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Biomedical subjects

B C Das

Publications and source records attributed to B C Das.

At least 19 recordsLinked to original sources

Telomerase activity as an adjunct to high-risk human papillomavirus types 16 and 18 and cytology screening in cervical cancer.

Telomerase is a ribonucleoprotein comprising an RNA template, the telomerase-associated protein and its catalytic subunit, human telomerase reverse transcriptase (hTERT). Telomerase activation is a critical step in cellular immortalisation and development of cancer. Enhanced telomerase activity has been demonstrated in cervical cancer. In the present study telomerase activity and hTERT mRNA expression were evaluated and correlated with the presence of human papillomavirus (HPV) infection and cytological changes in the cervical lesions. Telomerase activity was assayed by telomeric repeat amplification protocol, hTERT mRNA expression by reverse transcriptase polymerase chain reaction and presence of high risk HPV (HR-HPV) infection by polymerase chain reaction. Out of 154 cervical samples of different cytology, 90 (58.44%) were positive for HR-HPV types 16/18, while among 55 normal cervical scrapes, 10 (18.18%) were HPV DNA positive. All 59 invasive cancer samples showed a very high telomerase activity. Among dysplasia, seven (63.6%) mild dysplasia, 18 (100%) of moderate, 20 (100%) of severe dysplasia and 6 (100%) carcinoma in situ (CIS) samples were positive with mild to moderate to high to very high telomerase activity respectively. Seven (12.7%) samples of apparently normal cervical scrapes were weakly positive for telomerase activity. We observed a good correlation (P<0.001) between telomerase activity and HR-HPV 16/18 positivity with a sensitivity of 88.1% for HPV and 100% for telomerase activity. It is suggested that telomerase activity may be used as an adjunct to cytology and HPV DNA testing in triaging women with cervical lesions.

DNA, Viral↗

BRCA1 and TP53 mutation spectrum of breast carcinoma in an ethnic population of Kashmir, an emerging high-risk area.

Breast cancer shows geographical variation in its incidence, even within areas of ethnic homogeneity. Kashmir valley (India), over past few years, witnesses an increase in incidence and occurrence of familial, early onset, and male breast cancer in its unexplored ethnic population. Here, we make a preliminary attempt to estimate the nature and frequency of BRCA1 and TP53 gene mutations of breast cancer patients from Kashmir. PCR-SSCP analysis followed by direct sequencing revealed the presence of only two germline intronic variations (c.199+67T>C and c.5396+187T>C) in BRCA1 gene in only 5.26% (2/38) patients while as 44% (11/25) of sporadic breast cancer patients harboured significant amount of somatic mutations in TP53 (p=0.0074; OR=0.053). The 17 mutations found in TP53 in 11 patients, comprised of 13 substitutions [11 single-base (9 transitions+2 transversions), 1 double-base and 1 complex] and four insertions. The 11 substitutions represent missense mutations, leading to aminoacid substitution while as rest two were silent mutations. The four insertions represented three frame-shifts and one non-sense mutation. The mutation effect data was found to be significant (p=0.0002). Significant amount of mutations were found in exon 6 (p=0.04; OR=0.273) and a combination of exons 6 and 7 (p=0.0145; OR=14.22) of TP53. Comparison of mutation profile with other ethnic populations and regions reflected both differences and similarities indicating co-exposure to a unique set of risk factors. The differences could be due to exposure to particular environmental carcinogens; different lifestyle, reproductive pattern; dietary or cultural practices of Kashmiri women that need further investigations. The infrequent presence of germline BRCA1 mutations in our study agree with the idea that a great proportion of moderate risk breast cancer population could be due to the susceptibility genes distinct from BRCA1. However, high frequency of somatic TP53 gene mutations implicates TP53 as a predominant factor for breast carcinogenesis in moderate risk ethnic Kashmiri population. The study also suggests TP53 as a potential molecular marker and prognostic tool, at least in a subset of sporadic breast tumors.

Adult↗

Genetic polymorphism at GSTM1 and GSTT1 gene loci and susceptibility to oral cancer.

GSTs are phase II enzymes which are involved in the detoxification of active metabolites of many potential carcinogens from tobacco smoke and therefore may play an important role in modulating susceptibility to tobacco related cancers. This study evaluates the influence of genetic polymorphisms of GSTM1 and GSTT1 gene loci on susceptibility to oral cancer. The genotyping was based on multiplex PCR assay that identified the GSTM1 and GSTT1 null (-/-) genotypes but didn't distinguish homozygous wild type+/+ and heterozygous +/- individuals. Genomic DNA was isolated from cases with oral cancer (n=40) and normal controls (n=87). The prevalence of the GSTM1 null genotypes was 29/87 (33.3%) and 21/40 (52.5%) in controls and oral cancer cases, respectively but the differences were not significant (OR=2.2; 95%CI=0.96-5.1; p=0.06). The frequency of homozygous GSTT1 null genotype in cancer cases was 17/40 (42.5%) as compared to 13/87 (14.94%) in controls and the differences were highly significant (OR=4.2; 95%CI=1.64-10.9; p=0.0002). Oral cancer cases had higher proportion of both GSTM1 and GSTT1 null genotypes as compared to controls but the differences were not statistically significant (OR=2.9; 95%CI=0.71-11.9; p=0.17). When individuals were categorized into two groups, no differences were observed for GSTM1 null genotype frequencies in control and cancer cases (OR=2.9; 95%CI=0.9-9.6; p=0.08) (OR=1.6; 95%CI=0.44-6.1; p=0.58) in <=50 yrs and >50 yrs of age groups. Significant differences between control and cancer cases were observed for GSTT1 null genotypes both in <=50 yrs and >50 yrs of age groups (OR=4.0; 95%CI=1.1-15.0; p=0.03) (OR=4.5; 95%CI=0.97-22.29; p=0.05), respectively. The effect of smoking on GSTM1 null individuals was not found significant (OR=1.0; 95%CI=0.19-4.86; p=0.75) but it was significant in case of GSTT1 null individuals (OR=6.33; 95%CI=1.0-44.1; p=0.02). Our results thus suggest that GSTT1 gene polymorphisms modulate susceptibility to tobacco-related cancer of the oral cavity.

Adolescent↗

Human papillomavirus (HPV) DNA detection in self-collected urine.

OBJECTIVE: Non-invasive sampling of human genitals to identify high-risk individuals with subclinical oncogenic HPV infection remains a challenge. The study was designed to see if self-collected urine can be used as a simple, non-invasive sampling for screening HPV, particularly for screening/monitoring general population or young adolescents or infants, if they are to be immunized by HPV vaccines. METHOD: Self-collected urine samples from 100 sexually unexposed college going girls and cervical scrapes from 104 normal healthy sexually active married women were used in this study. Additionally, a group of 55 women were recruited for collecting first urine and later scraped cervical cells to validate urine sampling by directly comparing HPV positivity between the two types of biological specimens. A dry 'paper smear' method for specimen collection and a simple single tube protocol was employed for PCR detection of HPV infection. RESULTS: Out of 100 sexually inexperienced college going girls, only 6 (6%) were positive for HPV infection as revealed by L1 consensus primer and 4 (4%) of them were positive for HPV 16 but none was found positive for HPV 18 DNA. Out of 104 sexually active married women who were cytologically reported as negative by Pap test, 11 (10.5%) were found HPV positive and 7 (6.7%) of them had infection of high-risk HPV type 16. Both urine and later cervical scrapes from a group of 55 women collected as dry 'paper smear' showed perfect matching positivity for HPV between urine and cervical scrape. CONCLUSIONS: The use of urine coupled with its dry collection as 'paper smear' facilitating their easy transport, storage and direct PCR detection of HPV DNA opens up an alternative non-invasive approach for population screening of HPV infection, at least in such cases as children and infants in whom invasive samples are difficult to obtain.

Adolescent↗

Presence of TT virus infection in chronic hepatitis patients from a hospital in New Delhi, India.

BACKGROUND & OBJECTIVE: The recent discovery of a novel parenterally transmitted, unenveloped, single-stranded DNA virus called TT virus (TTV) in chronic hepatitis patients with unclear pathogenesis throughout the world led us to investigate, its presence in chronic hepatitis patients attending a hospital in New Delhi, India, and to evaluate its role in liver disease. METHODS: TT virus DNA was investigated in serum samples of 70 patients with various types of chronic hepatitis, and 100 healthy subjects from New Delhi, India by nested PCR using the primers that belonged to UTR (A) region of the genome. RESULTS: TTV DNA was detected in 6 of 23 patients (26%) with type B chronic hepatitis, 3 of 20 patients (15%) with type C chronic hepatitis, and 12 of 100 subjects (12%) from healthy control group with normal liver function profile tests. None of the 27 non-B, non-C chronic hepatitis patients had TTV DNA positivity. The prevalence of TTV was significantly higher in type-B chronic hepatitis patients as compared to normal subjects (P< 0.05) but comparable to type C chronic hepatitis patients. The clinical course and biochemical profiles of type B, or type C chronic hepatitis patients co-infected with TTV did not differ significantly from those without TTV infection. INTERPRETATION & CONCLUSION: Interestingly, in chronic hepatitis patients, TTV was always associated with either hepatitis B or C virus indicating a likely parenteral route of transmission. All TTV-positive subjects in healthy control group showed normal clinical and biochemical profiles. Thus, the presence of TTV infection is unlikely to influence the course of chronic hepatitis related to hepatitis B virus (HBV) or hepatitis C virus (HCV) or cause liver diseases in healthy subjects.

Case-Control Studies↗

Studies on sodium and potassium metabolism and subsequent influence on electrocardiogram in unilaterally adrenalectomized black Bengal goat (Capra hircus).

Unilateral adrenalectomy was performed in six black Bengal goat (Capra hircus)to study electrocardiograph in connection with mineral metabolism with special reference to sodium and potassium and some other factors of physiological importance. The parameters were studied at every 12 hrs interval upto 120 hrs and 24 hrs interval from 120 to 240 hrs. Physiological parameters, like body weight and rectal temperature, changed non-significantly (p < 0.05) after adrenalectomy. Among minerals, plasma sodium (p < 0.01) and plasma potassium (p < 0.05) concentration were changed significantly between hours leaving impression in ECG as widening of QRS complex and peaked T wave with increased amplitude found after unilateral adrenalectomy. Heart rate also increased significantly (p < 0.01) between hours.

Adrenalectomy↗

Two new novel point mutations localized upstream and downstream of the HMG box region of the SRY gene in three Indian 46,XY females with sex reversal and gonadal tumour formation.

The Y chromosome-specific gene SRY is one of the key genes involved in human sex determination. The SRY gene encodes a testis-specific transcription factor that plays a key role in sexual differentiation and development in males and is located on the distal region of the short arm of the Y chromosome. Mutations in SRY gene result in XY sex reversal and pure gonadal dysgenesis. SRY expression initiates a network of gene activity that transforms the undifferentiated gonad, genital ridge into testis. Mutations in the SRY gene have been considered to account for only 10-15% of 46,XY gonadal dysgenesis cases, whereas the majority of the remaining cases may have mutation(s) in the SRY regulatory elements or other genes involved in the sex differentiation pathway. Patients both with gonadal dysgenesis and Y-chromosome presence are at high risk of developing gonadoblastoma. Using PCR, single strand conformational polymorphism (SSCP) and automated DNA sequencing, we analysed the mutations in the SRY gene in three 46,XY sex reversal patients. Two patients demonstrated nucleotide substitution (A-->G) within the open reading frame just outside and upstream of the conserved DNA-binding motif called the high-mobility group (HMG) box, replacing glutamine at codon 57 with arginine. Altered SSCP patterns were also observed in these patients. Histological examination of gonads in patient 1 revealed the formation of gonadoblastoma. Patient 3 demonstrated A-->T substitution which replaces serine at codon 143 with cysteine, just outside but downstream of the HMG box. Results suggest the involvement of SRY gene in sex reversal which further supports the relationship between SRY alterations, gonadal dysgenesis and/or primary infertility.

Adult↗

Role of transfusion-transmitted virus in acute viral hepatitis and fulminant hepatic failure of unknown etiology.

BACKGROUND AND AIM: The role of the newly described transfusion-transmitted virus (TTV), a circular single-stranded DNA virus, has been investigated in acute liver disease, comprising 36 patients with acute viral hepatitis (AVH) and 25 with fulminant hepatic failure (FHF), including 50 volunteer blood donors as controls. METHODS: Detection of TTV DNA sequences was carried out by polymerase chain reaction (PCR) using primers derived from the UTR(A) region of the TTV genome. The clinical course and biochemical profile when infected with TTV alone or coinfected with other classical hepatotropic viruses were analyzed. All patients were first evaluated for liver function profile and for the presence of various hepatotropic viruses using serological tests and PCR in serologically negative patients. RESULTS: Transfusion-transmitted virus DNA was detected in 80.6% (29/36) of the AVH cases and in 76% (19/25) of the FHF cases, which were significantly higher levels (P < 0.05) than the 52% (26/50) observed in volunteer blood donors. No significant difference in symptoms, clinical course, liver function and risk factor profile between TTV-positive and TTV-negative patients could be observed in both AVH and FHF patients. TTV was found to coexist with both parenterally and non-parenterally transmitted hepatotropic viruses in similar frequency in both AVH and FHF patients. Further, there was no significant difference in the mortality rates between TTV-positive and TTV-negative FHF patients. Also, there was no difference between patients coinfected by TTV and other hepatotropic viruses and those with TTV infection alone. CONCLUSION: Thus, it appears that TTV, although it exists in a very high frequency in the Indian population, appears to have no significant etiological role in AVH and FHF.

Acute Disease↗

Predominance of Chlamydia trachomatis serovars associated with urogenital infections in females in New Delhi, India.

Screening for Chlamydia trachomatis was done for 280 endocervical swab samples by PCR specific for endogenous plasmid. Age dependency was seen in symptomatic patients, with a high chlamydial prevalence rate (28%) found in younger women. Genotyping by restriction fragment length polymorphism analysis of omp1 PCR-positive samples showed serovars D, E, and F to be the most prevalent.

Adolescent↗

Evaluation & management of clinically labeled carcinoma head of the pancreas--a prospective study of 60 patients.

Carcinoma head of the pancreas are assessed by clinical examination, imaging, Endoscopic Retrograde Cholangio Pancreatography (ERCP), Fine Needle Aspiration Cytology (FNAC) and finally by laparotomy. Nevertheless still there is a dilemma in labeling these patients as having inoperable cancer pancreas because operable lesions may be wrongly labeled as inoperable or benign lesion may be thought to be malignant. The aim of this study is to evaluate these patients who present with clinical features of inoperable carcinoma of pancreas and to assess their status of inoperability. Efforts were taken to explore the possibilities of curative resection. If found inoperable, then tissue or cytological sampling of the lesion and the alternative palliation therapy offered to them. Palliative surgery and respective analysis of data was done in 60 patients with clinically labeled carcinoma head of the pancreas. Laparotomy was done for--(i) Assessment of inoperability, (ii) tissue or cytological sampling and (iii) Bilioenteric and gastro enteric bypass. The tumor was considered to be inoperable by peroperative assessment & trial dissection when it invaded the surrounding vital structure. Histological confirmation was made by intraoperative core needle biopsy; shave biopsy, biopsy of hepatic and lymph node metastasis. Cytological sampling was done by transduodenal and intralesional FNAC. Hepaticojejunostomy or Cholecystojejunostomy, Gastrojejunostomy and enteroenterostomy were performed as palliative procedure in all patients. Chemical splanchinectomy was performed in 25 patients. Twenty patients were diagnosed to have carcinoma by Endoscopic biopsy. In remaining 40 patients, peroperative tissue biopsy and cytological sampling yielded pancreatic carcinoma in 16 (40.0%), chronic pancreatitis in 6 (15.0%), pancreatic tuberculosis in 5 (12.5%), pancreatic non Hodgkin's lymphoma in 3 (7.5%) and metastatic pancreatic cancer in 2 (5.0%). However, it failed to reveal any definitive diagnosis in 8 (20.0%) patients. These interesting findings changed the preoperative diagnosis and guided us to plan the surgical procedure for cancerous and non-cancerous patients accordingly.

Aged↗

Analysis of 100 consecutive hepatectomies: risk factors in patients with liver cirrhosis or obstructive jaundice.

We analyzed various pre-, intra-, and postoperative variables in 100 consecutive patients treated by hepatectomy for various malignant and benign liver diseases to identify patients at risk of developing postoperative complications. Patients were divided into three groups: those with normal liver (NL, n = 53); those with liver cirrhosis (LC, n = 32); and those with obstructive jaundice (OJ, n = 15). The overall postoperative morbidity and mortality rates were 14% and 4% (due to liver failure), respectively. In the LC group the combined presence of abnormal levels of serum hyaluronic acid (HA, > 200 ng/ml), indocyanine green retention rate at 15 minutes (ICGR15, > 15%), and hepatic uptake ratio of (99m)Tc-galactosyl human serum albumin (GSA) at 15 minutes (LHL15, < 0.9) preoperatively was found to be a risk factor with a 100% morbidity rate. Operative blood loss of more than 1000 ml in LC patients was associated with high morbidity. In the OJ group preoperative parameters were almost normal after biliary drainage, but the extent of liver resection, blood loss > 2000 ml, and high serum interleukin-6 12 hours after hepatectomy correlated with high postoperative morbidity. No morbidity or mortality was reported in the NL group, except in a single patient who received long-term intraarterial chemotherapy preoperatively. Consequently, the extent of hepatectomy should be carefully determined according to the preoperative risk factors in LC patients; and in OJ patients hepatectomy, which tends to become extensive, should be carefully performed to minimize surgical stress because preoperative factors do not help predict outcome. Furthermore, the present study revealed that a serum HA level higher than 500 ng/ml on postoperative day 1 or day 7 (or both) was a useful marker for hepatic failure.

Adult↗

Surgical treatment of pancreatic cancer. Does extended lymphadenectomy provide a better outcome?

The rate of curative resection of pancreatic cancer has increased as a result of extended operations, but this has not led to any significant improvement in postoperative outcome. No definite conclusions were drawn in retrospective studies comparing outcome after standard and extended operations, and there was almost no difference in outcome between the two groups in a recent prospective randomized study. In addition, extended procedures are very stressful operations that, in most instances, impair the patient's quality of life (QOL). As a result, the need for performing extended surgery to treat pancreatic cancer has come into question. The outcome of advanced cancer in patients in whom curative resection cannot be achieved by extended operations is extremely poor, and we believe that, in such patients, priority should be given to QOL, by selecting bypass or limited operations instead. It is hoped that the value of extended surgery will be clarified by a very carefully planned multicenter prospective randomized study in the future.

Adenocarcinoma↗

Profile of hepatocellular carcinoma in India: an insight into the possible etiologic associations.

BACKGROUND: Several etiologic factors including hepatitis viruses, alcohol and aflatoxin have been implicated in the pathogenesis of hepatocellular carcinoma (HCC). There is, however, limited information from the Indian subcontinent. METHODS: Seventy-four consecutive cases of HCC were studied. A detailed history, tests for hepatitis B virus (HBV; HBsAg, HBeAg, anti-HBe, IgG anti-HBc, anti-HBs and HBV-DNA), hepatitis C virus (HCV; anti-HCV and HCV-RNA) infection, liver histopathology and HBV-DNA integration by using Southern blot hybridization were studied. A p53 gene mutation was also studied by using PCR and single-strand conformation polymorphism. RESULTS: Hepatocellular carcinoma patients were predominantly males (mean age 49.5 +/- 14.0 years). Portal hypertension and cirrhosis were seen in 56 (76%) patients, more often (P < 0.05) in viral marker positive cases. Forty-five percent of patients had features of hepatic decompensation at presentation. Evidence of HBV infection was present in 53 (71%) patients. Twenty-six (49%) of these patients had either HBeAg + ve, HBV-DNA + ve (n = 12), or HBsAg - ve, HBV-DNA + ve (n = 14) forms of HBV infection. Hepatitis B virus DNA integration in the liver tissue was seen in 10 of 17 (59%) patients. Infection with HCV alone was detected in three (4%) and dual HBV and HCV infection in six (8%) patients. A majority (78.5%) of the chronic alcoholics had associated viral infection. The etiology of HCC remained undetermined in 15 (20%) patients. The p53 gene mutations were detected only in three of 21 (14%) liver tissues. Aflatoxin toxicity, oral contraceptive use or metabolic disorder were not seen. CONCLUSIONS: In India: (i) HBV infection is the predominant factor for the development of HCC, often related to mutant forms of HBV; (ii) a majority of the HCC patients have overt cirrhosis of the liver; and (iii) HCV and alcohol per se are uncommonly associated.

Aflatoxin B1↗

P53 tumor suppressor gene mutations in hepatocellular carcinoma patients in India.

BACKGROUND: Specific mutations of the p53 tumor suppressor gene in hepatocellular carcinoma (HCC) have been reported from several parts of the world, but to the authors' knowledge to date the status of this gene has not been studied in HCC patients in India, where HCC is one of the major cancers and the frequency of chronic hepatitis B virus (HBV) as well as hepatitis C virus (HCV) infection and exposure to dietary aflatoxin B(1) is very high. The most frequent mutation of the p53 gene in HCC is an AGG(Arg) to AGT(Ser) missense mutation at codon 249 of exon 7. METHODS: Liver biopsy specimens from 21 HCC patients and 10 healthy controls were obtained through surgery or by needle biopsy technique. Phenol-chloroform-extracted DNA specimens were employed for the detection of HBV infection and p53 gene mutations. Nucleotide mutations of exons 4-9 of the p53 gene were analyzed by polymerase chain reaction (PCR), single strand confirmation polymorphism, and direct sequencing. Third-generation sandwich enzyme-linked immunosorbent assay (ELISA) was used for the serologic detection of HBV and HCV infection. RESULTS: Analysis of exons 4-9 of the p53 gene revealed only 3 mutations (3 of 21 specimens, 14.28%; 95% confidence interval, -0.7-29.3), 2 mutations at codon 249 showing G-->T transversions, and 1 mutation (4.7%) at codon 250 with a C-->T transition. The base substitutions at the third base of codon 249 resulted in a missense mutation leading to a change in amino acid from arginine to serine whereas at codon 250 it caused a change from proline to serine. Dot blot hybridization and PCR for HBV DNA from HCCs revealed 58.8% (10 of 17 specimens) and 90. 47% (19 of 21 specimens), positivity, respectively. ELISA for hepatitis B virus surface antigen in serum showed a positivity of 71. 42% (15 of 21 specimens), but there was only 40% positivity (8 of 20 specimens) for hepatitis B virus envelope antigen whereas 6 of 17 patients (35.29%) showed the presence of antibodies against hepatitis B virus envelope protein. No patient was found to be positive for the HCV antibody. CONCLUSIONS: The very low frequency of p53 mutations and the extremely high frequency of HBV infection (> 90%) in HCC indicate that the mutations in the p53 gene frequently found in HCC reported from different endemic areas of the world may not play a direct role in the development of HCC in India. HBV infection and, possibly, exposure to the dietary aflatoxin B(1) appear to play major roles in the molecular pathogenesis of HCC in India.

Adolescent↗

Anatomy of the hepatic hilar area: the plate system.

To surgically manage hilar bile duct carcinoma successfully, it is important to be familiar with the principal anatomical variations of the biliary and vascular components of the plate system in the hepatic hilar area, because all the variations in the bile ducts and vessels occur in the plate system. The plate system consists of bile ducts and blood vessels surrounded by a sheath. There are three plates in the hilar area: the hilar plate, the cystic plate, and the umbilical plate. The bile duct and blood vessel branches penetrate the plate system and form Glisson's capsule in all segments of the liver, except for the medial segment. The right hepatic duct is usually (in 53%-72% of individuals) formed by the union of the anterior segmental duct and the posterior segmental duct in the hilar area. However, three other variations have been found in which these segmental ducts do not form the right hepatic duct. Few anatomical variations have been identified in the left hepatic duct, but confusion arises because of the variations in the medial segment ducts (B4) which join the left hepatic duct at different sites. In 35.5% of individuals they join the hepatic duct in the vicinity of the hilar confluence (type I B4 anatomy), and in 64.5% of individuals they join the left hepatic duct some distance away from the confluence (type II B4 anatomy). Because B4 is very close to the hilar confluence in type I, hilar bile duct carcinoma can easily invade B4 and, for that reason, for curative resection of hilar bile duct carcinoma, resection of S4a (the inferior part of the medial segment) should be considered along with the resection of extrahepatic bile duct and caudate lobe. Variations in the portal vein and hepatic artery are found in 16%-26% and 31%-33% of individuals, respectively. Because a considerable number of anatomical variations in the bile ducts and vessels persist in the hilar area, and the reported proportions of the different variations vary, it is necessary to have a good knowledge of the plate system and the variations in the bile ducts and blood vessels in the hilar area to perform safe and curative surgery for hilar bile duct carcinoma.

Bile Ducts↗

Surgical anatomy of the bile duct branches of the medial segment (B4) of the liver in relation to hilar carcinoma.

In some patients, hilar bile duct carcinoma can easily spread to the bile duct branches of the caudate lobe (B1) as well as to the bile duct branches of the medial segment (B4), and resection of the inferior portion of the medial segment (S4a) is then required. It is therefore important to understand the detailed anatomy of the B4, its confluence patterns, and its relation to the B1 in order to be able to identify such patients. The confluence pattern of the B4 was studied in 141 specimens (68 adult cadavers and 73 liver casts) and the distance between the left bile duct branches of the caudate lobe (B11) and the B4 was measured in 56 of the 73 casts in which both B11 and B4 were present. Two main gross types of B4 were recognized: type I, in which B4 joined the left hepatic duct (LHD) close to the hilar confluence (35.5%), and type II, in which B4 joined the LHD far from the hilar confluence (54.6%). Analysis of the relationship between B11 and B4 revealed a mean distance between B11 and B4 of 8 mm in type 1, and 17 mm in type II. When the distance is less than 10 mm, B11 and B4 are considered to be located very close to each other, and in such individuals hilar bile duct carcinoma can infiltrate the B4 easily, thereby necessitating the resection of S4a, together with a caudate lobectomy for curative resection. Also, the confluence pattern of the B4 often creates a problem when the LHD is divided and reconstructed during hepatectomy, because of the numerous anatomical variations of the B4 itself. We therefore concluded that a good anatomical knowledge of the B4 and its relation to the B11 is essential in making the decision to perform S4a resection in selected patients with hilar bile duct carcinoma with the aim of curative resection.

Adult↗