at 10 years was largely due to genes, although this finding was nonsignificant.

Conclusions:

This study adds to our understanding of the temporal precedence of sleep problems and depression and the risks underlying their associations. There are implications regarding the value of specifying genes linked to sleep problems and potential opportunities for informing early intervention strategies in high-risk groups at key points in the progression to developing more serious problems.

Citation:

Gregory AM; Rijsdijk FV; Lau JYF; Dahl RE; Eley TC. The direction of longitudinal associations between sleep problems and depression symptoms: a study of twins aged 8 and 10 years. SLEEP 2009;32(2):189–199.     

Outbreak of Intestinal Infection Due to Rhizopus microsporus

Sinopulmonary and rhinocerebral zygomycosis has been increasingly found in patients with hematological malignancies and bone marrow transplantation, but intestinal zygomycosis remains very rare in the literature. We investigated an outbreak of intestinal infection due to Rhizopus microsporus in 12 patients on treatment for hematological malignancies over a period of 6 months in a teaching hospital. The intake of allopurinol during hospitalization (P < 0.001) and that of commercially packaged ready-to-eat food items in the preceding 2 weeks (P < 0.001) were found to be independently significant risk factors for the development of intestinal zygomycosis. A total of 709 specimens, including 378 environmental and air samples, 181 food samples, and 150 drug samples, were taken for fungal culture. Among them, 16 samples of allopurinol tablets, 3 prepackaged ready-to-eat food items, and 1 pair of wooden chopsticks were positive for Rhizopus microsporus, which was confirmed by ITS1-5.8S-ITS2 rRNA gene cluster (internal transcribed spacer [ITS]) sequencing. The mean viable fungal counts of allopurinol obtained from wards and pharmacy were 4.22 × 10³ CFU/g of tablet (range, 3.07 × 10³ to 5.48 × 10³) and 3.24 × 10³ CFU/g of tablet (range, 2.68 × 10³ to 3.72 × 10³), respectively, which were much higher than the mean count of 2 × 10² CFU/g of food. Phylogenetic analysis by ITS sequencing showed multiple clones from isolates of contaminated allopurinol tablets and ready-to-eat food, of which some were identical to patients'' isolates, and with one isolate in the cornstarch used as an excipient for manufacture of this drug. We attempted to type the isolates by random amplification of polymorphic DNA analysis, with limited evidence of clonal distribution. The primary source of the contaminating fungus was likely to be the cornstarch used in the manufacturing of allopurinol tablets or ready-to-eat food. Rhizopus microsporus is thermotolerant and can multiply even at 50°C. The long holding time of the intermediates during the manufacturing process of allopurinol amplified the fungal load. Microbiological monitoring of drugs manufactured for highly immunosuppressed patients should be considered.Zygomycosis has become an important emerging infection in patients with hematological malignancy undergoing chemotherapy or bone marrow transplantation (24), especially with the availability of voriconazole as antifungal prophylaxis (25, 28, 44). Breakthrough zygomycosis in patients on voriconazole prophylactic treatment is usually manifested as sinopulmonary or rhinocerebral disease, since the fungal spores are ubiquitously found in the environment and could therefore be acquired through inhalation or traumatic inoculation through the skin or mucosa. Gastrointestinal zygomycosis has been a rare clinical entity (50, 54), but cases or outbreaks of tongue, gastric, or cutaneous zygomycosis due to Rhizopus microsporus after exposure to contaminated wooden tongue depressors have been reported (23, 26, 33).The Rhizopus microsporus species group, which belongs to the class Zygomycetes and the order Mucorales, can cause life-threatening infections in immunocompromised patients (9, 39, 46). The laboratory diagnosis of R. microsporus relies mainly on the characteristic microscopic and phenotypic features of the fungal mycelium culture on agar medium. A molecular diagnostic test for this fungus is not widely available. PCR amplification and sequencing of the 18S and 28S rRNA genes (58, 64), internal transcribed spacer (ITS) region of rRNA (27), and recently PCR restriction fragment length polymorphism (22) and high-affinity iron permease gene sequence have been used to identify members of the clinically important Zygomycetes (30).Here we report an unprecedented outbreak of intestinal zygomycosis due to R. microsporus as a result of the oral intake of contaminated allopurinol tablets and ready-to-eat food items in patients with hematological malignancies undergoing chemotherapy and bone marrow transplantation. The clinical spectrum of this outbreak of intestinal infection by R. microsporus ranges from asymptomatic colonization to mucosal involvement to invasive disease.     

Avid F-FDG uptake of pectoralis major muscle: an equivocal sequela of strenuous physical exercise

Avid functional (18)F-FDG uptake of skeletal muscle is a known false positive finding of PET-CT study especially after involuntary muscle exercise just prior to the study. We describe the case of a 50-year-old man in whom the finding of avid (18)F-FDG uptake of pectoralis major muscle was encountered during investigation of metastatic melanoma.     

FGF8b oncogene mediates proliferation and invasion of Epstein-Barr virus-associated nasopharyngeal carcinoma cells: implication for viral-mediated FGF8b upregulation

The fibroblast growth factor 8b (FGF8b) oncogene is known to be primarily involved in the tumorigenesis and progression of hormone-related cancers. Its role in other epithelial cancers has not been investigated, except for esophageal cancer, in which FGF8b overexpression was mainly found in tumor biopsies of male patients. These observations were consistent with previous findings in these cancer types that the male sex-hormone androgen is responsible for FGF8b expression. Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer of head and neck commonly found in Asia. It is etiologically associated with Epstein-Barr Virus (EBV) infection, inflammatory tumor microenvironment and relatively higher male predominance. Here, we reported for the first time that FGF8b is overexpressed in this EBV-associated non-hormone-related cancer of the head and neck, NPC. More importantly, overexpression of FGF8b mRNA and protein was detected in a large majority of NPC tumors from both male and female genders, in addition to multiple NPC cell lines. We hypothesized that FGF8b overexpression may contribute to NPC tumorigenesis. Using EBV-associated NPC cell lines, we demonstrated that specific knockdown of FGF8b by small interfering RNA inhibited cell proliferation, migration and invasion, whereas exogenous FGF8b stimulated these multiple phenotypes. Further mechanistic investigation revealed that in addition to NF-κB signaling (a major inflammatory signaling pathway known to be activated in NPC), an important EBV oncoprotein, the latent membrane protein 1 (LMP1), was found to be a direct inducer of FGF8b overexpression in NPC cells, whereas androgen (testosterone) has minimal effect on FGF8b expression in EBV-associated NPC cells. In summary, our study has identified LMP1 as the first viral oncogene capable of directly inducing FGF8b (an important cellular oncogene) expression in human cancer cells. This novel mechanism of viral-mediated FGF8 upregulation may implicate a new role of oncoviruses in human carcinogenesis.