Targeted therapy of gastrointestinal stromal tumours

Gastrointestinal stromal tumours(GISTs) are mesen-chymal 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 majo-rity 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 role of liver transplantation for hilar cholangiocarcinoma

BACKGROUND: Hilar cholangiocarcinoma is a devastating disease. Surgery is the only potentially curative modality. However, the results of surgical resection for hilar cholangiocarcinomas are disappointing. The introduction of liver transplantation for this condition has brought new hope for the management of this disease. The aim of this review is to discuss the role of liver transplantation in this disease. DATA SOURCES: A MEDLINE search was conducted for the articles on liver transplantation for hilar cholangiocarcinoma. Their results have been compiled and compared with the existing literature on resection for this disease. RESULTS: The earlier series on liver transplantation for hilar cholangiocarcinoma were not encouraging because of poor patient selection. The Mayo Clinic protocol of neoadjuvant chemoradiation followed by liver transplantation has shown remarkable success (survival at 1-, 3-, and 5-year post-transplantation being 92%, 82%, and 82%, respectively). With better patient selection and integration of neoadjuvant chemoradiation, the long-term survival is superior to that of the patients who undergo resection, as shown by the published literature on resection. The limitations of organ availability can be overcome by the living donor liver transplantation programme. This review article discusses the rationale, pros and cons of liver transplantation vis-à-vis resection for hilar cholangiocarcinoma.CONCLUSIONS: Liver transplantation, especially living donor liver transplantation, is a new and exciting alternative to resection for hilar cholangiocarcinoma. Integration of neoadjuvant chemoradiation has the potential to further improve the curative potential of liver transplantation. The strategy of combining neoadjuvant chemoradiation and liver transplantation brings new hope for the treatment of this difficult disease.

Role of positron emission tomography-computed tomography in non-small cell lung cancer

Lung cancer is the leading cause of cancer-related mortality worldwide. Non-small cell carcinoma and small cell carcinoma are the main histological subtypes and constitutes around 85% and 15% of all lung cancer respectively. Multimodality treatment plays a key role in the successful management of lung cancer depending upon the histological subtype, stage of disease, and performance status. Imaging modalities play an important role in the diagnosis and accurate staging of the disease, in assessing the response to neoadjuvant therapy, and in the follow-up of the patients. Last decade has witnessed voluminous upsurge in the use of positron emission tomography-computed tomography(PET-CT); role of PET-CT has widened exponentially in the management of lung cancer. The present article reviews the role of 18-fluoro-deoxyglucose PET-CT in the management of non small cell lung cancer with emphasis on staging of the disease and the assessment of response to neoadjuvant therapy based on available literature.

Surgical resection of adrenal metastasis from primary liver tumors:a report of two cases

BACKGROUND:Although the treatment of extrahepatic metastases from primary liver tumors is essentially palliative,solitary metastasis from such tumors offers a possibility of cure by surgical resection.The adrenal gland is an uncommon site for metastasis from primary liver tumors. METHOD:We report two cases of adrenalectomy for solitary adrenal metastasis:one from intrahepatic cholangiocarcinoma and the other from hepatocellular carcinoma. RESULTS:The patient with intrahepatic cholangiocar- cinoma had a synchronous adrenal metastasis and underwent simultaneous liver resection and adrenalectomy. However,he developed recurrent disease 17 months following surgery for which he is presently on palliative chemotherapy.The other patient underwent adrenalectomy for adrenal metastasis 3 months following liver transplantation for hepatocellular carcinoma.He is presently alive and disease-free 27 months after adrenalectomy. CONCLUSION:Carefully selected patients with solitary metastasis from primary liver tumors may be considered for resection.

Malaria after living donor liver transplantation:report of two cases

BACKGROUND:Infectious complications are common during the postoperative course of a liver transplant recipient. Malaria, however, is a rare complication in such a setting. METHOD:We report post-transplantation malaria causing elevation of liver enzymes in two recipients. RESULTS:Both patients who had undergone living donor liver transplantation showed elevated levels of liver enzymes and fever during the postoperative course. Investigations (including liver biopsy in one patient) were initially inconclusive in determining the cause of liver dysfunction. The diagnosis of malaria was established in both cases by peripheral blood smear. Liver function transiently worsened with antimalarial treatment but subsequently became normal. CONCLUSION:This report highlights the importance of excluding such uncommon causes of post-transplantation liver dysfunction, especially when either the recipient or the donor comes from a region endemic for malaria.

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 locoregional 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.

Isolated hepatosplenic tuberculosis

BACKGROUND:Tuberculosis rarely involves the liver and spleen and when it does so,it is usually associated with disseminated disease. METHOD:We report a patient with isolated tuberculosis of the liver and spleen. RESULTS:A 50-year-old man presented with weakness and loss of weight for two months.CT scan of the abdomen showed multiple small hypodense lesions in the liver and spleen.Image-guided biopsy of liver lesion was inconclusive as it showed normal hepatocytes with interspersed lymphocytes.On laparotomy,the liver and spleen were studded with multiple small nodules.A 5-cm wedge of the liver was resected.Histopathological examination confirmed the diagnosis of tubercular hepatitis.A detailed work-up failed to identify any other focus of tuberculosis. CONCLUSION:Although rare,tuberculosis should also be considered in the differential diagnosis for multiple nodules in the liver and spleen,along with lymphoproliferative diseases and metastatic lesions.

Modified skin bridge technique for ilio-inguinal lymph node dissection:A forgotten technique revisited

Ilio-inguinal lymph node dissection(IILD) is a commonly performed surgical procedure for a number of malignant conditions involving mainly the male and female genitalia, and the skin; however the postoperative morbidity of IILD, due to high frequency of flap necrosis, wound infection and seroma formation, has always been a major concern for the surgeons. The aim of the study is to highlight a modified skin bridge technique of IILD using two parallel curvilinear incisions to minimize postoperative skin flap necrosis. This technique was successfully employed in 38 IILD during May 2012 to November 2013. None of the patient had flap necrosis. Two patients developed seroma while another two patients had superficial surgical site infection; they were managed conservatively. Modified skin bridge technique for IILD is an effective method to minimize flap necrosis without compromising the oncological safety.

Local Cell Mediated Immune Reaction in Primary Obstructive Male Infertility

Increased intra-epididymal pressure due to obstruction causes a breach in the epididymal lining exposing the highly antigenic sperms to the interstitium. When the exposure is small and intermittent, it is likely to induce a local humoral response which may affect sperm maturation and also react with the epididymal epithelium producing irreversible histological changes. The present study on 30 patients of primary obstructive infertility found direct and indirect evidence of the production of antisperm antibodies locally. ELISA for antisperm antibodies was positive in the epididymal fluid in 16/30 (53%) of the patients. Indirect evidence of the role of local antigen-antibody reaction in the epididymis is apparent in 22/30 (73%) patients who had a lymphocytic infiltrate. The local presence of antisperm antibodies in the epididymal fluid correlated well with the presence of lymphocytic infiltration in the interstitium (p < 0.05). In our study 16/30 patients had a positive ELISA for antisperm antibody and all these patients had interstitial lymphocytic infiltration. In addition eight patients with a negative ELISA also showed interstitial lymphocytic infiltration. Thus 22/30 (73%) patients had an evidence of a local immune reaction directly in the form of a positive ELISA for antisperm antibodies in the epididymal fluid and / or indirect evidence in the form of lymphocytic infiltrate in the interstitium. None of the five controls had either a positive ELISA or lymphocytic infiltrate, this difference was found to be statistically significant (p < 0.005).