Yasushi Rino

Postoperative functional evaluation of pylorus-preserving gastrectomy for early gastric cancer compared with conventional distal gastrectomy.

BACKGROUND Malnutrition, gallbladder dysfunction, dumping syndrome, reflux esophagitis, and gastritis of the remnant stomach are unfavorable sequelae in patients undergoing gastrectomy. Operative procedures should be improved to ensure such patients a satisfactory quality of life. METHODS After operation, gallbladder function, reflux gastritis, gastric emptying, and caloric intake were evaluated in 20 patients with early gastric cancer undergoing pylorus-preserving gastrectomy (PPG) and 25 patients undergoing conventional distal gastrectomy (CDG). RESULTS The resting gallbladder area increased significantly after CDG. In contrast, after PPG the gallbladder area showed no significant change and the contraction rate decreased slightly. After CDG, emptying was much more rapid for the first 30 minutes after ingestion of a meal. Although delayed emptying was observed early after PPG, the rate of emptying increased with time. Gastric pH was lower and gastric mucosal injury was milder in patients undergoing PPG. These results are attributed to preserved pyloric function. The caloric intake and changes in body weight after operation were similar in both the CDG and PPG groups. CONCLUSIONS PPG has advantages over CDG in terms of gallbladder function, the condition of the remnant stomach, and gastric emptying, PPG should be used in carefully selected patients with early gastric cancer to improve their quality of life.

Expression of circadian genes correlates with liver metastasis and outcomes in colorectal cancer.

Circadian rhythms are daily oscillations in various biological processes, generated by the feedback loops of eight core circadian genes: Period1 (Per1), Period2 (Per2), Period3 (Per3), Cryptochrome1 (Cry1), Cryptochrome2 (Cry2), Clock, Bmal1 and Casein Kinase I ε (CKIε). Recent studies have suggested that circadian genes participate in the growth and development of various cancers. This study examined the relations of circadian gene expression to clinicopathological factors and outcomes in patients with colorectal cancer. We studied surgical specimens of cancer tissue and adjacent normal mucosa obtained from 202 patients with untreated colorectal cancer. The relative expression levels of the circadian genes in the specimens were measured by quantitative real-time, reverse-transcription polymerase chain reaction. Expression of the Clock gene and the CKIε gene in cancer tissue were significantly higher compared to that in adjacent normal mucosa. Expression of the Per1 and Per3 genes in cancer tissue was significantly lower compared to that in adjacent normal mucosa. Analysis of the relations between clinicopathological features and expression of the eight circadian genes in cancer tissue showed that high expression of the Bmal1 gene and low expression of the Per1 gene correlated with liver metastasis. On analysis of the relations between outcomes and gene expression, high expression of the Per2 gene was associated with significantly better outcomes than low expression of the Per2 gene. Overexpression of the Bmal1 gene and reduced expression of the Per1 gene may thus be useful predictors of liver metastasis. Moreover, reduced expression of the Per2 gene may be a predictor of outcomes in patients with colorectal cancer.

Prognostic value of the IASLC/ATS/ERS classification of lung adenocarcinoma in stage I disease of Japanese cases

A new classification of adenocarcinoma (ADC) was proposed by the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society (IASLC/ATS/ERS) in 2011. The present study evaluates its prognostic value in stage I disease of Japanese cases. One‐hundred‐and‐seventy‐nine cases with pathological stage I ADC were classified according to the new classification system and their association with disease recurrence was analyzed. Eighteen (10.1%) and 24 (13.4%) cases were adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), respectively. One‐hundred‐and‐thirty‐seven cases (76.5%) were invasive adenocarcinoma (IVA), in which 43 (24.0%) were lepidic (LEP), 59 (33.0%) were acinar (ACN), 16 (8.9%) were papillary (PAP), 1 (0.6%) was micropapillary (MPAP), 12 (6.7%) were solid predominant subtypes (SOL), and 6 (3.4%) were invasive mucinous adenocarcinoma (MUC). The5‐year disease‐free survivals (DFS) of patients with AIS and MIA were 100%. Those of LEP, ACN, PAP, SOL and MUC were 93.5%, 83.7%, 75.0%, 44.4% and 62.5%, respectively. Multivariate analysis showed that high‐histological grade (SOL, MPAP, MUC) had an independent prognostic value to predict post‐operative recurrence (HR 3.661, 95% CI 1.421–9.437, P = 0.007). In conclusion, the present study demonstrates a prognostic value of the 2011 IASLC/ATS/ERS classification of ADC in Japanese cases.

Microscopic regional lymph node status in papillary thyroid carcinoma with and without lymphadenopathy and its relation to outcomes

AimThe aim of this study was to evaluate microscopic nodal status in papillary thyroid carcinoma (PTC) with and without lymphadenopathy and its relation to outcomes.Materials and methodsWe retrospectively analyzed 134 patients with PTC who underwent initial thyroidectomy. Forty-two patients with lymphadenopathy underwent therapeutic modified neck dissection (MND) and 92 without lymphadenopathy underwent prophylactic MND. The frequencies, numbers, and percentages of lymph node metastasis (LNM) were determined to evaluate nodal status; then, whether each nodal status influence to outcomes was analyzed. Disease-free survival (DFS) and disease-specific survival (DSS) were assessed (Kaplan–Meier method and log-rank test).ResultsLymphadenopathy was significantly related to local recurrence and DFS, but not DSS. The frequency (100 vs 67.4%), number (15.8 vs 2.7), and percentage (49.7 vs 17.8%) were significantly higher in patients with lymphadenopathy than in those without lymphadenopathy (p < 0.0001). Similarly, these were significantly higher in patients who developed recurrence than in those who did not. Recurrence was frequent in older patients with lymphadenopathy. The frequency, number, and percentage were also higher in older patients who developed local recurrence.ConclusionsLymphadenopathy and microscopic nodal status are significantly related to recurrence. Only a few nodes seem to be involved pathologically when no lymphadenopathy.

Prognostic value of KRAS mutations and Ki-67 expression in stage I lung adenocarcinomas.

The purpose of the present study was to establish accurate prognostic markers to predict the post-operative recurrence of stage I lung adenocarcinomas (ADC). One-hundred and ninety cases of stage I ADC were examined for KRAS mutations and Ki-67 expression, and their associations with disease recurrence were analyzed. KRAS-mutated cases showed a significantly higher risk of recurrence than cases without mutations (5-year disease-free survival (DFS) 61.0% vs. 85.8%, P=0.017: adjusted Hazard ratio (HR) 4.55, 95% Confidence Interval (CI) 1.61-12.82, P=0.004). Ki-67 high-expressers (labeling index >10%) also showed a higher risk of recurrence than low-expressers (5-year DFS 68.7% vs. 93.2%, P<0.001: adjusted HR 3.84, 95% CI 1.18-12.45, P=0.025). Ki-67 high-expressers with KRAS mutations showed an additional higher risk of recurrence compared to low-expressers without mutations (5-year DFS 37.5% vs. 93.3%, P<0.001: adjusted HR 16.82, 95% CI 3.77-74.98, P<0.001) and their 5-year DFS was nearly equivalent to that of stage II non-small cell lung cancer (NSCLC) in our facility (37.5% vs. 37.2% for stage II NSCLC, p=0.577). The combined use of KRAS status and Ki-67 expression level could be an excellent prognostic marker to predict the post-operative recurrence of stage I ADC.

Cyclooxygenase‐2 mRNA is up‐regulated in cirrhotic or chronic hepatitis liver adjacent to hepatocellular carcinoma

Background and Aim: Hepatocellular carcinoma (HCC) is unique in that its carcinogenesis is related to inflammatory changes and regenerative activities in the background liver. Although there are some data on cyclooxygenase (COX)‐2 expression in HCC by immunohistochemical studies, little is known about the possible role of COX‐2 in inducing hepatitis and/or carcinoma. To elucidate whether COX‐2 is involved in a part of these processes, we attempted to examine COX‐2 mRNA both in the adjacent non‐tumoral liver and in HCC.

The clinicopathological features of colorectal mucinous adenocarcinoma and a therapeutic strategy for the disease

BackgroundThe guidelines established by the National Comprehensive Cancer Network do not describe mucinous histology as a clinical factor that should influence the therapeutic algorithm. However, previous studies show conflicting results regarding the prognosis of colorectal mucinous adenocarcinoma. In this study, we described the clinicopathological features of mucinous adenocarcinoma in Japan, to identify optimal therapeutic strategies.Methods144 patients with mucinous and 2673 with non-mucinous adenocarcinomas who underwent primary resection in two major centers in Yokohama, Japan were retrospectively evaluated for clinicopathological features and treatment factors. A multivariate analysis for overall survival followed by the comparison of overall survival using Cox proportional hazard model were performed.ResultsPatients with mucinous adenocarcinoma had larger primary lesions, higher preoperative CEA levels, a deeper depth of invasion, higher rates of nodal and distant metastasis, and more metastatic sites. A multivariate analysis for overall survival revealed a mucinous histology to be an independent prognostic factor. In the subgroup analysis stratified by stage, Patients diagnosed as StageIII and IV disease had a worse survival in mucinous adenocarcinoma than non-mucinous, while survival did not differ significantly in patients diagnosed as Stage0-II disease. In StageIII, local recurrence in rectal cases and peritoneal dissemination were more frequently observed in patients with a mucinous histology.ConclusionsOur study indentified that mucinous adenocarcinoma was associated with a worse survival compared with non-mucinous in patients with StageIII and IV disease. In rectal StageIII disease with mucinous histology, additional therapy to control local recurrence followed by surgical resection may be a strategical alternative. Further molecular investigations considering genetic features of mucinous histology will lead to drug development and better management of peritoneal metastasis

Osteoclast-like giant cell tumor of the pancreas.

Abstract. A rare case of osteoclast-like giant cell tumor of the pancreas is reported. A 45-year-old woman presented with upper abdominal pain and weight loss. Examination revealed a tumor in the tail of pancreas, and distal pancreatectomy with splenectomy was performed. Pathological findings showed the tumor was composed of two cell types: atypical mononuclear round cells and abundant osteoclast-like multinucleated giant cells with central nucleoli. Immunohistochemical study showed that the atypical cells were strongly reactive for vimentin and negative for CD68, while the giant cells were immunoreactive for CD68, but negative for vimentin. The tumor was diagnosed as osteoclast-like giant cell tumor of the pancreas. We report this case and review 31 cases previously described in the literature.

Close association between high serum ALT and more rapid recurrence of hepatocellular carcinoma in hepatectomized patients with HCV-associated liver cirrhosis and hepatocellular carcinoma.

We investigated whether or not a high serum alanine aminotransferase (ALT) level is associated with a more rapid recurrence of hepatocellular carcinoma (HCC) in hepatectomized patients with hepatitis C virus (HCV)-associated liver cirrhosis (LC) (HCV-LC) and HCC. Thirty-three hepatectomized patients with HCV-LC and HCC of a single nodule who had no histologic evidence of portal or hepatic vein invasion and who had been followed up for more than 3 years were included in the study. They were subdivided into two groups according to their serum ALT levels, ALT being a well-known marker of inflammatory necrosis in the liver. Seventeen patients whose serum ALT levels showed several peaks or plateaus above 80 international units (IU) were designated as the high ALT group, and 16 patients whose serum ALT levels showed a sustained low level below 80 IU until the first recurrence were designated as the low ALT group, and the interval between hepatectomy and the first recurrence was observed. In the high ALT group, HCC recurred within 3 years in 70.6% of the patients. In contrast, it recurred in only 18.8% of the low ALT group within the same period (p < 0.05). There was a significant difference (p = 0.0201) between the two groups in the cumulative nonrecurrence rate. The mean interval in recurrent patients between hepatectomy and the first recurrence in the high ALT group (23.6 ± 2.8 months; mean ± SE) was significantly (p < 0.02) shorter than that in the low ALT group (49.3 ± 9.7 months). The expected interval between hepatectomy and recurrence was as short as 2.8 ± 0.5 years (mean ± SE) in the high ALT group, compared with 5.8 ± 0.7 years in the low ALT group (p < 0.05). These results showed that the recurrence of HCC was accelerated in the high ALT group, suggesting that suppression of the rise in ALT level after hepatectomy by treatment with anti-inflammatory drugs may prolong the interval until recurrence by about 2 years in hepatectomized patients with HCC and HCV-LC.

A prospective validation study to diagnose serosal invasion and nodal metastases of gastric cancer by multidetector-row CT.

BackgroundMultidetector-row CT (MDCT) may provide accurate preoperative staging of resectable gastric cancer. However, the standard methods and criteria to diagnose the T and N stages to select the patients who are good candidates for neoadjuvant chemotherapy have not been established yet.MethodsThe aim of this prospective study was to evaluate the accuracy of MDCT to diagnose the serosal invasion and nodal metastases of gastric cancer. Patients who had gastric adenocarcinoma underwent MDCT scanning using a standardized method. The T and N stage were diagnosed by prespecified criteria. The analyses were performed in the patients who had cN0–2 and M0 tumors and underwent curative gastrectomy as a primary treatment. The accuracy was calculated by comparing the results of MDCT with the histopathological findings.ResultsA total of 315 patients were analyzed. The overall diagnostic accuracy (95 % confidence interval) of T staging was 71.4 % (225 of 315, 66.2–76.1). The accuracy, sensitivity, and specificity for serosal invasion were 85.7 % (81.4–89.1), 54.5 % (42.6–66.0), and 94.0 % (90.3–96.3), respectively. The false-positive rate for serosal invasion was 6.0 % (2.9–7.7). The overall diagnostic accuracy of N staging was 75.9 % (239 of 315, 70.9–80.3). The accuracy, sensitivity, and specificity for nodal metastases were 81.3 % (76.6–85.2), 46.4 % (36.8–56.3), and 96.8 % (93.5–98.4), respectively. The false-positive rate for nodal metastases was 3.2 % (1.6–6.5 %).ConclusionsThese results suggest that MDCT provides an accurate diagnosis with high specificity and a low false-positive rate and can be used to select the patients who are candidates for preoperative chemotherapy.