RECENT ADVANCES IN THE MOLECULAR PATHOLOGY OF HYPERPARATHYROIDISM

1 INTRODUCTIONThe term “hyperparathyroidism”refers tometabolic derangement owing to increased productionof the parathyroid hormone(PTH).Over the pastdecade,increased information,particularly on the ge-netic basis,makes us able to identify various types ofhyperparathyroidisms precisely.Now hyper-parathyroidisms could be classified as sporadic primaryhyperparathyroidism(PHPT),secondary or tertiaryhyperparathyroidism(SHPT or THPT),familial hy-     

THE KEY ROLE OF THE TRANSFORMING GROWTH FACTOR-β SYSTEM IN THE PATHOGENESIS OF DIABETIC NEPHROPATHY

Progressive renal injury in diabetes mellitus leads to majormorbidity and mortality. The manifestations of diabetic nephropathy may bea consequence of the actions of certain cytokines and growth factors. Prominentamong these is transforming growth factor-beta (TGF-β) because it promotesrenal cell hypertrophy and stimulates extracellular matrix accumulation, thetwo hallmarks of diabetic renal disease. In cell culture, high ambient glucoseincreases TGF-β m RNA and protein in proximal tubular, glomerular epithelial,and mesangial cells. Neutralizing anti-TGF-β antibodies prevent the hypertrophicand matrix stimulatory effects of high glucose in these cells. In experimentaland human diabetes mellitus, several reports describe overexpression of TGF-βin the glomeruli and tubulointerstitium. We demonstrate that short-term treatmentof diabetic mice with neutralizing monoclonal antibodies against TGF-βsignificantly reduces kidney weight and glomerular hypertrophy and attenuatesthe increase in extracellular matrix mRNAs. Long-term treatment of diabeticmice further improves the renal pathology and also ameliorates the functionalabnormalities of diabetic nephropathy. Finally, we provide evidence that therenal TGF-β system is significantly up-regulated in human diabetes. Thekidney of a diabetic patient actually elaborates TGF-β1 protein intothe circulation whereas the kidney of a non-diabetic subject extracts TGF-β1from the circulation. The data we review here strongly support the hypothesisthat elevated production or activity of the TGF-β system mediates diabeticrenal hypertrophy and extracellular matrix expansion.     

THE LATEST PROGRESS OF GASTRIC CANCER SURGERY IN JAPAN

Mortality rate of gastric cancer in Japan had been the highest in the world. Development of early detection and effective treatment was the most impor-tant social demand. For the early detection, Japan de-veloped “double contrast X-ray”, “endoscopy and en-doscopic biopsy”, and “mass screening system”. The Japanese nationwide registry collected data of 273,142 gastric cancer patients in the last 30 years. By the ef-forts of early detection, proportion of Stage I cancer increased from 22.5% to 58.1% in the registry. Cu-mulative 5 year survival rate of resected cases was improved from 37.5% （1962） to 68.8% （1991）. Im-provement was remarkable for Stage-II; from 47.7% to 70.3%, and for Stage-III, from 26.4% to 45.0%.     

IS LOBECTOMY NECESSARY IN THE TREATMENT OF PULMONARY HYDATID CYSTS?

BACKGROUND: Hydatidosis is endemic in Turkey and many other areas of the world. The definitive treatment for pulmonary hydatidosis is surgical. The purpose of this study was the review of surgical therapy of our patients with pulmonary hydatid disease and the necessity of lobectomy. METHODS: We reviewed 107 patients: 26 of whom were women and 81 were men. The median age was 30 years (range, 7-57 years). Chest roentgenogram, abdominal ultrasound and computed tomography of the chest and upper abdomen were carried out as diagnostic study. All patients underwent thoracotomy and cystotomy with or without capitonnage. RESULTS: Four patients had two cysts in the same lobe and one patient had three cysts (one perforated and two intact) in the left lower lobe (4.6%). In nine patients, the cysts were >10 cm in diameter (8.4%). In 18 patients, the cysts were suppurative (16.8%). None of the patients required lobectomy. Of the 107 patients, prolonged air leaks (n = 8), atelectasis (n = 3) and empyema (n = 3; two had empyema preoperatively because of pleural perforation of cysts and the other had prolonged air leak) were observed in the postoperative period. There was no death. CONCLUSION: The effective treatment of hydatid cysts in the lung is the complete excision of the cyst with maximum preservation of lung parenchyma. We believe that the decision of lobectomy must be taken very carefully, even in the case of infected hydatid cysts, atelectasis, giant cysts and multiple cysts in the same lobe.     

CUT OR PASTE? THE USE OF GLYCERYL TRINITRATE PASTE IN THE TREATMENT OF ACUTE AND CHRONIC ANAL FISSURE

Background : Anal fissure unresponsive to conservative measures such as stool softeners frequently requires surgical intervention. The present study describes the use of glyceryl trinitrate (GTN) in the treatment of acute and chronic anal fissure. Methods : Eighteen consecutive patients with anal fissure were treated with 0.5% GTN paste in soft white paraffin applied twice daily to the anus. These patients were followed at regular intervals to assess symptom control, rate of healing, adverse effects and recurrence rate. Results : Two patients were lost to follow‐up. Twelve of the remaining 16 were cured. Of these, symptomatic relief was obtained for most within 2 days, and for all within 1 week. No patient required cessation of treatment due to adverse effects. Treatment failed in four of 16 patients. Two of these patients subsequently underwent successful surgical procedures, and two patients (while not completely cured) had sufficient symptomatic relief to decide against surgery. Conclusions : The use of GTN paste in the treatment of acute and chronic anal fissure may be a safe and effective modality that can be considered as first‐line treatment for this condition.     

IS SURVEILLANCE NECESSARY FOR INVERTED PAPILLOMA IN THE URINARY BLADDER AND URETHRA?

BACKGROUND: A case series of inverted papilloma of the urinary bladder and urethra is presented, together with a review of the literature with respect to multiplicity, recurrence rate and association with transitional cell carcinoma, and a discussion on surveillance of the lesion. METHODS: Cases of inverted papilloma of the lower urinary tract in a single centre were reviewed. Patient and tumour characteristics, recurrence and associated transitional cell carcinoma are reported. RESULTS: Twenty patients were included (18 male, two female). The mean age was 60.8 years (range 35-78 years). All had solitary tumours ranging from 3 mm to 30 mm in size. Median cystoscopic follow up was 30 months (range 2-140 months). There was no recurrence. One patient was associated with subsequent transitional cell carcinoma 44 and 76 months later. Together with the present 20 cases, review of the English literature with respect to inverted papilloma of the lower urinary tract identified a total of 322 cases reported, with a recurrence rate of 3.85%. Moreover, 1.55%, 5.90% and 1.54% were associated with previous, simultaneous and subsequent transitional cell carcinoma, respectively. CONCLUSIONS: Recurrence is not uncommon and risk of subsequent transitional cell carcinoma is not rare, such that non-invasive surveillance with flexible cystoscopy is recommended for inverted papilloma of the lower urinary tract.     

RADICAL CYSTECTOMY FOR BCG FAILURE: HAS THE TIMING IMPROVED IN RECENT YEARS?

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? High‐grade Ta‐T1‐carcinoma in situ bladder cancer is a heterogeneous group; long‐term studies have shown that intravesical BCG therapy can be inadequate in a substantial percentage. Despite concerns about delay in performing RC for patients failing one or more courses of BCG, in our study we have not observed a trend towards a lower pathological stage for patients undergoing RC after BCG.

OBJECTIVE

• ? To analyse if there is a trend in recent years towards performing radical cystectomy (RC) before muscle invasion or extravesical spread after failure of bacille Calmette–Guérin (BCG) for high grade Ta/T1 bladder cancer. Although BCG is indicated for prophylaxis after endoscopic tumour resection there is still a risk of progression.

PATIENTS AND METHODS

• ? A retrospective analysis of our RC database (1992–2008) was performed to identify patients who underwent RC after receiving BCG.
• ? Relevant clinical and pathological data for the patients with clinical stage Ta, T1 and/or Tis at initial transurethral resection of bladder tumour were analysed.
• ? Pathological stage and survival for patients undergoing RC from 2003 to 2007 (group 2) were compared with those for patients operated between 1992 and 2002 (group 1).

RESULTS

• ? A total of 152 patients were included (75 in group 2 and 77 in group 1). Both groups were similar in T‐stage before BCG initiation, number of BCG cycles received and time interval to RC.
• ? There was no change in the proportion of patients undergoing RC with ≥pT2 bladder cancer in recent years (P= 0.5).
• ? Fifty‐two percent of group 2 and 43% of group 1 had ≥pT2 BC. The 5‐year survival was similar.

CONCLUSIONS

• ? Despite concerns about delay in performing RC for patients failing one or more courses of BCG we have not observed a trend towards a lower pathological stage for patients undergoing RC after BCG.
• ? A high proportion of patients have muscle‐invasive bladder cancer; more than 10% have lymph node metastasis.