Rajesh C. Mistry

Prognosis of operable squamous cell carcinoma of the esophagus. Relationship with clinicopathologic features and DNA ploidy

Background. Reports on the influence of various prognostic factors in carcinoma of the esophagus are conflicting. The prognostic value of a set of clinicopathologic factors and DNA ploidy were examined in 74 patients with surgically resected squamous cell carcinoma of the lower and middle third of the esophagus.

Impact of age and sex on survival after curative resection for carcinoma of the esophagus

Background. The impact of age and sex‐related changes in the endogenous hormonal milieu on survival after curative resection for esophageal epithelial cancer is explored. Adami et al. have suggested that the event of puberty has a favorable impact on survival after treatment of epithelial cancers.

Effect of Short-term vs Prolonged Nasogastric Decompression on Major Postesophagectomy Complications: A Parallel-Group, Randomized Trial

HYPOTHESIS Controversy exists over the need for prolonged nasogastric decompression after esophagectomy. We hypothesized that early removal of the nasogastric tube would not adversely affect major pulmonary complications and anastomotic leak rates. DESIGN Single-center, parallel-group, open-label, randomized (1:1) trial. SETTING A tertiary referral cancer center with high esophagectomy volume. PATIENTS One hundred fifty patients undergoing esophagectomy with gastric tube reconstruction. INTERVENTIONS Either conventional nasogastric decompression for 6 to 10 days (75 patients) or early removal (48 hours) of nasogastric tube (75 patients) with stratification for pyloric drainage and anastomotic technique. MAIN OUTCOME MEASURES The primary (composite) end point was the occurrence of major pulmonary complications and anastomotic leaks. Secondary end points were the need for nasogastric tube reinsertion and patient discomfort scores. Analysis was performed on an intent-to-treat basis. RESULTS No significant differences were seen in the occurrence of the composite primary end point of major pulmonary and anastomotic complications between the delayed (14 of 75 patients [18.7%]) and early (16 of 75 patients [21.3%]) removal groups, respectively (P = .84). Nasogastric tube reinsertion was required more often (23 of 75 patients [30.7%] vs 7 of 75 patients [9.3%]) in the early group (P = .001). Mean patient discomfort scores were significantly higher in the delayed (+1.3; 95% CI, 0.4-2.2; P = .006) than in the early removal group. Significantly more patients in the delayed removal group (26 of 75 patients [34.7%] vs 10 of 75 patients [13.3%] in the early removal group; P = .002) identified the nasogastric tube as the tube causing the most discomfort. CONCLUSIONS Early removal of nasogastric tubes does not increase pulmonary or anastomotic complications after esophagectomy. Patient discomfort can be significantly reduced by early removal of the nasogastric tube. TRIAL REGISTRATION Clinical Trials Registry of India Identifier: CTRI/2010/091/003023.

Prognostic Factors and Outcome in Askin-Rosai Tumor: A Review of 104 Patients

PURPOSE To evaluate the prognostic factors and treatment outcome of patients with Askin-Rosai tumor of the chest wall treated at a single institution. METHODS AND MATERIALS Treatment comprised multiagent chemotherapy and local therapy, which was either in the form of surgery alone, radical external-beam radiotherapy (EBRT) alone, or a combination of surgery and EBRT. Thirty-two patients (40%) were treated with all three modalities, 21 (27%) received chemotherapy and radical EBRT, and 19 (24%) underwent chemotherapy followed by surgery only. RESULTS One hundred four consecutive patients aged 3-60 years were treated at the Tata Memorial Hospital from January 1995 to October 2003. Most (70%) were male (male/female ratio, 2.3:1). Asymptomatic swelling (43%) was the most common presenting symptom, and 25% of patients presented with distant metastasis. After a median follow-up of 28 months, local control, disease-free survival, and overall survival rates were 67%, 36%, and 45%, respectively. Median time to relapse was 25 months, and the median survival was 76 months. Multivariate analysis revealed age ≥18 years, poor response to induction chemotherapy, and presence of pleural effusion as indicators of inferior survival. Fifty-six percent of patients with metastatic disease at presentation died within 1 month of diagnosis, with 6-month and 5-year actuarial survival of 14% and 4%, respectively. CONCLUSION Primary tumor size, pleural effusion, response to chemotherapy, and optimal radiotherapy were important prognostic factors influencing outcome. The combination of neoadjuvant chemotherapy, surgery, and radiotherapy resulted in optimal outcome.

Autonomous aldosterone-secreting ovarian tumor

The case of a young woman with primary aldosteronism originating extraadrenally--ovarian tumor--is reported. Clinically she presented with uncontrolled hypertension. Biochemical and hormonal profiles showed features of aldosteronism. The primary was found in the left ovary. Following excision of the tumor, aldosteronism regressed completely. Microscopically, the tumor was of the lipid cell type. Nine months after surgery she is asymptomatic and well. Review of the literature uncovered three previous reports of aldosterone-secreting ovarian tumors.

IL-10 production in non-small cell lung carcinoma patients is regulated by ERK, P38 and COX-2.

Immune dysfunction is hallmark of patients with non–small cell lung carcinoma (NSCLC). The molecular mechanism involved in COX‐2– and PGE2‐mediated production of immunosuppressive cytokine IL‐10 is not well‐understood. Our study addresses the involvement of T cell downstream signalling intermediates, cytokines (IL‐10 and IFN‐γ) and their transcription factors (T‐bet and GATA‐3) in COX‐2–mediated regulation of lymphocyte functions in NSCLC patients. In comparison to healthy individual, a marked decrease in lymphocyte proliferation to anti‐CD3 MAb was observed in NSCLC patients by thymidine incorporation assay. Using flow cytometry, decrease in intracellular calcium release with increase in reactive oxygen species was observed in lymphocytes of NSCLC patients. These patients showed increased IL‐10 and PGE2 with reduced IFN‐γ production by ELISA. Results demonstrated defect in regulation of transcription factors T‐bet and GATA‐3 as analysed by Western blotting (WB), immunoprecipitation and EMSA. Overexpression of p‐p38, p‐ERK and COX‐2 were observed with diminished p‐JNK by WB. IL‐10/IFN‐γ levels were found to be differentially regulated via p38 and ERK mitogen‐activated protein kinase (MAPK) pathways in cooperation with COX‐2. Inhibition of these pathways using selective inhibitors lead to increased lymphocyte proliferative response to anti‐CD3 MAb and IFN‐γ production with decrease in IL‐10 production. Studies showed involvement of ERK, p38 and COX‐2 pathways in high IL‐10 production, driven by lung tumour derived PGE2. The selective COX‐2 inhibitor rofecoxib showed ability to alter the cytokine balance by affecting regulation of T‐bet and GATA‐3 transcription factors.

Role of nitric oxide in heat shock protein induced apoptosis of γδT cells

Activation induced cell death (AICD) has been proposed to serve as a mechanism to limit T lymphocyte proliferation induced by antigenic stimulation. Heat shock proteins (hsp60 and hsp70) expressed on oral tumor cells serve as ligands for peripheral blood γδT lymphocytes. Tumor cell lysis by γδT lymphocytes is mediated via recognition of hsp expressed on tumor cells. In the present study, we report that upon stimulation with hsp, γδT lymphocytes isolated from oral cancer patients undergo AICD as confirmed by DNA ploidy, annexin V staining and confocal microscopy. In cocultures of γδT lymphocytes and tumor cells, addition of antihsp60 and antihsp70 MAb, but not anti‐Fas MAb (ZB4), inhibited DNA fragmentation of γδT lymphocytes. Flow cytometric analysis revealed a down regulation of Fas expression on γδT lymphocytes upon incubation with hsp60 and hsp70. Increased expression of iNOS was observed in hsp‐stimulated γδT lymphocytes. Addition of monomethyl L‐arginine monoacetate, competitive inhibitor of NOS, inhibited nitric oxide (NO) production and apoptosis of γδT lymphocytes induced by hsp60 and hsp70. The NO‐induced apoptosis of γδT lymphocytes involves activation of caspase‐9 and loss of mitochondrial membrane potential. The present study explains a novel strategy adopted by tumor cells to evade immune recognition by γδT lymphocytes.

Cervical lymph node metastases of squamous cell carcinoma from an unknown primary: Outcomes and patterns of failure

CONTEXT Management of cervical lymph nodes metastases of squamous cell carcinoma (SCC) from primary of unknown origin (PUO) is contentious and there is insignificant data from India on this subject. AIMS To present experience of management of these patients treated with curative intent at a single institution. SETTINGS AND DESIGN Retrospective study of patients treated between 1989-1994 in a tertiary referral cancer centre. MATERIALS AND METHODS Eighty-nine patients were evaluated in the study period and their survival compared with patients with common sites of primary in the head and neck with comparable node stage. STATISTICAL ANALYSIS USED Kaplan-Meier method. RESULTS The clinical stage of the neck nodes at presentation was N1 in 11%, N2a in 28.5%, N2b in 22.5%, N3 in 35% and Nx in 3.4% patients. All patients underwent surgery and 70 patients received more than 40Gy postoperative radiotherapy. Twenty-nine (32.6%) patients had relapse of which 19 (21%) were in the neck. Postoperative radiotherapy did not influence the neck relapse (p=0.72). Primary was detected in 13 patients (14.6%) on subsequent follow up. The overall five and eight-years survival was 55% and 51% respectively. The overall five-year survival was better compared to patients with known primary with comparable node stage. CONCLUSIONS Patients with cervical lymph nodes metastases of SCC from PUO have reasonable survival and low rate of development of subsequent primary when treated with surgery and radiotherapy. The overall survival is comparable to that of patients with known primary and hence an attempt at cure should always be made.

Hyperkalemia during surgery: is it an early warning of propofol infusion syndrome?

We present a case of severe hyperkalemia in a 48-year-old man after short-term infusion of an average dose of propofol. We suspected that the hyperkalemia in this patient was a sign of propofol infusion syndrome. The patient was undergoing a video-assisted esophagectomy, for which one-lung ventilation, with air/oxygen, isoflurane, and continuous epidural analgesia was supplemented with propofol infusion. In the intraoperative period, the patient developed severe hyperkalemia with mild acidosis but no cardiovascular failure. There were no other evident causes of hyperkalemia as documented by laboratory data. The procedure was abandoned and the patient was taken to postoperative recovery, where his potassium levels returned to normal at the end of 10 h.

Novel cost-effective method of laparoscopic feeding- jejunostomy

A feeding jejunostomy tube placement is required for entral feeding in a variety of clinical scenarios. It offers an advantage over gastrostomies by eliminating the risk of aspiration. Standard described laparoscopic methods require special instrumentation and expensive custom-made tubes. We describe a simple cost-effective method of feeding jejunostomy using regular laparoscopic instruments and an inexpensive readily available tube. The average operating time was 35 min. We had no intra-operative complications and only one post-operative complication in the form of extra-peritoneal leakage of feeds due to a damaged tube. No complications were encountered while pulling out the tubes after an average period of 5–6 weeks.