The Smad family and its role in pancreatic cancer.

One of the major signaling pathways that determine the tumor aggression and patient outcome in pancreatic cancer is the transforming growth factor-beta (TGF-ß) pathway. It is inactivated at various levels in pancreatic cancer and plays a dual role in tumor initiation and progression. The Smad family of proteins transduce signals from the TGF-ß superfamily ligands that regulate cell proliferation, differentiation and death through activation of receptor serine/threonine kinases. This review discusses the structure, function and regulation of various participating Smad family members, and their individual roles in determining the progression and outcome of pancreatic cancer patients, with a special emphasis on Smad4.

A comprehensive examination of Smad4, Smad6 and Smad7 mRNA expression in pancreatic ductal adenocarcinoma.

Background: Smad4, Smad6 and Smad7 are important molecules in TGF-beta pathway, which plays an important role in pancreatic ductal adenocarcinoma (PDAC) biology. Aims : This study examined the expression profiles of Smad4, Smad6 and Smad7 mRNA in patient samples of PDAC and their relationship to Smad protein expression, SMAD4 gene mutations, clinicopathological parameters and patient survival. Settings and Design: Surgically resected, paired normal and tumor tissues of 25 patients of PDAC were studied. Materials and Methods: Protein and mRNA levels were assessed by immunohistochemistry and RT-PCR, respectively. Statistical Methods: Statistical analysis was done using Student's t-test, Pearson's chi-square test, Spearman's Rank Correlation, Pearson's Correlation test and Kaplan-Meier Logrank test. Results: While there was a highly significant difference in the protein levels of all three Smads in tumor as compared to normal samples, mRNA levels were significantly different only for Smad4. Protein levels did not correlate significantly with mRNA levels for any of the three Smads. The mRNA levels of Smad4 and Smad6, Smad4 and Smad7, and Smad6 and Smad7 in tumor samples showed a significant positive correlation. The relationship of Smad4 mRNA expression to SMAD4 gene status and Smad4 protein expression was discordant and there was no significant correlation between mRNA expression and clinicopathological parameters and patient survival. Conclusion : The absence of concordance between SMAD4 gene status, mRNA expression and Smad4 protein expression suggests the presence of other regulatory mechanisms in Smad4 transcription and translation in PDAC.

High frequency of loss of allelic integrity at Wilms' tumor suppressor gene-1 locus in advanced breast tumors associated with aggressiveness of the tumor.

Background: The product of Wilms' tumor suppressor gene (WT1), a nuclear transcription factor, regulates the expression of the insulin-like growth factor (IGF) and transforming growth factor (TGF) systems, both of which are implicated in breast tumorigenesis and are known to facilitate angiogenesis. In the present study, WT1 allelic integrity was examined by Loss of Heterozygosity (LOH) studies in infiltrating breast carcinoma (n=60), ductal carcinoma in situ (DCIS) (n=10) and benign breast disease (n=5) patients, to determine its possible association with tumor progression. Methods: LOH at the WT1 locus (11p13) as determined by PCR-RFLP for Hinf1 restriction site and was subsequently examined for its association with intratumoral expression of various growth factors i.e. TGF-β1, IGF-II, IGF-1R and angiogenesis (VEGF and Intratumoral micro-vessel density) in breast carcinoma. Results: Six of 22 (27.2%) genetically heterozygous of infiltrating breast carcinoma and 1 of 4 DCIS cases showed loss of one allele at WT1 locus. Histologically, the tumors with LOH at WT1 were Intraductal carcinoma (IDC) and were of grade II and III. There was no correlation in the appearance of LOH at WT1 locus with age, tumor stage, menopausal status, chemotherapy status and lymph node metastasis. The expression of factor IGF-II and its receptor, IGF-1R was significantly higher in carcinoma having LOH at WT1 locus. A positive correlation was observed between the TGF-β1, VEGF expression and IMD scores in infiltrating carcinoma. Conclusions: The current study indicates that the high frequency of loss of allelic integrity at Wilms' tumor suppressor gene-1 locus in high-graded breast tumors is associated with aggressiveness of the tumor.

Comparison of multidetector computed tomographic colonography and conventional colonoscopy for detection of colorectal polyps and cancer.

BACKGROUND: Computed tomographic colonography (CTC) is a new technique for detecting colonic neoplasms. Data on the utility of this method in the Indian population are limited. METHODS: Forty-two patients with symptoms of colonic disease underwent CTC and conventional colonoscopy (CC) within one week of each other and the findings at these two investigations were compared. RESULTS: The entire colon could be evaluated in 38 patients on CTC and in 23 patients on CC. Of the 19 patients who had incomplete CC, 14 had occlusive colonic lesions. Of the 86 lesions detected on CC, 76 (88.4%) were correctly identified on CTC with regard to location and size. CTC was false negative for 10 lesions and false positive for 5 lesions in 3 patients. The sensitivity and specificity of CTC were 65% and 77%, respectively, for lesions 1-5 mm; 97% and 83% for 6-9 mm-sized lesions; and 100% and 100% for lesions 10 mm or larger. Extracolonic findings were seen in 24 of 42 patients (57%). CONCLUSIONS : CTC is reliable for detecting lesions 6 mm or larger in size. It permits evaluation of the region proximal to an occlusive growth, which is often not possible with CC.

Xanthogranulomatous cholecystitis.

Twelve cases of xanthogranulomatous cholecystitis are reported. The clinical presentation was similar to chronic cholecystitis. All patients had associated gallstones. The diagnosis was achieved at histopathological examination of the resected gall bladders and none had any focus of malignancy. Cholecystectomy was curative.

Pneumobilia--clue to an unusual cause of diarrhea.

A 65-year lady presented with diarrhea and weight loss of six months duration. Initial evaluation suggested that malabsorption was the possible underlying mechanism for the diarrhea. Work up for the common etiologies of malabsorption was non-contributory. Presence of pneumobilia raised the suspicion of a bilio-enteric fistula, which was subsequently confirmed on barium enema and endoscopic cholangio-pancreaticography to be a cholecystocolic fistula. At surgery, a fistulous tract from the fundus of the gallbladder was found to be communicating with the hepatic flexure. Fistulectomy with cholecystectomy resulted in prompt relief of symptoms. Cholecystocolic fistula (CCF) is a rare biliary fistula with diverse presentation.

Gastrointestinal stromal tumors the assessment of malignant potential.

GISTS are the largest category of non-epithelial neoplasms of stomach and small bowel. Numerous immunohistochemical, ultrastructural and flow cytometry studies have been carried out for evaluation of prognostic factors which could predict malignant behaviour of these neoplasms. Tumor size of 5 cm and mitosis of 2/10 hpf were suggested as two important parameters which could predict the chances of recurrence and clinically aggressive course. The aim of this study is to examine predictive value of these two important parameters in assigning the tumors as high, intermediate and low risk groups. Using these two parameters we categorized 30 cases of GIST over a period of 6 years (1990-95) into low, intermediate and high risk groups and examined other features of these cases. Based on these two parameters alone we found that 4 cases each in low and intermediate group could be assigned to a higher risk group clinically as there were presence of adjacent organ infiltration, lymphatic emboli, serosal nodules, lymph node metastasis and transmural infiltration. Hence, other features like hemorrhage, necrosis and anaplasia should also be included in risk assessment. Metaplastic tissues like bone, cartilage and adipose tissues were seen only in high-risk categories.

Concurrent renal transitional cell carcinoma and right colon cancer.

A 45-year-old man who had undergone right radical nephrectomy for transitional cell carcinoma 3 months earlier was admitted with right colonic tumor. Review of CT done for right kidney tumor was suggestive of right colon pathology. Right hemicolectomy was performed, followed by a course of chemotherapy for mucinous adenocarcinoma, and he is well a year later.

Usefulness of percutaneous transhepatic biliary drainage in patients with surgical jaundice--a prospective randomised study.

BACKGROUND: Patients with obstructive jaundice undergoing surgical procedures have a significant risk of morbidity and mortality. The role of preoperative percutaneous transhepatic biliary drainage (PTBD) was evaluated in a randomized trial. METHODS: A total of 40 patients were assigned to either preoperative PTBD (n = 20), or surgery alone (n = 20). PTBD was performed under ultrasound guidance. There were no major complications related to the procedure. RESULTS: Ultrasound guided drainage was a successful and safe method of preoperative biliary decompression. There was a marked relief from pruritus and significant reduction of hyperbilirubinaemia from a mean of 386.48 mumol/L to 116.10 mumol/L (p < 0.001). Mean duration of drainage was 42.5 days. Postoperative complications occurred in five patients in PTBD group (25%) compared to 11 patients (55%) in the control group. One death (5%) occurred in PTBD group compared to four deaths (20%) in the control group (significant at 5% level with probability 0.2). CONCLUSIONS: Ultrasound guided drainage is a useful preoperative supportive measure in preparing deeply jaundiced patients for surgery and permits hepatic function to return to a near normal state preoperatively. The improved results in our study were due to longer duration of drainage.

Primary gastrointestinal lymphoma--disease spectrum and management: a 15-year review from north India.

OBJECTIVE: To analyze retrospectively the disease spectrum and outcome of primary gastrointestinal lymphoma (PGIL) in a tertiary referral center in north India. MATERIAL: Seventy five patients presenting with PGIL between January 1971 and December 1985 were evaluated. RESULTS: The 49 males and 26 females were aged 3.5-69 years (mean 34) at presentation. Abdominal pain, weight loss and vomiting were cardinal symptoms at presentation; the stomach was the most common site of involvement. Histologically, a majority of patients were classified as having diffuse poorly-differentiated lymphocytic lymphoma (46.7%) and diffuse histiocytic type (30.7%). Twenty seven (36%) patients had stage I disease, 31 (40%) stage II, 11 (14.7%) stage III, and 6 (8%) stage IV. At laparotomy, primary resection and anastomosis was carried out in 66 patients, while only biopsies were taken in nine. Forty eight patients received adjuvant radiation with or without chemotherapy. The mean follow-up was 3.9 years (range 1-14). The 5-year actuarial survival was 34%, 25% and 16% for stages I, II, and higher-stage disease, respectively. The survival was significantly better (p < 0.01) for gastric location (44%) compared to other sites (24%). CONCLUSION: PGIL was more common in the 3rd and 4th decades of life, with the stomach being the predominant site of involvement. Survival was better among patients with stages I and II disease, and gastric location of lesion.

Pancreatoduodenectomy in abdominal trauma: a viable alternative.

Pancreatoduodenectomy was performed in five patients with severe pancreatoduodenal trauma following vehicular accidents. Three of them presented within five hours of injury and two patients, four and ten days later. Surgery was performed within 6-12 hours of hospitalization. All patients underwent pancreatoduodenectomy; in one the pancreatic stump was closed completely owing to its friability. Three patients survived; two succumbed to ongoing preoperative septicemia due to late presentation. The results of pancreato-duodenectomy are good when patients are operated on early, before the development of sepsis.

Abdominal cocoon in a male: rare cause of intestinal obstruction.

Abdominal cocoon, which is characterised by encasement of bowel by a fibrous membrane, is a rare cause of intestinal obstruction. It occurs primarily in females with only three cases reported earlier in males. We report a male patient presenting with small bowel obstruction and detected to have abdominal cocoon at surgery. Incision of thick membrane and lysis of adhesions led to relief of obstruction without any recurrence.

Eosinophilic gastroenteritis presenting as acute intestinal obstruction.

Eosinophilic gastroenteritis is a rare disorder of the gastrointestinal tract. Three cases of eosinophilic gastroenteritis presenting as intestinal obstruction are reported. Two patients had stenotic lesions in the jejunum whereas the ileum was involved in the third. None had peripheral eosinophilia. All underwent resection-anastomosis of the bowel and are symptom-free at follow-up ranging from 8 months to 6 years.

Colovesical fistula complicating colonic diverticulosis.

Two cases of colovesical fistulae secondary to colonic diverticulosis are reported. Urinary symptoms were the prominent presenting features. Barium enema was helpful in documenting the fistulae, which cystoscopically was not localised. Definitive treatment included resection of the fistula and the diseased segment of the intestine. Both patients are well on follow-up. Diverticulosis coli should be considered in the differential diagnosis of colovesical fistulae even in tropical countries.

An audit of pneumatic dilatation and oesophagomyotomy in patients with achalasia cardia.

The role of pneumatic dilatation and oesophagomyotomy in the management of achalasia cardia was evaluated. Twenty patients with achalasia cardia managed either by pneumatic dilatation (n = 10) and oesophagomyotomy (n = 10) were studied. Patients undergoing dilatation were followed up for a mean of 20 months (12-30 months) and those undergoing myotomy for 17 months (6-48 months). The patients were evaluated clinically, radiologically and endoscopically. Relief of dysphagia was excellent in 20%, good in 50% and fair in 30% of those who underwent dilatation. In the myotomy group, 60% had an excellent result, 30% had a good result and fair results was observed in 10%. Oesophagitis on endoscopic evaluation, was found in two patients in myotomy group. The diameter of the gastro-oesophageal junction increased from a mean of 2 mm (range 1 to 4 mm) to a mean of 11 mm (range 4 to 15 mm) in dilatation group while in myotomy group it changed from a mean of 2 mm (range 0.5 to 8 mm) to a mean of 9 mm (range 5 to 15 mm). Symptomatic improvement was better after myotomy than after pneumatic dilatation and correlated poorly with radiological features.

Management of duodenal trauma.

The surgical management of fifteen cases of duodenal trauma is reported. Blunt injury of the abdomen was the commonest mode of injury. Thirteen patients (86.6%) had associated intra-abdominal and/or extra-abdominal injuries. Diagnosis of duodenal injury was made at laparotomy in all patients. In the majority of patients (n = 11), either duodenal repair, or anastomosis with the pylorus or jejunum was done. Duodenal diverticulization or pancreaticoduodenectomy were undertaken in 2 patients each. Feeding jejunostomy was an important adjunct for nutritional support. Septicemia with multisystem organ failure and duodenal fistula were lethal complications. Mortality in the present series was 46.6%.

Long common channel syndrome as etiology of choledochal cysts and pancreatitis--two instructive cases.

The aetiology of choledochal cysts is controversial. The authors report two cases of Type I C and Type IV B choledochal cysts; both showing axial dilatation of the common bile duct and common hepatic ducts, single fusiform (Type IC) and multiple cysts of extrahepatic ducts only (Type IVB). Both had anomalous junction of the pancreaticobiliary ductal system as delineated on ERCP leading to the formation of a long common channel. Both these female patients presented in the third decade of life with 7-8 years history of repeated episodes of right upper abdominal and epigastric pain suggestive of pancreatitis. Similar pain was precipitated in both patients following ERCP with raised serum amylase. Hepatico-enterostomy gave lasting relief in both these patients.