Serpins promote cancer cell survival and vascular co-option in brain metastasis.

Brain metastasis is an ominous complication of cancer, yet most cancer cells that infiltrate the brain die of unknown causes. Here, we identify plasmin from the reactive brain stroma as a defense against metastatic invasion, and plasminogen activator (PA) inhibitory serpins in cancer cells as a shield against this defense. Plasmin suppresses brain metastasis in two ways: by converting membrane-bound astrocytic FasL into a paracrine death signal for cancer cells, and by inactivating the axon pathfinding molecule L1CAM, which metastatic cells express for spreading along brain capillaries and for metastatic outgrowth. Brain metastatic cells from lung cancer and breast cancer express high levels of anti-PA serpins, including neuroserpin and serpin B2, to prevent plasmin generation and its metastasis-suppressive effects. By protecting cancer cells from death signals and fostering vascular co-option, anti-PA serpins provide a unifying mechanism for the initiation of brain metastasis in lung and breast cancers.

Current treatment and recent progress in gastric cancer.

Gastric cancer is not a top-10 malignancy in the United States but represents one of the most common causes of cancer death worldwide. Biological differences between tumors from Eastern and Western countries add to the complexity of identifying standard-of-care therapy based on international trials. Systemic chemotherapy, radiotherapy, surgery, immunotherapy, and targeted therapy all have proven efficacy in gastric adenocarcinoma; therefore, multidisciplinary treatment is paramount to treatment selection. Triplet chemotherapy for resectable gastric cancer is now accepted and could represent a plateau of standard cytotoxic chemotherapy for localized disease. Classification of gastric cancer based on molecular subtypes is providing an opportunity for personalized therapy. Biomarkers, in particular microsatellite instability (MSI), programmed cell death ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2), tumor mutation burden, and Epstein-Barr virus, are increasingly driving systemic therapy approaches and allowing for the identification of populations most likely to benefit from immunotherapy and targeted therapy. Significant research opportunities remain for the less differentiated histologic subtypes of gastric adenocarcinoma and those without markers of immunotherapy activity.

Reproducible preclinical models of androgen receptor driven human prostate cancer bone metastasis.

BACKGROUND: Preclinical models recapitulating the metastatic phenotypes are essential for developing the next-generation therapies for metastatic prostate cancer (mPC). We aimed to establish a cohort of clinically relevant mPC models, particularly androgen receptor positive (AR+) bone metastasis models, from LuCaP patient-derived xenografts (PDX) that reflect the heterogeneity and complexity of mPC. METHODS: PDX tumors were dissociated into single cells, modified to express luciferase, and were inoculated into NSG mice via intracardiac injection. The progression of metastases was monitored by bioluminescent imaging. Histological phenotypes of metastases were characterized by immunohistochemistry and immunofluorescence staining. Castration responses were further investigated in two AR-positive models. RESULTS: Our PDX-derived metastasis (PDM) model collection comprises three AR+ adenocarcinomas (ARPC) and one AR- neuroendocrine carcinoma (NEPC). All ARPC models developed bone metastases with either an osteoblastic, osteolytic, or mixed phenotype, while the NEPC model mainly developed brain metastasis. Different mechanisms of castration resistance were observed in two AR+ PDM models with distinct genotypes, such as combined loss of TP53 and RB1 in one model and expression of AR splice variant 7 (AR-V7) expression in another model. Intriguingly, the castration-resistant tumors displayed inter- and intra-tumor as well as organ-specific heterogeneity in lineage specification. CONCLUSION: Genetically diverse PDM models provide a clinically relevant system for biomarker identification and personalized medicine in metastatic castration-resistant prostate cancer.

Differences in Lymph Node Metastases Patterns Among Non-pancreatic Periampullary Cancers and Histologic Subtypes: An International Multicenter Retrospective Cohort Study and Systematic Review.

BACKGROUND: Standard lymphadenectomy for pancreatoduodenectomy is defined for pancreatic ductal adenocarcinoma and adopted for patients with non-pancreatic periampullary cancer (NPPC), ampullary adenocarcinoma (AAC), distal cholangiocarcinoma (dCCA), or duodenal adenocarcinoma (DAC). This study aimed to compare the patterns of lymph node metastases among the different NPPCs in a large series and in a systematic review to guide the discussion on surgical lymphadenectomy and pathology assessment. METHODS: This retrospective cohort study included patients after pancreatoduodenectomy for NPPC with at least one lymph node metastasis (2010-2021) from 24 centers in nine countries. The primary outcome was identification of lymph node stations affected in case of a lymph node metastasis per NPPC. A separate systematic review included studies on lymph node metastases patterns of AAC, dCCA, and DAC. RESULTS: The study included 2367 patients, of whom 1535 had AAC, 616 had dCCA, and 216 had DAC. More patients with pancreatobiliary type AAC had one or more lymph node metastasis (67.2% vs 44.8%; P < 0.001) compared with intestinal-type, but no differences in metastasis pattern were observed. Stations 13 and 17 were most frequently involved (95%, 94%, and 90%). Whereas dCCA metastasized more frequently to station 12 (13.0% vs 6.4% and 7.0%, P = 0.005), DAC metastasized more frequently to stations 6 (5.0% vs 0% and 2.7%; P < 0.001) and 14 (17.0% vs 8.4% and 11.7%, P = 0.015). CONCLUSION: This study is the first to comprehensively demonstrate the differences and similarities in lymph node metastases spread among NPPCs, to identify the existing research gaps, and to underscore the importance of standardized lymphadenectomy and pathologic assessment for AAC, dCCA, and DAC.

Impact of Oophorectomy on Survival and Improving Nutritional Status in Ovarian Metastasis from Colorectal Adenocarcinoma.

INTRODUCTION: Ovarian metastasis of colorectal cancer is known to have a poor prognosis. This study aimed to elucidate the characteristics of patients who underwent oophorectomy for ovarian metastasis from colorectal cancer. METHODS: This retrospective study included 16 patients who underwent oophorectomy for colorectal cancer metastasis to the ovary from January 2004 to December 2017. Improvement in patient's symptoms and pre- and postoperative changes in various nutritional and inflammatory indicators were assessed. Survival analysis and identification of prognostic factors were conducted with a median follow-up of 40.7 (5-109) months. RESULTS: Of 16 patients, 12 had (75%) synchronous and 4 (25%) had metachronous metastasis. Fourteen patients were symptomatic but symptoms resolved postoperatively. Thirteen patients (81.3%) had ascites and 5 (31.3%) had pleural effusion on preoperative computed tomography that disappeared after surgery in all cases. The median value of prognostic nutritional factor was significantly increased postoperatively (36.0 [preoperatively] vs. 47.5, p < 0.0001). The median (interquartile range) values for lymphocyte-C-reactive protein ratio were 715.2 (110-2,607) preoperatively and 6,095.2 (1,612.3-14,431.8) postoperatively (p = 0.0214). The median survival of the entire cohort was 60.4 months. The 3-year survival rates for R0 + R1 and R2 cases were 83% and 24% (p = 0.018), respectively. Univariate analysis showed that R2 resection and low postoperative lymphocyte-C-reactive protein ratio were associated with poor prognosis. CONCLUSIONS: Oophorectomy for ovarian metastasis from colorectal cancers was safely performed. It improved the patients' symptoms and nutritional status and may result in improved prognosis.

The Nlrp3 Inflammasome Suppresses Colorectal Cancer Metastatic Growth in the Liver by Promoting Natural Killer Cell Tumoricidal Activity.

The crosstalk between inflammation and tumorigenesis is now clearly established. However, how inflammation is elicited in the metastatic environment and the corresponding contribution of innate immunity pathways in suppressing tumor growth at secondary sites are poorly understood. Here, we show that mice deficient in Nlrp3 inflammasome components had exacerbated liver colorectal cancer metastatic growth, which was mediated by impaired interleukin-18 (IL-18) signaling. Control of tumor growth was independent of differential cancer cell colonization or proliferation, intestinal microbiota effects, or tumoricidal activity by the adaptive immune system. Instead, the inflammasome-IL-18 pathway impacted maturation of hepatic NK cells, surface expression of the death ligand FasL, and capacity to kill FasL-sensitive tumors. Our results define a regulatory signaling circuit within the innate immune system linking inflammasome activation to effective NK-cell-mediated tumor attack required to suppress colorectal cancer growth in the liver.

Artificial Intelligence Imaging Diagnosis Using Super-Resolution and Three-Dimensional Shape for Lymph Node Metastasis of Low Rectal Cancer: A Pilot Study From a Single Center.

BACKGROUND: Although accurate preoperative diagnosis of lymph node metastasis is essential for optimizing treatment strategies for low rectal cancer, the accuracy of present diagnostic modalities has room for improvement. OBJECTIVE: The study aimed to establish a high-precision diagnostic method for lymph node metastasis of low rectal cancer using artificial intelligence. DESIGN: A retrospective observational study. SETTINGS: A single cancer center and a college of engineering in Japan. PATIENTS: Patients with low rectal adenocarcinoma who underwent proctectomy, bilateral lateral pelvic lymph node dissection, and contrast-enhanced multidetector row CT (slice ≤1 mm) between July 2015 and August 2021 were included in the present study. All pelvic lymph nodes from the aortic bifurcation to the upper edge of the anal canal were extracted, regardless of whether within or beyond the total mesenteric excision area, and pathological diagnoses were annotated for training and validation. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. RESULTS: A total of 596 pathologically negative nodes and 43 positive nodes from 52 patients were extracted and annotated. Four diagnostic methods, with and without using super-resolution images and with and without using 3-dimensional shape data, were performed and compared. The super-resolution + 3-dimensional shape data method had the best diagnostic ability for the combination of sensitivity, negative predictive value, and accuracy (0.964, 0.966, and 0.968, respectively), whereas the super-resolution only method had the best diagnostic ability for the combination of specificity and positive predictive value (0.994 and 0.993, respectively). LIMITATIONS: Small number of patients at a single center and the lack of external validation. CONCLUSIONS: Our results enlightened the potential of artificial intelligence for the method to become another game changer in the diagnosis and treatment of low rectal cancer. See Video Abstract . DIAGNSTICO POR IMGENES CON INTELIGENCIA ARTIFICIAL MEDIANTE SUPERRESOLUCIN Y FORMA D PARA LA METSTASIS EN LOS GANGLIOS LINFTICOS DEL CNCER DE RECTO BAJO UN ESTUDIO PILOTO DE UN SOLO CENTRO: ANTECEDENTES:Aunque el diagnóstico preoperatorio preciso de metástasis en los ganglios linfáticos es esencial para optimizar las estrategias de tratamiento para el cáncer de recto bajo, la precisión de las modalidades de diagnóstico actuales tiene margen de mejora.OBJETIVO:Establecer un método de diagnóstico de alta precisión para las metástasis en los ganglios linfáticos del cáncer de recto bajo utilizando inteligencia artificial.DISEÑO:Un estudio observacional retrospectivo.AJUSTE:Un único centro oncológico y una facultad de ingeniería en Japón.PACIENTES:En el presente estudio se incluyeron pacientes con adenocarcinoma rectal bajo sometidos a proctectomía, disección bilateral de ganglios linfáticos pélvicos laterales y tomografía computarizada con múltiples detectores con contraste (corte ≤1 mm) entre julio de 2015 y agosto de 2021. Se resecaron todos los ganglios linfáticos pélvicos desde la bifurcación aórtica hasta el borde superior del canal anal, independientemente de si estaban dentro o más allá del área de escisión mesentérica total, y se registraron los diagnósticos patológicos para entrenamiento y validación.PRINCIPALES MEDIDAS DE RESULTADO:Sensibilidad, especificidad, valor predictivo positivo, valor predictivo negativo y precisión.RESULTADOS:Se extrajeron y registraron un total de 596 ganglios patológicamente negativos y 43 positivos de 52 pacientes. Se realizaron y compararon cuatro métodos de diagnóstico, con y sin imágenes de súper resolución y sin datos de imagen en 3D. El método de superresolución + datos de imagen en 3D tuvo la mejor capacidad de diagnóstico para la combinación de sensibilidad, valor predictivo negativo y precisión (0,964, 0,966 y 0,968, respectivamente), mientras que el método de súper resolución solo tuvo la mejor capacidad de diagnóstico para la combinación de especificidad y valor predictivo positivo (0,994 y 0,993, respectivamente).LIMITACIONES:Pequeño número de pacientes en un solo centro y falta de validación externa.CONCLUSIONES:Nuestros resultados iluminan el potencial de la inteligencia artificial para que el método se convierta en otro elemento de cambio en el diagnóstico y tratamiento del cáncer de recto bajo. (Traducción ---Dr. Fidel Ruiz Healy ).

Short- and long-term outcomes of surgical treatment for inguinal lymph node metastasis in rectal and anal canal adenocarcinoma.

AIM: The significance of lymphadenectomy and its indications in patients with inguinal lymph node metastasis (ILNM) of anorectal adenocarcinoma is unclear. This study aimed to clarify the surgical outcomes and prognostic factors of inguinal lymphadenectomy for ILNM. METHOD: This study included patients who underwent surgical resection for ILNM of rectal or anal canal adenocarcinoma with pathologically positive metastases between 1997 and 2011 at 20 participating centres in the Study Group for Inguinal Lymph Node Metastasis from Colorectal Cancer organized by the Japanese Society for Cancer of the Colon and Rectum. Clinicopathological characteristics and short- and long-term postoperative outcomes were retrospectively analysed. RESULTS: In total, 107 patients were included. The primary tumour was in the rectum in 57 patients (53.3%) and in the anal canal in 50 (46.7%). The median number of ILNMs was 2.34. Postoperative complications of Clavien-Dindo Grade III or higher were observed in five patients. The 5-year overall survival rate was 38.8%. Multivariate analysis identified undifferentiated histological type (P < 0.001), pathological venous invasion (P = 0.01) and pathological primary tumour depth T0-2 (P = 0.01) as independent prognostic factors for poor overall survival. CONCLUSION: The 5-year overall survival after inguinal lymph node dissection was acceptable, and it warrants consideration in more patients. Further larger-scale studies are needed in order to clarify the surgical indications.

Risk of metastasis among patients diagnosed with high-risk T1 esophageal adenocarcinoma who underwent endoscopic follow-up.

Esophagectomy and lymphadenectomy have been the standard of care for patients at high risk (HR) of lymph node metastasis following a diagnosis of early esophageal adenocarcinoma (OAC) after endoscopic resection (ER). However, recent cohorts suggest lymph node metastasis risk is lower than initially estimated, suggesting organ preservation with close endoscopic follow-up is a viable option. We report on the 3- and 5-year risk of lymph node/distant metastasis among patients diagnosed with early HR-T1 OAC undergoing endoscopic follow-up. Patients diagnosed with HR-T1a or T1b OAC following ER at a tertiary referral center were identified and retrospectively analyzed from clinical records between 2010 and 2021. Patients were included if they underwent endoscopic follow-up after resection and were divided into HR-T1a, low risk (LR)-T1b and HR-T1b cohorts. After ER, 47 patients underwent endoscopic follow-up for early HR OAC. In total, 39 patients had an R0 resection with a combined 3- and 5-year risk of LN/distant metastasis of 6.9% [95% confidence interval (CI): 1.8-25] and 10.9% (95% CI, 3.6-30.2%), respectively. There was no significant difference when stratifying by histopathological subtype (P = 0.64). Among those without persistent luminal disease on follow-up, the 5-year risk was 4.1% (95% CI, 0.6-26.1). Two patients died secondary to OAC with an all-cause 5-year survival of 57.5% (95% CI, 39.5-71.9). The overall risk of LN/distant metastasis for early HR T1 OAC was lower than historically reported. Endoscopic surveillance can be a reasonable approach in highly selected patients with an R0 resection and complete luminal eradication, but clear, evidence-based surveillance guidelines are needed.

Risk of lymph node metastasis in T1 esophageal adenocarcinoma: a meta-analysis.

Patients with early (T1) esophageal adenocarcinoma (EAC) are increasingly having definitive local therapy endoscopically. Endoscopic resection is not able to pathologically stage or treat lymph node metastasis (LNM). Accurate identification of patients having nodal metastasis is critical to select endoscopic therapy over surgery. This study aimed to define the risk of LNM in T1 EAC. A meta-analysis of studies of patients who underwent surgery and lymphadenectomy with assessment of LNM was performed according to PRISMA. Main outcome was probability of LNM in T1a and T1b disease. Secondary outcomes were risk factors for LNM and rate of LNM in submucosal T1b (SM1, SM2, and SM3) disease. Registered with PROSPERO (CRD42022341794). Twenty cohort studies involving 2264 patients with T1 EAC met inclusion criteria: T1a (857 patients) with 36 (4.2%) node positive and T1b (1407 patients) with 327 (23.2%) node positive. Subgroup analysis of T1b lesions was available in 10 studies (405 patients). Node positivity for SM1, SM2, and SM3 was 16.3%, 16.2%, and 29.4%, respectively. T1 substage (odds ratio [OR] 7.72, 95% confidence interval [CI] 4.45-13.38, P < 0.01), tumor differentiation (OR 2.82, 95% CI 2.06-3.87, P < 0.01), and lymphovascular invasion (OR 13.65, 95% CI 6.06-30.73, P < 0.01) were associated with LNM. T1a disease demonstrated a 4.2% nodal metastasis rate and T1b disease a rate of 23.2%. Endoscopic therapy should be reserved for T1a disease and perhaps select T1b disease, which has a moderately high rate of nodal metastasis. There were inadequate data to stratify T1b SM disease into 'low-risk' and 'high-risk' based on tumor differentiation and lymphovascular invasion.

Multispecialty Management of Metastatic Colon Adenocarcinoma Involving the Extraocular Muscles: Primary Excision and Simultaneous Treatment of Strabismus With a Review of the Literature.

Metastatic colon adenocarcinoma involving the extraocular muscles is extremely rare. It usually develops following the diagnosis of the systemic disease and therefore, management and treatment require a multispecialty approach. Within this manuscript, we provide a summary of cases of orbital metastasis secondary to colon cancer. We further discuss a detailed case of a 42-year-old male patient who developed recent-onset diplopia in the left gaze. Orbital CT imaging showed a localized, well-circumscribed enlargement of the right medial rectus muscle. The biopsy of the right medial rectus showed adenocarcinoma originating from the gastrointestinal system. Further workup revealed colon adenocarcinoma with multiple metastatic sites. The patient started systemic chemotherapy. After 2 months of chemotherapy (5-fluouracil, oxaliplatin, irinotecan, and leucovorin), all systemic metastatic sites regressed; however, his medial rectus muscle continued to grow, causing compressive optic neuropathy. The patient underwent excisional biopsy of the right medial rectus muscle with simultaneous repair of the strabismus with transposition of superior and inferior recti muscles. He continued with systemic chemotherapy. Follow up in 1 year revealed no local orbital tumor recurrence with excellent visual acuity and no diplopia in primary gaze.

[Clinical characteristics and prognosis analysis of gastric cancer patients with bone metastasis].

Objectives: To investigate the clinical characteristics and prognosis of bone metastasis of gastric cancer, analyze the influencing factors of bone metastasis and the effects of different treatment methods, and provide a basis for early detection and treatment optimization of bone metastasis of gastric cancer. Methods: A total of 142 gastric cancer patients with bone metastasis admitted to the First Hospital of Lanzhou University from January 2011 to December 2021 were enrolled, including 60 cases of simple bone metastasis and 82 cases of bone metastasis combined with extraosseous metastasis. 142 patients with stage Ⅲgastric cancer without distant metastasis and 142 gastric cancer patients with visceral metastasis admitted to this hospital during the same period were also enrolled for comparison. Logistic regression analysis was used to determine the influencing factors of bone metastasis, and the Cox proportional hazards regression model was used to evaluate the influencing factors of overall survival (OS) of patients with bone metastasis. Results: Among the 142 patients with bone metastasis, poorly differentiated adenocarcinoma was the main type (123 cases), and 45 patients had simultaneous bone metastasis. Rib metastasis (100 cases), spine metastasis (88 cases), and pelvis metastasis (84 cases) were more common. A total of 110 patients had multiple bone metastasis, and 82 patients had extraosseous metastasis. Results of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extraosseous metastasis group were compared. There were significant differences in age, degree of differentiation, Borrmann type, alkaline phosphatase, lactate dehydrogenase, serum calcium, alanine aminotransferase, aspartate aminotransferase, creatine kinase isoenzyme, lymphocyte, hemoglobin, platelet, CEA, CA19-9, and CA724 (all P<0.05). Multivariate logistic regression analysis showed that Borrmann type was an independent protective factor of bone metastasis of gastric cancer (type 3: OR=0.07, 95%CI: 0.01-0.64, P=0.018). Alkaline phosphatase (OR=2.54, 95% CI: 1.07-6.01, P=0.034), serum calcium (OR=2.71, 95% CI: 1.15-6.41, P=0.023), creatine kinase isoenzyme (OR=16.33, 95% CI: 1.83-145.58, P=0.012), platelet (OR=10.08, 95% CI:1.89-53.85, P=0.007), and CA19-9 (OR=2.40, 95% CI: 1.14-5.05, P=0.021) were independent risk factors of bone metastasis of gastric cancer. The median OS of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extrabony group were 47, 13, 18, and 6 months, respectively, and the difference was statistically significant (P<0.001). The median OS of patients with bone metastasis only who underwent primary tumor surgery was 33 months, better than 6 months of patients without surgery (P=0.048). Multivariate Cox regression analysis showed that extraosseous metastasis (HR=2.45, 95% CI: 1.56-3.85, P<0.001) and decreased hemoglobin (HR=1.54, 95%CI: 1.02-2.34, P=0.042) were independent risk factors of OS of gastric cancer patients with bone metastasis. Conclusions: The prognosis of gastric cancer patients with bone metastasis alone is significantly better than that of other stage Ⅳ patients. For such patients, surgery on the primary site combined with chemotherapy after full evaluation may prolong the survival time.

Krukenburg tumour: Role of 18F-FDG PET/CT in identifying the primary site.

Krukenberg tumours are a rare form of metastatic tumours of the ovary. They primary site is usually the gastro-intestinal system with the most common being gastric cancer. We present the case of a 35-year-old female coming in with a large pelvi-abdominal mass for investigation. This pelvic mass showed mild to moderate metabolic activity. 18F-FDG PET-CT was able to identify the primary gastric carcinoma. Subsequent histopathology confirmed this to be gastric adenocarcinoma with metastases to the ovary.

Tumor-to-tumor metastasis of an adenocarcinoma to a glioblastoma with review of the literature on tumor-to-tumor metastasis to gliomas.

Tumor-to-tumor metastasis (TTM) is a process where one tumor metastasizes to another tumor. It is an exceedingly rare phenomenon, particularly in the central nervous system, where it most commonly occurs with meningiomas as the recipient. Herein, we present a case of tumor-to-tumor metastasis of an adenocarcinoma to a glioblastoma in a 75-year-old female. The patient had a history of high-grade ductal carcinoma in situ of the breast 8 years prior, treated with lumpectomy and radiation. She presented with a left fronto-parietal mass. Histologically, the lesion showed a glioblastoma, IDH-wildtype, WHO grade 4, associated with a metastatic adenocarcinoma (positive for estrogen receptor, progesterone receptor, and mammaglobin), suggesting a breast primary. The patient passed away 5 months after surgery. Involvement of glioblastoma by TTM is especially rare; only 1 case of TTM to glioblastoma is thus far reported in the English literature. The mechanism by which TTM occurs is poorly understood. TTM may be the first presentation of an occult malignancy and warrants thorough clinical, laboratory, and imaging investigation.

Lytic bone lesion as the first manifestation of late recurrence of gastric cancer.

The incidence of gastric cancer has declined worldwide, it is the second most common cancer worldwide and two thirds of these occurs in developing countries. In Peru, this neoplasm, has one of the highest incidence and mortality rates. The main sites of gastric adenocarcinoma metastasis are the liver and lung; In contrast, bone metastasis are an uncommon finding up to 0.9 to 2% of patients and is associated with an ominous prognosis. We present the case of a 48-year-old female patient diagnosed with gastric cancer treated surgically and with regular controls. 5 years later, she was admitted due to pain in the left knee and increased volume. Knee radiographs reported a lytic lesion in the medial condyle and distal diaphysis of the left femur, with soft tissue involvement, wide transition zone, cortical rupture. Bone scintigraphy described bone oligo metastatic disease. Extension studies were negative for visceral metastasis. Palliative biopsy and curettage of the femur lesion was performed; the pathology was consistent with gastric adenocarcinoma metastasis.

Cutaneous metastasis as a first sign of adenocarcinoma of the cervix.

Cervical cancer remains one of the most common malignancies diagnosed in women as well as a leading cause of cancer related deaths in women worldwide. Cutaneous metastasis associated with cervical malignancy is a remarkably rare phenomenon. We present a patient whose cutaneous signs led to the diagnosis of metastatic adenocarcinoma of the cervix.

[Gefitinib Monotherapy Afforded Long-Term Survival of an Octogenarian Patient with a Postoperative Recurrence of a Pulmonary Adenocarcinoma-A Case Report].

An 83-year-old(at the time of postoperative recurrence)female clinically diagnosed with primary lung cancer underwent right upper lobectomy and lymph node dissection(ND2a-2). Postoperative pathological staging revealed a Stage ⅠB (pT2aN0M0)adenocarcinoma that was EGFR mutation-positive(exon 21: L858R). Fifty-one months after surgery, the patient developed a mediastinal lymph node metastasis, and radiotherapy was delivered. Next, gefitinib(250 mg daily)was prescribed as first-line therapy. She developed mild anemia but we took a wait-and-see approach. A complete response was evident after 58 months of monotherapy. However, she then developed grade 3 anemia(Hb 6.2 g/dL)and gefitinib was discontinued. She requested(and received)follow-up computed tomography. No progressive disease was evident, but she died of non-cancer disease 16 months after discontinuation of gefitinib(thus 125 months after surgery and 74 months after the postoperative recurrence). Thus, we here present an unusual case. Gefitinib monotherapy afforded long-term survival of an octogenarian patient with a postoperative recurrence of a pulmonary adenocarcinoma.

[A Case of Cardiodiaphragmatic Corner Lymph Node Recurrence after Surgery for Ascending Colon Cancer].

The case is a female, 50s. She presented to our hospital because of her intestinal obstruction. A CT scan at her visit showed wall thickening of her ascending colon. Colonoscopy revealed type 2 advanced cancer in the ascending colon. The pathological examination was a diagnosis of adenocarcinoma. Laparoscopic right hemicolectomy was performed for cT3N1M0, cStage Ⅲb ascending colon cancer. The pathological result was pT3N1M0, Stage Ⅲb. Contrast-enhanced CT was performed 10 months after the operation. As a result, she was found to have recurrent multiple liver metastases. A laparoscopic partial hepatectomy was performed at the site of recurrence. The pathological result was adenocarcinoma. It was a diagnosis of metastasis recurrence from colorectal cancer. A CT scan 16 months after primary surgery revealed enlarged cardiodiaphragmatic lymph nodes. A PET-CT scan revealed an accumulation of SUVmax 3.0 in the same area. She was diagnosed with lymph node recurrence of colorectal cancer and underwent resection. Histopathological result was adenocarcinoma. It was diagnosed as metastasis from ascending colon cancer.

[A Rare Case of Advanced Gastric Cancer with Duodenal Intramural Metastasis].

Here we report the case of a patient with advanced gastric cancer who presented with duodenal intramural metastasis based on the pathological results after surgery. The patient was 78-year-old female, who was referred to our department for further evaluation and treatment of upper abdominal pain. An upper gastrointestinal series demonstrated a tumor occupying the lesser curvature of the gastric body. Biopsy specimens from the tumor demonstrated moderately to poorly differentiated adenocarcinoma. A computed tomography scan showed thickening of the gastric wall and swelling of the regional lymph nodes. The patient underwent distal gastrectomy and D2 lymph node dissection for gastric cancer. A histopathological examination disclosed that the gastric tumor was poorly differentiated adenocarcinoma with severe lymphatic permeation and also demonstrated the other poorly differentiated adenocarcinoma occupying the part of the muscularis propria layer of the duodenum. The gastric tumor was not contiguous with the duodenal tumor, and the duodenal cancer cells had the same pathological characteristics as the primary gastric cancer cells; therefore, we diagnosed the duodenal tumor as an intramural metastasis from gastric cancer. The patient's disease was staged as pT4aN3bM1, Stage Ⅳ according to the TNM classification. We report this rare case along with a discussion of the literature.

[Long-Term Survival after Resection of Two Lung Metastases That Appeared Five Years after Pancreatic Cancer Surgery-A Case Report].

A woman in her 70s was diagnosed with cancer of pancreatic head. She underwent subtotal stomach-preserving pancreatoduodenectomy. Moderately differentiated adenocarcinoma, positive peripancreatic exfoliation surface, and R1 resection was diagnosed by histopathological examination. She underwent adjuvant chemotherapy(S-1), but 5 years and 6 months after the operation, a single nodule(16×9 mm)appeared on anterior segment of left lung. She underwent thoracoscopic left upper lobectomy on suspicion of primary lung cancer. Adenocarcinoma consistent with pancreatic cancer metastasis was diagnosed by histopathological examination. She didn't choose chemotherapy after second operation. 1 year and 1 month after the left pneumonectomy, a single nodule(11×10 mm)reappeared in lateral basal segment of right lung. Although it was difficult to diagnose whether it was primary or metastatic, she decided to undergo thoracoscopic partial lung resection. Histopathological examination revealed that the histology was similar to that of the previous lung lesion and was consistent with pancreatic cancer metastasis. After that, she also didn't choose chemotherapy. She has been alive for 7 years and 7 months after her first pancreatic cancer surgery without any new obvious recurrence.