Peritoneal Involvement Research Articles

Extrauterine high-grade serous carcinomas with bilateral adnexal involvement as the only two disease sites are clonal based on tp53 sequencing results: implications for biology, classification, and staging.

A previous multicenter study of 67 cases of Stage I/II tubo-ovarian high-grade serous carcinoma with complete tubal sampling identified 7 cases in which there were only two disease sites, comprising tumor involving opposite adnexa with no extra-adnexal involvement. This study aimed to determine whether such low-stage extrauterine high-grade serous carcinomas with only two sites of involvement, located on opposite adnexa, have identical or different TP53 mutations in order to investigate their clonal relationship. DNA extracted from both sites of involvement was subjected to TP53 sequencing (n=6) or sequencing of one site and mutation confirmation by droplet digital PCR for the other site (n=1). Of the 7 cases analyzed, 1 case had unilateral serous tubal intraepithelial carcinoma with contralateral ovarian high-grade serous carcinoma, 3 had tubal high-grade serous carcinomas (±serous tubal intraepithelial carcinoma) with contralateral ovarian high-grade serous carcinoma, 2 had bilateral ovarian high-grade serous carcinomas with normal tubes, and 1 had bilateral fallopian tube high-grade serous carcinoma with normal ovaries. All 7 cases showed identical TP53 mutations in tumor from both disease sites. Therefore, these rare cases of high-grade serous carcinoma confined to opposite adnexa all show clonal identity between the two sites of involvement, suggesting unifocal origin and metastasis rather than multifocal origin. Our results suggest that serous tubal intraepithelial carcinoma or adnexal high-grade serous carcinoma can metastasize to the contralateral adnexa without peritoneal involvement. Given the clonal relationship between the two sites, such cases should be considered stage II, with stage I reserved for cases with unilateral and unifocal adnexal involvement. Furthermore, serous tubal intraepithelial carcinoma without invasion should be taken to constitute a disease site for staging purposes.

Peritoneal Involvement Is More Common Than Nodal Involvement in Patients With High-Grade Appendix Tumors Who Are Undergoing Prophylactic Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Right hemicolectomy is routinely recommended in patients with histologic findings of high-grade appendix tumors after appendicectomy. Undetected peritoneal disease may be encountered at surgery. In high-grade appendix tumors with disease detected radiologically, complete cytoreduction may not be possible and outcomes poor. For these reasons, we adopted a policy of prophylactic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. The purpose of this study was to quantify the rates of peritoneal and nodal metastatic disease in patients with high-grade appendix tumors without obvious metastatic disease and to report the long-term outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in these patients. Data regarding peritoneal and nodal metastatic disease were extracted from surgical and histologic records. The study was conducted at a high-volume tertiary referral center for peritoneal malignancy. Patients referred with histologically high-grade appendix tumors at appendicectomy, without detectable metastatic spread, between January 1994 and September 2016 were included MAIN OUTCOME MEASURES:: A total of 62 patients with high-grade pathology at appendicectomy, without clinical or radiological peritoneal disease, underwent complete cytoreduction with hyperthermic intraperitoneal chemotherapy. Thirty-five (57%) of 62 patients had peritoneal disease (median peritoneal cancer index 5 (range, 1-28)). Eleven (31%) of 35 had microscopic peritoneal disease. Overall, 23 (37%) of 62 had peritoneal disease beyond the confines of a standard right hemicolectomy. Nine (15%) of 62 had nodal involvement. Mean overall and disease-free survival were 110.9 (95% CI, 94.8-127.0 mo) and 102.1 months (95% CI, 84.3-119.9 mo), with 5-year overall and disease-free survival of 83.2% and 76.0%. The retrospective nature limits the interpretation of these results. Complete cytoreduction was achieved in all of the patients, with excellent long-term survival. The incidence of peritoneal spread (57%) compared with nodal involvement (15%) supports cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as definitive treatment rather than prophylaxis in patients with high-grade appendix tumors, even without radiologically detectable disease. High-grade appendix tumors benefit from early aggressive operative management to deal with potential peritoneal and nodal spread and should be considered for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. See Video Abstract at http://links.lww.com/DCR/A360.

Locally Advanced Colorectal Cancer: True Peritoneal Tumor Penetration is Associated with Peritoneal Metastases

BackgroundFindings show T4 colorectal cancer (CRC) to be a risk factor for the development of peritoneal metastases (PM). Heterogeneity regarding peritoneal involvement of T4 tumors might explain the wide range of reported PM incidences (8–50%). Hyperplastic and mesothelial inflammatory reactions complicate evaluation of the exact primary tumor involvement of the peritoneal layer. This retrospective cohort study aimed to assess the association between either inflammatory peritoneal reaction or peritoneal involvement of the primary tumor and the risk of PM.MethodsSince 2010, pathologists at UZ Leuven have systematically categorized peritoneal involvement in peritoneal reaction with tumor less than 1 mm from the peritoneal surface or true peritoneal penetration. All patients undergoing resection of CRC between January 2010 and July 2013 who fulfilled either of these pathologic criteria were included in this study.ResultsThe study enrolled 159 CRC patients. Peritoneal reaction with tumor less than 1 mm from the peritoneal surface was present in 43 patients and true peritoneal penetration in 116 patients. Overall, 29 patients (18%) had synchronous PM, and 30 patients (23%) had metachronous PM. In the multivariable analysis, true peritoneal penetration, in contrast to peritoneal reaction with tumor less than 1 mm from the peritoneum, was associated with greater risk of PM (odds ratio [OR], 2.518; range, 1.038–6.111; p = 0.041) and lymph node involvement (N1: OR, 1.572; range, 0.651–3.797 vs N2: OR, 4.046; range, 1.549–10.569; p = 0.014).ConclusionHistologically confirmed true peritoneal penetration by CRC, rather than inflammatory peritoneal reaction constitutes a high risk for PM. With evolving treatment strategies that aim to treat PM in an earlier phase, identification of high-risk patients becomes highly important clinically.

Bladder Urothelial Carcinoma with Peritoneal Involvement: Benefit of Continuous Maintenance Chemotherapy.

We investigated bladder urothelial carcinoma with peritoneal involvement. Inclusion criteria were: pathology-confirmed urothelial carcinoma; peritoneal spread identified on computed tomographic (CT) scans performed initially or after either cystectomy or concomitant chemoradiotherapy (CCRT), and absence of visceral metastases; and chemotherapy administered after peritoneal spread was diagnosed. Forty-seven cases included initial modes of therapy with chemotherapy in 24 patients (51%), cystectomy in 17 (36%), and CCRT in six (13%), only given as a result of under-staging. After local therapy, these patients received a continuous maintenance chemotherapy regimen of 5-fluorouracil, leucovorin, cisplatin, and gemcitabine. The overall response rate was 85%, and the side-effects were mild and tolerated. The median survival time was 28 months. The survival time of cases initially treated only with chemotherapy was not statistically different to that of those with local disease. Bladder urothelial carcinomas with peritoneal involvement can benefit from continuous maintenance chemotherapy.

The Importance of Comprehensive Surgical Staging Including Para-Aortic Lymph Node Dissection of Presumed Early Stage Epithelial Ovarian Cancer: A Contemporary Prospective Evaluation

Objective: It is the conventional belief that comprehensive staging of presumed early ovarian cancer results in upstaging of the disease in ∼30% of patients. With the latest developments in modern technology and wider use of diagnostic imaging, the importance of such surgical staging needed prospective evaluation. Materials and Methods: This was a prospective cohort study. It was conducted in a tertiary cancer hospital over a period of 18 months, starting in June 2014. All willing women with clinically suspected early stage epithelial ovarian cancer, based on preoperative contrast-enhanced computerized tomography of the abdomen and pelvis and serum CA-125 levels, were included. At laparotomy, the diseased ovary was removed from each patient and sent for frozen- section confirmation for epithelial cancer. Patients with confirmation of epithelial cancer underwent comprehensive surgical staging, including systematic pelvic and para-aortic lymph node dissection (PAND) as prescribed by the International Federation of Gynecology and Obstetrics. Results: A total of 42 patients underwent complete surgical staging, of whom 4 were excluded at final analysis. On comprehensive staging, the disease was upstaged in 8 (21%) patients: 4 had retroperitoneal nodal metastases (11%); 2 had paracolic peritoneal involvement (5%); and 2 patients had omental involvement (5%). A mean of 16 pelvic and 13.76 para-aortic nodes were removed. The para-aortic nodes were involved in 3 (75%) of the 4 patients with retroperitoneal nodal involvement. Of the parameters analyzed, no statistically significant factors were found that could have predicted the lymph nodal involvement. Conclusions: Comprehensive staging, including systematic PAND, is still the “gold standard” in the management of early stage ovarian cancer. (J GYNECOL SURG 33:184)

Grading and staging mucinous neoplasms of the appendix: a case series and review of the literature

The grading and staging of appendiceal mucinous neoplasms is challenging and fraught with terminology problems, but has critical prognostic and therapeutic implications. We utilized a small case series to examine the grading and staging systems of appendiceal mucinous neoplasms and outline the evidence for the new systems proposed in the upcoming 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual. We reviewed 33 cases of appendiceal mucinous neoplasms with available clinical follow-up data, 6 of which were widely disseminated in the peritoneum. An additional 4 cases with disseminated peritoneal involvement were also reviewed. A detailed review of the literature was performed with an emphasis on features associated with disease recurrence and correlation of grade with outcome. Recurrence was not seen in 64 low-grade appendiceal mucinous neoplasms (LAMNs) confined to the muscularis propria in our series (n=21) or in the literature (n=43). Of cases of LAMN with neoplastic epithelium present beyond the muscularis propria, 64% (57/89) had peritoneal disease at the time of diagnosis or follow-up. A majority of studies of disseminated appendiceal mucinous neoplasms showed significant five-year survival differences using a three-tier grading scheme. Thus, LAMNs confined to the muscularis propria are best considered as in situ tumors, as these are cured with complete excision. A three-tier system has prognostic significance and should be used for grading of disseminated appendiceal mucinous neoplasms. The conclusions of this case series and literature review provide evidence to support the changes proposed in the 8th edition of the AJCC Staging Manual.

Prognostic factors in patients with loco-regionally advanced gastric cancer

BackgroundThe aim of this study was to investigate epidemiologic and prognostic factors relevant to the treatment of loco-regionally advanced gastric cancer (GC).MethodsTwo hundred and fifty-five patients with GC were identified in Uppsala County between 2000 and 2009. Patient records were analyzed for loco-regionally advanced GC defined as tumor with peritoneal involvement, excluding serosal invasion from the primary tumor only, at primary diagnosis or during follow-up. The presence or not of distant metastasis (DM), including hematogenous metastases (e.g., liver, lung, and bone) and/or distant lymph node metastases, was also analyzed. The Cox proportional hazard model was used for multivariate analysis of factors influencing survival.ResultsOne hundred and twenty patients (47% of all patients with GC; median age 70.5 years) had loco-regionally advanced disease, corresponding to an incidence of 3.8 per 100,000 person-years. Forty-one percent of these also had DM. Median overall survival (mOS) from the time of the diagnosis of loco-regionally advanced disease was 4.8 months for the total patient cohort, 5.1 months for the subgroup of patients without DM, and 4.7 months for the subgroup with DM. There was no significant difference in mOS between the subgroups with synchronous versus metachronous loco-regionally advanced GC: 4.8 months (range 0.0–67.4) versus 4.7 months (range 0.0–28.3). Using multivariate Cox analysis, positive prognostic factors for survival were good performance status at diagnosis and treatment with palliative chemotherapy and/or radiotherapy. Synchronous DM was a negative prognostic factor. The mOS did not differ when comparing the time period 2000–2004 (5.1 months, range 0–67.4) with the period 2005–2009 (4.0 months, range 0.0–28.3).ConclusionPeritoneal involvement occurred in almost half of the patients with GC in this study and was associated with short life expectancy. New treatment strategies are warranted.

Surgical outcomes of laparoscopic endometriosis surgery: a 6 year experience

Objectives: The aim of the present study was to review 6 year experience on the surgical outcomes of laparoscopic endometriosis surgery.Methods: A cohort study was performed in Shiraz University of Medical Sciences using data from medical records of 1315 cases of patients with endometriosis undergoing laparoscopic surgery with follow-up of 6 to 72 months.Results: This study concerned a cohort of 1315 patients diagnosed with endometriosis operated between April 2010 and April 2016, 1086 (82.5%) of whom were in stage III and IV; 968 (73.61%) had endometrioma (regardless of having deep infiltrative endometriosis [DIE] or peritoneal involvement) and 347 (26.39%) of patients had either DIE or peritoneal involvement without endometrioma. Regarding the patients, unilateral endometrioma was statistically significant in the left ovary (p = .002). One hundred and thirty-three (10.7%) rectal wall, 7 (0.32%) sigmoid colon, 4 (0.18%) vagina, 125 (5.6%) ureter and 33 (1.52) bladder involvements were detected. Prior to operation, the pain VAS score was 8.23 ± 2.03, which decreased to 4.46 ± 2.47 in 93.07% of patients. Fifty-three patients (6.56%) needed reoperation. Sixty-six (33.1%) infertile women had spontaneous pregnancy and 15 (25%) became pregnant using intrauterine insemination (IUI) or assisted reproductive technique (ART) post-operatively.Conclusion: Surgical treatment of endometriosis seems to be an effective treatment. DIE can be present in the absence of endometrioma. The rate of left endometrioma is higher due to the pressure effect of the sigmoid colon. Nonetheless, if an expert surgeon performs this procedure, not only the rate of post-operative complications, but also the possibility of recurrence would decrease.

Ileus in Adults.

Ileus is one of the more common suspected diagnoses in everyday clinical practice. The term can refer either to mechanical or to functional ileus. Any physician who takes care of patients can be confronted with these entities; thus, all should be familiar with them and competent in their management. Recommendations are summarized for the diagnostic evaluation and treatment of ileus of various causes on the basis of a selective literature review. The manifestations of ileus and its degree of severity generally depend on the site of blockage. The rule until recently was that a patient with suspected mechanical ileus should be taken to surgery within 12 hours; today, however, ileus-particularly of the small bowel-can often be successfully treated conservatively. Likewise, functional ileus only rarely requires surgery: supportive measures, depending on the etiology, usually suffice. Proper treatment depends on the timely determination of the pathogenesis (mechanical versus functional) and on close interdisciplinary collaboration. A special challenge is posed by patients with peritoneal involvement with cancer who present with symptoms of ileus, in whom a clear distinction between mechanical and functional causation cannot always be drawn.

Surgery for pancreatic ductal adenocarcinoma.

Surgical resection is the only potentially curative option in the treatment of pancreatic ductal adenocarcinoma. Preoperative radiological imaging allows to rule out the presence of metastases. Three resectability categories are established based on the radiological findings depending on the degree of contact between the tumor and the blood vessels. Histological confirmation of malignancy is only required in cases of borderline or non-resectable tumors, prior to neoadjuvant treatment initiation. Diagnostic laparoscopy is recommended in the presence of large tumors of the body or tail and in borderline tumors to explore the possibility of resection and to apply treatment with curative intent, as well as in those cases with high level of biomarkers to rule out peritoneal involvement. Prior to surgery preoperative nutritional measures as well as endoscopic biliary drainage can be applied to optimize patient's conditions. Cephalic pancreaticoduodenectomy is the recommended surgical technique in tumors located in the head of the pancreas. The benefits from pyloric preservation, type or reconstruction (one vs. two loops), type of anastomosis (pancreaticojejunostomy vs. pancreaticogastrostomy), intraoperative biopsy of the pancreatic resection margin or the use of intraperitoneal drainages are inconclusive. Total pancreatectomy and/or portal resection should only be performed in particular cases; however, arterial resections have shown no benefits. Radical antegrade modular pancreaticosplenectomy, that can be performed laparoscopically, is the technique used for those tumors located in the pancreatic body-tail.

Bilateral blockade of MEK- and PI3K-mediated pathways downstream of mutant KRAS as a treatment approach for peritoneal mucinous malignancies.

Mucinous colorectal adenocarcinomas (MCAs) are clinically and morphologically distinct from nonmucinous colorectal cancers (CRCs), show a distinct spectrum of genetic alterations (higher KRAS mutations, lower p53, high MUC2), exhibit more aggressive behavior (more prone to peritoneal dissemination and lymph node involvement) and are associated with poorer response to chemotherapy with limited treatment options. Here, we report the effectiveness of combinatorial targeting of two KRAS-mediated parallel pathways in reducing MUC2 production and mucinous tumor growth in vitro and in vivo. By knockdown of mutant KRAS we show that, mutant KRAS (a) is necessary for MUC2 production in vitro and (b) synergistically engages PI3K/AKT and MEK/ERK pathways to maintain MUC2 expression in MCA cells. These results define a novel and a previously undescribed role for oncogenic KRAS in mucinous cancers. MCA cells were sensitive to MEK inhibition suggesting cellular dependence (‘addiction’) of KRAS-mutant MCA cells on hyperactivation of the MEK-driven pathway. Interestingly, MCA cells, though initially sensitive, were later resistant to PI3K single agent inhibition. Our studies suggest that this resistance involves dynamic rewiring of signaling circuits mediated through relief of RTK inhibition and MEK-ERK rebound activation. This resistance however, could be overcome by co-targeting of PI3K and MEK. Our studies thus provide a rational basis for MEK- and PI3K-targeted combination therapy for not only KRAS mutant MCA but also for other related mucinous neoplasms that overproduce MUC2 and have a high rate of KRAS mutations such as pseudomyxoma peritonei.

Clinical Presentation in a Series of Eight Children with Abdominal Tuberculosis: Experience of a Single-Center in Turkey

Background: Abdominal tuberculosis, the sixth commonest extrapulmanory tuberculosis, is easily misdiagnosed due to nonspecific gastrointestinal symptoms. The diagnosis is highly dependent on clinician’s suspicion of the disease; therefore to increase awareness we retrospectively reviewed clinical features of eight children in a four year-period. Methods: The medical records of children with abdominal TB were retrospectively reviewed. The diagnosis of abdominal TB was defined as Mycobacterium tuberculosis infection of gastrointestinal tract along with peritoneal or solid organ involvement. Results: There were six girls and two boys with a mean age of 13.6 ± 2.8 years (range, 7 - 16 years). Abdominal pain and weight loss were common complaints in all patients (100%) at presentation; fever was present in four (50%) patients and abdominal distension in two (25%) patients. Mean duration of symptoms before diagnosis was 2.5 ± 1 months. Laparotomy performed in six patients, and the peritoneum was the most common infection site (in 5 patients). Chest X-rays of 7 patients indicated lung involvement. The most common abdominal computed tomography and ultrasonography finding was ascites. Bowel wall thickening was recorded in 2 patients and ileal thickening in 1 patient. Inguinal lymphadenopathy and multiple mesenteric lymphadenitis were present as single cases. Conclusions: The abdominal tuberculosis should be suspected in children with ongoing abdominal pain, fever, and abdominal distension, laparoscopy or laparotomy could be useful in the differential diagnosis and utilizing imaging techniques, invasive methods with clinical suspicion may prevent delay of the diagnosis.

Neoplasms of the Appendix: Pictorial Review with Clinical and Pathologic Correlation.

Appendiceal neoplasms are uncommon tumors of the gastrointestinal tract that may manifest with symptoms of appendicitis, right lower quadrant pain, or palpable mass, leading to imaging or surgical intervention. The majority of appendiceal masses consist of primary epithelial neoplasms and neuroendocrine tumors (NETs). Epithelial neoplasms-mucinous and nonmucinous types-are more often detected at imaging than NETs due to their larger size and propensity for peritoneal spread and metastatic disease. Epithelial mucinous neoplasms are defined by the presence of mucin, detected at radiologic and pathologic examination. A mucocele or pseudomyxoma peritonei from epithelial mucinous tumors are the two most common cross-sectional imaging findings of appendiceal mucinous neoplasms. Nonmucinous epithelial tumors are less common and manifest as masses similar to colonic-type malignancies. NETs are often discovered incidentally at appendectomy due to their small size and nonaggressive behavior. Imaging findings of primary appendiceal tumors may overlap with those of acute appendicitis. Additionally, an appendiceal mass may cause acute appendicitis, obscuring the underlying mass. Other neoplasms including lymphoma, sarcoma, mesenchymal and nerve sheath tumors, or secondary malignant involvement of the appendix are rare. Treatment depends on the histologic subtype and extent of disease. Detailed description of organ, nodal, and peritoneal involvement informs surgical management with the goal of complete cytoreduction. Novel treatments such as hyperthermic intraperitoneal chemotherapy have increased survival for patients with mucinous tumors. ©RSNA, 2017.

Ginsenoside Rg3 to regulate the EMT induced by TGF-in gastric cancer.

e23200 Background: To discuss the regulate effect of Ginsenoside Rg3 during the TGF-β1 induced EMT in human gastric cancer SNU-601 cell line. Methods: In the first part of our experiment, ninety-nine patients who were diagnosed as gastric cancer were admitted to this study eventually. The Luminex® xMAP technology was used to measure the plasma levels of TGF-β1. In the second part, human gastric cancer SNU-601 cell line were cultured normally. Inverted microscope was used to observe morphological changes. The cell relative growth rate of proliferation was analyzed by MTT assay. Wound-healing assay and transwell invasion assay were carried out to predict the capacity of Ginsenoside Rg3 in inhibiting migration and invasion. Western Blot was performed to analyze the influence of Ginsenoside Rg3 and TGF-β1 on the protein expression of E-cadherin and Vimentin. Results: The plasma cytokine levels of TGF-β1 were associated with vessel invasion, peritoneal involvement, TNM stage, T stage, N stage in gastric cancer patients. In Vitro Study, TGF-β1 stimulated epithelial-mesenchymal transition in SNU-601 cell lines. Ginsenoside Rg3 inhibited the TGF-β1 induced morphological changes, cell proliferation increase, cell migration and cell invasion. Ginsenoside Rg3 markedly increased expression of the epithelial marker E-cadherin, and repressed the upregulation and expression of the mesenchymal marker Vimentin during the TGF-β1 induced EMT in SNU-601 cell line. Conclusions: The plasma cytokine levels of TGF-β1 were associated with vessel invasion, peritoneal involvement, tumor stage in gastric cancer patients. TGF-β1 stimulated biological malignant behavior through EMT in gastric cancer. Ginsenoside Rg3 could inhibit the EMT induced by TGF-β1 in SNU-601 cell lines.

Retrospective study of nonmucinous appendiceal adenocarcinomas: role of systemic chemotherapy and cytoreductive surgery

BackgroundMucinous appendiceal adenocarcinomas (AAs) are the most common histological subset of AAs. Nonmucinous AAs have been infrequently studied. We performed a single-center retrospective study to investigate this histological subtype.MethodsWe reviewed 172 patient records with nonmucinous AAs treated at MD Anderson Cancer Center from Jan, 1990 to Jun, 2015 and recorded patient demographics, tumor characteristics, treatment, and outcomes. Response rate (RR) was assessed semi-quantitatively (response/no response) according to the treating physician’s findings. Survival outcomes were calculated using the Kaplan-Meier product-limit method and compared using the log-rank test.ResultsMedian age at diagnosis was 52.9 years. Most patients presented with advanced-stage disease: stage I-II (35%), stage III (15%), and stage IV (50%). Moderate and poorly differentiated histology was seen in 56% and 44% tumors, respectively. Median overall survival (OS) of all patients was stage-dependent and was 88.5, 39.2, and 28.3 months for stages I-II, stage III, and stage IV disease, respectively (p < 0.0001). In patients with metastatic disease, only 10% had extraperitoneal disease without peritoneal involvement. Cytoreductive surgery (CRS) was attempted in 31/69 (45%) patients with disease confined to the peritoneum. Complete CRS was achieved in 18. Median OS for patients receiving complete CRS was 48.6 months. Systemic chemotherapy was administered to 109 (86%) patients with metastatic disease; a large majority of patients received either an oxaliplatin-based (55%) or irinotecan-based (27%) regimen. Chemotherapy resulted in a semi-quantitative RR of 54% and median time to progression (TTP) of 9.4 months (95% CI, 8.03–11.50). Patients who received combination chemotherapy (either oxaliplatin or irinotecan-based) showed significantly longer median OS (p = 0.003), compared to those receiving fluoropyrimidine monotherapy.ConclusionsThis is one of the first studies to report specifically on nonmucinous AAs. Nonmucinous AAs presented with moderate or poorly differentiated histology with a predilection for peritoneal metastasis. Systemic chemotherapy is active in this AA subtype. Though CRS was infrequently used, complete CRS appears beneficial and warrants further investigation.

Prevalence and clinical impact of vitamin D deficiency on abdominal tuberculosis.

Vitamin D is recognised to have multiple actions, including role in immune modulation. The prevalence and impact of vitamin D deficiency (VDD) in abdominal tuberculosis is unknown. We report the prevalence and clinical impact of VDD in patients with abdominal tuberculosis. The patients were divided into two groups: VDD (<20 ng/ml) or vitamin D sufficient (VDS) (⩾20 ng/ml). Groups were compared for extent (abdominal alone or extra-abdominal also) of disease and pattern of involvement (intestinal, peritoneal or both) and inflammatory response [serum C-reactive protein (CRP)]. Of 63 patients, 53 had complete data (mean age: 36.3 ± 14.43, 31 males). Fourty-five (84.9%) patients had VDD and mean VD levels were 11.1 ± 10.1 ng/ml. Of 8 patients with VDS, 1 (12.5%) had extra-abdominal involvement while 13 (28.9%) with VDD had extra-abdominal involvement (p = 0.066). The mean CRP in patients with VDD was 42.9 ± 34.9 mg/dl vis-a-vis 105.38 ± 64.8 in VDS (p ⩽ 0.05). All seven patients with both intestinal and peritoneal involvement had VDD. VDD is common in abdominal tuberculosis and may be associated with more extensive involvement albeit a reduced inflammatory response.

Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer

Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection. The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie-fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013. Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT. The primary end point was overall survival. In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized peritoneal involvement (4 [6.7%]), or other (8 [13.3%]) incurable sites. Median overall survival was 22.9 months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7 months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (P < .001). The response rate for arm B was 60% (complete, 10%; partial, 50%), which is higher than the 43.3% for arm C. In arm B, 36 of 60 patients (60%) proceeded to surgery. The median overall survival was 31.3 months (95% CI, 18.9-upper level not achieved) for patients who proceeded to surgery and 15.9 months (95% CI, 7.1-22.9) for the other patients. Patients with limited metastatic disease who received neoadjuvant chemotherapy and proceeded to surgery showed a favorable survival. The AIO-FLOT3 trial provides a rationale for further randomized clinical trials. clinicaltrials.gov identifier: NCT00849615.

Adnexal masses associated with peritoneal involvement: diagnosis with CT and MRI.

Given the unique intra-peritoneal anatomic location of the adnexa, tubo-ovarian diseases can commonly spread into the peritoneal cavity. Peritoneal seeding may occur in a spectrum of adnexal conditions including infectious diseases, endometriosis, and benign or malignant primary or secondary ovarian tumors. CT is usually the imaging modality on which the concomitant involvement of the peritoneum and the ovary is depicted. The first diagnosis to be considered by the radiologist is generally peritoneal carcinomatosis from ovarian cancer but other conditions cited above have also to be borne in mind and may be suggested on the basis of careful assessment of CT findings or on further MR findings. MRI may indeed help characterize the lesions in some cases. The purpose of this review is to describe the clinical and imaging patterns of peritoneal involvement that may be found in association with different ovarian lesions. Familiarity with these patterns and diagnoses will help the radiologist narrow the differential diagnosis and make an accurate diagnosis, thus facilitating patient management and avoiding unnecessary invasive treatment.

Estimating 12-week death probability in patients with refractory metastatic colorectal cancer: the Colon Life nomogram

Regorafenib and TAS-102 have recently demonstrated statistically significant survival gains in patients with refractory metastatic colorectal cancer (mCRC). Life expectancy ≥12weeks was an inclusion criterion in registrative trials, and the identification of proper clinical selection tools for the daily use of these drugs in heavily pre-treated patients is needed to improve the cost-benefit ratio. We aimed at building a nomogram able to predict death probability within 12weeks from the date of assessment of refractory mCRC. Four hundred eleven refractory mCRC patients with ECOG performance status (PS) ≤2 receiving regorafenib, TAS-102 or other treatments were used as developing set. Putative prognostic variables were selected using a random forest model and included in a binary logistic model from which the nomogram was developed. The nomogram was externally validated and its performance was evaluated by examining calibration (how close predictions were to the actual outcome) and discriminative ability (Harrell C index) both on developing (internal validation) and validating (external validation) sets. Four variables were selected and included in the nomogram: PS (P < 0.0001), primary tumor resection (P = 0.027), LDH value (P = 0.0001) and peritoneal involvement (P = 0.081). In the developing set, the nomogram discriminative ability was high (C = 0.778), and was confirmed in the validating set (C = 0.778), where the overall outcome was better as a consequence of the enrichment in patients receiving regorafenib or TAS-102 (46% versus 34%; P < 0.0001). Our nomogram may be a useful tool to predict the probability of death within 12weeks in patients with refractory mCRC. Based on four easy-to-collect variables, the 'Colon Life' nomogram and free app for smartphones may improve mCRC patients' selection for later-line therapies and assist researchers for the enrollment in clinical trials in this setting.

The relationship between tumor location, tumor microenvironment, systemic inflammation, and cancer-specific survival in patients undergoing surgery for colon cancer.

689 Background: Evidence from clinical trials and cohort studies suggest primary tumour location is a prognostic factor in patients with advanced colorectal cancer and that right and left colonic tumours should be considered as distinct clinical and biological entities. The aim of the present study was to examine the relationship between tumour location, tumour microenvironment, systemic inflammatory response (SIR), and cancer-specific survival (CSS) in patients undergoing surgery for colon cancer. Methods: Clinicopathological characteristics were extracted from a prospective database of patients who underwent potentially curative surgery for colon cancer between 1997 and 2016, at a single centre. The tumour microenvironment was assessed retrospectively using routine H&amp;E pathological sections. Results: 722 patients were included. The majority of patients were over the age of 65 years (69%), were male (52%), had right-sided (RS) tumour location (63%), had TNM stage I/II disease (64%) and 25% received adjuvant chemotherapy. RS location was associated with poor tumour differentiation ( p =&lt; 0.001) and high venous invasion ( p =0.003) but not with TNM stage (p= 0.310), perineural invasion ( p= 0.286), tumour budding ( p= 0.568), margin involvement ( p= 0.424), peritoneal involvement ( p= 0.689), tumour necrosis ( p= 0.423) or tumour cell proliferation ( p= 0.605). RS location was not associated with tumour inflammatory cell infiltrate at the margin (CD3+ p= 0.103, CD8+ p= 0.620) or in the tumour (CD3+ p= 0.540, CD8+ p= 0.713) or with tumour stroma percentage ( p= 0.843). RS location was associated with high mGPS ( p =0.007) and neutrophil:platelet score ( p =0.001) but not NLR ( p= 0.387). Finally, there was no difference between RS and left sided tumour location in the administration of adjuvant chemotherapy (p= 0.901) or CSS ( p= 0.951). Conclusions: Few clinicopathological features were associated with tumour location in patients undergoing surgery for colon cancer. However, RS tumour location was consistently associated with a higher SIR. This may account for the poor prognosis associated with RS tumours in patients with advanced colon cancer.