Prognostic factors associated with survival in patients with hepatocellular carcinoma undergoing transarterial chemoembolisation: an Australian multicenter cohort study

Aim: Transarterial chemoembolisation (TACE) is recommended therapy for intermediate-stage hepatocellular carcinoma (HCC). However, the wide variations in outcom...     

Association of genetic polymorphism of glutathione S-transferase M1, T1, P1 and susceptibility to bladder cancer

OBJECTIVE: Glutathione-S-transferases (GSTs) are active in the detoxification of wide variety of endogenous or exogenous carcinogens. We examined the association of the GST gene polymorphism with sporadic bladder cancer patients in Northern India. MATERIAL AND METHODS: The study constituted of 106 bladder cancer cases and 370 age-matched controls. The GSTT1 and GSTM1 null genotypes were identified by multiplex PCR and GSTP1313 A/G by Polymerase Chain Reaction/Restriction Fragment Length Polymorphism method (PCR/RFLP). RESULTS: We observed non-significant association in null alleles of the GSTM1 (p = 0.611, OR = 1.12, 95% CI = 0.72-1.74 and GSTT1 (p = 0.135, OR = 1.45, 95% CI = 0.89-2.37) with risk of bladder cancer. However, the G/G genotype of the GSTP1 gene polymorphism was highly significant when compared to controls (p=0.000, OR = 7.12, 95% CI = 3.14-16.16). The combined analysis of the three risk genotypes demonstrated further increase in the risk of bladder cancer (p = 0.000, OR = 7.29 95% CI = 2.81-18.93). CONCLUSION: Our study demonstrated that GSTP1313 G/G polymorphism is a strong predisposing risk factor for bladder cancer. Combination of three GST genotypes association exhibiting gene-gene interaction further substantiates the increased risk of bladder cancer.     

Conjunctival Melanoma in Asian Indians: A Study of 42 Patients

Purpose: To describe the clinical features, treatment, and outcomes of conjunctival melanoma in Asian Indians.

Methods: Retrospective study of 42 patients.

Results: The mean age at presentation of conjunctival melanoma was 43 years (median, 45 years; range, 9–78 years). There were 20 (48%) males and 22 (52%) females. Nineteen patients (45%) had a known history of a preexisting pigmented conjunctival lesion. Bulbar conjunctiva (n = 28; 67%) was the most common tumor epicenter, and medial ocular surface quadrant (n = 15; 36%) was more commonly involved. The mean tumor basal diameter was 12 mm (median, 10 mm; range, 4–30 mm), and the mean tumor thickness was 4 mm (median, 2 mm; range, 1–30 mm). Majority of the patients had a pigmented tumor (n = 33; 79%). The tumors arose de novo (n = 17, 41%) or were associated with conjunctival nevus (n = 9; 21%) or primary acquired melanosis (n = 16, 38%). Wide excisional biopsy, adjunctive cryotherapy, and amniotic membrane grafting were performed in 27 (71%) patients, 11 (29%) underwent orbital exenteration, and 4 were lost to follow-up prior to definitive treatment. Over a mean follow-up period of 24 months (median, 9 months; range, <1 to 136 months), four (11%) patients had tumor recurrence, seven (18%) had locoregional lymph node metastasis, and four (11%) developed systemic metastasis and died due to metastatic disease.

Conclusion: Conjunctival melanoma predominantly occurs in middle-aged Asian Indians and is associated with a high rate of systemic metastasis and death.     

Circadian Rhythmicity as a Predictor of Quality of Life in Allogeneic Hematopoietic Cell Transplant Patients

Context

Quality of life (QoL) is increasingly recognized as an important outcome of cancer treatment. Previous studies have examined clinical predictors of QoL, but with the increasing prevalence of wearable sensors that monitor sleep and activity patterns, further investigation into whether these behaviors are predictive of post-treatment QoL is now feasible. Among patients receiving aggressive cancer treatment such as hematopoietic cell transplantation (HCT), analysis of circadian rhythms (24-hour patterns of sleep and activity) via wearable sensors is limited.

Minimally invasive mitral valve surgery

BACKGROUND: To reduce surgical trauma and the drawbacks associated with sternotomy, we performed robotically controlled, video-assisted mitral valve surgery, using either the port-access or the transthoracic clamp technique. METHODS AND RESULTS: Between September 1997 and September 2000, 221 patients (78 males, 143 females) underwent mitral valve surgery through a small right minithoracotomy using the port-access endovascular cardiopulmonary bypass system. Mitral valve exposure was facilitated with an endoscope attached to a voice-controlled robotic arm (AESOP 3000) allowing stabilization and voice-activated camera positioning. Twenty-six patients underwent mitral valve repair and 195 had valve replacement. In 197 patients, mitral valve surgery was the primary operation, while 24 were redo cases. Skin-to-skin mean operating time was 3.5 +/- 1.2 hours and aortic cross-clamp time was 58 +/- 16 min, mean intensive care unit stay was 22 +/- 7 hours and hospital stay 6.4 +/- 1.2 days. There was no re-exploration for bleeding. There was no late death or re-operation on mean follow-up of 16.4 +/- 12.2 months. Patients showed improvement in their NYHA functional class from 2.6 +/- 0.5 to 1.4 +/- 0.8 postoperatively. Outcomes were compared with those of our previous 220 patients who underwent mitral valve surgery with the median sternotomy approach. CONCLUSIONS: The use of video and robotic assistance in port-access mitral valve surgery not only minimizes the length of the incision, but also gives full visualization of the entire mitral valve apparatus. This approach provides comparable results with the sternotomy approach, as well as marked advantages of reduced intensive care unit stay. ,ower blood transfusion requirement, better cosmesis and earlier hospital discharge.     

Inclusion of supine period in short-duration pH monitoring is essential in diagnosis of gastroesophageal reflux disease

Prolonged esophageal pH monitoring is the most accurate method for detecting abnormal gastroesophageal reflux (GER) in patients with gastroesophageal reflux disease (GERD). However, some investigators have found that short-duration postprandial pH monitoring in the upright position is also useful, while others have failed to find such results. Therefore, we have compared a 6-hr period of pH monitoring (3-hr postprandial period after daytime meal and 3-hr supine period) with a total 24-hr period in detecting abnormal gastroesophageal reflux. Sixty-five patients (44 men, mean age 41.3 years) with GERD and 16 healthy volunteers (11 men, mean age 34.3 years) underwent 24-hr pH monitoring according to a standard protocol. Various reflux parameters during 24-hr pH monitoring were compared with reflux parameters during the 6-hr period. Abnormal GER was detected in 56 patients presenting with typical symptoms of GERD (sensitivity 86.2%). These patients could be further divided into upright (N=18), supine (N=15), and combined (N=23) refluxers, depending on the posture in which abnormal reflux occurred. Esophageal pH monitoring during the 3-hr postprandial upright period showed abnormal reflux in only 35 patients (sensitivity 53.8%;P<0.00005, compared with the 24-hr pH monitoring period). Abnormal GER was identified in 13 of 18 upright, 19 of 23 combined, and only one of 15 supine refluxers, as well as in two of nine patients with normal 24-hr pH-metry. However, inclusion of the 3-hr supine monitoring period in the 3-hr postprandial upright period improved detection of abnormal GER to 78.5% (51 patients;P=NS compared with 24-hr pH monitoring period). This was related mainly to improved detection of abnormal GER in supine refluxers (11 of 15; 73.3%). Esophageal acid exposure time correlated significantly with severity of esophagitis only during the total and supine periods of both the 24- and 6-hr periods and not during the upright period. Esophageal acid clearance correlated significantly with increasing grades of esophagitis for the supine and total periods only. We conclude that 3-hr postprandial pH monitoring, as has been conventionally practiced, is not appropriate in the detection of abnormal GER; inclusion of a supine period in the short-duration pH monitoring schedule increases the detection of pathological reflux. We therefore recommend that a supine period should be included in short-duration pH monitoring schedules. We also found that supine reflux was the most important factor in the development of esophagitis.     

Redo mitral valve surgery using the port-access system

Redo mitral valve surgery is hazardous, hence we explored an alternative approach using a port-access system that avoids reentry. Between October 1997 and December 2000, 32 patients underwent mitral reoperation using the system. All patients had previous cardiac operations. This procedure consisted of a right anterolateral minithoracotomy and femorofemoral cannulation using special port-access instruments and endoaortic clamping in 24 patients or direct transthoracic sliding-rod aortic clamping in 8. The valve disease was of rheumatic etiology in 28 patients and degenerative in 4. The valve was replaced in 31 cases and a paravalvular leak after mitral valve replacement was closed in 1. In 2 cases, the tricuspid valve was repaired along with mitral valve replacement. Mean total operating time was 4.5 +/- 1.2 hours, cardiopulmonary bypass time 162 +/- 72 minutes, and aortic crossclamp time 62 +/- 21 minutes. There was no mortality, and mean stay in the intensive care unit was 22 +/- 7 hours and hospital stay 6.4 +/- 1.2 days. Postoperative blood transfusion was required in 12 patients. In view of the favorable results, we recommend using the port-access system as a standard approach for mitral reoperation.     

Morbidity compression or expansion? A temporal analysis of the age at onset of non-communicable diseases in India

While there is evidence of morbidity compression in many countries, temporal patterns of non-communicable diseases (NCDs) in developing countries, such as India, are less clear. Age at onset of disease offers insights to understanding epidemiologic trends and is a key input for public health programs. Changes in age at onset and duration of major NCDs were estimated for 2004 (n = 38,044) and 2018 (n = 43,239) using health surveys from the India National Sample Survey (NSS). Survival regression models were used to compare trends by sociodemographic characteristics. Comparing 2004 to 2018, there were reductions in age at onset and increases in duration for overall and cause-specific NCDs. Median age at onset decreased for NCDs overall (57 to 53 years) and for diabetes, hypertension, heart disease, asthma, mental diseases, eye disease, and bone disease in the range of 2–7 years and increased for cancer, neurological disorders, some genitourinary disorders, and injuries/accidents in the range of 2–14 years. Hazards of NCDs were higher among females for cancers (HR 1.51, 95% CI 1.19–1.90) and neurological disorders (HR 1.18, 95% CI 1.06–1.32) but lower for heart diseases (HR 0.88, 95% CI 0.79–0.97) and injuries/accidents (HR 0.87, 95% CI 0.77–0.99). Hazards were greater among those with lower educational attainment at younger ages and higher educational attainment later in life. Unlike many countries, chronic disease morbidity may be expanding in India for many chronic diseases, indicating excess strain on the health system. Public health programs should focus on early diagnosis and prevention of NCDs.

     

Fluorescent in vivo tracking of hematopoietic cells. Part I. Technical considerations

We report a new technology for in vivo tracking of hematopoietic cells, using fluorescent lipophilic probes. Because the probe is irreversibly bound in the lipids of the cell membrane; substantial numbers of dye molecules can be incorporated per cell and thus substantial signal to noise can be achieved. Although this technology can be used for all hematopoietic cells, these first findings are reported on red blood cells (RBCs) owing to the importance of the membrane to RBC function and integrity. We demonstrated that labeling 10% of the RBCs of a rabbit and reinjecting them into the animal makes possible the tracking of these cells at various times after injection. Furthermore, the labeling appears not to affect in vivo cell lifetime or cellular volume changes in response to hypotonic shock. The single cell fluorescence intensity of the labeled RBCs remains relatively constant for 60 days, and an immune response appears not to be generated against labeled cells. That labeled RBCs have lifetime kinetics in vivo, as shown in other studies, indicates that the membranes are functioning normally and are unaltered by the labeling technology. The technology we present is also applicable to white blood cells, bone marrow, and platelets.