Successful continuance of CDK4/6 inhibitor treatment with palbociclib after abemaciclib-induced hepatotoxicity in breast cancer: a case report.

Abemaciclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, causes severe hepatotoxicity, a severe adverse event associated with the loss of treatment opportunities. We report a case of liver injury (grade 4) during treatment with abemaciclib, in which the patient was switched to palbociclib and successfully treated with this CDK4/6 inhibitor. A 73-year-old woman with bone metastatic breast cancer (hormone-positive, HER2-negative) was treated with abemaciclib, fulvestrant, denosumab, and precipitated calcium carbonate with cholecalciferol and magnesium carbonate (pCCCM). On day 17, the patient developed skin rashes on her trunk and arms. On day 22, abemaciclib and pCCCM were discontinued due to drug eruption. Grade 3 aspartate aminotransferase (AST) and grade 4 alanine aminotransferase (ALT) levels increased on day 29. Therefore, fulvestrant and denosumab were suspended as the causes of severe hepatotoxicity, in addition to the two drugs suspected of causing the skin eruption. On day 43, AST and ALT levels did not improve, and the patient was referred to a hepatologist. The hepatologist diagnosed hepatotoxicity as a drug-induced liver injury through additional tests and interviews. Fulvestrant treatment was resumed on day 78, and palbociclib on day 92, and denosumab and pCCCM on day 134. On day 287, treatment with the CDK4/6 inhibitor was continued without evidence of liver dysfunction. This case suggests that rechallenge with palbociclib after severe liver injury with abemaciclib may allow for continued treatment with CDK4/6 inhibitors.

A case study of pyloric stenosis caused by metastatic lobular carcinoma of breast.

Metastasis to the gastrointestinal tract is rare. A 59-year-old woman who had a history of an invasive lobular carcinoma of breast with clinical complete response visited our hospital and complained of an upper abdominal pain and distension. We performed an upper gastrointestinal endoscopy which showed only a gastric ulcer without any malignant findings. She experienced a recurrence of symptoms 2 months after this visit. An endoscopy revealed pyloric stenosis, which did not improve with balloon dilatation. We performed a gastro-jejunal and cecal-transverse colonic bypass surgery. Diffuse wall thickening of the antrum was verified during the surgery, and a biopsy sample was collected. The diagnosis of gastric metastasis from breast was confirmed since it showed the same immunohistochemistry pattern as the prior breast lesion. Pyloric stenosis has still been confirmed with an endoscopy, she has been alive with satisfactory oral food intake for >10 years.

Laparoscopic repair of diaphragmatic hernia associating with radiofrequency ablation for hepatocellular carcinoma: A case report.

BACKGROUND: Radiofrequency ablation (RFA) is an effective treatment for early-stage hepatocellular carcinoma (HCC). Although RFA is a relatively safe technique compared with surgery, several complications have been reported to be following/accompanying this treatment. Delayed diaphragmatic hernia caused by RFA is rare; however, the best surgical approach for its treatment is uncertain. We present a case of laparoscopic repair of diaphragmatic hernia due to RFA. CASE SUMMARY: An 80-year-old woman with segment VIII HCC was treated twice in 5 years with RFA; 28 mo after the second RFA, the patient complained of right hypochondriac pain. Computed tomography revealed that the small intestine was incarcerated in the right thorax. The patient was diagnosed with diaphragmatic hernia and underwent laparoscopic repair by non-absorbable running sutures. The patient's postoperative course was favorable, and the patient was discharged on postoperative day 12. The diaphragmatic hernia has not recurred 24 mo after surgery. CONCLUSION: Laparoscopic treatment of iatrogenic diaphragmatic hernia is effective and minimally invasive.

Successful Stabilization of Symptomatic Bone Marrow Metastasis Two Times in a Breast Cancer Patient.

BACKGROUND: Bone marrow metastasis is very uncommon in breast cancer. Cancer patients showing a dramatic response to chemotherapy with full recovery are very rare. CASE REPORT: This is a case report of a 62-year-old woman who underwent partial mastectomy six years previously. The patient presented with increased fatigue and her hemoglobin level was 6.7 g/dl. Pathological examination of a bone marrow biopsy showed metastasis from breast cancer. Systemic therapy was initiated with doxorubicin and cyclophosphamide and pancytopenia was steadily improved. However, 15 months later, she felt severe fatigue again. Eribulin was administered and the patient showed sufficient recovery. She had two bone marrow metastases that caused pancytopenia including severe anemia. However, she survived twice with chemotherapy. CONCLUSION: Bone marrow metastasis of breast cancer is life-threatening; however, chemotherapy may significantly improve survival.

Inflammatory breast cancer associated with amyopathic dermatomyositis: a case report.

BACKGROUND: Dermatomyositis is associated with malignant tumors including breast cancer, and inflammatory breast cancer is considered to have a poorer prognosis than most breast cancers. CASE PRESENTATION: A 74-year-old Asian woman, developed erythema on her face, back, and the back of her hands, 3 weeks before attending our department. At the same time, she had noticed a right breast mass and redness of the skin of the breast. The clinical findings and vacuum aspiration biopsy diagnosed inflammatory breast cancer and neoadjuvant chemotherapy was performed. The mass and enlarged axillary lymph nodes had shrunk, therefore a total mastectomy was performed. The sentinel lymph node biopsy was negative. She was discharged 7 days after surgery without any complications. She has received a postoperative aromatase inhibitor and is alive without recurrence. The dermatomyositis also began to improve with the start of her chemotherapy and has not recurred since the surgery. CONCLUSIONS: Neoadjuvant chemotherapy was performed for inflammatory breast cancer with dermatomyositis, and tumor shrinkage was confirmed. A total mastectomy without axillary lymph node dissection was performed. Dermatomyositis and breast cancer have not recurred. Dermatomyositis may have been a paraneoplastic syndrome due to breast cancer.

[Resection of a Granulocyte Colony-Stimulating Factor-Producing Anaplastic Carcinoma of the Pancreas, Associated with Humoral Hypercalcemia of Malignancy].

We herein report the case of a 65-year-old man who presented with an anaplastic carcinoma of the pancreas, producing granulocyte colony-stimulating factor (G-CSF). The patient's laboratory data showed an increase in his serum CA19-9 levels 1 year after he had undergone surgery for transverse colon cancer. Computed tomography (CT) showed a mass in the pancreatic head. Following a diagnosis of primary or metastatic pancreatic cancer, we performed the pancreatoduodenectomy. The postoperative course was uneventful. However, on postoperative day 28, he suffered a disturbance of consciousness and demonstrated hypercalcemia with elevated serum levels of parathyroid hormone-related protein (PTHrP). CT revealed multiple liver metastases and massive ascites. His serum Ca level decreased temporarily, and he subsequently died 58 days after the pancreatoduodenectomy. A pathological examination revealed pleomorphic-type anaplastic carcinoma of the pancreas. Immunohistochemical staining showed the tumor cells to be positive for G-CSF. To the best of our knowledge, there have been no reports of G-CSF-producing anaplastic carcinoma of the pancreas associated with humoral hypercalcemia of malignancy.

Invasive Solid Papillary Carcinoma of the Nipple With Pagetoid Extension and Nodal Metastasis.

We report a case of invasive solid papillary carcinoma (SPC) of the nipple with Pagetoid extension to the skin and lymph node metastasis. SPC is an uncommon primary breast cancer accounting for less than 1% of all breast cancers. Only 2 cases occurring in the nipple have been reported. However, both cases were without Pagetoid extension or lymph node metastasis. The presently reported tumor consisted of irregularly shaped solid cell nests with delicate fibrovascular cores. The tumor cells had round nuclei with low-grade atypia and eosinophilic cytoplasm. Neuroendocrine differentiation was confirmed by immunohistochemical positivity for CD56, synaptophysin, and chromogranin A. Immunohistochemistry also confirmed the absence of myoepithelial cells around the tumor cell nests. Therefore, a diagnosis of invasive SPC was made. Additionally, tumor cell deposits in the intramammary and axillary lymph nodes were identified, and these deposits had the same histological characteristics as the invasive SPC of the nipple. The invasiveness of SPC can be difficult to determine. However, the tumor cell nests in the current case exhibited a retraction artifact, which is known to be associated with invasive carcinoma and a poor prognosis, as well as morphological patterns that have been previously identified as characteristic of invasive SPC. Although SPC is widely recognized as having a favorable outcome, the existence of exceptionally aggressive cases occurring in the nipple must be recognized. Additional cases of invasive SPC of the nipple are needed to analyze the clinicopathological correlation.

Perforation of abdominal esophagus following nasogastric feeding tube intubation: A case report.

INTRODUCTION: Perforation of the abdominal esophagus caused by nasogastric tube (NGT) intubation has been rarely reported in adults. PRESENTATION OF CASE: A 73-year-old man was admitted to our hospital with pneumonia. He had been bedridden long-term and had previously undergone a gastrectomy for gastric ulcer. Since admission was prolonged, and he required enteral feeding because of his inability to swallow, a NGT was inserted blindly. The next day, he had a high fever and abdominal pain. Abdominal computed tomography scan revealed that the tube was inserted through the wall of the abdominal esophagus into the abdominal cavity. In the emergency surgery, we sutured the perforated site of abdominal esophagus and patched it with lesser omentum. The postoperative course was good. DISCUSSION: Abdominal esophageal perforation due to NGT insertion is very rare. The cause of perforation was suggested to be an abnormal deformity created by adhesion due to previous distal gastrectomy and long-term bedridden status. A chest X-ray usually is performed to confirm the position of the NGT tube. In this case, a frontal radiographic view apparently showed the NGT placed in the stomach. CONCLUSION: When NGT is inserted to such patients, frontal and lateral radiographic views or fluoroscopic guidance should be obtained.

[Surgical Resection of an Intraductal Papillary Mucinous Carcinoma Observed on Imaging Four Years after the Initial Diagnosis].

We herein report a 75-year-old woman who presented with an intraductal papillary mucinous carcinoma(IPMC)who was treated with surgical resection 4 years after the initial diagnosis was made. She previously underwent a high anterior resection of the rectum for rectal cancer at 71 years of age. Preoperative CT revealed a multilocular cystic mass measuring 6 cm in size in the body of the pancreas, which was considered benign. We followed up the intraductal papillary mucinous neoplasm(IPMN) by using annual CT imaging for 4 years. CT revealed a gradual increase in the size of the mass and the development of an intramural nodule in the IPMN. Endoscopic retrograde pancreatography revealed dilatations of the main pancreatic duct communicating with the multilocular cystic lesion. The cytology of the pancreatic juice demonstrated class III b. We therefore diagnosed the patient as having IPMC and performed total pancreatectomy. The postoperative course was uneventful without any recurrence. To our knowledge, only few reports have described the natural history of IPMNs. This resected case of IPMC is rare on the basis of our observation of the natural history of an IPMN using long-term imaging studies.

Duodenal rupture due to giant inguinal hernia: A case report.

INTRODUCTION: Giant inguinal hernia is unusual, and duodenal rupture accompanying it is particularly very rare and significantly hard to manage surgically. PRESENTATION OF CASE: An 81-year-old man was admitted to our institution with upper abdominal pain. He had tenderness of the upper mid abdomen and a bilateral large inguinal hernia but he did not have pain in the inguinal-scrotal area. Computed tomography (CT) showed slight dilatation of the small bowel and stomach. There were no remarkable signs of incarceration of the inguinal hernia. Therefore, he was admitted to the internal ward. On the second day in hospital, he suddenly went into shock. CT revealed that there was free air and ascites in the inguinal hernia and therefore an emergency operation was performed. The tranverse colon, ascending colon, and ileum were incarcerated, and perfolation of the cecum was found. We also detected duodenal rupture at the inferior duodenal angle. We resected the terminal ileal (almost 90cm) and ileocecal area, followed by side-to-side anastomosis of duodenum and jejunum. We only repaired the peritoneum at the internal hernia ring. After the operation, despite intensive-care therapy, this patient passed away on the 18th postoperative day. DISCUSSION: The mesocolon and third portion of the duodenum were strongly pulled down into giant inguinal hernia, probably causing the rupture of the inferior duodenal angle. CONCLUSION: Giant inguinal hernia possibly provokes duodenal rupture and therefore should definitively be repaired if feasible.

Excessive visceral fat area as a risk factor for early postoperative complications of total gastrectomy for gastric cancer: a retrospective cohort study.

BACKGROUND: Obesity is a known risk factor for complications after digestive surgery. Body mass index (BMI) is commonly used as an index of obesity but does not always reflect the degree of obesity. Although some studies have shown that high visceral fat area (VFA) is associated with poor outcomes in digestive surgery, few have examined the relationship between VFA and total gastrectomy. In this study, we demonstrated that VFA is more useful than BMI in predicting complications after total gastrectomy. METHODS: Seventy-five patients who underwent total gastrectomy for gastric cancer were enrolled in this study; they were divided into two groups: a high-VFA group (n = 26, ≥100 cm(2)) and a low-VFA group (n = 49, <100 cm(2)). We retrospectively evaluated the preoperative characteristics and surgical outcomes of all patients and examined postoperative complications within 30 days of surgery (including cardiac complications, pneumonia, ileus, anastomotic leakage, pancreatic fistula, incisional surgical site infection [SSI], abdominal abscess, and hemorrhage). RESULTS: The incidence of anastomotic leakage (p = 0.03) and incisional SSI (p = 0.001) were higher in the high-VFA group than in the low-VFA group. No significant differences were observed in the other factors. We used univariate analysis to identify risk factors for anastomotic leakage and incisional SSI. Age and VFA were risk factors for anastomotic leakage, and BMI and VFA were risk factors for incisional SSI. A multivariate analysis including these factors found that only VFA was a predictor of anastomotic leakage (hazard ratio [HR] 4.62; 95 % confidence interval [CI] 1.02-21.02; p = 0.048) and incisional SSI (HR 4.32; 95 % CI 1.18-15.80; p = 0.027]. CONCLUSIONS: High VFA is more useful than BMI in predicting anastomotic leakage and SSI after total gastrectomy. Therefore, we should consider the VFA value during surgery.

Retroperitoneal Biloma due to Spontaneous Perforation of the Left Hepatic Duct.

BACKGROUND: Spontaneous perforation of the bile duct in adults is very rare, particularly in cases accompanied by retroperitoneal biloma. We report a patient with retroperitoneal biloma due to a spontaneous perforation of the left hepatic duct. CASE REPORT: An 82-year-old man was admitted to our institution with abdominal pain and a high fever. He had tenderness at the epi-mesogastrium. Computed tomography showed several stones in the gall bladder and common bile duct (CBD) and a few ascites. A substantial amount of fluid had collected from the dorsal stratum of the duodenum and pancreas head to the right paracolic gutter and anterior side of the right iliopsoas. Laboratory examination revealed a high inflammation score. He underwent emergent laparotomy. Biliary fluid was revealed after the mobilization of the pancreas head, duodenum, and right side of the colon. Bile duct perforation was suspected. Therefore, we exfoliated the dorsal side of the CBD to the cranial side, and intraoperative cholangiography was performed. However, the perforation site could not be detected. Cholecystectomy and choledocholithotomy were performed. A retrograde transhepatic biliary drainage tube was inserted, and primary closure of the CBD incision site was achieved. Postoperative cholangiography revealed leakage from the left hepatic duct near the caudate branch. CONCLUSIONS: There are a few reports of spontaneous bile duct perforation cases in the literature, particularly on infants or children with congenital anomalies, but it is rare in adults. It usually causes bile peritonitis, although bile duct perforation should be considered in the differential diagnosis of spontaneous retroperitoneal fluid collection in adults.

[Complete Response in Far-Advanced Esophageal Cancer Treated with Induction Chemotherapy Followed by Definitive Chemoradiotherapy].

We report a case of far-advanced esophageal cancer in which induction chemotherapy followed by chemoradiotherapy achieved complete remission. A 61-year-old female presented to our hospital with dyspnea and hoarseness. CT revealed a tumor at the cervical esophagus invading and narrowing the trachea, a bulky metastasis at the right paraesophageal node, and nodal metastases at levels II and III of the left neck. No finding indicated other distant metastases. According to findings of CT and endoscopy, she was diagnosed with unresectable cancer at the cervical esophagus(cT4bN1M1[LYM], according to UICC-TNM 7 th). After 2 courses of induction chemotherapy(DTX, CDDP, and 5-FU), the tumor's volume was remarkably reduced. Thereafter, chemoradiotherapy with CDDP, 5-FU, and 60 Gy/30 Fr was administered. After 7 months of systemic chemotherapy with paclitaxel following chemoradiotherapy, the patient was judged to have complete remission based on CT and endoscopic findings. After additional administration of S-1 for 5 months, systemic chemotherapy was ceased. The patient has survived without disease progression for 22 months following initiation of treatment. It is thought that induction chemotherapy followed by chemoradiotherapy might improve local control and survival of patients with far-advanced esophageal cancers, such as our patient.

Total mastectomy and chest reconstruction for a rapidly progressing giant phyllodes tumor with skin necrosis: a case report.

Phyllodes tumors are rare fibroepithelial neoplasms of the breast. In the literature, borderline or malignant tumors have been reported to present with unusual characteristics including a short clinical history and extremely rapid tumor growth. Skin necrosis and infection sometimes accompanies these malignancies. Giant phyllodes tumors have a good prognosis when treated with total mastectomy, but reconstruction of the chest wall has been a challenge because of the need for a wide-range excision. We report a case of a malignant phyllodes tumor that was initially diagnosed as borderline because sudden growth of the tumor contrarily induced sparse to moderate stroma cellularity in the sections of the tumor that were biopsied. Total mastectomy without axillary lymph node resection and chest wall reconstruction using a full-thickness mesh skin graft was performed. The patient has remained free from infection and recurrence for over a year since diagnosis.

Lobectomy of pulmonary metastasis of endometrial stromal sarcoma.

Pulmonary metastasis of low-grade endometrial stromal sarcoma is rare. A 61-year-old woman visited our hospital due to an abnormal chest shadow. Computed tomograhy showed a mass that was composed of a cystic and solid lesion, in the right lower lobe. She had undergone a combination of a hysterectomy and adnexectomy for a low-grade endometrial stromal sarcoma 57 months previously, and undergone adjuvant radiation therapy at the local site. To obtain a definitive diagnosis of the lung tumor, we performed lobectomy of the right lower lobe and lymph node dissection. To avoid possible dissemination, the tumor was resected not using video-assisted thoracic surgery but using thoracotomy. The pathologic diagnosis was pulmonary metastasis of the low-grade endometrial stromal sarcoma. Now, medroxyprogesterone acetate is being administered, and no signs of recurrence have been detected in the 24 months since the lung resection.

[A patient with advanced gastroesophageal junction cancer responding completely to S-1 monotherapy].

A 74-year-old woman was referred to our hospital for a close examination. A gastrointestinal endoscopic examination revealed an advanced gastroesophageal junction cancer type 3, which was diagnosed as well-differentiated adenocarcinoma. Computed tomography(CT)showed liver and para-aortic lymph node metastases.She was treated with oral S-1 at 100mg/ day for 28 days, followed by a 14-day rest. After 3 courses of treatment, the primary tumor was greatly reduced. After 18 months of treatment, CT showed a complete response of the liver and also the para-aortic lymph node metastases. She is alive without severe adverse effects and recurrence 2.5 years after the start of S-1 administration.

Pulmonary inflammatory pseudotumor observed by bronchoscopy and resected using video-assisted thoracic surgery.

Pulmonary inflammatory pseudotumor is rare. A 34-year-old woman visited our hospital due to an abnormal chest shadow. Computed tomograhy showed a nodule in the right upper lobe. Bronchoscopy showed a polypoid endobronchial nodule obstructing most of the orifice of B2a. The nodule was white, glossy, and smooth, and it seemed to be covered with bronchial mucosa. However, transbronchial biopsy could not facilitate a diagnosis. To obtain a definitive diagnosis, we performed lobectomy of the right upper lobe using video-assisted thoracic surgery and removed the nodule completely. The pathologic diagnosis made during surgery was inflammatory pseudotumor. Immunohistochemical examination showed proliferating spindle cells were positive for vimentin and smooth muscle actin, but negative for epithelial markers. These findings were consistent with the staining pattern of inflammatory pseudotumor previously reported. Careful follow-up is necessary to detect any sign of local recurrence and distant metastases.

Flexible enantioselectivity of tryptophanase attributable to benzene ring in heterocyclic moiety of d-tryptophan.

The invariance principle of enzyme enantioselectivity must be absolute because it is absolutely essential to the homochiral biological world. Most enzymes are strictly enantioselective, and tryptophanase is one of the enzymes with extreme absolute enantioselectivity for L-tryptophan. Contrary to conventional knowledge about the principle, tryptophanase becomes flexible to catalyze D-tryptophan in the presence of diammonium hydrogenphosphate. Since D-amino acids are ordinarily inert or function as inhibitors even though they are bound to the active site, the inhibition behavior of D-tryptophan and several inhibitors involved in this process was examined in terms of kinetics to explain the reason for this flexible enantioselectivity in the presence of diammonium hydrogenphosphate. Diammonium hydrogenphosphate gave tryptophanase a small conformational change so that D-tryptophan could work as a substrate. As opposed to other D-amino acids, D-tryptophan is a very bulky amino acid with a benzene ring in its heterocyclic moiety, and so we suggest that this structural feature makes the catalysis of D-tryptophan degradation possible, consequently leading to the flexible enantioselectivity. The present results not only help to understand the mechanism of enzyme enantioselectivity, but also shed light on the origin of homochirality.

Cricopharyngeal myotomy for primary cricopharyngeal dysfunction caused by a structural abnormality localized in the cricopharyngeus muscle: report of a case.

Primary cricopharyngeal dysfunction (PCD) is a rare idiopathic disorder of the upper esophageal sphincter (UES), characterized by oropharyngeal dysphagia, frequent aspiration, and narrowing at the level of the UES. Cricopharyngeal myotomy (CPM) has been used to treat oropharyngeal dysphagia of different causes including anatomic, neuromuscular, iatrogenic, inflammatory, neoplastic, and idiopathic; however, the indications for CPM and predictors of its outcome are not clearly defined. We report a case of PCD with hypertonic UES caused by a structural abnormality localized in the cricopharyngeus muscle, visualized as a cricopharyngeal bar, which we treated successfully by CPM, achieving long-term relief.