Posterior Superior Mesenteric Artery (SMA) First Approach vs. Standard Pancreaticoduodenectomy in Patients with Resectable Periampullary Cancers: a Prospective Comparison Focusing on Circumferential Resection Margins.

BACKGROUND: The 'SMA-first' (P-SMA) pancreatoduodenectomy (PD) allows dissection directly on the right lateral aspect of superior mesenteric artery (SMA) which may decrease circumferential resection margin (CRM) positivity. This comparative study between standard PD (sPD) and P-SMA approach was planned focusing on CRM involvement. METHODS: This was a prospective study comparing consecutive patients with resectable periampullary cancers (PACA) undergoing PD using the standard or P-SMA approach. The perioperative outcomes and the CRM positivity rates (specimens analysed according to the standardized Leeds pathology protocol (LEEPP)) were compared. RESULTS: Overall, 39 patients (28 men; mean age 54 years; sPD 21, P-SMA 18) were included. Both groups were comparable with regard to demographic/tumour characteristics and perioperative outcomes. The P-SMA technique was significantly faster (321.1 ± 54.0 vs. 357.6 ± 55.8 min; p = 0.05). Though the mean tumour size (2.2 vs. 2.1 cm; p = 0.84) and T stage (T2 and T3) distribution were similar in both groups, lymph node yield was significantly higher in the P-SMA group (10.7 vs. 5.95; p = 0.001; mean 8 (2-21)). Though CRM positivity (margin <1 mm) occurred in 8 (21.1%), we did not find the P-SMA PD to yield significantly lower CRM positivity rates compared to the sPD (3/17 (17.6%) vs. 5/21(23.8%); p = 0.71). At a median follow-up of 28 months, fewer patients in the P-SMA PD group developed recurrence (2/15 vs. 5/19; p = 0.3) or died (3/15 vs. 7/19; p = 0.19), though this difference was not significant. CONCLUSIONS: In patients with resectable PACA, P-SMA PD was significantly faster and yielded higher lymph node counts in the specimen but did not lower the rate of CRM positivity as determined by the LEEPP.

Impact on outcome of the route of conduit transposition after transhiatal oesophagectomy: A randomized controlled trial.

AIM: To assess the influence of the route of conduit transposition after transhiatal oesophagectomy on the postoperative morbidity and mortality and late outcome at 6 months. METHODS: Patients with oesophageal carcinoma, undergoing transhiatal oesophagectomy (gastric conduit), were randomized to either anterior or posterior route of conduit transposition. Patients with advanced tumour, distant metastasis, extensive invasion of the stomach, previous gastric surgery, any anterior mediastinal abnormality detected on preoperative imaging, ASA grade III/IV and poor preoperative pulmonary function were excluded. Intraoperative complications, postoperative morbidity and mortality and late outcomes were compared. RESULTS: Of the 49 patients (34 men), 24 patients were randomized to the anterior mediastinal route and 25 to the posterior. The mean duration of the operative procedure (anterior: 235min; posterior: 225min) and the mean blood loss (anterior: 531ml; posterior: 538ml) were not statistically different. The most common complications were pulmonary and cardiac and comparable in both groups. Four patients died postoperatively. At 6-month follow-up the incidence of dysphagia, anastomotic stricture, anastomotic recurrence, aspiration and reflux symptoms and weight gain were similar. CONCLUSIONS: The route of conduit transposition did not affect the outcome. However, an individualized approach depending upon the operative findings, radicality of the procedure, and perceived need for postoperative adjuvant therapy may be useful.

Esophageal carcinoma during pregnancy: a case report.

Association of pregnancy with esophageal cancer is an extremely rare event. The symptoms are frequently masked by factors related to normal pregnancy and diagnostic approaches are restricted by physical and psychological clinical events. Hence, the cancer stage is usually advanced at the time of diagnosis. The approach to cancer surgery and chemotherapy must be modified in pregnant patients to minimize fetal and maternal risks. We present an extremely rare case of carcinoma esophagus during pregnancy.

Evaluation of Pringle maneuver during liver resection in a rat model of surgical obstructive jaundice.

Temporary portal triad clamping (Pringle maneuver) during liver resection reduces intraoperative blood loss. A normal liver can safely tolerate normothermic ischemia for up to 60 min. However, its safety in patients with surgical obstructive jaundice (SOJ) is not known. Therefore, we investigated the effect of hepatic ischemia in an experimental rat model of SOJ created by ligating the bile duct. Four groups of rats were created: Group I (sham operation, 10 days later, liver resection); Group II (sham operation, 10 days later, liver resection with 5 min of hepatic ischemia); Group III (bile duct ligation, 10 days later, liver resection); and Group IV (bile duct ligation, 10 days later, liver resection with 5 min of hepatic ischemia). The ischemic injury was assessed by the survival of rats, liver tissue malondialdehyde and total glutathione (markers of free radical injury), serum alanine aminotransferase, aspartate aminotransferase, and liver histology. The results showed decreased survival (47.6% vs. 90% [p = .046]), increased liver tissue malondialdehyde (161 +/- 35 vs. 129 +/- 33 microg/gm liver tissue [p = .05]), and decreased liver tissue total glutathione (565 +/- 169 vs. 1075 +/- 276 nmol/gm liver tissue [p = .05]) in rats with SOJ subjected to hepatic ischemia when compared to nonjaundiced rats. The changes in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase showed an increasing trend in the SOJ group but were not statistically significant. Ischemic changes in liver histology were seen more often in the SOJ group but were not statistically significant. These data suggest that temporary portal triad clamping in an experimental model of SOJ is detrimental to the outcome of liver resection.

Gallbladder cancer in India: a dismal picture.

BACKGROUND: Gallbladder cancer (GBC) is one of the most common gastrointestinal malignancies. The data regarding GBC are, however, limited. METHODS: Records of 634 patients with GBC over a 10-year period were examined with regard to the clinical presentation, investigative findings, treatment, operative findings and outcome. RESULTS: The mean age of patients was 51 +/- 11 years and men : women ratio was 0.36:1.00. Pain, jaundice and hepatomegaly were seen in 81.0%, 76.0% and 61.5% patients, respectively. On imaging, a mass replacing the gallbladder was seen in 73% patients. Gallstones were present in 54% patients. Surgery was carried out in 291 (46%) patients and endoscopic treatment in 72 (19%) patients but no intervention was carried out in the remaining patients because of disseminated disease. Among the patients who were operated on, 2.0% had stage I GBC, 3.4% stage II, 17.5% stage III, 47.0% stage IVa and 29.8% stage IVb. Radical resection was possible in 133 (46%) patients. The 30-day mortality was 10% with most (90%) deaths in patients with stage IV disease. The median survival after simple cholecystectomy and radical surgery was 33.5 and 12.0 months, respectively. However, among those who underwent debulking, palliative bypass or exploratory laparotomy alone, the survival ranged between 1 and 3 months. Logistic regression analysis showed that only radical resection improved the long-term survival (P < 0.05). CONCLUSIONS: The majority of patients with GBC in India have advanced unresectable disease. Detection of GBC at an early stage is incidental and rare but is associated with long-term survival. Radical surgery, when feasible, is the only option for achieving long-term survival.

Thoracic duct injury during esophagectomy: 20 years experience at a tertiary care center in a developing country.

Thoracic duct injury is an uncommon complication of esophagectomy. Experience in managing these cases is limited to large centers performing esophagectomies in good numbers. We analyzed the prospectively maintained esophageal diseases database of patients presenting to a surgical unit between 1982 and 2002. Among 552 esophagectomies during this period we had encountered 14 cases of chylothorax (2.54%). We analyzed the type and site of lesion and the impact of neoadjuvant therapy on the incidence of thoracic duct injury. Among 459 patients of transhiatal esophagectomy, 11 developed postoperative chylothorax (2.40%). In 93 transthoracic resections, there were three cases of chylothorax (3.23%; (P = 0.9185)). The incidence following preoperative radiotherapy was 2.17%. None of the 31 patients, who had undergone esophagectomy for benign diseases had developed chylothorax. In the carcinoma group the incidence in middle third lesions was 5.85% and in lower third lesions was 0.80% (P = 0.0018). Seven patients were managed conservatively. Two of these patients, for whom surgery had been planned, died before they could be taken up for surgery. In the remaining seven patients transthoracic ligation of the thoracic duct was performed. Two patients in this group died. The average hospital stay was 20 days in the conservative group and 12 days in the surgery group. Among the factors studied, patients with middle third lesions were at increased risk of developing postoperative chylothorax, when compared to upper or lower third lesions.

Intussusception due to gastrointestinal stromal tumour of the colon: diagnosis by colonoscopy.

Intussusception of the intestine is rare in adults. We report a case of a 45-year-old male who presented with long-standing pyrexia of unknown origin, abdominal pain, gastrointestinal bleeding and constitutional symptoms. Colonoscopic examination revealed a large invaginated mass suggestive of colonic intussusception due to gastrointestinal stromal tumour of the colon. His symptoms disappeared after surgical removal of the tumour.

Functional outcome and patient satisfaction after ileal pouch anal anastomosis for ulcerative colitis in a developing country.

AIM: To study the long-term outcome and patient satisfaction of patients with an ileal pouch-anal anastomosis (IPAA) for ulcerative colitis in India. PATIENTS AND METHODS: We studied 35 patients who had undergone IPAA for ulcerative colitis between 1985 and 1998 and had intestinal continuity restored for more than 6 months. These patients were asked to answer a detailed questionnaire on their bowel function, urogenital function, etc. A complete haemogram, serum iron studies, liver function tests and D-Xylose absorption test were done. In addition hepatobiliary ultrasound, stool microscopy, pouchoscopy and pouch biopsies were also performed. Patient satisfaction after the procedure was also evaluated. RESULTS: Thirty-five patients (17 men and 18 women) underwent a complete evaluation. The duration after restoration of continuity ranged from 6 months to 164 months (mean 78.6 months). The mean stool frequency was 7.2 stools per 24 hours. Five patients had urgency of stool, 9 had occasional soiling and 1 had major incontinence. Four patients had minimal restriction of social activities and 1 discontinued his employment. All patients were sexually satisfied except one man who had impotence and one woman who had dyspareunia. Fifteen patients had abnormal serum iron studies (Haemoglobin < 9 g/dl in 11). Eleven patients had D-Xylose absorption below normal values. Two patients were found to have gallstones. All pouch biopsies showed chronic inflammation and 1 patient had histological evidence of pouchitis. Eighty-five percent of patients reported that they were very satisfied with the procedure. CONCLUSION: Good functional recovery and acceptance of the procedure over the long term suggests that it is a valid procedure to be recommended for patients with ulcerative colitis in India.

Esophageal squamous cell carcinomas with DNA replication errors (RER+) are associated with p16/pRb loss and wild-type p53.

PURPOSE: Microsatellite instability (MSI) as a determinant of propensity to esophageal squamous cell carcinoma (ESCC) at seven microsatellite markers at 2p (2p15-16), 3p (3p13, 3p14.1-3, 3p25, and 3p26) and 16q (16q12.1-3) was investigated to analyze their putative role as indicators of predisposition to esophageal malignancies. METHODS: Seven microsatellite loci were amplified by polymerase chain reaction, from surgically resected tumor tissues from 30 ESCC patients from Indian population, to assess the loss of heterozygosity (LOH) and replication error repeats (RER) and to correlate these alterations with aberrations in major cell cycle regulatory proteins and histopathological parameters. RESULTS: LOH and RER analyses at these loci demonstrated moderate microsatellite alterations, suggesting the involvement of MSI in esophageal tumorigenesis in a subset of the Indian population. MSI, defined as RER in at least two or more of the loci studied, was observed in ten of 30 (33%) patients. Twenty-two of 30 patients (73%) showed LOH at one or more loci, while 17 of the 30 patients (60%) showed RER in at least one of the loci studied. RER-positive patients showed a trend towards better prognosis when compared to RER-negative patients. MSI demonstrated a significant association with concomitant loss of p16 and pRb (p16-/pRb- phenotype) (P=0.046). Interestingly, we observed an inverse correlation between MSI and p53 mutations (P=0.03) suggesting that MSI may provide a p53-independent pathway for esophageal tumorigenesis in RER+ patients. MSI showed a trend towards longer survival and absence of distant organ metastasis (P=0.06). CONCLUSIONS: The present study demonstrates the probable role of MSI in esophageal squamous cell carcinoma in the Indian population. Instability associated with the repetitive sequences--the revealing marks of loss of DNA replication fidelity may serve as an indicator of predisposition to esophageal cancer.

Circulating p53 antibodies, p53 gene mutational profile and product accumulation in esophageal squamous-cell carcinoma in India.

Esophageal cancer (EC) in the Indian population presents in advanced stages with poor prognosis and warrants the identification of a non-invasive marker for early detection and better prognostic assessment. We have previously reported high prevalence of p53 protein accumulation in esophageal squamous-cell carcinomas (ESCCs). The present study was designed to determine (i) if esophageal cancer patients elicit a humoral immune response to intra-tumoral p53 protein accumulation and (ii) their relationship with p53 gene mutations. The goal was to compare the cellular events, p53 protein accumulation and gene mutations with the presence of serum anti-p53 antibodies (p53-Abs) and to assess the utility of serological p53-Ab analysis as a surrogate marker for p53 alterations in esophageal cancer. A high prevalence of circulating p53-Abs was observed in 36 of 60 (60%) ESCC patients. In a subset of 44 ESCCs, exons 5-9 of the p53 gene were examined for mutations by PCR and direct sequencing of PCR products. Mutational data have been correlated with p53-Abs and p53 protein accumulation in ESCCs. Circulating p53-Abs in ESCC patients were significantly associated with intra-tumoral p53 protein accumulation (p=0.0005). A strong correlation observed between humoral immune response against p53 protein, missense gene mutations and protein accumulation warrants the application of serological p53-Abs as a non-invasive surrogate marker in screening high-risk populations for early detection of malignancy.

Bcl-2 expression is correlated with low apoptotic index and associated with histopathological grading in esophageal squamous cell carcinomas.

The aim of this study was to examine the relationship between apoptosis, protein expression of apoptosis mediator and inhibitor genes p53 and bcl-2 and various histopathological grades of squamous cell carcinoma of the esophagus. Apoptotic index was evaluated in thirty human esophageal squamous cell carcinomas and adjoining normal tissue by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL). Protein expression of bcl-2 and p53 was measured by immunohistochemical staining of cryocut sections and Western blotting. Apoptototic cells were seen mainly around areas of keratinization and the apoptotic index was highest in well-differentiated squamous cell carcinomas. High Bcl-2 expression correlated inversely with the apoptotic index. p53 protein expression did not correlate with the grade of the tumor or the apoptotic index. We propose that deregulation of apoptosis contributes to the pathogenesis of esophageal squamous cell carcinoma.

Crystallization of Helix pomatia agglutinin (HPA), a protein from the edible snail.

Crystals of Helix pomatia agglutinin (HPA) have been grown by the hanging-drop technique using polyethylene glycol as the precipitant at 293 K. Over a period of one to two weeks the crystals grew to maximum dimensions of 0.10 x 0.05 x 0.02 mm. The crystals belong to space group P6(3)22, with unit-cell dimensions a = b = 63.3, c = 105. 2 A and Z = 12 identical monomers of M(r) = 13 kDa, aggregating into two 78 kDa hexameric protein molecules per unit cell, each with symmetry 32 (D(3)). The diffraction pattern extends to 3.6 A at 293 K.

Crystallization of Pleurotus ostreatus (oyster mushroom) lectin.

Crystals of Pleurotus ostreatus (oyster mushroom) lectin have been grown by the hanging-drop technique using ammonium sulfate as the precipitant at 293 K. Over a period of between two and three weeks, crystals of hexagonal bipyramidal morphology grew to maximum dimensions of 0.2 x 0.2 x 0.5 mm. The crystals belong to space group P6(1)22 or P6(5)22, with unit-cell parameters a = b = 155.9, c = 149. 8 A, V = 3153078 A(3), Z = 12 (assuming 50% solvent), and diffract to 4.1 A at 293 K.

Telomerase activity in Indian patients with carcinomas of the aerodigestive tract.

The activation of telomerase, a ribonucleoprotein maintaining telomeric length, might represent an additional required event in the multigenetic process of tumorigenesis in human cancer. To investigate whether telomerase activity is a prerequisite or a useful indicator of malignant potential, we assayed the enzyme in squamous cell carcinomas and tried to observe any correlation with clinical staging and histopathological grading. We have studied telomerase activity in 23 samples of squamous cell carcinomas of the aerodigestive tract and in 22 corresponding samples of adjoining tissues using the telomerase repeat amplification assay. Telomerase activity was detected in 100% of the tumor samples studied. The telomerase activity increased with tumor grading, but was not statistically significant. Low levels of enzyme activity were also detected in 60.86% of the adjoining normal tissue samples. Reactivation of telomerase may play an important role in the carcinogenesis of aerodigestive tract tumors. Detection of enzyme activity in the adjoining normal tissue is suggestive of microinvasion of tumor cells and/or early activation of telomerase in the progression towards cancer, before possible pathological identification.

Adenocarcinoma of distal esophagus and gastroesophageal junction: long-term results of surgical treatment in a North Indian Center.

This retrospective study reports our experience managing 78 patients with adenocarcinoma of the esophagus and gastroesophageal junction operated between January 1982 and December 1996. Altogether 18 patients presented with stage I and II disease, and 60 patients had stage III and IV disease at presentation; 56 patients (71.8%) were found to have resectable disease. Of these, transhiatal esophagectomy was possible in 51 patients. Transthoracic esophagectomy was done in 3 patients, and a left thoracoabdominal approach was used in 2 patients. The stomach was used as conduit in 50 patients and the colon in 6 patients. Twenty-two patients were found to have unresectable lesions at laparotomy and underwent various palliative procedures. Overall operative mortality was 6.3%. Mortality in the resectable group was only 3.6%. Follow-up ranges from 3 to 128 months, with four patients lost to follow-up at 1, 6, 8, and 10 months. The 5-year survival of the whole group according to Kaplan and Meier survival analysis was 21.27% with a median survival of 13.48 months. Univariate analysis using the log-rank test revealed stage of the disease and resectability to be significant predictors of survival. On multivariate analysis, curative resection appeared to be the most significant predictor of survival in patients undergoing resection.

Video assisted thoracoscopic surgery (VATS) in the diagnosis of intrathoracic pathology: initial experience.

We report our experience with the use of video-assisted thoracoscopic surgery [VATS] in the diagnosis of intrathoracic disease of unknown origin. In the last two years, 32 patients (18 males) underwent this procedure for diagnostic purposes. Of them, 18 patients had lung pathology, eight mediastinal and six pleural disease. All attempts at achieving a tissue diagnosis were unrewarding. In all of them, diagnostic thoracotomy was being contemplated to procure tissue for histopathological diagnosis. Diagnostic thoracoscopy was successful in providing tissue diagnosis in all the patients with lung disease; seven of the eight patients with mediastinal pathology and five of the six patients with pleural lesions. Diagnostic thoracoscopy was associated with minimal morbidity, short hospital stay, better cosmetic result and quicker return to work as compared to conventional thoracotomy. We conclude that video-assisted thoracoscopy is an excellent diagnostic tool to confirm tissue diagnosis in patients with undiagnosed chest diseases.

Relative merits of ultrasonography, computed tomography and cholangiography in patients of surgical obstructive jaundice.

Fifty consecutive patients with surgical obstructive jaundice were evaluated prospectively with ultrasonography (US), computed tomographic scans (CT scan) and cholangiography-percutaneous transhepatic cholangiography (PTC) or endoscopic retrograde cholangio-pancreaticography (ERCP). The diagnostic accuracy of ultrasound in defining the level of obstruction was 86% as compared to 86% and 94.8% for CT scan and cholangiography, respectively. To measure the etiology of the obstruction, the accuracy of ultrasound, CT scan and cholangiography were 84%, 86% and 75%, respectively. The sensitivity of CT scans and cholangiography in the diagnosis of choledocholithiasis was 100%, 81.8% and 90%, respectively, whereas specificity was 97%, 100% and 100%, respectively. Sensitivity for a diagnosis of malignant disease was 100% for both US and CT scans whereas specificity was 90% and 81%, respectively. Ultrasonography as a single radiological investigation is sufficient in the evaluation of the majority of patients with surgical obstructive jaundice. CT scan and cholangiography should be done only when US gives equivocal findings or if concomitant therapeutic procedures like basketing and stenting are also planned.

Dumping syndrome in the intra-thoracic stomach.

Thirty seven patients who survived at least 6 months after oesophagectomy and cervical oesophagogastrostomy for benign and malignant diseases of the oesophagus were evaluated for dumping syndrome. Twenty two of these patients had a pyloroplasty and fifteen had no drainage procedure. All these patients were subjected to a dumping provocation test. Evidence of dumping was noted in four patients, all having a pyloroplasty. Clinically, these four patients had mild symptoms which improved with dietary adjustment. We conclude that dumping does occur following thoracic transposition of the stomach and seems to occur more in patients with pyloroplasty than those without it.