[A Case of Multicentric HER2-Positive Breast Cancer with Alterations of the Intrinsic Subtype].

In cases where there are 2 or more tumors, it is crucial to conduct core needle biopsies on each of them. A 39-year-old woman presented at our hospital with pain in her left breast. Ultrasonography(US)revealed the presence of 2 contiguous tumors: a 35 mm tumor(tumor 1)and a 20 mm tumor(tumor 2)in the AC area of the left breast. US-guided core needle biopsies(CNB)were performed. The histological findings confirmed an invasive ductal carcinoma, characterized by ER(-)/ PR(-)/HER2(3+). Neoadjuvant chemotherapy indicated tumor 1 as PD and tumor 2 as PR, and surgery was subsequently performed(Bt plus SLN). Upon histopathological examination, the findings demonstrated a non-pCR invasive ductal carcinoma, featuring an ER(+)/PR(-)/HER2(-)profile. Depending on the specific subtype identified, post-operative treatment included HER2-targeted therapy or ER/PR-targeting hormone therapy in conjunction with chemotherapy.

[A Case of Splenectomy for Isolated Splenic Metastasis after Surgery for Gastric Cancer].

Splenic metastasis of gastric cancer is rare. Cases of long-term survival after the resection of metachronous solitary splenic metastasis have been reported, and proactive resection should be performed. A 77-year-old man was presented to our hospital with anorexia. Further investigation showed type 2 gastric cancer in the greater curvature of the stomach in the lower body. Subsequently distal gastrectomy was performed on October 2018. The pathological stage was T3N2M0, Stage ⅢA, and the patient was treated with S-1 as adjuvant chemotherapy for 1 year. Two years after surgery, enhanced computed tomography(CT)showed a solitary splenic tumor with a diameter of 10 mm. Six months later, the tumor had grown to 25 mm, and PET-CT revealed no other tumors. Thus we diagnosed the patient as metachronous solitary splenic metastasis of gastric cancer, and splenectomy was performed on June 2021. Histopathological diagnosis was a metastasis of gastric cancer. The patient was treated with S-1 and remains recurrence-free for 1 year after the second operation.

[A Case of Long-Term Survival of Anaplastic Transformation of Thyroid Cancer in Lymph Node Metastasis Due to Radiation Therapy and Lenvatinib].

An 82-year-old woman who underwent total thyroidectomy and left cervical lymph node dissection 21 years ago admitted our hospital because of left cervical pain. Neck CT scan showed a 6 cm tumor on the left clavicle. Pathological diagnosis by needle biopsy revealed poorly differentiated to undifferentiated carcinoma, positive for TTF-1, and diagnosed as thyroid cancer lymph node metastasis anaplastic transformation. Administration of lenvatinib was started after radiation therapy. Since thrombocytopenia was observed, lenvatinib was gradually reduced from 14 mg and the dose was continued at 4 mg. The tumor shrinked and the effect of chemotherapy was partial response. She survived for 3 years while continuing lenvatinib. We reported long-term survival due to radiation therapy and lenvatinib of anaplastic transformation of thyroid cancer in lymph node metastasis due to radiation therapy and lenvatinib.

[A Case of Hepatectomy for Primary Hepatic Neuroendocrine Tumor, Preoperatively Diagnosed with Hepatocellular Carcinoma].

A 65-year-old man has pointed out a hepatic tumor when he was rushed to the hospital because of disturbance of consciousness associated with hypoglycemia. Abdominal dynamic CT images showed a tumor, 2.5 cm in diameter, in S2/3 close to the umbilical portion of the portal vein, and it had enhancement in the arterial phase and became washout in the portal phase. We performed left lateral segmentectomy with a diagnosis of hepatocellular carcinoma. The tumor was histopathologically diagnosed as a Grade 1 neuroendocrine tumor(NET). As additional examinations could not detect a primary lesion in any other site, the tumor was considered as a primary hepatic NET(PHNET). PHNETs are rare and because of the possibility that an unknown primary lesion exists, we have to observe for years carefully.

[A Case of Retroperitoneal Primary Well-Differentiated Liposarcoma Treated by Laparoscopic Surgery].

A 76-year-old woman visited the hospital due to occult blood in her urine. An abdominal CT scan showed a low-density tumor inside the left iliopsoas muscle in the retroperitoneum, and a well-differentiated liposarcoma was suspected. Therefore, laparoscopic tumor resection was performed. The tumor was on the inside of the left iliopsoas muscle, without any invasion around it. The macroscopic appearance of the resected tumor showed a yellow, fat-like, solid mass and it was histopathologically diagnosed as a well-differentiated liposarcoma. We conclude that a retroperitoneal primary well-differentiated liposarcoma can be treated by laparoscopic surgery, as in our case.

[A Case of Curative Resection of Locally Advanced Gastric Cancer after Nutrition Therapy and Chemotherapy with S-1 and Oxaliplatin Using Elemental Diet Tube].

We report a case of advanced gastric cancer with stenosis under severe malnutrition, in which nutritional treatment along with chemotherapy using an elemental diet(ED)tube led to complete resection of the tumor. A 66-year-old man who presented with difficulty in dietary intake came to our hospital. He was emaciated with a body mass index(BMI)score of 13.5 and a prognostic nutritional index(PNI)score of 33.8 and was admitted to the hospital for an emergency. He was diagnosed with advanced gastric cardia cancer invading the distal pancreas, spleen, and left diaphragm(U, type 3, tub2, cT4bN3M0, cStage ⅢC, HER2 score 0). There was obstruction of the passage of food due to the tumor, we performed nutrition therapy and chemotherapy consisting of 3 courses of S-1 and oxaliplatin using an ED tube. After chemotherapy, the primary tumor and lymph nodes were reduced, and we performed total gastrectomy with D2 lymph node, distal pancreas, spleen, and left partial diaphragm dissection. Histopathological diagnosis was ypT4aN1M0, ypStage ⅢA, indicating a pathological partial response(Grade 1). Adjuvant chemotherapy was performed for 6 months, and there has been no relapse for 3 years since the operation.

[A Case Report of Lung Resection for Lung Metastasis from Pancreatic Cancer].

A 66-year-old man had an elevated CEA level. Further examinations showed a pancreatic head tumor. A pancreaticoduodenectomy was then performed. The histopathological examination showed a mixed tumor of papillary adenocarcinoma and neuroendocrine cancer. In addition, a tumor in the upper lobe of the right lung was found 18 months after the initial pancreatic resection, and the bronchoscope indicated lung metastasis. The patient underwent partial pneumonectomy. After the pneumonectomy, he received S-1 chemotherapy. Thirty -nine months after the pneumonectomy, CEA was slightly elevated. We changed the chemotherapy to gemcitabine and nab-paclitaxel without further examinations to confirm the recurrence. The patient discontinued chemotherapy after CEA fell within the normal range. He has been alive without tumor relapse for 64 months since the second operation for the lung metastasis. We report a successful case of lung resection for lung metasta- sis from pancreatic cancer.

[A Case of Treated with Laparoscopic Surgery for Intussusception Up to the Splenic Flexion Region Due to Cecum Cancer].

A 93-year-old woman was admitted to the hospital because of respiratorydiscomfort. A chest CT scan indicated aspiration pneumonitis and, simultaneously, intussusception was observed in the splenic flexure region. Abdominal enhance CT scan revealed a tumor in the advanced region of intussusception. Laparoscopy-assisted ileocecal resection was performed. Since the intussusception was difficult to reduce laparoscopically, the ileocecum was mobilized and the intussusception was reduced manually. In the resected specimen, a type 1 tumor was observed in the cecum and histopathologic ally diagnosed as cercal cancer. We report a case with intussusception due to colorectal cancer treated bylaparoscopic surgery.

[A Case of Rectal Gastrointestinal Stromal Tumor(GIST)with Long-Term Survival Treated with Multidisciplinary Therapy].

We report a case of gastrointestinal stromal tumor(GIST)with long-term survival treated by multidisciplinary therapy, including surgery and imatinib to prevent repeated recurrence. A 76-year-old woman visited our hospital with difficulty in defecation and bloody bowel discharge. She was diagnosed with rectal GIST and underwent transanal partial resection of the rectum. Local recurrence occurred 1 year after the operation, and the tumor was resected transanally. Hepatic metastasis occurred 8 months after the second operation. The patient was administered imatinib for 2 months, which caused the tumor to shrink, and extended left lobectomy was performed. Imatinib was administered for 2 years after hepatectomy. After another 2 years, metastasis to the liver and thoracic and lumbar vertebrae occurred. The recurrent tumors reverted to cystic lesions after 6 months of imatinib treatment. She has been alive without tumor progression during re-treatment with imatinib for 7 years(13 years after the first surgery).

Preoperative predictors for early recurrence of resectable pancreatic cancer.

BACKGROUND: The first-line treatment for resectable pancreatic cancer (RPC) is surgical resection. However, our patients have often experienced early recurrence after curative resection for RPC, with desperately poor prognosis. Some reports indicated that minimally distant metastasis not detected at operation might cause early recurrence. The present study aimed to identify preoperative clinicopathological features of early recurrence after curative resection of RPC. METHODS: Ninety RPC patients who underwent curative resection between 2000 and 2014 at our institution were retrospectively analyzed. RESULTS: Of the 90 patients, 32 had recurrence within 1 year. Univariate analysis demonstrated that preoperative serum carbohydrate antigen (CA19-9) ≥529 U/mL (P = 0.0011), preoperative serum s-pancreas-1 antigen (SPan-1) ≥37 U/mL (P = 0.0038), and histological grades G2-G4 (P = 0.0158) were significantly associated with recurrence within 1 year after curative resection. Multivariate analysis demonstrated that preoperative serum CA19-9 ≥ 529 U/mL (P = 0.0477) and histological grade G2-G4 (P = 0.0129) were independent predictors of recurrence within 1 year. Recurrent cases within 1 year postoperatively had significantly more distant metastasis than cases with no recurrence within 1 year (P < 0.001). CONCLUSIONS: Preoperative serum CA19-9 ≥ 529 U/mL and histological grades G2-G4 were independent predictive factors for recurrence within 1 year after pancreatectomy for RPC. Furthermore, recurrent cases within 1 year had more frequent distant metastasis than cases with no recurrence within 1 year. These results suggest that RPC patients with preoperative serum CA19-9 ≥ 529 U/mL should receive preoperative therapy rather than surgery.

[A Case of Paget-Type Recurrence 20 Years after Breast Conserving Surgery for Invasive Ductal Carcinoma].

We report an 85-year-old female suffered Paget-type recurrence at right remnant breast. The patient had undergone breast conserving surgery(BCS)20 years ago in another hospital for invasive ductal carcinoma of the right breast(pT1N0M0, Stage I ). Her chief complain was a skin ulcer of the right nipple. The pathological diagnosis for biopsy specimen from the areola was Paget's disease. She underwent total mastectomy. Paget cells were detected pathologically in the epidermis of the nipple and nearby mammary duct connected with fibrous tissue after BCS, suggesting Paget-type recurrence of invasive breast carcinoma.

Establishment and characterization of new cell lines of anaplastic pancreatic cancer, which is a rare malignancy: OCUP-A1 and OCUP-A2.

BACKGROUND: Anaplastic pancreatic cancer (APC) cell lines have been scarcely established. METHODS: The morphology, gene expressions, karyotyping and epithelial-mesenchymal transition markers of newly established APC cell lines OCUP-A1 and OCUP-A2 were analyzed. Their abilities of proliferation under normoxia and hypoxia, migration and invasion were compared to 4 commercially available pancreatic ductal adenocarcinoma (PDA) cell lines. Their induction of angiogenesis, stem-like cell population and subcutaneous tumor growth in nude mice were estimated, comparing 2 PDA cell lines examined here. RESULTS: OCUP-A1 and OCUP-A2 cells continuously grew with spindle and polygonal shapes, respectively. Gene analysis revealed 9 gene mutations including KRAS and TP53. Karyotyping clarified numerical structural abnormalities in both cells. Loss of E-cadherin and expression of vimentin in both cell lines were observed. The doubling time of both cell lines was approximately 20 h. Proliferation, migration and invasion abilities were not notable compared to other PDA cell lines. However stem-like cell population of both cell lines was superior to a part of PDA cell lines. Moreover OCUP-A1 showed stronger hypoxia tolerance and induction of angiogenesis than other PDA cell lines. The tumorigenicity in vivo of OCUP-A2 was stronger than conventional PDA cell lines. CONCLUSIONS: The OCUP-A1 and OCUP-A2 cell lines of rare malignancies might be useful for investigating the biology of pancreatic cancer.

Salvage surgery after chemotherapy with S-1 plus cisplatin for α-fetoprotein-producing gastric cancer with a portal vein tumor thrombus: a case report.

BACKGROUND: Patient with α-Fetoprotein (AFP)-producing gastric cancer usually has a short survival time due to frequent hepatic and lymph node metastases. Gastric cancer with portal vein tumor thrombus (PVTT) is rare and has an extremely poor prognosis. CASE PRESENTATION: A 63-year-old man was found to have a huge Type 3 gastric cancer with a PVTT and a highly elevated serum AFP level. Chemotherapy with S-1 plus cisplatin was given to this patient with unresectable gastric cancer for 4 months. The serum AFP level decreased from 6,160 ng/mL to 60.7 ng/mL with chemotherapy. Since the PVTT disappeared after the chemotherapy, the patient underwent total gastrectomy. Histological findings of the primary tumor after chemotherapy showed poorly differentiated adenocarcinoma without hepatoid cells and viable tumor cells remaining in less than 1/3 of the neoplastic area of mucosa and one lymph node. The cancerous cells were immunohistochemically stained by anti-AFP antibody. The patient has survived for 48 month without recurrence. CONCLUSIONS: AFP-producing gastric cancer with a PVTT has an extremely poor prognosis, but long-term survival was achieved for this dismal condition by salvage surgery after chemotherapy.

[Complete Response to Chemotherapy after Resection of Rectal Cancer with Virchow's Lymph Node Metastasis].

A 62-year-old woman was admitted to our hospital because of bloody stool. Colonoscopy revealed stenosis by a type 2 tumor of the recto-sigmoid colon. A biopsy specimen contained moderately differentiated adenocarcinoma. Thoraco-abdominal computed tomography (CT) showed liver metastasis (S7, 10 mm) and enlargement of Virchow's lymph node (17 mm) and several para-aortic lymph nodes (15 mm on average). Because of oozing from the tumor and severe stenosis of the recto-sigmoid colon, we performed laparoscopic-assisted high anterior resection of the primary lesion. After surgery, 3 courses of mFOLFOX6, 20 courses of mFOLFOX6 plus bevacizumab, and 5 courses of infusional 5-FU plus Leucovorin plus bevacizumab were administered. Thoraco-abdominal CT demonstrated complete response to the 1 year 2 months of chemotherapy. The patient has been alive without relapse for 2 years after surgery.

Clinical and pathological features of five-year survivors after pancreatectomy for pancreatic adenocarcinoma.

BACKGROUND: Clinical factors determining short-term survival after pancreatectomy have been well studied, but factors predicting long-term survival with curative resection are poorly understood in pancreatic carcinoma. Our objective was to identify clinical and pathological features of five-year disease-free survivors after surgical resection of pancreatic adenocarcinoma. METHODS: The clinical and pathological data from 147 patients who underwent a potentially curative resection for pancreatic adenocarcinoma at our institution between 1988 and 2012 were retrospectively analyzed. RESULTS: Of 147 patients, 18 survived for more than five years after surgery without disease recurrence. A univariate analyses demonstrated that: two or fewer lymph node metastases (P=0.014), a preoperative serum carbohydrate antigen 19-9 (CA19-9) level of 40 U/mL or less (P=0.0018), an absence of intrapancreatic nerve invasion (P=0.028), and undergoing an R0 resection (P=0.011) were significantly associated with five-year survival. A logistic regression model identified the following independent cancer-related predictors of five-year survivors: having two or fewer lymph node metastases (odds ratio (OR): 6.02; 95% confidence interval (CI): 1.08 to 112.98; P=0.0385), a preoperative serum CA19-9 level of 40 U/mL or less (OR: 5.02; 95% CI: 1.68 to 16.48; P=0.0036), and undergoing an R0 resection (OR: 3.63; 95% CI: 1.12 to 14.28; P=0.0316). CONCLUSIONS: We conclude that number of lymph node metastases being two or less, a preoperative serum CA19-9 level of 40 U/mL or less, and undergoing an R0 resection may be independent predictive factors to identify actual five-year survivors after pancreatectomy for pancreatic adenocarcinoma.

Prognostic indicator for the resection of liver metastasis of colorectal cancer.

PURPOSE: We investigated the predictive indicator for a good prognosis of surgical resection for liver metastasis of colorectal cancer. METHOD: Between 1990 and 2009 at our institute, 117 patients underwent 132 hepatic resections for liver metastasis of colorectal cancer. The clinical, pathological, and outcome parameters affecting their prognoses were analyzed. The extent of the liver metastases was subdivided according to the Japanese Classification of Colorectal Carcinoma (JCCRC), and the patients were classified into different grades based on the JCCRC classification and the status of the nodal involvement of the primary tumor. RESULT: The median survival time (MST) of the 117 patients was 58 months, and the actuarial survival rates at 1, 3, and 5 years were 92.3, 60.0, and 46.1 %, respectively. A multivariate analysis revealed that the JCCRC Grade classification was an independent prognostic indicator (Grade A vs. B vs. C: MST, 72 vs. 41 vs. 23 months; 5-year survival, 59.0 vs. 38.6 vs. 0 %: p < 0.0001). CONCLUSION: Our findings indicate that the JCCRC Grade classification for liver metastasis of colorectal cancer is a significant prognostic indicator and may be useful for making decisions regarding the treatment of liver metastasis.

[A case of a villous tumor of the rectum with electrolyte depletion syndrome].

We report a case of a villous tumor of the rectum with electrolyte depletion syndrome (EDS). A 76-year-old woman developed general fatigue, and on investigation, we found a large laterally spreading tumor of the rectum using bowel enema and colon fiber. Pathologically, the biopsy specimen was graded Group 4. We intended to perform a laparoscopy-assisted low anterior resection in the patient. However, the operation was interrupted by a short-run type of ventricular premature contraction (VPC) due to EDS-induced hypokalemia. After treating the hypokalemia, low anterior resection or laparotomy was performed. The tumor was 19 × 13 cm in size and occupied the circumference of the rectum. Histological examination revealed well differentiated tubular adenocarcinomas with tubulovillous adenoma. Pathological staging was pTis, pN0, M0, stage 0 according to the Japanese Classification of Colorectal Carcinoma (8th edition). It is now 6 months after the operation and hypokalemia has not recurred in the patient.

IGF-1 receptor and IGF binding protein-3 might predict prognosis of patients with resectable pancreatic cancer.

BACKGROUND: The present study aimed to elucidate the clinicopathologic role of insulin-like growth factor-1 receptor (IGF1R) and IGF binding protein-3 (IGFBP3) in patients with pancreatic cancer. The function of IGFBP3 is controversial, because both inhibition and facilitation of the action of IGF as well as IGF-independent effects have been reported. In this study, IGF1R and IGFBP3 expression was examined, and their potential roles as prognostic markers in patients with pancreatic cancer were evaluated. METHODS: Clinicopathological features of 122 patients with curatively resected pancreatic cancer were retrospectively reviewed, and expression of IGF1R and IGFBP3 was immunohistochemically analyzed. RESULTS: Expression of IGF1R and IGFBP3 was observed in 50 (41.0%) and 37 (30.3%) patients, respectively. IGF1R expression was significantly associated with histological grade (p = 0.037). IGFBP3 expression had a significant association with tumor location (p = 0.023), and a significant inverse association with venous invasion (p = 0.037). Tumors with IGF1R-positive and IGFBP3-negative expression (n = 32) were significantly frequently Stage II and III (p = 0.011). The prognosis for IGF1R positive patients was significantly poorer than that for IGF1R negative patients (p = 0.0181). IGFBP3 protein expression did not correlate significantly with patient survival. The subset of patients with both positive IGF1R and negative IGFBP3 had worse overall survival (8.8 months versus 12.6 months, respectively, p < 0.001). CONCLUSION: IGF1R signaling might be associated with tumor aggressiveness, and IGFBP3 might show antiproliferative effects in pancreatic cancer. Both high IGF1R expression and low IGFBP3 expression represent useful prognostic markers for patients with curatively resected pancreatic cancer.

Prognostic predictive values of gemcitabine sensitivity-related gene products for unresectable or recurrent biliary tract cancer treated with gemcitabine alone.

BACKGROUND: Gemcitabine is a pyrimidine nucleoside analog that is a commonly used chemotherapeutic agent for unresectable or recurrent biliary tract cancer (BTC). Several molecules involved in gemcitabine metabolism, including human equilibrative nucleoside transporter (hENT1), deoxycytidine kinase (dCK), and ribonucleotide reductase subunit M1 (RRM1), have been investigated as predictive biomarkers of gemcitabine efficacy, mostly in pancreatic cancer. The aim of this study is to clarify which biomarker is the most reliable among hENT1, dCK, and RRM1 to predict survival in patients with advanced BTC treated with gemcitabine alone. METHODS: The analysis was performed on samples from 28 patients with unresectable or recurrent BTC who were treated with gemcitabine alone as first-line therapy. The starting date of overall survival (OS) and progression-free survival (PFS) was defined as the date of first treatment with gemcitabine. Intratumoral hENT1, dCK, and RRM1 expressions were examined by immunohistochemistry. RESULTS: The expressions of hENT1, dCK, and RRM1 had no significant relationships with age, gender, primary tumor site, recurrence/unresectable, or histological type. Among the three molecules, only hENT1 expression was a significant factor affecting OS and PFS in univariate analysis; OS was 11.4 months for high hENT1 expression versus 5.7 months for low, P = 0.0057; PFS was 7.7 months for high versus 2.5 months for low, P = 0.0065. Multivariate analyses also identified hENT1 expression as an independent predictive factor for OS. CONCLUSIONS: hENT1 is the most reliable predictive marker of survival in patients with advanced BTC treated with gemcitabine.

In vitro effects of lapatinib with gemcitabine for pancreatic cancer cells.

BACKGROUND/AIMS: We investigated whether lapatinib plus gemcitabine has synergistic or antagonistic effects on the pancreatic cancer cell lines MiaPaca-2 and PANC-1. Furthermore, the changes of gemcitabine sensitivity-related genes by lapatinib treatment were examined. METHODOLOGY: The effects of lapatinib, gemcitabine, and combined treatment with both agents on cell viability were examined by methyl thiazolyl tetrazolium analysis. Synergy between lapatinib and gemcitabine was assessed by median effect analysis. The mRNA amounts of human equilibrative nucleoside transporter (hENT1), deoxycytidine kinase (dCK) and ribonucleotide reductase subunit M1 (RRM1) genes were measured by quantitative real-time polymerase chain reaction in cells exposed to lapatinib for 48 h, as compared with untreated cells. RESULTS: No synergistic effects were observed with combined treatment in either cell line. In contrast, antagonistic effects occurred on MiaPaca-2 cells with the two agents. Specific changes in gemcitabine sensitivity-related genes induced by lapatinib were not detected in either MiaPaca-2 or PANC-1. CONCLUSIONS: Lapatinib may not enhance the anti-tumor effects of gemcitabine for pancreatic cancer.