[A Case of De Novo Stage â £ Breast Cancer Successfully Treated with Surgery and Multiple Endocrine Therapies Over a Long Period of Time].

Here we present a case of de novo Stage Ⅳ breast cancer successfully treated with surgery and multiple endocrine therapies over a long period of time. A 75-year-old female presented with a breast tumor with skin invasion and multiple lung metastases. Diagnosed with infiltrating breast cancer of Luminal A-like subtype, endocrine therapy with anastrozole was initiated. Despite initial response to the treatment in both the primary site and lung metastases, the primary tumor regrew and surgery with lumpectomy was performed. After a 3-year-treatment of tamoxifen, axillary lymphadenopathy and bone metastases developed. The patient was treated with fulvestrant for 5 years, resulting in clinical complete response. The now 88-year-old patient has been free of disease without treatment for a year and a half. Generally, primary tumor resection of Stage Ⅳ breast cancer does not improve prognosis, but in this case it provided good local control and enabled long-term endocrine therapy, resulting in prolonged disease-free survival.

[A Case of Primary Gastric Lymphoma with Spontaneous Perforation].

An 85-year-old female patient presented to the emergency department with the chief complaint of sudden upper abdominal pain. The patient suffered from anorexia and epigastric pain for a month, and a local physician suspected a diagnosis of gastric ulcer. An abdominal computed tomography(CT)scan showed intraperitoneal free air as well as irregular thickening and thinning of the gastric wall. Gastric ulcer perforation was suspected, and an emergency operation was performed. Surgical findings showed thickening of the gastric wall in the pylorus and gastric corpus but partial thinning of areas of the anterior wall of the gastric corpus with a perforation measuring 5 mm. A distal gastrectomy and reconstruction were performed using the Billroth Ⅱ method. The histopathological diagnosis was malignant gastric lymphoma(diffuse large B- cell lymphoma). Considering the patient's age and general condition, chemotherapy was not administered after surgery. The patient was alive without recurrence 8 months after the operation.

[Resectable Pancreatic Cancer Successfully Treated with Neoadjuvant Chemotherapy Regimen Change to Modified FOLFIRINOX-A Case Report].

A 72-year-old woman presented with obstructive jaundice. Computed tomography revealed a 12-mm low-density mass in the head of the pancreas. She was diagnosed as having pancreatic cancer by endoscopic ultrasound-guided fine-needle aspiration. She received gemcitabine plus nab-paclitaxel as preoperative chemotherapy. After 2 courses, hepatoduodenal lymph node metastasis appeared and was accompanied by increased tumor marker levels. The regimen was changed to modified FOLFIRINOX. After 5 courses, the lymph node metastasis was reduced in size and the tumor marker levels were decreased, so subtotal stomach-preserving pancreaticoduodenectomy was performed. Adjuvant chemotherapy was administered postoperatively. The patient was alive and well without recurrence 2 years and 9 months after the surgery, but died of sepsis. Nevertheless, this case highlights that when preoperative chemotherapy for resectable pancreatic cancer appears to be ineffective, a change in regimen may be useful.

[Locally Advanced HER2-Positive Breast Cancer Successfully Treated with Trastuzumab Emtansine].

Although the prognosis of HER2-positive breast cancer(BC)has been improving than before, that of locally advanced cases is not satisfactory. A 41-year-old female presented with a huge breast lump and massive lymphadenopathy, which was diagnosed as HER2-positive, unresectable, locally advanced BC. The first treatment, consisting of docetaxel, trastuzumab and pertuzumab, had only a limited and temporary effect, with subsequent mass regrowth. After initiation of the second treatment, trastuzumab emtansine(TDM1), the mass gradually shrank, and mastectomy and axillary lymphadenectomy were performed successfully. Histologically, several tiny invasive foci were observed in the mammary gland. No lymph node metastases were observed. The patient subsequently underwent radiation therapy and a 1-year course of TDM1 treatment. The patient has been in remission for 5 years. HER2-positive, locally advanced BC can be successfully treated with multimodal therapy, including anti-HER2 therapy, timely surgery and radiation therapy.

[A Case of Pancreatic Invasive Micropapillary Carcinoma That Survived Seven Years after Resection and Chemotherapy].

We present the case of a 47-year-old man who underwent a subtotal stomach-preserving pancreaticoduodenectomy for pancreatic head cancer. Histopathological diagnosis revealed that the majority of the cancer was an invasive micropapillary carcinoma(IMPC). Postoperative adjuvant chemotherapy using S-1 was continued for 4 years, at the end of which, multiple lymph node metastases were identified. Therefore, gemcitabine plus S-1 therapy was initiated. The treatment reduced the lymph node in size and resulted in the maintenance of a partial response for a year and a half. However, increased lymph node metastases recurred, and multiple lung metastases were noted. The patient died 7 years and 2 months after the resection of the primary lesion. Although pancreatic IMPC has a poor prognosis, long-term survival may be achieved by resection of the primary region, the administration of adjuvant chemotherapy and management of recurrent lesions by chemotherapy.

[Total Pancreatectomy for Remnant Pancreatic Cancer with Positive Washing Cytology after Conversion to Negative Cytology Following Gemcitabine plus Nab-Paclitaxel Therapy-A Case Report].

A 53-year-old woman underwent subtotal stomach-preserving pancreaticoduodenectomy(SSPPD)for resectable pancreatic cancer after neoadjuvant chemotherapy. Postoperatively, she received hepatic arterial infusion of 5-FU and S-1 chemotherapy. Two years after SSPPD, abdominal computed tomography showed a 2-cm mass in the remnant pancreas, which was diagnosed as recurrence of cancer by endoscopic ultrasound-guided fine-needle aspiration. Staging laparoscopy was performed and peritoneal washing cytology(CY)was positive. She then received gemcitabine plus nab-paclitaxel chemotherapy for 8 months. After that, staging laparoscopy was performed again and negative CY was confirmed. A total remnant pancreatectomy with splenectomy was performed. She received chemotherapy after pancreatectomy and is now alive and well without recurrence 2 years and 1 month after the second surgery. Although positive CY is a poor prognostic factor, surgery combined with perioperative chemotherapy may contribute to prolonged survival for some patients who have recurrence in the remnant pancreas with positive CY.

[Breast Cancer Metastasis to the Mesentery Diagnosed Via Laparoscopic Biopsy-A Case Report].

Breast cancer can metastasize to organs all over the body, but isolated mesenteric metastases are rare. A 72-year-old female, with a history of invasive lobular carcinoma of the breast treated with breast-conserving therapy and axillary lymphadenectomy 7 years previously and 5 years of endocrine therapy, presented with asymptomatic elevated serum carcino- embryonic antigen. Computed tomography(CT)revealed no obvious distant metastasis, but showed increased adipose tissue density around the pancreas suggestive of acute pancreatitis. During follow-up, in addition to the abnormality around the pancreas, mild thickening of the mesentery was observed on CT. Definitive diagnosis of mesenteric metastasis of invasive lobular carcinoma was confirmed via laparoscopic biopsy. It was supposed that the breast cancer had first metastasized to the retroperitoneum via the hematogenous route, and had then directly infiltrated the mesentery. Laparoscopic biopsy is effective for diagnosis of intra-peritoneal metastases.

[A Case of Surgical Resection of Anaplastic Carcinoma of the Pancreas(Pleomorphic Cell Type)with Poor Response to Neoadjuvant Chemotherapy].

A 62-year-old man was incidentally found to have a pancreatic tumor by CT. He was diagnosed with pancreatic cancer by EUS-FNAB. Gemcitabine(GEM)plus nab-paclitaxel(PTX)was started as neoadjuvant chemotherapy(NAC)for resectable pancreatic cancer. However, after the end of the second course, the tumor grew rapidly and invaded the stomach, so NAC was discontinued, and surgery was performed. The pathological diagnosis was anaplastic ductal carcinoma of the pleomorphic cell type, and the histological response was Grade 1a. Multiple liver metastases appeared during adjuvant chemotherapy with S-1, so GEM plus nab-PTX and modified FOLFIRINOX were administered, but the therapeutic response was poor, the patient died 9 months after surgery. Anaplastic carcinoma has a poor response to chemotherapy and may be included with cancers showing treatment resistance to NAC, as seen in our case. It is necessary to pay attention to anaplastic carcinoma during the course of NAC for pancreatic cancer.

[A Case of Long-Term Survival of a Patient with Liver Metastasis of Colon Cancer and Suspected Inferior Vena Cava Invasion].

A 58-year-old woman was diagnosed with a sigmoid colon cancer and synchronous liver metastasis. Because an obstruction of the sigmoid colon was identified, the patient underwent sigmoidectomy. Computed tomography(CT)findings suggested possible vena cava and hepatic vein invasion. Therefore, the decision was made to offer systemic chemotherapy. The patient underwent 6 courses of chemotherapy with 5-fluorouracil, Leucovorin, and oxaliplatin (mFOLFOX6). After 4 courses of chemotherapy, CT scans showed a significant reduction of the liver metastasis (reduction rate of 5 0%; a partial response) and demonstrated improved exclusion of the inferior vena cava and hepatic vein. After 6 courses of chemotherapy, we performed right trisegmentectomy of the liver and resection of the inferior vena cava and diaphragm. Postoperative pathological findings revealed negative margins, and no invasion of the inferior vena cava. The pathological response grade of the tumor after chemotherapy was determined to be Grade 2. Adjuvant chemotherapy was not performed because of the patient 's poor performance status. The patient was alive with no recurrence 8 years after resection of the liver metastasis.

A rare case of invasive ductal carcinoma with hyperprolactinemia.

We report here a rare form of invasive ductal carcinoma composed of a mass protruding from the tip of the nipple in a 43-year-old woman with hyperprolactinemia. She had been amenorrheic for 15 years following an incomplete pituitary adenomectomy for prolactinoma. She presented with a mass on the left nipple that had been growing for 6 months. Morphologically, the mass resembled adenoma of the nipple. Another mass was located in the subareolar region. She underwent mastectomy after invasive ductal carcinoma was diagnosed. Histopathologically, the tumor of the nipple was invasive ductal carcinoma, which had extended intraductally from another invasive ductal carcinoma in the subareolar region, and had infiltrated the epidermis of the nipple (Paget's disease). MR mammography successfully detected the relationship between the tumors. Postoperatively, the plasma prolactin level was abnormally high, while the plasma estradiol level was quite low, although macro-pituitary adenoma was not detected by MRI. The patient was treated with bromocriptine mesilate, in addition to adjuvant chemotherapy for breast cancer, and the plasma prolactin level has since normalized.

Two cases of gastrointestinal stromal tumor of the stomach with lymph node metastasis.

Lymph node metastasis from gastrointestinal stromal tumor (GIST) is quite rare. We report two cases of gastric GIST with nodal metastases and results of their mutation analyses. In the first case (78-year-old male), a mass 4.0 cm in size was located at the gastric cardia. Proximal gastrectomy was performed. In the other case (40-year-old female), the gastric tumor was 2.5 cm in size. Computed tomography scan revealed a hepatic metastasis. Imatinib mesylate was administered as primary treatment, at the patient's preference, but the tumors exhibited no response. Wedge resection of the stomach and partial hepatectomy were performed. In both cases, histological examination revealed that the tumors consisted of spindle cells. In the former case, there was an isolated lymph node metastasis at the right cardia. In the latter, three of 5 sampled nodes adjacent to the tumor were positive. In both cases, immunohistochemical analyses showed that primary and metastatic tumors were diffusely positive for CD117 and CD34 and negative for desmin and S100-protein. In the former case, there was a deletion mutation in CD117 exon 11, the most common genotype in GIST. In the latter, there were no detectable mutations in CD117 or platelet-derived growth factor receptor alpha.

Breast signet-ring cell lobular carcinoma presenting with duodenal obstruction and acute pancreatitis.

We report here an extremely rare case of breast signet-ring cell carcinoma (SRCC) initially manifesting as duodenal metastasis and acute pancreatitis. A 62-year-old female presented with duodenal obstruction and swollen head of the pancreas, and the diagnosis of acute pancreatitis was initially made. Upper gastrointestinal endoscopy revealed duodenal stenosis with erosive mucosa, with signet-ring cells infiltrating the submucosal layer, suggesting duodenal metastasis of SRCC. Despite absence of a palpable mass in both breasts, computed tomography revealed diffuse enhancement of the left breast in addition to left axillary lymphadenopathy. Histological examination of mammary needle biopsy samples revealed SRCC with a non-invasive lobular carcinoma component. Primary breast SRCC with duodenal metastasis was therefore diagnosed. The patient underwent palliative surgery twice for intestinal obstruction due to peritoneal dissemination. She has remained alive without bowel obstruction for 18 months while being treated with cytotoxic chemotherapies.

Invasive Paget's disease of the male nipple: a case report.

Male mammary Paget's disease (MPD) is extremely rare. Furthermore, MPD with invasion downward into the dermis of the male nipple has been reported rarely. A 56-year-old Japanese man presented with a lump and eczema in the right nipple-areola area. Ultrasonography revealed only a cystic lesion below the right areola. With a diagnosis of MPD with invasion into the dermis associated with ductal carcinoma in situ, mastectomy and sentinel lymph node biopsy were performed. MPD with dermal invasion is extremely rare, and only one male case has been reported in the English literature; therefore, the current case is the second case of male MPD with dermal invasion.

Coexistence of malignant phyllodes tumor and her2-positive locally advanced breast cancer in distinct breasts: A case report.

INTRODUCTION: Phyllodes tumor of the breast is a rare biphasic neoplasm, accounting for less than 1% of all breast tumors. Coexistence of phyllodes tumor and breast cancer in distinct breasts is extremely rare. CASE PRESENTATION: A 47-year-old Japanese woman presented with bilateral breast lumps. A HER2-positive, unresectable invasive carcinoma in the right breast and fibroadenoma in the left were diagnosed via core needle biopsy. During chemotherapy with anti-HER2 therapy, the breast cancer shrank quickly, while the left breast lump suddenly enlarged. Under a diagnosis of malignant neoplasm of the breast, left mastectomy was performed. Malignant phyllodes tumor was diagnosed by postoperative histological examination and recurred in multiple areas as early as 2 months after surgery. DISCUSSION: Only 10 cases of coexisting phyllodes tumor and breast cancer in distinct breasts have been reported in the English literature. Phyllodes tumor associated with breast cancer in distinct breasts tends to be malignant. This is the first case of phyllodes tumor rapidly enlarging during anti-HER2 chemotherapy for locally advanced HER2-positive breast cancer. CONCLUSION: Even during effective treatment of advanced or recurrent breast cancer, attention should also be paid to the contralateral breast for the possible association of a second malignancy such as phyllodes tumor.

Effects of omega-3 fatty acids on orexigenic and anorexigenic modulators at the onset of anorexia.

In cancer anorexia, a decrease in food intake (FI) occurs concomitant with changes in orexigenic peptides such as neuropeptide Y (NPY) and anorexigenic peptides such as alpha-melanocyte-stimulating hormone (alpha-MSH) and anorexigenic neurotransmitter serotonin. omega-3 Fatty acid (omega-3FA) inhibits cytokine synthesis, and delays tumor appearance, tumor growth, and onset of anorexia in tumor-bearing rats. We hypothesize that, in cancer anorexia, omega-3FA is associated with quantitative reversal of hypothalamic NPY, alpha-MSH, and serotonin receptor (5-HT(1B)-receptor) enhancing FI. Fischer rats were divided into: MCA tumor bearing fed chow (TB-Chow) or omega-3FA diet (TB-omega-3FA) and controls: non-tumor bearing fed chow (NTB-Chow) or omega-3FA diet (NTB-omega-3FA). Rats were euthanized at anorexia and brains were removed for hypothalamic immunohistochemical study, using NPY, alpha-MSH, and 5-HT(1B)-receptor-specific antibodies and slides assessed by image analysis. Immunostaining specificity was controlled by omission of primary or secondary antibodies and pre-absorption test. At anorexia, FI decreased (P < 0.05) in TB-Chow but did not change in TB-omega-3FA rats. In TB-omega-3FA vs. TB-Chow, NPY immunoreactivity increased 38% in arcuate nucleus (ARC; P < 0.05), and 50% in magnocellular paraventricular nucleus (mPVN; P < 0.05). alpha-MSH decreased 64% in ARC and 29% in mPVN (P < 0.05). 5-HT(1B)-receptor immunoreactivity decreased 13% only in supraoptic nucleus (P < 0.05). No immunoreactivity was found in the control sections. omega-3FA modified hypothalamic peptides and 5-HT-(1B)-receptor immunoreactivity at anorexia, concomitant with an increase in FI, were probably mediated by omega-3FA inhibition of tumor-induced cytokines.

Changes in hypothalamic neuropeptide Y and monoaminergic system in tumor-bearing rats: pre- and post-tumor resection and at death.

BACKGROUND: Cancer anorexia is influenced by the neuropeptidergic and monoaminergic systems. We hypothesize that serotonin (5-HT), dopamine (DA) and neuropeptide Y (NPY) concentrations in paraventricular (PVN), ventromedial (VMN), and lateral hypothalamus (LHA) areas are abnormal in tumor-bearing rats. METHODS: Fifty-five Fischer rats (240-280 g) were divided into MCA tumor-bearing (TB), nontumor-bearing (NTB), pair-fed (PF), TB sacrificed at the end of experiment (TB-Terminal), TB resection (TB-Resection), NTB sham-operated (NTB-Sham) and pair-fed sham-operated (PF-Sham) groups. Rats were sacrificed at onset of anorexia (TB, NTB, and PF) and 9 days after tumor resection (TB-Resection, NTB-Sham, PF-Sham, and TB-Terminal). Bilateral PVN, VMN, and LHA were harvested for NPY, 5-HT, and DA analyses. RESULTS: Food intake decreased in TB versus NTB (P < .05). In TB versus NTB, an increase of 5-HT in PVN and VMN occurred with a concomitant decrease in DA. NPY in PVN, VMN, and LHA decreased (P < .05). In TB-Resection versus NTB-Sham, 5-HT, DA, NPY, and FI normalized after tumor resection. CONCLUSIONS: Cancer anorexia is associated with abnormal serotonin, dopamine, and NPY concentrations, expressed by an increase in 5-HT and a decrease in DA and NPY. After tumor resection, these alterations normalized, providing evidence that the levels of these substances change with anorexia in tumor-bearing rats.

Tumor anorexia: effects on neuropeptide Y and monoamines in paraventricular nucleus.

Paraventricular (PVN) concentrations of neuropeptide Y (NPY), serotonin (5-HT) and dopamine (DA) in anorectic tumor-bearing (TB) rats were measured before and after tumor resection. At onset of anorexia in TB versus non-tumor bearing (NTB) Controls 5-HT increased from 12.19+/-0.49 pg/microg to 14.89+/-0.81 pg/microg ( P<0.05 ) while DA and NPY decreased from 7.34+/-0.42 pg/microg to 4.97+/-0.56 pg/microg and 23.47+/-4.27 pg/microg to 13.64+/-1.44 pg/microg, respectively ( P<0.05 ). After tumor resection, these neuromediators normalized when compared to sham-operated NTB rats. NTB pair-fed Controls were also studied. We conclude that the increased 5-HT and the decreased DA and NPY concentrations in PVN are associated with cancer anorexia and that the NPY food stimulatory effect is linked to serotoninergic and dopaminergic systems in hypothalamus.

Effects of omega-3 fatty acid supplementation on tumor-bearing rats.

BACKGROUND: Dietary fish oil (rich in omega-3 fatty acids: eicosapentaenoic acid and docosahexaenoic acid) suppresses synthesis and activity of proinflammatory cytokines that induce anorexia. We hypothesized that dietary fish oil reverses the feeding pattern of tumor anorexia, increasing food intake and retarding tumor growth. STUDY DESIGN: Thirty-two Fischer rats were placed in Automated Eater Meter cages and randomly divided into four groups: tumor bearing (TB) rats eating normal chow diet (TB-Chow); TB rats eating chow diet supplemented with omega-3 fatty acids (TB-omega-3FA); Controls, non-tumor bearing (NTB) rats eating normal chow (NTB-Chow); and NTB rats with omega-3 fatty acid supplementation (NTB-omega-3FA). Doses of 10(6) methylcholanthrene (MCA) sarcoma cells were subcutaneously injected in TB rats. Daily food intake, meal size (MZ), meal number (MN), body weight, and tumor volume were measured, and rats were euthanized at onset of anorexia. Data were statistically analyzed using analyses of variance (ANOVA) and t-tests. Data are reported as mean +/- SE. RESULTS: Tumor appeared significantly earlier in TB-Chow than in TB-omega-3FA rats (7.5 +/- 0.3 days versus 11.6 +/- 0.8 days, p < 0.05). Daily food intake declined significantly in TB-Chow versus TB-omega-3FA rats 18 days after tumor inoculation and, at onset of anorexia, was 9.41 +/- 1.77 g/day versus 13.32 +/- 0.81 g/day, p < 0.05. Food intake decreased initially by decrease in meal number (at day 15) followed by a decrease in meal size (at day 18). At onset of anorexia, meal size and meal number were significantly decreased in TB-Chow versus TB-omega-3FA rats (0.75 +/- 0.067 g/meal versus 1.05 +/- 0.08 g/meal, p < 0.05) and (9.5 +/- 1.32 versus 12.79 +/- 0.93 meals/day, p < 0.05), respectively. Tumor volume was significantly smaller in TB-omega-3FA versus TB-Chow rats (7.6 +/- 0.6 cm(3) versus 16.5 +/- 1.0 cm(3), p < 0.05), as was tumor weight (7.5 +/- 2.2 g versus 18.1 +/- 1.6 g, p < 0.05). CONCLUSIONS: In TB rats, omega-3FA improved food intake; restored normal eating pattern, delayed onset of anorexia, tumor appearance, and growth; and prevented body weight loss. Supplementation of omega-3 fatty acids has therapeutic potential in cancer anorexia.

Plasma leptin, insulin and free tryptophan contribute to cytokine-induced anorexia.

Cytokines contribute to anorexia of diseases. Tumor Necrosis Factor (TNF) and/or interleukin-1 (IL-1) stimulate leptin release, but not insulin. Both affect hypothalamus to decrease food intake (FI). Hypothalamic serotonin (5HT) decreases FI. Its synthesis depends on brain availability of precursor, tryptophan (TRP), which depends on plasma free TRP. Purpose is to test involvement of plasma leptin, insulin, TRP, and thus hypothalamic 5HT in cytokine-induced anorexia in rats. In male rats, IL-1alpha (10 mg/kg/d; n=9), TNFalpha (30 mg/kg/d; n=9), Il-1alpha+TNFalpha (10:30 mg/kg/d; n=9), TRP (100 mg/kg/d, n=8) and saline (n=8; Control) were injected sc for 2 days. FI, BW, plasma free and total TRP, leptin and insulin, and body fat were measured. Data analyzed via ANOVA. IL-1alpha and IL-1alpha+TNFalpha vs others decreased FI and BW. TNFalpha and TRP did not change FI and BW. Plasma total TRP was higher in TRP vs IL-1alpha, TNFalpha, and IL-1alpha+TNFalpha. Plasma free TRP was higher in IL-1alpha and IL-1alpha+TNFalpha vs Control. IL-1alpha and IL-1alpha+TNFalpha decreased leptin and body fat. Insulin in Control was lower than others. Data suggest: i) IL-1alpha increases plasma free TRP, but not total TRP, thus increases hypothalamic 5HT synthesis, resulting in anorexia; ii) leptin does not mediate anorexia, but; iii) insulin may contribute to anorexia induced by cytokines.

Ductal carcinoma in situ with isolated tumor cells in the sentinel lymph node in a 17-year-old adolescent girl.

We report here a quite rare case of ductal carcinoma in situ (DCIS) with isolated tumor cells in the sentinel lymph node in a 17-year-old adolescent girl whose mother also had advanced breast cancer. Findings included an elastic mass in the right breast accompanied by serous nipple discharge. DCIS of the breast was diagnosed following core needle biopsy. Although no invasive focus was clearly observed in the mastectomy sample, isolated tumor cells were found in the sentinel lymph node. Although the family refused genetic testing, a hereditary abnormality may have played a role in the carcinogenesis in this case.