Hirokazu Noshiro

Surgical treatment of patients with T2 gallbladder carcinoma invading the subserosal layer.

BACKGROUNDnBecause T2 carcinoma of the gallbladder that invades perimuscular connective tissue without extension beyond serosa or into the liver has a hope for longterm survival, we attempted to clarify significant prognostic factors with respect to tumor- and surgery-related variables.nnnSTUDY DESIGNnOf 65 patients with gallbladder carcinoma who had undergone surgical resection from 1983 to 1999, 28 had T2 carcinoma histologically proved. The significance of variables for survival was examined by the Kaplan-Meier method and log-rank test followed by multivariate analyses using Coxs proportional hazard model.nnnRESULTSnThere were 17 patients with stage II carcinoma (T2 N0 M0), 6 with stage III (T2 N1 M0), and 5 with stage IVB. Lymph node metastasis was present in 11 patients (39%) and it reached to the peripancreatic head region (N2) in 5 of them. Lymphatic, venous, and perineural invasions were found in 68%, 57%, and 43%, respectively. With respect to tumor factors, the absence of perineural invasion (Odds ratio [OR] 16.77, 95% confidence interval [CI] 2.17-129.94, p = 0.0069), absence of lymph node metastasis (OR 15.00, 95% CI 2.08-108.33, p = 0.0073), and stage II (II versus III and IVB, OR 15.00, 95% CI 2.08-108.33, p = 0.0073) were significant factors related to good postoperative survival in the multivariate analysis. Surgical procedure (radical resection versus cholecystectomy, OR 4.31, 95% CI 1.34-13.82, p = 0.0142) and surgical margin (OR 7.41, 95% CI 2.19-25.13, p = 0.0013) were significant factors in the univariate analysis. Cancer-free surgical margins provided a significantly better survival (5-year survival rate, 62%); none with cancer-positive surgical margins survived for more than 27 months. In the multivariate analysis, surgical procedure was significant (OR 25.49, 95% CI 1.62-400.72, p = 0.021). Radical surgery, including extended cholecystectomy (resection of the gallbladder together with the gallbladder bed of the liver) and anatomic resection of liver segment 5 and of the lower part of segment 4, gave a significantly better 5-year survival rate than cholecystectomy (59% versus 17%). The 5-year survival rate after radical resection in patients with stage II was 75%; that in patients with stage III and IVB was 33%.nnnCONCLUSIONSnResults suggest that radical surgery is the treatment of choice for patients with T2 carcinoma of the gallbladder. The presence of lymph node metastasis, perineural invasion, or both suggests the necessity of additional treatment after radical surgery.

Laparoscopically assisted distal gastrectomy with standard radical lymph node dissection for gastric cancer

BackgroundLaparoscopically assisted distal gastrectomy (LADG) with limited lymph node dissection (D1+alpha) has been used to treat a subset of patients with early gastric cancer. Technical advances have expanded indications for LADG to more advanced gastric cancers. However, little data are available on the feasibility or advantages of LADG with standard radical D2 lymph node dissection for patients with gastric cancer.MethodsThis study reviewed the clinical features of 37 patients who underwent LADG with D2 lymph node dissection for preoperatively diagnosed gastric carcinoma, then compared the results with the features of 31 patients who underwent conventional open distal gastrectomy (ODG) with D2 lymph node dissection.ResultsThe laparoscopic procedure was not converted to laparotomy in any patient. There was no operative mortality and no serious morbidity among the patients who underwent LADG with D2 lymph node dissection. As compared with the ODG group, the LADG group had less operative blood loss (p < 0.001), earlier recovery of bowel activity (p = 0.012), and a shorter duration of fever after surgery (p = 0.015), despite the longer operation time (p = 0.007).ConclusionsAccording to this study, LADG with D2 lymph node dissection is feasible and provides several advantages similar to those of limited lymph node dissection (D1+alpha). Depending on surgeons’ technical proficiency, LADG can be used with standard radical lymph node dissection for patients with gastric cancers.

Laparoscopic gastric surgery in a Japanese institution: analysis of the initial 100 procedures

BACKGROUNDnAlthough endoscopic surgical procedures are popular in various fields, reports on its use in gastric surgical procedures are limited. This study was designed to review our initial experience with laparoscopic gastric surgical techniques to evaluate indications and surgical results.nnnSTUDY DESIGNnWe undertook a retrospective analysis of 100 patients (66 men and 34 women, mean age 63 years) who underwent laparoscopic gastric surgical procedures between 1995 and 2001. Procedures performed were distal gastrectomy (n = 76), wedge resection (n = 20), and intragastric surgical procedures (n = 4). Patients were divided into two groups according to the date of the procedure, from the earliest to the most recent.nnnRESULTSnThere were 85 patients with gastric cancers, 14 submucosal tumors, and 1 duodenal ulcer. In 8 cases conversion was made to an open surgical procedure. Operation times required for distal gastrectomy, wedge resection, and intragastric surgical procedures were 330 +/- 69, 144 +/- 34, and 298 +/- 106 min, and blood loss was 354 +/- 251, 56 +/- 94, and 33 +/- 58 g, respectively. Complications included transient anastomotic stenosis (n = 5), leakage (n = 4), and bleeding (n = 1) after distal gastrectomy, and bleeding (n = 1) after intragastric surgical procedures. There were no complications after wedge resection. Comparing the first and second halves of the series, the percentage of distal gastrectomy significantly increased from 66% to 86% (p = 0.02) and the number of dissected lymph nodes at this procedure increased from 20 +/- 13 to 33 +/- 17 (p < 0.01).nnnCONCLUSIONSnLaparoscopic gastric surgical procedures are safe and feasible for early gastric cancers and submucosal tumors. Technical advances in lymph node dissection have made distal gastrectomy a leading and increasingly popular laparoscopic procedure for early gastric cancer.

Completion radical surgery after cholecystectomy for accidentally undiagnosed gallbladder carcinoma

Survival time of 73 patients with undiagnosed gallbladder carcinoma incidentally found after cholecystectomy treated between 1982 and 2000 was evaluated in relation to various variables, with special reference to the significance of the radical second resection. The most significant prognostic factor was the depth of tumor invasion as assessed by univariate and multivariate analyses (odds ratio 3.40, 95% CI 1.65–7.00, p < 0.001). None of the 23 pT1 patients received radical second resection, and all of them were doing well without recurrence at their last follow-up examination. The 3-year survival rate was 68% for patients with pT2 and 14% for patients with pT3. Patient characteristics for the 18 pT2 patients who underwent radical second resection were similar to the characteristics of the 25 pT2 patients who did not; nor did postoperative survival times differ significantly. Survival time was not correlated with the interval from initial to second surgery or the type of initial cholecystectomy (open vs laparoscopic). In 11 patients with pT2 whose surgical margin was judged positive at initial cholecystectomy, the radical second resection significantly lengthened survival time. Radical second resection tended to prolong the median survival period from 7 to 15 months in 7 patients with pT3, although the difference was not significant. In conclusion, patients with pT1 undiagnosed carcinoma need no further treatment. The redo surgery was found to prolong survival only in patients with pT2 with positive surgical margin at initial cholecystectomy.

Mucinous cystic neoplasm of the pancreas or intraductal papillary-mucinous tumour of the pancreas

OBJECTIVEnTo compare clinicopathological findings in patients with mucinous cystic neoplasms and intraductal papillary-mucinous tumours.nnnDESIGNnRetrospective study.nnnSETTINGnUniversity department of surgery, Japan.nnnSUBJECTSn21 patients with mucinous cystic neoplasms (group 1) and 48 with intraductal papillary-mucinous tumours (group 2).nnnRESULTSnThe mean age was younger in group 1 (53(3.4) years) than in group 2 (65(1) years, p < 0.0001). The male:female ratio was smaller in group 1 than in group 2, being 0.17 (3/18) and 1.4 (28/20), respectively, (p = 0.0007). The main sites of the lesions were also significantly different: in group 1 four (19%) were located in the head and 17 in the body or tail, while 32 (67%) were in the head of the pancreas and 16 (33%) in the body or tail in group 2 (p = 0.0007). A unique endoscopic finding, excretion of mucin from the patulous orifice of the papilla, was present in two (9%) of the 21 mucinous cystic tumours and in 21 (45%) of the 47 intraductal papillary-mucinous tumours examined (p = 0.006). Metachronous or synchronous malignant diseases were found in the pancreas or other organs in one (5%) of the 21 patients with mucinous cystic neoplasm and in 13 (27%) of the 48 with intraductal papillary-mucinous tumours (p = 0.03). The three- and five-year survival rates of 11 patients with mucinous cystadenocarcinoma were 45% and 27%, while those of 15 with intraductal papillary-mucinous carcinoma were 85% and 42%.nnnCONCLUSIONSnThese findings suggest that mucinous cystic neoplasm and intraductal papillary-mucinous tumours are different clinicopathological entities. Aggressive surgery with peripancreatic lymph node dissection is recommended, particularly for mucinous cystadenocarcinoma, and postoperative follow-up with attention given to the presence of other malignancy is necessary as well as to local recurrence and haematogenous spread.

Role of surgery for gallbladder carcinoma with special reference to lymph node metastasis and stage using western and Japanese classification systems.

Abstract. The role of radical resection in the treatment of gallbladder carcinoma was examined with special reference to lymph node metastasis using two classifications: one proposed by the American Joint Committee on Cancer (AJCC) and the other by the Japanese Society of Biliary Surgery (JSBS). Histologic evaluations for the depth of tumor invasion (T), lymph node metastasis (N), stage, and follow-up for a mean period of 38 months (range 4–185 months) were completed in 52 patients with gallbladder carcinoma who underwent surgical resection from 1982 to 1997. The definition of T was similar in the two classifications. The extent of nodal involvement (N, AJCC; n, JSBS), stage, and survival were examined. In the absence of lymph node metastasis, the 5-year survival rate reached 71%. The 5-year survival rate in patients with involved nodes confined to the hepatoduodenal ligament, posterosuperior pancreaticoduodenal region, or along the common hepatic artery (N1 and part of N2 by AJCC; n1 and n2 by JSBS) approximated 28%. In contrast, postoperative survival was poor in the presence of more extensive nodal involvement (rest of N2 by AJCC; n3 and n4 by JSBS), with no 2-year survivors. The definition of stage I was the same in both classifications, and all patients in this stage are alive. The 5-year survival rates in stages II and III by the AJCC were 70.7% and 22.4%, respectively, and those by JSBS 61.9% and 23.1%, respectively. Thus the survival rates in stages I to III were essentially similar irrespective of the staging system. Stage IV showed significantly worse survival than stage III by the JSBS classification. In contrast, the differentiation of stage IV from III by the AJCC was not significant because of the better survival in stage IV that contained any T with nodal involvement in the posterosuperior pancreaticoduodenal region and along the common hepatic artery. Radical resection should be considered for patients with stage I to III disease defined by either classification and applied to the tumor invasion up to T3 with nodal involvement confined to the hepatoduodenal ligament, posterosuperior pancreaticoduodenal region, and along the common hepatic artery. The role of radical surgery seems to be limited in patients with more extensive tumor invasion or lymph node metastasis.

Interleukin 1β Enhances Invasive Ability of Gastric Carcinoma through Nuclear Factor-κB Activation

Purpose: We examined the role of interleukin (IL)-1β in activation of nuclear factor κB (NF-κB) and the biological function of activated NF-κB in gastric carcinoma cells. Experimental Design: Human gastric carcinoma cell line GCTM-1 was used to examine NF-κB activation by immunostaining and electrophoretic mobility shift assay. Matrix metalloproteinase (MMP)-9 expression, which plays an important role in tumor invasion, was assessed by semiquantitative reverse transcription-PCR, Western blotting, and immunostaining. The invasive ability of GCTM-1 cells was measured by Matrigel invasion assay. In vivo expression of IL-1β and MMP-9 and activation of NF-κB in 10 surgically resected gastric carcinoma specimens were examined immunohistochemically. Results: IL-1β enhanced NF-κB activation, MMP-9 expression, and the invasive ability of GCTM-1. A NF-κB inhibitor, pyrrolidine dithiocarbamate, suppressed both MMP-9 expression and invasiveness of IL-1β-treated GCTM-1 cells. IL-1β did not increase the invasive ability of GCTM-1 cells transfected with MMP-9 antisense oligonucleotide. Concomitant expression of IL-1β and nuclear NF-κB was observed in 3 of 10 gastric carcinoma specimens. Cells producing IL-1β were tumor-infiltrating macrophages in two specimens and gastric carcinoma cells in one specimen. Conclusions: One of the molecules that may play a role in NF-κB activation in some gastric carcinomas is IL-1β. The present results suggest that IL-1β increases the invasive ability of carcinoma cells through activation of NF-κB and the resulting MMP-9 expression.

Fibronectin : a possible factor promoting cholesterol monohydrate crystallization in bile

To examine the hypothesis that fibronectin physiologically present in bile might be a possible nucleating factor, the concentrations of fibronectin in gallbladder bile were determined and its induced effect on nucleation time and on the form of vesicle were examined in bile-model and human gallbladder bile. The gallbladder bile samples taken from patients with cholesterol gallstone had a significantly higher concentration of fibronectin and the faster nucleation time than the control. However, no significant correlation was found between nucleation time and endogenous fibronectin concentration. The addition of 0.5, 1.2, 10 micrograms/ml of fibronectin into two kinds of bile-model significantly shortened the nucleation time in a dose-related manner. Nucleation time was significantly shortened by the addition of 1 microgram/ml exogenous fibronectin into abnormal bile while such an effect was absent in the control. The addition of fibronectin increased the size of vesicles observed by the electron microscope. The results suggest that fibronectin physiologically present in bile may be one of the possible nucleating factors.

High vesicular cholesterol and protein in bile are associated with formation of cholesterol but not pigment gallstones.

To examine the differentiating parameters between cholesterol and pigment gallstones, we compared the nucleation times, concentrations of biliary lipid and protein, and the distribution of vesicular cholesterol in gallbladder bile of 16 patients with cholesterol, eight patients with black pigment gallstones, and nine gallstone-free control patients. Cholesterol monohydrate crystals were present in the fresh bile of only the cholesterol gallstone group. The nucleation time was significantly faster in the cholesterol stone group (3.3±3.2 days) than in the other two groups (pigment stone: 15.8±6.6, control: 16.9±5.7). The cholesterol saturation indices and the distribution of vesicular cholesterol were significantly higher in the cholesterol gallstone group than those in the other two groups. The total biliary protein concentration was significantly (P<0.01) higher in the cholesterol gallstone group [2.57±1.91 (sd) mg/ml] than that in the black pigment stone group (1.09±0.59). All parameters in patients with black pigment gallstone were essentially similar to the controls. We conclude that the presence of cholesterol crystals, rapid nucleation time, high vesicular cholesterol distribution, elevated cholesterol saturation index, and high protein concentration are associated with cholesterol gallstones but not with black pigment gallstones.

Laparoscopic Wedge Resection of Gastric Submucosal Tumors

Background/Aims: The purpose of this study was to evaluate the clinical utility of laparoscopic surgery for gastric submucosal tumor. Methods: The records of 11 patients who underwent laparoscopic wedge resection (LR group) for gastric submucosal tumors were reviewed and compared with those of 8 patients who underwent open surgery (OS group). Results: Mean operation time was 145 ± 43 min in the LR group and 127 ± 33 min in the OS group (p = 0.301). Mean blood loss was 97 ± 107 and 107 ± 47 g, respectively (p = 0.387). Patients in the LR group began walking 1.4 ± 0.7 days after surgery, which was significantly earlier than those in the OS group (2.7 ± 1.3 days, p = 0.021). The first flatus (1.5 ± 0.5 vs. 3.1 ± 0.6 days, respectively, p = 0.0004) and resumption of oral food intake (3.0 ± 1.7 vs. 4.3 ± 0.9 days, respectively, p = 0.020) were also earlier in the LR group. White blood cell count on the first postoperative day was lower (7,000 ± 2,100 vs. 11,900 ± 3,580/mm3, respectively, p = 0.004) in the LR group than in the OS group, and the duration of fever (>38.0°C; 0.1 ± 0.3 vs. 0.9 ± 0.8 days, respectively, p = 0.014) and the period of postoperative hospitalization (13.2 ± 3.7 vs. 20.8 ± 6.1 days, respectively, p = 0.014) were significantly shorter in the LR group than in the OS group. No complications occurred in either group. Conclusion: Laparoscopic surgery was superior to open surgery in terms of postoperative recovery time with comparable operation time and blood loss. Laparoscopic wedge resection is a promising surgical alternative for the treatment of gastric submucosal tumors.