KL-6 mucin expression in carcinoma of the ampulla of Vater: association with cancer progression.

AIM: To assess histochemical expression of KL-6 and its clinicopathological significance in carcinoma of the ampulla of Vater. METHODS: Ampullary carcinoma tissues were collected from 38 patients who underwent pancreatoduodenectomy or local resection. Tissues were subjected to immunohistochemical analysis using KL-6 antibody. RESULTS: Positive staining of ampullary carcinoma cells was observed in 26 (68.4%) cases. Staining was not found in the surrounding non-cancer regions of the ampullary tissues. Remarkable KL-6 expression was observed in invasive carcinoma cells in pancreatic and duodenal tissues and in metastatic carcinoma cells in lymph nodes. Positive KL-6 expression was related to lymph node metastasis (P = 0.020), pancreatic invasion (P = 0.016), duodenal invasion (P = 0.034), and advanced stage of TNM clinical classification (P = 0.010). Survival analysis showed that positive expression of KL-6 was related to a poorer prognosis (P = 0.029). CONCLUSION: The aberrant expression of KL-6 mucin is significantly related to unfavorable behaviors of carcinoma of the ampulla of Vater.

Histochemical expression of sialoglycoconjugates in carcinoma of the papilla of Vater.

BACKGROUND/AIMS: Cell surface glycosylation changes during oncogenesis and is thought to correlate with the malignant potential of cancers. To investigate the role of sialylation in carcinoma of the papilla of Vater, histochemical analyses were performed using sialic acid-binding lectins, Maackia amurensis leukoagglutinin and Sambucus nigra agglutinin. METHODOLOGY: Thirty-six papillary carcinoma tissues and 8 normal papillary tissues were subjected to lectin-histochemical staining. The relationship between lectin staining characteristics and clinicopathological parameters was statistically analyzed. RESULTS: Epithelial cells of glands in normal tissues were stained with Sambucus nigra agglutinin but not with Maackia amurensis leukoagglutinin. Of 36 papillary carcinoma tissues, 20 showed Maackia amurensis leukoagglutinin-positive staining in cancer cells, whereas all 36 were Sambucus nigra agglutinin-positive in cancer cells. According to Maackia amurensis leukoagglutinin-staining characteristics, the 36 cases were divided into two groups: positive (n=20) and negative (n=16). Statistical analysis indicated that positive staining in cancer cells was frequent in cases of lymph node metastasis (p=0.001) and in cases classified > or = T2 by TNM classification (p=0.036). CONCLUSIONS: Aberrant expression of sialoglycoconjugates recognized by Maackia amurensis leukoagglutinin might participate in lymph node metastasis and in an advanced stage of invasion in carcinoma of the papilla of Vater.

Assessment of hepatic reserve for indication of hepatic resection: decision tree incorporating indocyanine green test.

Preoperative assessment of liver function and prediction of postoperative remaining functional liver parenchymal mass and reserve is of paramount importance to minimize surgical risk, especially in patients with hepatocellular carcinoma (HCC), the majority of whom have liver cirrhosis as a complication. We have established a decision tree for deciding the safe limit of hepatectomy based on three variables: whether ascites is present, the serum total bilirubin level, and the indocyanine green retention rate at 15 minutes (ICGR-15), an indicator of sinusoidal capillarization. In patients who show a sign of decompensated cirrhosis as reflected by an elevated bilirubin value or uncontrollable ascites, hepatectomy is not indicated. In patients without ascites and with normal bilirubin level, the ICGR-15 value becomes the main determinant for the resectability and hepatectomy procedure. Incorporation of ICGR-15 into the decision tree enables patients conventionally classified into Child-Turcotte-Pugh class A or score 5-6 to be subdivided into several groups in which various hepatectomy procedures are feasible: enucleation, limited resection, segmentectomy, mono- to bisectoriectomy, and trisectriectomy. During strict application of this decision tree to 1429 consecutive hepatectomies, of which 685 were performed on HCC patients, during the last 10 years, we encountered only a single mortality.

Des-gamma-carboxyprothrombin expression in cancer and/or non-cancer liver tissues: association with survival of patients with resectable hepatocellular carcinoma.

Des-gamma-carboxyprothrombin (DCP), also known as a protein induced by vitamin K absence or antagonist II, is an abnormal prothrombin. The level of serum DCP is used in clinical diagnosis and prognosis of patients with hepatocellular carcinoma (HCC). Our previous immunohistochemical study showed that DCP is expressed not only in cancer tissues but also in the surrounding non-cancer tissues of HCC patients. However, clinical significance of DCP expression in non-cancer tissues of HCC patients remains unclear. In this study, we examined the relationship between histochemical expression of DCP in cancer and/or non-cancer tissues and the clinical outcome of the HCC patients. A retrospective study was performed of 132 patients each with a single primary HCC nodule. Expression of DCP in tissues was evaluated with immunohistochemical staining using anti-DCP antibody (MU-3). Serum DCP levels were determined using enzyme immunoassay with a double antibody sandwich system. Experimental and clinical data were processed by univariate and multivariate statistical analyses. DCP expression, even if it was observed only in non-cancer tissues, was related to poorer prognosis. Univariate and multivariate analyses showed that DCP expression in cancer and/or non-cancer tissues was a significant prognostic factor. Furthermore, the combined evaluation of tissue DCP expression and serum DCP levels showed that prognosis was poorest for patients showing positive tissue DCP expression and high levels of serum DCP. These results suggest that immunohistochemical evaluation of DCP expression not only in cancer but also in non-cancer tissues serves as a valuable factor in the prognosis of HCC patients and that the combined evaluation of tissue DCP expression and serum DCP level will be more valuable than either factor alone in the effective treatment and prognosis.

Single and multiple resections of multiple hepatic metastases of colorectal origin.

BACKGROUND: Indications for hepatectomy in patients with 4 or more hepatic colorectal metastases remain controversial. METHODS: A retrospective cohort study was performed with data from 131 patients who underwent a total of 198 hepatectomies. Patients were grouped according to the number of metastases at the initial hepatectomy (analysis 1) or by the total number of metastases removed by multiple hepatectomies (analysis 2). RESULTS: In analysis 1, the risk ratios for death of patients with 4 to 9 and 10 nodules to those with 1 to 3 nodules were 2.12 (95% CI, 0.99-4.23) and 7.32 (95% CI, 2.82-16.9), respectively. In analysis 2, the risk ratios for death were 1.32 (95% CI, 0.66-2.59) and 3.07 (95% CI, 1.41-6.36), respectively. These values in 106 patients with negative surgical margins were 1.52 (95% CI, 0.51-3.73) and 5.40 (95% CI, 1.25-16.5), and 1.06 (95% CI, 0.45-2.32) and 1.70 (95% CI, 0.49-4.61), respectively. In analysis 2, the 5-year survival rates of patients with 1 to 3, 4 to 9, and 10 or more nodules were 51%, 46%, and 25%, respectively. CONCLUSION: Hepatic resection for patients with 4 to 9 nodules clearly is warranted. On the other hand, for patients with 10 or more tumor nodules, surgery cannot be ensured absolutely to be contraindicated in high volume centers at which the surgical mortality rate is nearly zero.

Pringle's maneuver and selective inflow occlusion in living donor liver hepatectomy.

While inflow occlusion techniques such as Pringle's maneuver are accepted methods of reducing bleeding without inducing liver injury during liver surgery, donor hepatectomy for living donor liver transplantation is currently performed without inflow occlusion for fear that injury to the graft may result. We have performed donor hepatectomy for 12 years using selective intermittent inflow occlusion, a technique in which the portion used to form the graft is perfused during hepatectomy. Starting in November 2000, we applied intermittent Pringle's maneuver to donor hepatectomy in 81 cases of living donor liver transplantation. We reviewed our experience with Pringle's maneuver and selective inflow occlusion techniques in donor hepatectomy in living donor liver transplantation. The quality of the grafts was assessed and compared by determining maximum postoperative aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values. Neither primary nonfunction nor dysfunction occurred. Maximum AST values in the recipients were the same whether the liver segments that formed the grafts were totally ischemic during dissection (total ischemia), partially ischemic (partial ischemia), perfused only with arterial blood flow (portal ischemia), or not ischemic at all (no ischemia). Maximum ALT values in the recipients of the total ischemia group was lower, albeit not significantly, than in other groups. Total inflow occlusion can be applied to living donor hepatectomy without causing graft injury. In conclusion, because the transection surface is blood-free, there is decreased risk to the donor during living donor liver transplantation surgery, and surgeons should not hesitate to apply this technique because it contributes to donor safety.

The repeated hepatectomy for frequent recurrence of hepatic metastasis from gastrointestinal stromal tumor of the stomach.

Although in recent years hepatic resection has become a safe procedure, there are few data on repeat liver resection for hepatic metastases from gastrointestinal stromal tumor. A 60-year-old Japanese man underwent partial gastrectomy and extended right hepatectomy for gastrointestinal stromal tumor of the stomach with liver metastasis. However, liver metastasis recurred at the interval of less than 1 year. Therefore, the patient underwent a total of six liver resections. The liver resections comprised four R0, one R1 and one R2 resection. To our knowledge, six times for liver resection performed on one patient is a maximum. This patient survived 43 months after the first surgery. Despite frequent recurrence of hepatic metastasis from gastrointestinal stromal tumor, repeated hepatectomy provides a survival benefit if complete removal of all tumorous masses appears possible.

Pringle's manoeuvre in living donors.

The safety of the donor is paramount in living donor liver transplantation. The most important risk to the donor during hepatectomy is bleeding, and the inflow occlusion technique (Pringle's manoeuvre) has been reported to decrease bleeding without inducing liver injury in liver surgery. However, most transplant centres are doing donor hepatectomies without this technique for fear that it would result in ischaemic injury to the graft. We have done 46 living donor hepatectomies with Pringle's manoeuvre without any negative outcome on the quality of the graft. Surgeons should not hesitate to apply this technique in living donor hepatectomy.