Tumor disappearance on positron emission tomography computed tomography after S-1 treatment for postoperative local recurrence of gallbladder cancer

Objective: Gallbladder cancer (GBC) typically follows an aggressive course with the standard of care for advanced disease; complete responses are rarely encountered. We report a case in which tumor disappearance on positron emission tomography computed tomography (PET-CT) was treated with S-1 as the second-line treatment for local recurrence of GBC after gemcitabine (GEM) plus cisplatin (CDDP) (GC) combination therapy. Case Presentation: A 69-year-old woman was referred to our hospital with complaints of right hypochondrial pain. Based on ultrasound, CT, and magnetic resonance imaging (MRI) findings, we diagnosed patient with suspected GBC. Results: We performed the resection of the gallbladder base, partial resection of the transverse colon, and partial resection of the stomach for GBC. At four months after the surgery, PET-CT showed local recurrence. First-line chemotherapy with GC therapy was initiated. After 9 courses, PET-CT showed increased local recurrence. We concluded that GC treatment was ineffective. Second-line chemotherapy with S-1 was initiated for two weeks, followed by a 7-day rest period. PET-CT in September 2019 showed the markedly reduction of the local recurrence, and PET-CT in October 2021 showed the complete disappearance of the local recurrence. At 20 months after the discontinuation of S-1, PET-CT showed the complete disappearance of the local recurrence. Conclusions: Chemotherapy with S-1 can be managed safely and was demonstrated to be effective in treating the local recurrence of GBC recurrence

Clinicopathological study of small bowel gastrointestinal stromal tumor with surgical intervention

Objective: Gastrointestinal stromal tumors (GISTs) present with different clinical and immunohistochemical characteristics depending on the anatomic site. The present study clarified the clinicopathological characteristics of small bowel (SB) GISTs, which are relatively infrequent. Patients and Methods: The clinicopathological characteristics of 15 cases of small intestinal GISTs resected at our hospital were reviewed. SBGISTs were divided into duodenal (d) GISTs and jejunal/ ileal (ji) GISTs for the comparison. Results: The tumors included six cases in the duodenum, six in the jejunum, and three in ileum. All patients underwent duodenal wedge resection for dGIST and partial SB resection for jiGIST. The stage was I in seven patients, II in two patients, IIIB in five patients, and IV in one patient. The median postoperative observation period was 67 (11-175) months. Ten patients had no recurrence, two had hepatic and peritoneal recurrence, one had multiple hepatic recurrence, one had peritoneal recurrence, and one had lymph node recurrence. On comparing dGISTs and jiGISTs, recurrence was significantly more frequent in jiGISTs than in dGISTs. Conclusions: In five cases of recurrence, chemotherapy and surgery at the appropriate time seemed effective for achieving a long-term survival. Recurrence was significantly more frequent in jiGISTs than in dGISTs

S-1 and oxaliplatin regimen neoadjuvant chemotherapy followed by surgery for resectable advanced gastric cancer with multiple lymph-node metastasis

Objective: The prognosis of patients with advanced gastric cancer (GC) with multiple lymph-node metastasis is poor. The present study evaluated a neoadjuvant S-1 and oxaliplatin regimen (SOX) followed by D2 gastrectomy for advanced GC with lymph-node metastasis. Patients and Methods: Ten patients with resectable clinical advanced gastric cancer with multiple lymph-node metastasis who received preoperative SOX therapy were included in this study from 2015 to 2021. Results: A clinical evaluation by RECIST version 1.1 criteria after SOX therapy showed 8 cases of partial response (PR), 2 cases of stable disease (SD), and no progress disease (PD). The histopathological stages were IB in 3 patients, IIA in 2, IIB in 2, IIIA in 2, and IIIB in 1, and downstaging was observed in 8 of 10 patients (80%). Histopathological effects were Grade 1a in 4 patients, Grade 1b in 3 patients, Grade 2a in 2 patients, and Grade 2b in 1 patient; there were no Grade 3 patients. Adverse events of neoadjuvant chemotherapy (NAC) according to the CTCAE criteria were Grade 1 anemia, nausea, dysgeusia, and peripheral neuropathy in one patient each; Grade 2 anemia in two patients; and diarrhea in one patient. No grade ≧3 adverse events were observed. The surgical techniques were distal gastrectomy in four cases, total gastrectomy in five cases, and total gastrectomy and caudal pancreatectomy in one case; all patients underwent D2 dissection, and all received R0 surgery. One patient had local recurrence, and one patient had peritoneal recurrence and is on chemotherapy. The remaining eight patients are alive without recurrence. Conclusions: In the future, neoadjuvant chemotherapy with SOX therapy may become a treatment option for advanced resectable GC with multiple lymph-node metastasis

Clinical study of small bowel adenocarcinoma with surgical intervention

Objective: Small bowel adenocarcinoma (SBA) is a rare disease but its clinical features have been clearly elucidated. The present study clarified the clinicopathological characteristics, the effectiveness of the surgical procedure, neoadjuvant chemotherapy, and adjuvant chemotherapy of the patients with SBA. Patients and Methods: The clinicopathological characteristics of 9 cases of SBA resected at our hospital were reviewed between 2004 and 2017. Results: The mean age of the 9 patients (4 men, 5 women) was 69.6 (57-83) years. The sites included the duodenum (n=3), jejunum (n=3), and ileum (n=3). As neoadjuvant chemotherapy, S-1 was administered to a patient with a large duodenal adenocarcinoma invading the portal vein. The surgical procedures included partial resection of jejunum (n=3); partial resection of ileum (n=3); pylorus-preserved pancreatoduodenectomy (PD) (PPPD) with right hemicolectomy due to invasion of ascending colon (n=1); subtotal stomach-preserving PD (SSPPD) (n=1); and wedge resection of the duodenum (n=1). The stage was classified as follows: stage I (n=1), stage IIA (n=1), stage IIB (n=3), stage IIIA (n=1), stage IIIB (n=2), and unknown, (n=1). As adjuvant chemotherapy, S-1 was administered to three stage IIB patients, one IIIA patient, and one IIIB patient. Tegafur uracil (UFT) + calcium folinate (LV) was administered to one stage IIIB patient. The cumulative five-year survival rate was 77.8%. Conclusions: Aggressive esophagogastroduodenoscopy, double-balloon endoscopy, and colonoscopy for symptoms such as anemia and abdominal pain, as well as intraoperative during abdominal surgery, would improve the prognosis of SBA

Clinicopathological outcomes and risk factors for postoperative recurrent and hospital mortality in patients with perforated colorectal cancer

Objective: Even after surgery and intensive postoperative treatment, the mortality rate of patients with perforated colorectal cancer (CRC) is high. The purpose of this retrospective study was to evaluate risk factors for postoperative recurrence and hospital mortality in patients with perforated CRC. Patients and Methods: We experienced a total of 142 patients who were diagnosed with colorectal perforation and who underwent emergency surgery from 2008 to 2021. First, we performed a clinicopathological study of patients with perforated CRC. Next, we examined the clinicopathological characteristics of the CRC and non-CRC groups. We investigated the histopathological characteristics and risk factors for postoperative recurrence and hospital mortality in 32 patients with perforated CRC. Results: The Hinchey stage of the CRC group was significantly higher than that of the non-CRC group (p=0.00619), and that in the proximal site group was significantly higher than that of the cancer site group (p=0.00489). The rate of recurrence in the proximal site perforation group was significantly higher than that in the cancer site perforation group (p=0.0135). Patients with T4 disease showed a significantly higher rate of recurrence than those with T3 disease (p=0.0443). The number of dissected lymph nodes in the recurrence-free group was significantly higher than that in the recurrence group (p=0.0377). There was a tendency for more patients in the recurrence-free group to receive postoperative adjuvant chemotherapy; however, this difference was not statistically significant. The preoperative shock rate in the hospital mortality group was significantly higher than that in the alive at discharge group (p=0.0169). Conclusions: The proximal site perforation, T4 disease, and the small number of dissected lymph nodes were the risk of the recurrence. The large number of preoperative shocks was the risk of the hospital mortality

Clinicopathological features and prognostic factors for survival in patients with primary appendiceal adenocarcinoma

Objective: Primary appendiceal adenocarcinoma accounts for 1% of colorectal tumors and is a rare malignancy. Peritoneal dissemination commonly occurs as part of the natural course of disease, following the sequence of luminal wall invasion, obstruction, and perforation. Patients and Methods: Twenty patients with appendiceal adenocarcinoma were surgically treated in our hospital between 1990 and 2021. The clinicopathological features, preoperative diagnosis, intraoperative diagnosis, surgical techniques, postoperative adjuvant chemotherapy, chemotherapy, outcome, and prognostic factors for survival of patients with primary appendiceal adenocarcinoma were reviewed. Results: Patients (8 males, 12 females), with an age from 35 to 94 years (mean: 72.8 years), were involved in the study. Before surgery, 7 (35%) patients were diagnosed with primary appendiceal adenocarcinoma and 13 were diagnosed with other conditions. 10 patients had stage I or II disease and 10 patients had stage III or IV disease. Sixteen patients received curative resection, while 4 received non-curative resection. The cumulative five-year survival rate was 62.1%. The preoperative and intraoperative diagnoses, pathological stage, and curative resection had a significant impact on survival. Conclusions: The preoperative and intraoperative diagnoses, pathological stage, and curative resection had an important impact on survival of patients with primary appendiceal adenocarcinoma

Airway smooth muscle relaxation results from a reduction in the frequency of Ca(2+ )oscillations induced by a cAMP-mediated inhibition of the IP(3 )receptor

BACKGROUND: It has been shown that the contractile state of airway smooth muscle cells (SMCs) in response to agonists is determined by the frequency of Ca(2+ )oscillations occurring within the SMCs. Therefore, we hypothesized that the relaxation of airway SMCs induced by agents that increase cAMP results from the down-regulation or slowing of the frequency of the Ca(2+ )oscillations. METHODS: The effects of isoproterenol (ISO), forskolin (FSK) and 8-bromo-cAMP on the relaxation and Ca(2+ )signaling of airway SMCs contracted with methacholine (MCh) was investigated in murine lung slices with phase-contrast and laser scanning microscopy. RESULTS: All three cAMP-elevating agents simultaneously induced a reduction in the frequency of Ca(2+ )oscillations within the SMCs and the relaxation of contracted airways. The decrease in the Ca(2+ )oscillation frequency correlated with the extent of airway relaxation and was concentration-dependent. The mechanism by which cAMP reduced the frequency of the Ca(2+ )oscillations was investigated. Elevated cAMP did not affect the re-filling rate of the internal Ca(2+ )stores after emptying by repetitive exposure to 20 mM caffeine. Neither did elevated cAMP limit the Ca(2+ )available to stimulate contraction because an elevation of intracellular Ca(2+ )concentration induced by exposure to a Ca(2+ )ionophore (ionomycin) or by photolysis of caged-Ca(2+ )did not reverse the effect of cAMP. Similar results were obtained with iberiotoxin, a blocker of Ca(2+)-activated K(+ )channels, which would be expected to increase Ca(2+ )influx and contraction. By contrast, the photolysis of caged-IP(3 )in the presence of agonist, to further elevate the intracellular IP(3 )concentration, reversed the slowing of the frequency of the Ca(2+ )oscillations and relaxation of the airway induced by FSK. This result implied that the sensitivity of the IP(3)R to IP(3 )was reduced by FSK and this was supported by the reduced ability of IP(3 )to release Ca(2+ )in SMCs in the presence of FSK. CONCLUSION: These results indicate that the relaxant effect of cAMP-elevating agents on airway SMCs is achieved by decreasing the Ca(2+ )oscillation frequency by reducing internal Ca(2+ )release through IP(3 )receptors

CATs and HATs: the SLC7 family of amino acid transporters

The SLC7 family is divided into two subgroups, the cationic amino acid transporters (the CAT family, SLC7A1-4) and the glycoprotein-associated amino acid transporters (the gpaAT family, SLC7A5-11), also called light chains or catalytic chains of the hetero(di)meric amino acid transporters (HAT). The associated glycoproteins (heavy chains) 4F2hc (CD98) or rBAT (D2, NBAT) form the SLC3 family. Members of the CAT family transport essentially cationic amino acids by facilitated diffusion with differential trans-stimulation by intracellular substrates. In some cells, they may regulate the rate of NO synthesis by controlling the uptake of l-arginine as the substrate for nitric oxide synthase (NOS). The heterodimeric amino acid transporters are, in contrast, quite diverse in terms of substrate selectivity and function (mostly) as obligatory exchangers. Their selectivity ranges from large neutral amino acids (system L) to small neutral amino acids (ala, ser, cys-preferring, system asc), negatively charged amino acid (system xc −) and cationic amino acids plus neutral amino acids (system y+L and b0,+-like). Cotransport of Na+ is observed only for the y+L transporters when they carry neutral amino acids. Mutations in b0,+-like and y+L transporters lead to the hereditary diseases cystinuria and lysinuric protein intolerance (LPI), respectivel