Serum ferritin and the risk of hepatocellular carcinoma in chronic liver disease of viral etiology: a case-control study.

BACKGROUND: The worldwide incidence rates of hepatocellular carcinoma (HCC) vary widely. Some countries like India have a low incidence despite having a large burden of chronic hepatitis B (HBV) and C virus (HCV) infection. We hypothesized that long-term iron deficiency could attenuate the hepatic inflammation and lead to a lower incidence of HCC in India than expected. METHODS: We evaluated the association of serum ferritin levels and HCC in Indian patients with HBV- or HCV-related chronic liver disease (CLD) using a case-control study design. We enrolled 141 patients with HCC (cases) and 240 patients having chronic HBV or HCV infection-related CLD (controls). Study participants were grouped on the basis of ferritin values into low-normal, high-normal, and high subgroups. RESULTS: Mean ferritin values were higher in cases as compared to controls (425.8 vs. 135.6 ng/mL, p = 0.000). A significant dose-response effect for serum ferritin levels and HCC was seen with an odds ratio (95 % confidence interval) of 3.0 (1.6-5.9, p = 0.001) for subjects with high-normal ferritin levels and 8.2 (4.1-16.5, p = 0.000) for subjects with high ferritin levels in a multivariate model. Other significant independent risk factors in the multivariate model included older age, male gender, alcohol and tobacco use, elevated alanine aminotransferase, higher family income, and coffee drinking. CONCLUSION: We found an independent association between serum ferritin levels and HCC in patients with CLD of viral etiology. Further prospective studies are needed to confirm the hypothesis that iron deficiency protects against HCC in CLD.

A comparative observational study of early versus delayed feeding after percutaneous endoscopic gastrostomy.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is the procedure of choice for long-term enteral feeding. OBJECTIVE: This prospective observational study was carried out to compare the safety of commencing feeding 3 h compared to 16-24 h after PEG tube placement. METHODS: One hundred and ten patients with oropharyngeal malignancies who had consented for PEG were enrolled. Trial-specific consent and IRB approval were not obtained because at the time when this study was done, this was not mandatory for observational studies which involved standard procedures. Alternate patients were started on early feeding within 3 h (group I) or after overnight observation of 16 to 24 h (group II). Five hundred milliliters of Ringer's lactate was infused over 4 h initially, followed 2 h later by 200 mL of formula feed. The patients were advised to take bolus feeds of 200 mL every 2 h and oral feeds ad libitum from the next day. All patients were evaluated on days 1, 2, 7, and 30. RESULTS: There were 55 patients (47 males) in group I and 54 patients (38 males) in group II who were matched for age (mean age 46.1 and 46.1 years, respectively). Complications included PEG site infection (1), peristomal leak (3), and displacement of the PEG tube (1) in group I. PEG site infection was seen in five patients in group II. All the complications were managed conservatively on an ambulatory basis. CONCLUSION: Initiation of tube feeding 3 h after an uncomplicated PEG was safe, well tolerated, and helped to reduce the hospital stay.

Escalated radiation dose alone vs. concurrent chemoradiation for locally advanced and unresectable rectal cancers: results from phase II randomized study.

PURPOSE: This trial was undertaken to compare the rates of resectability between patients treated with neoadjuvant concurrent chemoradiation vs. boosted radiotherapy alone. MATERIALS AND METHODS: Patients with clinically unresectable rectal cancer were randomized to receive external beam radiation therapy (EBRT) to pelvis (45 Gy) with concurrent oral Capecitabine (CRT group; Arm 1) or EBRT to pelvis (45 Gy) alone followed by 20 Gy dose of localized radiotherapy boost to the primary tumor site (RT with boost group, Arm 2). All patients were assessed for resectability after 6 weeks by clinical examination and by CT scan and those deemed resectable underwent surgery. RESULTS: A total of 90 patients were randomized, 46 to Arm 1 and 44 to Arm 2. Eighty seven patients (44 in Arm 1 and 41 in Arm 2) completed the prescribed treatment protocol. Overall resectability rate was low in both the groups; R0 resection was achieved in 20 (43 %) patients in Arm 1 vs. 15 (34 %) in Arm 2. Adverse factors that significantly affected the resectability rate in both the groups were extension of tumor to pelvic bones and signet ring cell pathology. Complete pathological response was seen in 7 and 11 %, respectively. There was greater morbidity such as wound infection and delayed wound healing in Arm 2 (16 vs. 40 %; p = 0.03). CONCLUSION: Escalated radiation dose without chemotherapy does not achieve higher complete (R0) tumor resectability in locally advanced inoperable rectal cancers, compared to concurrent chemoradiation.

Clinicopathological study of 113 gastrointestinal stromal tumors.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the gastrointestinal tract. A retrospective study was done to evaluate the clinical and pathological features and the effect of adjuvant treatment with imatinib. METHOD: The case records of 113 GIST patients were retrospectively reviewed and the clinicopathological features, treatments, and outcomes were recorded. RESULTS: There were 82 males and 31 females, with a median age of 51 years. All patients were symptomatic (mean duration 4 months) and abdominal pain was the most common symptom. The primary sites of GIST were small intestine (38), stomach (36), and others (39). The tumor diameter on imaging varied from 1 to 26 (mean 10.9) cm. Thirty percent of patients presented with metastasis. There was no association between tumor size and presence of metastasis (p = 0.9). Most common histology was spindle cell morphology followed by mixed spindle cell and epithelioid morphology. Seventy percent patients had high risk (HR) category as per Fletcher risk score. Fifty-three percent had curative resection, after which 34 % had adjuvant imatinib therapy. Recurrence rates were significantly lower in patients receiving adjuvant imatinib therapy (p = 0.003). No statistically significant association was noted between HR Fletcher score, Mib score >10, tumor size >10 cm, and the risk of recurrence (p = 0.29, 0.07, and 0.87, respectively). Liver was the most common site of metastasis. Side effects were tolerable and edema and fluid retention were the commonest. CONCLUSION: Sites of GIST in Indian patients were different from those in western studies. Adjuvant imatinib therapy significantly reduced the risk of recurrence.

Gastrointestinal stromal tumors: case series of 29 patients defining the role of imatinib prior to surgery.

BACKGROUND: The aim of this study was to assess the role of neoadjuvant imatinib in redefining treatment for gastrointestinal stromal tumors (GISTs). METHODS: A total of 76 patients were reviewed. Among them, 29 patients who were administered neoadjuvant imatinib for borderline resectable and locally advanced GISTs followed by surgery were analyzed. Adjuvant imatinib was administered based on risk stratification. RESULTS: The median age of the neoadjuvant imatinib group was 51 years. The median duration of neoadjuvant imatinib administration was 8.5 months. The response rate with neoadjuvant imatinib was 79.3%. Five patients, initially considered to have locally unresectable lesions, ultimately underwent resection (three R0, two R2). Another three patients, who had M1 disease, underwent R2 resection (due to the presence of metastasis) with complete resection of the primary lesion. In 19 patients, who would have originally required extensive surgery, underwent conservative surgery (R0). In two patients, neoadjuvant imatinib did not influence the final procedure. The postoperative complication rate was 13.8%, and there were no postoperative deaths. There was one locoregional recurrence and two cases of distant metastasis. The 1-, 2-, and 3-year overall survivals were each 100%. CONCLUSIONS: Neoadjuvant imatinib for locally advanced GISTs is a safe concept for downsizing, improving resectability, and aiding organ-preserving surgery. It also improves the chance of long-term survival. Surgery, however, remains the cornerstone of curative treatment of GISTs even after neoadjuvant imatinib.

A rare case of primary gastric plasmacytoma: an unforeseen surprise.

Primary plasmacytoma of the gastrointestinal tract is a rare entity. We report a case of a primary gastric plasmacytoma in a 57-year-old man who presented with upper-gastrointestinal bleeding. Endoscopy showed a nodular gastric mass with central umblication. Histological examination of the gastrectomy specimen revealed a monoclonal lambda-chain extramedullary plasmacytoma. Further staging was found to be negative for multiple myeloma. As other more common pathologic processes at this site may also be endowed with numerous plasma cells, awareness of this entity and distinction using immunohistochemistry are extremely crucial. Because systemic disease ultimately develops in many patients with localized plasmacytoma, such patients should be followed closely for the appearance of clinical, biochemical, and roentgenologic evidence of multiple myeloma.

Production of immunogenic human papillomavirus-16 major capsid protein derived virus like particles.

BACKGROUND & OBJECTIVE: Recombinant DNA technology allows expression of the human papillomavirus (HPV) major capsid protein (L1) in heterologous expression systems and the recombinant protein self assembles to virus-like particles (VLP). We took up this study to produce recombinant HPV-16 L1 in yeast, establish the process of recombinant L1 derived VLP preparation and develop an ELISA using VLP as the antigen for serological evaluation of anti HPV-16 L1 antibody status. METHODS: Complete HPV-16 L1 was amplified from genomic DNA of an esophageal cancer biopsy, cloned and the protein was expressed in a galactose-inducible Saccharomyces cerevisiae expression system. Self assembled VLP was purified by a two-step density gradient centrifugation process and the VLP preparation used to test its suitability in developing an ELISA. RESULTS: The recombinant protein was predominantly a ~55 KD species with distinct immunoreactivity and formed VLP as confirmed by electron microscopy. An ELISA using the VLP showed its efficacy in appropriate immunoreactivity to serum/plasma IgG. INTERPRETATION & CONCLUSION: Recombinant HPV-16 capsid protein derived VLP was produced and the VLP antigen based ELISA can be used to probe serological association of HPV with different clinical conditions. The VLP technology can be improved further and harnessed for future vaccine development efforts in the country.

Defining the role of surgery for complications after pancreatoduodenectomy.

BACKGROUND: Although mortality rates following pancreatoduodenectomy have drastically reduced over the last few decades, high morbidity rates have continued to trouble pancreatic surgeons across the world. Interventional radiology has reduced the need for re-exploration for complications following pancreatoduodenectomy. There remain specific indications for re-exploration in such scenarios. It is thus pertinent to identify those clinical scenarios where surgery still has a role in managing complications of pancreatoduodenectomy. The aim of the study was to define the role of surgery for dealing with complications following pancreatoduodenectomy. METHODS: One hundred and fifty-seven consecutive pancreatoduodenectomies carried out at a single institution between 1 January 2001 and 28 February 2007, were analysed. The database was looked into to identify patients who underwent re-exploration for complications and to define the indications for the exploration in these patients. RESULTS: Out of the 157 pancreatoduodenectomies, there were, in all, 39 complications (24.2%) in 38 patients. Most of these complications were successfully managed conservatively and with the help of interventional radiology. Seventeen patients had to be re-explored (10.8%). The indications were primarily for haemorrhage, clinically significant pancreatic leaks, biliary leaks, adhesive intestinal obstruction and burst abdomen. The overall mortality rate was 3.1%. The mortality rate in the patients undergoing re-exploration was 11.7%. CONCLUSION: Early haemorrhage (from the pancreatic stump or anastomotic line), clinically significant pancreatic anastomotic leak with discharge from the main wound and an early biliary anastomotic leak are prime indications for re-exploration in patients with complications following pancreatoduodenectomy.

Infusion chemotherapy with cisplatinum and fluorouracil in the treatment of locally-advanced and metastatic gallbladder cancer.

BACKGROUND: Gallbladder cancer (GBC) has a poor prognosis. Chemotherapy is traditionally considered to be ineffective. The goal of the current study was to evaluate the efficacy of infusional 5-fluorouracil (5-FU) and cisplatinum (CDDP) in patients with inoperable GBC. MATERIALS AND METHODS: A total of 65 patients with inoperable GBC received palliative chemotherapy with CDDP and 5-FU. All the patients had clinically measurable disease as well as adequate bone marrow, hepatic, and renal function. Response was assessed after three cycles of chemotherapy. RESULTS: A total of 19 patients had locally advanced unresectable cancer and 46 patients had metastatic cancer. There were 39 females and 26 males, with a median age of 50 years. A total of 212 chemotherapy cycles were administered to the patients. Response evaluation after three cycles of chemotherapy revealed complete response in five patients [7.69%; 95% confidence interval (95% CI): 2.87-16.22], partial response in 17 patients (26.15%; 95% CI: 16.57-37.81), stabilization of disease in 9 patients (13.85%; 95% CI: 6.96-23.88), and progression in 21 patients (32.30%; 95% CI: 21.80-44.35). At 6 months 44.6% patients were alive and 18.5% patients were alive at 12 months. The median overall survival was 5.7 months and the median time to disease progression was 3.1 months. This chemotherapy combination was well tolerated. There were no chemotherapy-related deaths. CONCLUSIONS: Infusion chemotherapy with CDDP and 5-FU appears to have a fair amount of activity in patients of inoperable GBC, with acceptable toxicity. Tumor shrinkage following treatment with this regimen enabled surgical resection in two patients. We believe that this promising combination must be tested against gemcitabine-based combinations in patients with inoperable GBC.

Simultaneous gallbladder and bile duct cancers: revisiting the pathological possibilities.

The pathogenesis of gallbladder cancer presenting synchronously with malignancy of the bile duct has not been clearly understood. The possible causes for the simultaneous presence of these tumors could be due to local spread, metastases, de novo multifocal origin, or as part of a field change in the extrahepatic biliary apparatus. In this article, we discuss the cases of four patients with simultaneous gallbladder and bile duct malignancies and analyze their individual pathologies to provide an explanation into the mechanisms that may play a role in such conditions.

A new scoring system for gallbladder cancer (aiding treatment algorithm): an analysis of 335 patients.

BACKGROUND: There is currently no preoperative staging/scoring system available for gallbladder cancer. Unfortunately, in gallbladder cancer, patients manifest advanced stages of the disease. There is need for a methodology that can aid accurate preoperative staging and the subsequent treatment algorithm. We thus sought to validate a new scoring system, the Tata Memorial Hospital Staging System (TMHSS), for gallbladder cancer. METHODS: TMHSS is based on the cumulative impact of specific features of computed tomographic scan, presence or absence of jaundice, and serum cancer antigen 19-9 levels. This scoring system was first proposed in 2004. Patients with gallbladder cancer were enrolled onto the testing sample for TMHSS to ascertain its validity. A total of 335 consecutive patients with gallbladder cancer who sought care at the Tata Memorial Hospital between May 1, 2005, and December 31, 2006, were studied. Treatment was suggested on the basis of current existing protocols. Each patient was assigned a TMHSS score, and the treatment decision taken was compared with the algorithm generated for each individual score. Concurrence of the decision taken with the score generated algorithm was tested by the Kendall tau-b test. RESULTS: Ordinal-by-ordinal analysis of the value of the test was .75, which showed excellent concurrence and a statistically significant P value (P < .0001). CONCLUSION: TMHSS provides an excellent correlative treatment plan for patients with gallbladder cancer. It has the potential to reduce unnecessary surgical explorations and to direct patients to the ideal treatment strategy, thereby offering a degree of prognostication.