Cytological Comparison between Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma by Image Analysis Software Using Touch Smear Samples of Surgically Resected Specimens.

To investigate useful cytological features for differential diagnosis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), this study cytologically compared HCC to ICC using image analysis software. Touch smear specimens of surgically resected specimens were obtained from a total of 61 nodules of HCC and 16 of ICC. The results indicated that the major/minor axis ratio of ICC is significantly larger than that of HCC (1.67 ± 0.27 vs. 1.32 ± 0.11, p < 0.0001) in Papanicolaou staining. This result means that the nucleus of HCC is close to round and the nucleus of ICC is close to an oval. This significant difference in the major/minor axis ratio between ICC and HCC was consistently observed by the same analyses using clinical samples of cytology (4 cases of HCC and 13 cases of ICC) such a fine-needle aspiration, brushing and ascites (ICC: 1.45 ± 0.13 vs. HCC: 1.18 ± 0.056, p = 0.004). We also confirmed that nuclear position center-positioned nucleus (p < 0.0001) and granular cytoplasm (p < 0.0001) are typical features of HCC tumor cells compared to ICC tumor cells. The research study found a significant difference in the nuclear morphology of HCC (round shape) and ICC (oval shape) in Papanicolaou-stained cytology specimens. This simple and objective finding will be very useful for the differential cytodiagnosis of HCC and ICC.

Cytological Appearances of Ovarian Seromucinous Borderline Tumor in Ascites: Presentation of 2 Cases.

BACKGROUND: Seromucinous borderline tumor (SMBT) is a rare neoplasm which was newly defined in the 2014 WHO classification. Although the clinical and histopathological characteristics of SMBT have been well described, its cytological characteristics have not. We recently experienced 2 cases of SMBT which were defined by cytological findings of ascites. CASE PRESENTATION: Case 1 was a 65-year-old Japanese woman. Preoperative imaging studies revealed abundant ascites and a cystic tumor, with a solid component measuring 13 cm on the left ovary. Radical surgery was performed during the intraoperative diagnosis of ovarian borderline tumor, made by histological examinations of frozen tumor sections. The cytological smears of preoperatively and intraoperatively collected ascites showed many atypical cells resembling reactive mesothelial cells. Alcian-blue staining of cell block sections revealed intracytoplasmic mucin, and the results of immunohistochemistry were consistent with SMBT. The final pathological diagnosis of tumor was SMBT. Case 2 was a 28-year-old Japanese woman. Preoperative imaging studies revealed a small amount of ascites and cystic tumors with solid components in the bilateral ovaries. She initially underwent fertility preservation surgery. SMBT was suspected by cytological examination of smears of intraoperatively collected ascites and the findings of cell block. She underwent additional radical surgery based on a final pathological diagnosis of SMBT. CONCLUSION: In our experience, the tumor cells of SMBT in ascites mimicked reactive mesothelial cells. The nuclear atypia of SMBTs was intermediate between that of reactive mesothelial cells and serous carcinoma. The immunohistochemistry and mucin staining using cell block were very helpful for facilitating the cytodiagnosis of SMBT.

Difficulty in the Cytodiagnosis of Mammary Analogue Secretory Carcinoma: Survey of 109 Cytologists with a Case Originating from a Minor Salivary Gland.

BACKGROUND: Mammary analogue secretory carcinoma (MASC) of the salivary gland shows morphologic similarities and shares an immunophenotype and characteristic ETV6-NTRK3 translocation with secretory carcinoma of the breast. We present a buccal case of MASC along with a survey-based debate about its cytologic diagnosis by fine-needle aspiration (FNA). CASE: FNA of the buccal nodule of a 58-year-old Japanese man was initially performed by 3 cytologists who gave different assessments of the Papanicolaou classification (i.e., class II, III, and V). To investigate the potential for discrepant diagnosis of MASC on a larger scale, we distributed a survey with questions about the cytological diagnosis of the present case to cytologists at other institutions. A total of 109 cytologists completed the survey, providing varying assessments of the Papanicolaou classification: class I/II (14%), class III (53%), and class IV/V (33%). Most of the respondents (72%) could not identify a particular tumor or disease. Even the respondents who identified a particular tumor suggested widely differing diagnoses, from a benign lesion to various malignant tumors. Only 2 respondents correctly identified MASC. CONCLUSION: Our experience and the results of the survey suggest difficulty in the cytodiagnosis of MASC.

Identification of Plants That Inhibit Lipid Droplet Formation in Liver Cells: Rubus suavissimus Leaf Extract Protects Mice from High-Fat Diet-Induced Fatty Liver by Directly Affecting Liver Cells.

Fatty liver disease is a condition in which abnormally large numbers of lipid droplets accumulate in liver cells. Fatty liver disease induces inflammation under conditions of oxidative stress and may result in cancer. To identify plants that protect against fatty liver disease, we examined the inhibitory effects of plant extracts on lipid droplet formation in mouse hepatoma cells. A screen of 98 water extracts of plants revealed 4 extracts with inhibitory effects. One of these extracts, Rubus suavissimus S. Lee (Tien-cha or Chinese sweet tea) leaf extract, which showed strong inhibitory effects, was tested in a mouse fatty liver model. In these mouse experiments, intake of the plant extract significantly protected mice against fatty liver disease without affecting body weight gain. Our results suggest that RSE directly affects liver cells and protects them from fatty liver disease.

[The feasibility of reduced port surgery for sigmoid colon and rectal (Rs) cancer].

Laparoscopic surgery for colorectal cancer has the advantage of being less invasive and delivering better cosmetic appearance. Although single-incision laparoscopic surgery produces excellent cosmetic results, it is considered very difficult to perform. We performed reduced port surgery (single-incision plus one or 2 ports) on 42 patients in our institute. The operation time, number of dissected lymph nodes, morbidity rates, and length of hospital stay after the operation were not inferior to those in conventional laparoscopic surgery. The estimated blood loss in reduced port surgery was less than in conventional laparoscopic surgery. In conclusion, the procedure of reduced port surgery should be further standardized to make it safer and more feasible, and to provide a favorable cosmetic result for selected patients.

[Laparoscopic hemi-double stapling and reduced-port laparoscopic distal gastrectomy for gastric cancer].

INTRODUCTION: The hemi-double stapling method (HDS) is typically used for extracorporeal Billroth-I anastomosis. We used HDS for reduced-port surgery. Laparoscopic HDS is used for intracorporeal Billroth-I anastomosis after laparoscopic distal gastrectomy. We performed reduced-port laparoscopic distal gastrectomy for gastric cancer. METHODS: Reduced-port laparoscopic distal gastrectomy was performed using the multi-trocar method with 5mm and 3mm ports. Laparoscopic HDS was performed using an umbilical incision and a left upper abdominal incision. A total of 17 patients underwent reduced-port laparoscopic distal gastrectomy. A D1+or D1 lymph node dissection was performed, and laparoscopic HDS was used for reconstruction. RESULTS: The patients had no short-term complications. CONCLUSIONS: Laparoscopic HDS and reduced-port laparoscopic distal gastrectomy are safe and feasible procedures.

[A case of an adenocarcinoma in a duplication cyst of the esophagogastric junction].

Duplication cysts of the esophagogastric junction are an extremely rare disease entity. Computed tomography showed a cystic lesion in the wall of the esophagogastric junction ofa 75-year-old man. The cystic tumor gradually increased in size from 40 mm to 60 mm in diameter within 6 months. On the basis of magnetic resonance cholangiopancreatography and positron emission tomography, it was described as a cystic pathological alteration enclosing a solid lesion. The pre-operative diagnosis was a gastrointestinal stromal tumor in the stomach cardia, and we performed proximal gastrectomy under laparotomy. Histological findings showed gastric mucosa in the internal mucosa of the cyst and an adenocarcinoma inside the cyst. We diagnosed the cystic tumor as a duplication cyst of the esophagogastric junction with adenocarcinoma. It is important to carefully choose the procedure to be used for resection of cystic tumors adjacent to the alimentary canal.

[A case of long-term survival of small intestinal adenocarcinoma treated by resection and chemotherapy].

A 60-year-old man had visited our hospital a few times due to vomiting since July 2008. In January 2009, because he was no longer able to eat, he was hospitalized to receive close examination. Single balloon enteroscopy revealed jejunal adenocarcinoma. After examination of the whole body, as there was no distant metastasis, jejunum partial resection was performed in February 2009. One dissemination nodule was recognized on the serosa near the main tumor. We obtained the final pathological diagnosis as Stage IV. From April 2009, adjuvant chemotherapy with combination of oxaliplatin, 5-fluorouracil and Leucovorin (mFOLFOX6) was performed 8 times. In April 2009, a small metastatic lesion appeared in the upper lobe of the right lung. We started administering combination of irinotecan, 5-fluorouracil and Leucovorin (FOLFIRI) from January 2010, but stopped because of side effects after the second cycle. Administration of capecitabine was started in March 2010. The metastatic lesion had diminished for a time but was found to be enlarged in March 2011. Thus, a partial right lung resection was performed in April 2012. After lung resection, systemic chemotherapy was not performed. The patient remains alive without a recurrence 3 years after lung resection and over 5 years after detection of the small intestinal adenocarcinoma.

[A case of transverse colon cancer mimicking urachal cancer].

A 55-year-old man was admitted to our hospital because of abdominal distension. Computed tomography revealed an abscess in the anterior abdominal wall and invasion of the large intestine. Biopsy of the large intestine revealed adenocarcinoma. Immunohistochemically, the antigen expression profile of the tumor was positive for cytokeratin 7, cytokeratin 903 (34ßE12), and cytokeratin 20. We diagnosed the tumor as urachal cancer and performed surgery. Examination of the resected specimen showed that the tumor was located in the transverse colon. Finally, the patient was diagnosed as having transverse colon cancer with urachal abscess.

[A case of combined resection of multiple adjacent organs in a patient with locally advanced residual gastric cancer].

A 69-year-old man with a history of distal gastrectomy for early gastric cancer consulted our department concerning a possible diagnosis of sigmoid colon cancer. After detailed examination, he was diagnosed with type 3 advanced sigmoid colon cancer with colonic stenosis and large type 3 gastric cancer in the residual stomach with gross infiltration of the adjacent organs. The patient first underwent sigmoidectomy and then received a regimen of neoadjuvant combination chemotherapy with S-1, cisplatin( CDDP), and Lentinan( LNT)( S-1 80 mg/m2, CDDP 60 mg/m2, and LNT 2 mg/body twice weekly for 2 weeks) for gastric cancer( cT4b[ SI, liver, pancreas], N2M0H0, Stage IIIC). After 2 courses of treatment, the gastric tumor had reduced in size but had penetrated the transverse colon. We performed total resection of the gastric remnant, D2 lymph node dissection, and en bloc resection of the transverse colon, partial liver, pancreas body and tail, partial diaphragm, and pericardium. S-1/CDDP (a total of 11 courses) followed by single-agent S-1 therapy was continued as adjuvant chemotherapy. With a follow-up time of 3 years and 10 months, no recurrence was noted following total resection of the gastric remnant.

[A case of locally advanced residual gastric cancer treated with combined resection of multiple adjacent organs].

A 60-year-old man was diagnosed as having type 3 advanced gastric cancer in the gastric antrum and multiple liver metastases( S2, S3, S4, and S7)( cT3[ SS] N0M0H1, Stage IV). The patient received combined neoadjuvant chemotherapy with S-1 and cisplatin( CDDP). S-1( 80 mg/body/day) was administered orally for 3 weeks followed by 2 drug-free weeks as a course, and CDDP (60 mg/m2) was administered by intravenous infusion on day 8. The gastric tumor reduced in size and the liver metastases improved after 5 courses of treatment. Distal gastrectomy, D2 lymph node dissection, and partial liver resection( 4 sites) were performed. S-1 alone was continued as adjuvant chemotherapy; no recurrence was detected in 2 years and 2 months after surgery. Although there is insufficient evidence to support the benefit of surgical resection in patients with advanced gastric cancer with liver metastases, chemotherapy combined with surgical resection would improve the survival time without deterioration of quality of life of these patients. This case suggests that neoadjuvant chemotherapy is effective against advanced gastric cancer even with multiple liver metastases.

[A case of primary hepatic malignant lymphoma accompanied by cholecystitis].

A 50-year-old man visited a physician due to continued right hypochondrium pain for a period of about two months. He was diagnosed with cholecystitis and was referred to our hospital. On arrival, he presented with mild tenderness in the right upper quadrant. Abdominal computed tomography (CT) showed small gallstones and a thickened gallbladder wall. At the same time, a low-density area expanding from the gallbladder bed was revealed. Magnetic resonance cholangiopancreatography (MRCP) showed a smooth stricture of the common hepatic duct. We suspected chronic cholecystitis and inflammatory change in the liver because of cholecystitis. However, malignant diseases could not be excluded, and conservative treatment with antibiotics was therefore performed. On post-hospitalization day 26, cholecystectomy was performed. Rapid diagnosis of a surgical wedged biopsy specimen of the liver showed infiltration of the hepatic sinusoids by atypical lymphocytes. Malignant lymphoma was highly suspected. After further examination, we obtained the diagnosis of primary hepatic CD5+diffuse large B-cell lymphoma. Cyclophosphamide+doxorubicin+vincristine+prednisolone(CHOP) with rituximab therapy was performed. Complete remission was achieved after 8 courses of therapy. However, tumor recurrence in the floor of the mouth occurred one year after the operation. Salvage chemotherapy is now being performed.

[A case report of complete response by weekly paclitaxel and 5'-DFUR combination chemotherapy for recurrenced gastric cancer with peritoneal dissemination].

A 77-year-old man complained chiefly of chest pain and heartburn. He had type 3 gastric cancer on the posterior wall of vestibular part. Distal partial gastrectomy and D2 lymph node dissection were performed. The pathological findings were as follows: partially poor tub2, pT2 (SS), ly2, v0, pN1, H0, P0, CY0, M0, pStage II,and Cur A. S-1 was administered orally as an adjuvant therapy. Carbohydrate antigen(CA) 19-9 levels were elevated 16 months after the operation. Computed tomography revealed a small amount of ascitic fluid with no other significant findings. Endoscopy revealed an erythrogenic protruding lesion 20 cm from the anal verge. In the biopsy, the lesion was classified as Group V, indicating metastasis of gastric cancer. It was judged that the S-1 therapy had led to the recurrence of peritoneal dissemination. Weekly paclitaxel (PTX; 3-week administration followed by 1-week withdrawal) was used together with doxifluridine(5'-DFUR; daily oral administration). CA19-9 levels decreased gradually, becoming normal in 3 months. Most of the ascitic fluid disappeared in 4 months. In the endoscopy performed after 9 months, the lesion was classified as Group I, revealing a histological complete response (CR). No serious side effects were observed, although epilation occurred as an adverse event. Currently, 21 months after the start of treatment, the CR has persisted. These results suggest that despite a few side effects, concomitant therapy with weekly PTX and 5'-DFUR can be continued as ambulatory care, and it may be effective in patients treated previously with S-1 who exhibit recurrence of peritoneal dissemination of gastric cancer.

[Curative resection for bulky gastrointestinal stromal tumor with conversion therapy by imatinib].

Imatinib is a standard treatment for unresectable gastrointestinal stromal tumor (GIST). We described the case of a 66- year-old woman with bulky GIST of which a diameter was 25 cm. Therefore, we decided the tumor was unresectable. After 2-year administration of imatinib, the diameter of tumor was reduced to 6 cm. After 3-year administration of imatinib, the diameter of tumor was increased to 8 cm. The patient did not have any distant metastasis. He underwent a resection of the tumor. The historical examination showed that c-kit and CD34 were positive. The number of mitosis was 12/50 HPF. Conversion chemotherapy for bulky GIST may contribute to a curative resection.

[Non-functional pancreatic endocrine carcinoma with multiple liver metastases--a case report].

A 60-year-old woman was admitted to our hospital because of upper abdominal discomfort and body weight loss. Abdominal CT showed multiple liver tumors with early enhancement and delayed washout. There were no abnormal findings in other organs. IVR-CT showed hypervascular masses, but it is not a typical tumor staining of HCC. To obtain the diagnosis, we performed laparoscopic partial liver resection in the left lateral segment. Histological examination suggested a primary hepatic carcinoid a tumor. But primary hepatic carcinoid tumor is comparatively rare, so we underwent further examinations. Two months later after the liver resection, the tumor of pancreatic tail was detected by CT and MRI. We could obtain the diagnosis of pancreatic endocrine tumor by EUS-FNA. We conducted a distal pancreatectomy with splenectomy and partial colonic resection. She had no symptom related to neuroendocrinology. The final diagnosis was non-functional endocrine carcinoma of pancreas. After that, we added extended right hepatic lobectomy with radiofrequency ablation in left lobe. The woman remains alive without a recurrence after the surgery.

[Oral rehydration therapy with OS-1 for advanced and recurrent gastrointestinal cancer patients].

The aim of this study was to introduce an oral rehydration therapy with OS-1 for advanced and recurrent gastrointestinal cancer patients to reduce a hospital stay as well as having a good QOL. We targeted 10 advanced cancer patients. In this study, We recommended the OS-1 drinking amount to be 500 mL to 1, 000 mL whenever the following symptoms were observed:(1) the patient's meal consumption was decreased in half, (2) the volume of urine was decreased, and (3) the frequency of urine was decreased. Nine out of 10 patients were able to drink OS-1 in the range of 500 mL to 1, 000 mL. Most of the patients were taking the chemotherapy along with OS-1 therapy. We confirmed two distinct cases: The patients with OS- 1 short-term drinker at the time of appetite fall because of chemotherapy. Another case was the patients with OS-1 longterm drinkers due to the end of life stage which decreased in meal frequency. ORT with OS-1 may contribute to improve QOL of the terminal patient with chemotherapy.

[Skeletal muscle metastasis of rectal carcinoma--a case report].

Skeletal muscle metastasis of carcinoma is comparatively rare. We report a case of metastasis to the quadriceps femoris muscle after the operation for rectal carcinoma. A 70-year-old man underwent rectal amputation in May 2007 due to rectal carcinoma. In May 2008, he noticed a painful tumor in the right femoral region. We obtained the diagnosis of recurrent rectal carcinoma by open biopsy. Simultaneously, lung metastasis was revealed by a close examination. Metastatic tumor resection was performed before chemotherapy, because it was important to preserve his performance status. From June 2008, chemotherapy was started. A year after the second operation, lung metastatic lesions were gradually progressed. At present, new skeletal muscle metastasis is not found. He is receiving chemotherapy in outpatient care. The resection of skeletal muscle metastasis made a contribution to his quality of life.

[Ovarian metastasis after complete response of colon cancer].

We report a case of ovarian metastasis after complete response of colon cancer. A 55-year-old woman underwent a sigmoidectomy for sigmoid colon cancer with hepatic metastasis and para-aorta lymph node metastasis. After the operation, the patient was given chemotherapy with bevacizumab+mFOLFOX6. Nine months after the operation, the patient was judged to have achieved complete response. Thirteen months after the operation, right ovarian tumor was found and bilateral oophrectomy, hysterectomy and omentectomy were performed. Histopathologically the ovarian tumor was metastasized from colonic cancer. After the second operation, the patient was given chemotherapy with bevacizumab+FOLFIRI. At present, the patient remains disease-free for 6 months after the ovarian operation.

Osteopontin expression in chronic pancreatitis.

INTRODUCTION: Chronic pancreatitis (CP) is frequently associated with stone formation within the pancreatic duct system. The mechanism of pancreatic stone formation, however, is still unclear. AIMS: Osteopontin expression is related to urinary stone formation and several diseases associated with calcification such as atherosclerosis, breast cancer, and meningioma. We therefore hypothesized and studied whether that osteopontin may contribute to the formation of calculi in CP. METHODOLOGY: Twenty patients with CP who underwent elective surgery were included in the study. As controls, normal pancreas specimens were collected from five additional patients. We used reverse transcription polymerase chain reaction and reverse transcription in situ polymerase chain reaction to evaluate osteopontin mRNA expression and immunohistochemical staining to evaluate osteopontin-producing cells. RESULTS: No expression of osteopontin was seen in normal pancreas cells. Osteopontin expression was detected in acinar or ductal cells in all 11 cases of chronic calcifying pancreatitis, whereas in 5 of 9 CP cases without pancreatic stones there was no expression of osteopontin in acinar or ductal cells. The data revealed a high incidence of osteopontin expression in chronic calcifying pancreatitis in comparison with its expression in CP without stones (p = 0.0081). Osteopontin mRNA expression was observed in chronic calcifying pancreatitis samples but not in normal pancreas tissues. Signals corresponding to osteopontin mRNA were observed in the cytoplasm of ductal cells and macrophages. CONCLUSION: These results provide the first evidence that osteopontin may play an important role in stone formation in CP. Better understanding of the pancreatic stone formation process may lead to an effective therapeutic approach to the inhibition of pancreatic calcification associated with CP.

[A possibility of the prognosis factor of serum cross-linked carboxyterminal telopeptide region of type I collagen (ICTP) as a marker of bone metastasis].

We measured ICTP in 126 patients suffering from cancer in our palliative care unit to investigate the clinical significance of serum cross-linked carboxyterminal telopeptide region of type I collagen (ICTP) and divided them into 2 groups according to the absence or presence of bone metastasis. 1) There was a relationship that of ICTP = -22.6Loge (Ccr) + 111.4 (r = 0.63, p < 0.01) between ICTP and creatinine clearance (Ccr) in non-metastasis group. The ICTP increased as renal function deteriorated. 2) In cancer patients with normal renal function of 40 ml/min/1.73 m2, ICTP was significantly higher in the group of metastasis than non-metastasis group. 3) In cancer patients who died, ICTP was high in both metastasis and non-metastasis groups and no difference was found between 2 groups. Duration of disease was significantly short in non-metastasis group than in metastasis group. These results suggest that ICTP is one of markers of bone metastasis, but higher value of ICTP is influenced by various factors such as renal function and may reflect the prognosis.