Jyoti Sharma

Treatment with tacrolimus and prednisolone is preferable to intravenous cyclophosphamide as the initial therapy for children with steroid-resistant nephrotic syndrome

There are limited data on the relative efficacy and safety of calcineurin inhibitors and alkylating agents for idiopathic steroid-resistant nephrotic syndrome in children. To clarify this, we compared tacrolimus and intravenous cyclophosphamide therapy in a multicenter, randomized, controlled trial of 131 consecutive pediatric patients with minimal change disease, focal segmental glomerulosclerosis, or mesangioproliferative glomerulonephritis, stratified for initial or late steroid resistance. Patients were randomized to receive tacrolimus for 12 months or 6-monthly infusions of intravenous cyclophosphamide with both arms receiving equal amounts of alternate-day prednisolone. The primary outcome of complete or partial remission at 6 months, based on spot urine protein to creatinine ratios, was significantly higher in children receiving tacrolimus compared to cyclophosphamide (hazard ratio 2.64). Complete remission was significantly higher with tacrolimus (52.4%) than with cyclophosphamide (14.8%). The secondary outcome of sustained remission or steroid-sensitive relapse of nephrotic syndrome at 12 months was significantly higher with tacrolimus than cyclophosphamide. Treatment withdrawal was higher with cyclophosphamide, chiefly due to systemic infections. Compared to cyclophosphamide, 3 patients required treatment with tacrolimus to achieve 1 additional remission. Thus, tacrolimus and prednisolone are effective, safe, and preferable to cyclophosphamide as the initial therapy for patients with steroid-resistant nephrotic syndrome.

Targeted therapy of gastrointestinal stromal tumours

Gastrointestinal stromal tumours (GISTs) are mesenchymal neoplasms originating in the gastrointestinal tract, usually in the stomach or the small intestine, and rarely elsewhere in the abdomen. The malignant potential of GISTs is variable ranging from small lesions with a benign behaviour to fatal sarcomas. The majority of the tumours stain positively for the CD-117 (KIT) and discovered on GIST-1 (DOG-1 or anoctamin 1) expression, and they are characterized by the presence of a driver kinase-activating mutation in either KIT or platelet-derived growth factor receptor α. Although surgery is the primary modality of treatment, almost half of the patients have disease recurrence following surgery, which highlights the need for an effective adjuvant therapy. Traditionally, GISTs are considered chemotherapy and radiotherapy resistant. With the advent of targeted therapy (tyrosine kinase inhibitors), there has been a paradigm shift in the management of GISTs in the last decade. We present a comprehensive review of targeted therapy in the management of GISTs.

The surgical management of gallbladder cancer.

Among biliary tract cancers, gallbladder cancer (GBC) is a potentially lethal malignancy with abysmal long-term survival. Surgery is central to the management of GBC, and presently, provides the only ray of hope for long-term survival. Radical cholecystectomy, which includes cholecystectomy with a limited hepatic resection, regional lymphadenectomy and adjacent organ resection if required is used to encompass the tumor with negative margins – R‘0’ resection is the standard surgical treatment for the management of GBC. Absence of randomized controlled trials to address various surgical controversies due to rarity of disease in western world, advanced disease at presentation, high frequency of unresectability/inoperability at surgery, deficient neoadjuvant/adjuvant strategies and nihilistic views of oncologists due to aggressive disease biology has resulted in marked heterogeneity in surgical strategies employed to manage GBC across the surgical centers globally.

Pseudohypoparathyroidism Presenting with Bony Deformities Resembling Rickets

Pseudohypoparathyroidism (PHP), characterized by hypocalcemia, hyperphosphatemia and elevated parathormone level, may rarely be associated with bony deformities resembling rickets. The authors report two siblings with clinical and radiological features suggestive of rickets unresponsive to treatment with vitamin D. Low serum calcium, elevated serum phosphate, normal renal functions, raised tubular maximum of phosphate and high serum parathormone were suggestive of PHP. Treatment with 1-hydroxyvitamin D and calcium carbonate led to decrease in bone pain, increase in height and weight and resolution of radiological features. PHP should be suspected in patients with bony deformities, hypocalcemia, elevated blood phosphate levels and normal renal functions

Delayed isolated port-site metastasis of gallbladder cancer following laparoscopic cholecystectomy: report of two cases.

Laparoscopic cholecystectomy is the standard of care for gallstone disease [1]. The histopathological examination of all gallbladder specimens, though resected for gallstone disease, is recommended in order to detect the underlying gallbladder cancer [2]. The presence of incidentally detected gallbladder cancer following laparoscopic cholecystectomy, in most of the patients (except T1a tumors) warrants a completion radical surgery along with excision of port sites in order to lower the risk of locoregional and port-site metastasis [3]. Port-site metastasis usually manifests early following laparoscopic cholecystectomy, in the presence of underlying gallbladder cancer, and reflects an aggressive behavior of tumor; these patients are mostly not amenable to surgical treatment as they have associated disseminated peritoneal disease. We present two cases of delayed (more than 5 years) port-site metastasis following laparoscopic cholecystectomy; they were not diagnosed with gallbladder cancer at the time of cholecystectomy as their gallbladder specimens were not subjected to histopathological examination.

Preoperative therapy in locally advanced esophageal cancer

Esophageal cancer is an aggressive malignancy associated with dismal treatment outcomes. Presence of two distinct histopathological types distinguishes it from other gastrointestinal tract malignancies. Surgery is the cornerstone of treatment in locally advanced esophageal cancer (T2 or greater or node positive); however, a high rate of disease recurrence (systemic and loco-regional) and poor survival justifies a continued search for optimal therapy. Various combinations of multimodality treatment (preoperative/perioperative, or postoperative; radiotherapy, chemotherapy, or chemoradiotherapy) are being explored to lower disease recurrence and improve survival. Preoperative therapy followed by surgery is presently considered the standard of care in resectable locally advanced esophageal cancer as postoperative treatment may not be feasible for all the patients due to the morbidity of esophagectomy and prolonged recovery time limiting the tolerance of patient. There are wide variations in the preoperative therapy practiced across the centres depending upon the institutional practices, availability of facilities and personal experiences. There is paucity of literature to standardize the preoperative therapy. Broadly, chemoradiotherapy is the preferred neo-adjuvant modality in western countries whereas chemotherapy alone is considered optimal in the far East. The present review highlights the significant studies to assist in opting for the best evidence based preoperative therapy (radiotherapy, chemotherapy or chemoradiotherapy) for locally advanced esophageal cancer.

Extra-Hepatic Bile Duct Resection: an Insight in the Management of Gallbladder Cancer.

BackgroundInvolvement of extrahepatic bile duct in gallbladder cancer (GBC) is considered a sign of advanced disease; resection of extrahepatic bile duct in GBC has been a contentious issue considering the poor prognosis of the disease.MethodsThis retrospective study was done in two tertiary teaching hospitals of North India. The case records of all the GBC patients who underwent radical cholecystectomy with extra-hepatic bile duct resection were reviewed. Details concerning the clinical presentation, preoperative therapy, operative procedure, indication of bile duct resection, postoperative complications and outcome were retrieved from the case records. Kaplan–Meier analysis was done to estimate median disease-free survival and overall survival.ResultsThere were 17 GBC patients who underwent radical cholecystectomy with resection of extrahepatic bile duct. Median age of the patients was 51xa0years (range 35–62); male to female ratio was 5:12. Six patients were diagnosed after histopathological examination of resected gallbladder specimen following cholecystectomy (incidental gallbladder cancer). All the patients had R‘0’ resection. The indication for extra-hepatic bile duct resection was direct infiltration of hepatoduodenal ligament in nine, positive cystic duct margin in two, densely adherent pericholedochal lymphnodes in one and associated ampullary growth in one patient. Kaplan–Meier analysis predicted median disease-free survival of 20xa0months and median overall survival of 26xa0months.ConclusionExtrahepatic bile duct resection to achieve R‘0’ resection in the management of advanced gallbladder cancer is safe with acceptable postoperative morbidity and has potential to improve survival.

Xanthogranulomatous inflammation of gallbladder and bile duct causing obstructive jaundice masquerades gallbladder cancer: a formidable diagnostic challenge continues.

Xanthogranulomatous cholecystitis (XGC) is defined as a variant of chronic cholecystitis characterized by intense inflammation and accumulation of lipid laden macrophages [1]. Though XGC is a benign disease, it has the potential of inflammatory invasion and may involve adjacent organs such as duodenum, liver, colon, and common bile duct, and so, XGC has always bewildered the surgeons by its ability to masquerade gallbladder cancer very closely resulting into radical resection. Xanthogranulomatous involvement of bile duct, termed as xanthogranulomatous choledochitis [2] (XGCd), is a rarely reported condition; it may manifest with obstructive jaundice and mimic malignancy. We highlight a case of a 32-year-old who presented with obstructive jaundice and underwent radical resection in view of imaging findings suspicious locally advanced gallbladder cancer; however, histopathological examination of surgical specimen revealed XGC and XGCd. We also make an attempt to review the previously reported cases of XGCd who had presented with obstructive jaundice and imitated malignancy. Case Report

Lymphadenectomy in gastric cancer: Contentious issues.

The stomach is the sixth most common cause of cancer worldwide. Surgery is an important component of the multi-modality treatment of the gastric cancer. The extent of lymphadenectomy has been a controversial issue in the surgical management of gastric cancer. The East-Asian surgeons believe that quality-controlled extended lymphadenectomy resulting in better loco-regional control leads to survival benefit in the gastric cancer; contrary to that, many western surgeons believe that extended lymphadenectomy adds to only postoperative morbidity and mortality without significantly enhancing the overall survival. We present a comprehensive review of the lymphadenectomy in the gastric cancer based on the previously published randomized controlled trials.

Retroperitoneal lymphangiectasia: Images for surgeons

Whipples procedure. However, the selection of these procedures are dependent upon the extent of inflammation, tissue friability in the area and the time interval from perforation to accurate diagnosis. In this case, the presence of a precipitating cause of intestinal obstruction and the underlying sepsis with signs of haemodynamic instability required prompt surgical decompression and drainage. References