Neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel plus trastuzumab and pertuzumab followed by epirubicin and cyclophosphamide for operable HER2-positive primary breast cancer: a multicenter phase II clinical trial (PerSeUS-BC04).

BACKGROUND: Nanoparticle albumin-bound paclitaxel (nab-PTX) is a promising antibody partner for anti-human epidermal growth factor receptor 2 (HER2). We performed neoadjuvant chemotherapy (NAC) for HER2-positive breast cancer (BC) using nab-PTX plus trastuzumab (T-mab) and pertuzumab (P-mab), followed by epirubicin and cyclophosphamide (EC). METHODS: In this multicenter phase II clinical trial (January 2019-July 2020), patients with stage I (T1c)-IIIB HER2-positive primary BC were treated with four cycles of nab-PTX plus T-mab and P-mab, followed by four cycles of EC. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints were clinical response rate (RR), adverse events (AE), and tumor-infiltrating lymphocytes (TILs) in biopsy samples. RESULTS: In total, 43 patients were enrolled (mean age, 54 years). Twenty-two patients had HER2, and 21 patients had luminal/HER2-subtypes. The overall pCR rate was 53.5% (23/43, 95% CI: 42.6-64.1%, p = 0.184), whilst the pCR for HER2 was 68.2% (15/22, 95% CI: 45.1-86.1) and 38.1% for luminal/HER2 (8/21, 95% CI: 18.1-61.6%). The RR was 100% [clinical (c) CR:25, partial response (PR): 18]. AEs (≥ G3) included neutropenia (23.3%), leukopenia (7.0%), liver dysfunction (7.0%), and peripheral neuropathy (4.7%) when nab-PTX was administered. EC administration resulted in leukopenia (34.2%), neutropenia (31.6%), and febrile neutropenia (15.8%). The TILs in preoperative biopsy samples were significantly higher in pCR compared to non-pCR samples. CONCLUSION: Nab-PTX plus T-mab and P-mab induced a high pCR rate in HER2-positive BC, particularly in the HER2-subtype. Given that AEs are acceptable, this regimen is safe and acceptable as NAC for HER2-positive BC.

Drainage of Afferent Limb Obstruction via the Trans-gastric-bile Duct Formed after Endoscopic Ultrasound-guided Hepaticogastrostomy in a Patient with Pancreatic Cancer.

A 63-year-old man with advanced pancreatic cancer and pyloric obstruction underwent surgical gastrojejunostomy. Malignant biliary obstruction appeared eight months after surgery and was managed with endoscopic ultrasound (EUS)-guided hepaticogastrostomy (HGS). Subsequently, afferent limb obstruction caused by cancer invasion occurred. Although an intestinal metal stent could not be placed, a biliary metal stent was deployed via the HGS route, which successfully decompressed the afferent limb; the abdominal symptoms subsequently disappeared. In future similar cases, decompression of the dilated intestine through the HGS and biliary stent might be a viable treatment option.

[A Case of Neuroendocrine Carcinoma of the Stomach Treated with TAS-102].

A 77-year-old-woman underwent distal gastrectomy D2 lymph node dissection and cholecystectomy followed by Roux- en-Y reconstruction for Stage ⅢC gastric neuroendocrine cell carcinoma in January 2017. In July of the same year, an abdominal computed tomography scan revealed liver metastasis in segment 4. For treatment of recurrence, SP therapy(S-1 and cisplatin), ramucirumab plus weekly paclitaxel therapy, and nivolumab were administered in that order. TAS-102 was started as the fourth-line agent for multiple liver metastases, para-aortic lymph node metastases, and cancerous peritonitis. Although Grade 2 anemia, Grade 1 oral mucositis and general fatigue were observed during the treatment, both liver metastases and para-aortic lymph node metastases showed improvement after three courses, and the patient was able to continue 11 courses in 1 year. She died 1 year and 5 months after the first administration of TAS-102. TAS-102 can be effective after immune checkpoint inhibitor as a late treatment for gastric cancer and NEC. The appropriate timing for switching drug therapy may be important in the future. We report a favorable therapeutic effect of TAS-102 after immune checkpoint inhibitor treatment along with a review of the literature.

Laparoscopic surgery for appendiceal cancer with intestinal malrotation in an adult: A case report.

INTRODUCTION: Intestinal malrotation is a congenital anatomical anomaly resulting from abnormal midgut rotation. Many cases occur during childhood and present with intestinal obstruction and midgut volvulus. Intestinal malrotation rarely occurs in adults and is found incidentally because it is asymptomatic. We herein report a case of intestinal malrotation, and colorectal cancer operated laparoscopically. PRESENTATION OF CASE: A 78-year-old man presented to our Department of Surgical Gastroenterology with fecal occult blood. There were no abnormal findings in the physical examination. Colonoscopy revealed a type 3 tumor in the cecum. Contrast-enhanced computed tomography revealed that the tumor was located in the appendix along the midline of the abdomen. The small intestine and colon occupied the right and left sides of the abdominal cavity, respectively. The diagnosis was appendiceal cancer with nonrotation-type intestinal malrotation. A laparoscopy-assisted ileocecal resection was performed. During surgery, the right-side colon was not fixed to the retroperitoneum, and the right-side colon could be extracted out of the abdominal cavity through the umbilical wound with only adhesive dissection, and mesenteric and lymph node dissection can be performed outside the body. The postoperative course was uneventful. DISCUSSION: Appendiceal cancer with intestinal malrotation is managed with laparoscopic surgery because this method is safe and minimally invasive. CONCLUSION: The laparoscopic approach may be safer and less invasive than laparotomy, and extracorporeal lymph node dissection is safe and reliable for patients with intestinal malrotation.

Spontaneous bacterial peritonitis caused by Edwardsiella tarda: A case report.

INTRODUCTION: Edwardsiella tarda is a member of the Enterobacteriaceae family of gram-negative bacilli isolated from animals. Gastroenteritis is the most common manifestation of E. tarda infection. However, extraintestinal infections can occur in immunocompromised hosts as well as patients with hepatobiliary disease, malignancy, and/or diabetes mellites. The prognosis of sepsis caused by E. tarda is extremely poor, with a mortality rate of 38%. Here we report the occurrence of spontaneous bacterial peritonitis associated with E. tarda infection. PRESENTATION OF CASE: An 87-year-old man with Child-Pugh A cirrhosis secondary to hepatitis C virus infection presented with diarrhea and sudden-onset pain in the abdomen. On arrival, guarding and rebound tenderness were observed over the entire abdomen. Computed tomography revealed circumferential thickening of the cecum and a small volume of ascites in the pelvic cavity. A diagnosis of peritonitis was made, and surgery was performed. Surgical findings included redness and thickening of the cecal wall and purulent ascites without intestinal contents. Peritoneal fluid culture revealed E. tarda as the sole pathogen. The abdominal cavity was washed, a drain was placed in the pelvic cavity, and postoperative intravenous antibiotic therapy was initiated. The postoperative course was uneventful. DISCUSSION: E. tarda infection in the presence of an underlying disease such as hepatobiliary disease, malignancy, and/or diabetes mellitus has a poor prognosis. CONCLUSION: Although E. tarda infection is extremely rare, it is a life-threatening illness that can cause intestinal and extraintestinal infections. If necessary, early surgical intervention should be considered for cases of extraintestinal infection.

Complete resection of rectal cancer with a synchronous solitary adrenal metastasis: A case report.

INTRODUCTION: Solitary adrenal metastasis derived from colorectal cancer is rare. Adrenal metastasis is usually associated with systemic spread of the disease and is considered to be unsuitable for surgical resection. However, it has been reported that an aggressive surgical resection of adrenal metastasis results in improved overall survival in selected patients. We herein report an extremely rare case of complete resection of rectal cancer with a synchronous solitary adrenal metastasis. PRESENTATION OF CASE: A 70-year-old woman who presented with bloody stool was diagnosed with rectal cancer with a synchronous solitary adrenal metastasis and was suspected of having liver invasion. After a total of 2 cycles of chemotherapy with capecitabine and oxaliplatin, an abdominoperineal resection with D2 (proxD3) lymph node dissection and right adrenalectomy was performed and complete resection was possible. According to the TNM classification, the diagnosis was stage IVA (fT3N1bM1a[ADR]). At 18 months after surgery, the patient is alive with no evidence of recurrence and distant metastasis. DISCUSSION: Complete resection of adrenal metastasis may have a possibility of leading to a good prognosis in patients with a synchronous solitary adrenal metastasis. CONCLUSION: Adrenalectomy should be considered in patients who can undergo complete resection, as it may offer a good long-term prognosis.

Preoperative neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide for operable breast cancer: a multicenter phase II trial.

BACKGROUND: Recently, the use of taxane-based regimens before anthracycline-based regimens has been shown to achieve high pathological complete response (pCR) rates in patients with breast cancer. Nanoparticle albumin-bound paclitaxel (nab-PTX) has been reported as highly effective and less toxic compared with Cremophor-based Taxol. This phase II clinical trial evaluated the safety and efficacy of preoperative neoadjuvant chemotherapy (NAC) with nab-PTX followed by an epirubicin plus cyclophosphamide (EC)-based regimen for operable breast cancer. PATIENTS AND METHODS: From June 2012 to January 2014, four cycles of every-3-week (q3w) nab-PTX [plus q3w trastuzumab in cases of human epidermal growth factor 2 (HER2) positivity] followed by four cycles of q3w EC were administered to patients with operable breast cancer (stage IC-IIIA). The primary endpoint was the pCR rate (ypT0/TisypN0). RESULTS: A total of 55 patients were enrolled, 54 of whom received at least one nab-PTX dose. All patients underwent radical surgery after chemotherapy. The overall pCR rate was 22.2% (p = 0.006). The pCR rates for patients with the luminal B, luminal/HER2, HER2-rich, and triple-negative breast cancer subtypes were 10.5, 29.4, 60, and 15.4%, respectively. Stepwise logistic regression analysis revealed only HER2 as a significant factor for pCR (odds ratio 5.603; p = 0.024). The expression of secreted protein acidic and rich in cysteine showed no association with pCR. The clinical response rate was 70.4% (38/54), and the safety profile was tolerable. CONCLUSION: Preoperative NAC with nab-PTX followed by EC is effective and safe for operable breast cancer.

Preoperative diagnosis of an asymptomatic cancer restricted to the cystic duct.

INTRODUCTION: Even now, cystic duct cancer (CDC) as defined by Farrar is rare and has a better prognosis than gallbladder cancer, although CDC as defined by Ozden et al., the definition of which could apply to early and advanced cases of CDC, is not rare and has a poorer prognosis than the CDC defined by Farrar. PRESENTATION OF CASE: A 78-year-old woman with no complaints was found to have a tumor restricted to the cystic duct. Three cytology examinations of the patient's bile could not establish that the tumor was an adenocarcinoma. However, adenocarcinoma was suspected due to the hypervascularity shown on contrast-enhanced computed tomography. Cholecystectomy and extrahepatic bile duct resection with D2 lymph node dissection was performed. The pathological study revealed it to be CDC. Her postoperative course has been uneventful and without recurrence for 21 months. DISCUSSION: At their first medical examination, many CDC patients are found to have such advanced spread of the cancer to adjacent organs that an extended operation might be necessary. As in our case, better patient outcome results when no lymph node or remote metastasis is present. CONCLUSION: Diagnosing CDC as early as possible contributes to curative resections and favorable patient outcomes and also allows surgeons to recommend a mini-invasive procedure to their patients rather than extended resection including that of adjacent organs.

Predictive value of orotate phosphoribosyltransferase in colorectal cancer patients receiving 5-FU-based chemotherapy.

Pretreatment knowledge of chemosensitivity and side-effects of chemotherapy for colorectal cancer (CRC) patients are likely to ensure the best chemotherapeutic outcome. The aim of this study was to identify additional predictive factors of chemosensitivity to the key CRC treatment drug 5-fluorouracil (5-FU). Surgically obtained specimens from 106 patients treated for CRC were immunohistochemically assessed to investigate the correlation between the protein expression of the 5-FU metabolic enzymes orotate phosphoribosyltransferase (OPRT), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD), and clinicopathological characteristics as well as the correlation between the protein expression and outcomes of 5-FU-based chemotherapy. A correlation was detected between the high expression of the 5-FU metabolic enzyme OPRT and negative lymph node metastasis (P=0.0496), as well as between DPD and advanced Tumor-Node-Metastasis (TNM) grade cases (IIIA-IVB) and positive lymph node metastases (P=0.0414, respectively). In all 106 patients and in 79 patients undergoing 5-FU-based chemotherapy, survival was improved in those patients with a positive OPRT expression (P=0.0144 and 0.0167, respectively). OPRT expression was higher in the 79 patients with no recurrence (P=0.0179) as well as in patients treated with R0 surgery and 5-FU-based chemotherapy without side-effects (P=0.0126). Disease-free survival (DFS) rate was higher in patients without side-effects, and in patients with a positive OPRT expression without side-effects (P=0.0021 and 0.0031, respectively). Findings of this study demonstrated that OPRT expression positively correlated with fewer side-effects of 5-FU-based chemotherapy and longer patient survival.