Diagnosis and treatment of gallbladder and gastric multiple primary malignancies: a rare case report

Laparoscopic left hemihepatectomy by the hilar plate first approach (with video)

Lateral approach toward hepatoduodenal ligament during laparoscopic radical cholecystectomy for Gallbladder cancer

Multiple primary malignancies (MPM) are rare. In particular, synchronous gallbladder and gastric malignancies are extremely rare, are associated with a concealed onset and atypical symptoms, and are highly likely to be overlooked or misdiagnosed. The clinical data of two patients with synchronous gallbladder and gastric malignancies are herein reported and integrated with the relevant literature to retrospectively analyze and summarize the pathogenesis and clinical characteristics of MPM. Case 1 was a male 46-year-old patient who underwent laparoscopic cholecystectomy, and succumbed to extensive tumor metastasis 2 months after the operation. Case 2 was an 80-year-old female patient who was treated with distal gastrectomy for gastric cancer, cholecystectomy, gastrojejunostomy and dissection of 5 suprapyloric, 6 subpyloric, 7 left gastric and 8 common hepatic artery lymph nodes, and succumbed to multiple organ failure induced by extensive tumor invasion within 1 week after the operation. Clinical physicians must pay closer attention to early symptoms of MPM in order to make an accurate diagnosis, perform timely radical surgical treatment and achieve favorable therapeutic outcomes, in terms of significantly increasing long-term patient survival rates.

Gallbladder cancer (GBC) is rare in Western populations and data about treatment and outcomes are scarce. This study aims to analyze survival and identify opportunities for improvement using population-based data from a low-incidence country. GBC patients diagnosed between 2005 and 2016 with GBC were identified from the Netherlands Cancer Registry. Patients were grouped according to time period (2005–2009/2010–2016) and disease stage. Trends in treatment and overall survival (OS) were analyzed. In total 1834 patients were included: 661 (36%) patients with resected, 278 (15%) with non-resected non-metastatic, and 895 (49%) with metastatic GBC. Use of radical versus simple cholecystectomy (12% vs. 26%, p < 0.001) in early (pT1b/T2) GBC increased. More patients with metastatic GBC received chemotherapy (11% vs. 29%, p < 0.001). OS improved from 4.8 months (2005–2009) to 6.1 months (2010–2016) (p = 0.012). Median OS increased over time (2005–2009 vs. 2010–2016) in resected (19.4 to 26.8 months, p = 0.038) and metastatic (2.3 vs. 3.4 months, p = 0.001) GBC but not in unresected, non-metastatic GBC. In early GBC, patients with radical cholecystectomy had a median OS of 76.7 compared to 18.4 months for simple cholecystectomy (p < 0.001). Palliative chemotherapy showed superior (p < 0.001) survival in metastatic (7.3 versus 2.1 months) and non-resected non-metastatic (7.7 versus 3.5 months) GBC. In conclusion, survival of GBC remains poor. Radical surgery and palliative chemotherapy appear to improve prognosis but remain under-utilized.

e15516 Background: The biology of microsatellite instability-high (MSI-H) in elderly colorectal cancer (CRC) patients is attributed to hypermethylation of promoter region of genes coding for mismatch repair proteins. It is unknown if such patients are predisposed to other malignancies. It is also unknown if the presence or absence of multiple primary malignancies affects elderly MSI-H CRC patients' survival. We aimed to evaluate the clinicopathologic features and outcomes in elderly CRC patients with MSI-H and multiple primary malignancies. Methods: We analyzed the National Cancer Database and included elderly (≥ 65 years) patients with CRC diagnosed between 2010-2016. MSI status was determined using genetic and immunohistochemical testing and categorized as microsatellite stable (MSS) and MSI-H. We further categorized the population into single primary malignancy versus multiple primary malignancies. We compared the baseline characteristics using the Chi-square test. Kaplan-Meier and log-rank tests were performed to calculate the overall survival (OS). Results: Among 52,494 elderly CRC patients, 78.0% were MSS, and 22.0% were MSI-H. The probability of MSI-H disease increased with increasing age, female gender, and non-Hispanic White ethnicity (all p &lt; .001). MSI-H patients were associated with elevated CEA, wild-type KRAS, multiple neoplasms, right-sided tumors, stage II disease, and grade III/IV histology. The proportion of patients with multiple primary malignancies was higher in the MSI-H population versus MSS (36% vs. 31%, p &lt; 0.001). The rate of multiple primary malignancies increased with age in both groups. Among MSI-H CRC patients, the factors associated with multiple primary malignancies included female gender (61.6%), non-Hispanic White ethnicity (86.3%), comorbidity index ≥ 2 (14.8%), and right-sided tumors (77.2%). Multiple primary malignancies were more frequently associated with stage I-III CRC as compared to metastatic CRC. For stage III-IV elderly MSI-H patients, the utilization of chemotherapy was 57.8% overall, but it was not significantly different between single primary malignancy versus multiple primary malignancies groups. MSI-H patients with single primary malignancy had the highest OS, followed by MSS patients with single primary malignancy, MSI-H patients with multiple primary malignancies, and MSS patients with multiple primary malignancies (74.7, 66.7, 58.1, 54.8 mos, respectively) (log-rank p &lt; 0.001). Conclusions: Elderly CRC patients with MSI-H had a higher rate of multiple primary malignancies than MSS. This was associated with female gender, non-Hispanic White ethnicity, and right-sided tumor. MSI-H patients with single primary malignancy had the highest survival while the presence of multiple primary malignancies adversely affected survival in both MSI-H and MSS populations.

Background: Gallbladder cancer (GBC) is a highly lethal malignancy that is often asymptomatic in its early stages and difficult to treat once clinical symptoms appear. Although established risk factors include female sex, gallstones, and chronic biliary inflammation, other clinical contexts associated with GBC remain insufficiently characterized. Multiple primary malignancies (MPMs), in which more than one primary cancer develops in the same individual, have recently attracted attention; however, their relationship with GBC has only rarely been examined. In this study, we aimed to clarify the clinical features of MPM-related GBC and explore its implications for early detection. Methods: We retrospectively compared 22 patients with GBC associated with other malignancies (MPM-positive GBC) and 16 patients with GBC alone (MPM-negative GBC). Clinical characteristics, major risk factors, tumor presentation, and imaging findings were evaluated. Special attention was paid to the sequence of cancer development and the diagnostic utility of contrast-enhanced ultrasonography (CEUS). Results: In all MPM-positive cases, GBC occurred as a second primary malignancy, most commonly following gastrointestinal cancers (12/22). Gallstones were significantly less frequent in the MPM-positive group than in the MPM-negative group (2/22 vs. 6/16). The MPM-positive group showed a slight male predominance (12 males and 10 females). Neither pancreaticobiliary maljunction nor porcelain gallbladder was identified in either group. CEUS was useful for both the detection and qualitative diagnosis of GBC in all patients. Conclusions: MPM-related GBC frequently develops as a second primary malignancy in patients with prior gastrointestinal cancer and may arise in the absence of classical risk factors. Careful long-term surveillance after cancer treatment is therefore essential for identifying second primary GBC at a potentially resectable stage. The combined use of ultrasonography and CEUS may facilitate earlier and more accurate diagnosis in this clinical setting.

BACKGROUNDThe diagnosis of multiple primary malignancies (MPMs) has increased due to the improvements and development of diagnostic techniques, in conjunction with extended life span. Notably however, reports of synchronous quadruple primary malignancies remain extremely rare.CASE SUMMARYHerein we describe the case of a 56-year-old woman who was diagnosed with synchronous quadruple multiple primary cancers, namely an endocervical adenocarcinoma admixed with neuroendocrine features, localized endometrial endometrioid adenocarcinoma, unilateral endometrioid ovarian carcinoma, and gastric adenocarcinoma. All four of these tumors were removed in one combined surgical procedure.CONCLUSIONTo our knowledge the above-described combination of multiple synchronous primary malignancies has not been previously reported. The nature of the association between them is unknown. Further research should focus on the etiology and mechanisms involved in MPMs.

Multiple primary Malignancies in patients with HCC; Is it a poor prognosis factor for overall survival?

Curative surgical resection for initially unresectable metastatic gallbladder cancer following neoadjuvant chemotherapy: Case report and review of literature.

Introduction: Early diagnosis and effective local and systemic therapy has reduced the risk of relapse and death from breast cancer; thus, patients are living longer but experience an increased risk for the development of multiple primary malignancies (MPM). Risk factors for MPM may be genetic, related to environmental or behavioral factors, or to breast cancer treatments such as radiotherapy, chemotherapy or hormone therapy. Controversy exists over the role of obesity and breast cancer outcomes and there is little information on long-term survivors. LSUHSC-Shreveport provides care for a predominantly indigent with high rates of obesity. This allows us to study the role of obesity in MPM before and after breast cancer diagnosis. In this study, we sought to determine the prevalence and risk factors for MPM in women with early stage breast cancer with emphasis in the role of obesity. Methods: We performed a retrospective analysis of all patients treated for invasive breast cancer from 1980 through 2006 at LSUHSC Shreveport. Patients with stage IV at diagnosis were excluded. Multiple primary malignancies (MPM) were defined as a different diagnosis of primary malignancy in patients with a history of breast cancer. MPM were divided in two categories depending on the interval between malignancy and breast cancer diagnosis. Tumors diagnosed before and within 3 months after breast cancer diagnosis were termed prior/synchronous tumors (PST). Tumors diagnosed ≥ 3 months after breast cancer diagnosis were termed secondary tumors (ST). We reviewed the demographics, smoking status, BMI at diagnosis of breast cancer, tumor characteristics, breast cancer treatments, site and date of MPM and last follow up. Descriptive statistics were performed to characterize the group of patients who developed MPM. Log rank test was used to estimate differences in overall survival between patients with MPM and without it. Results: Of the 1246 patients analyzed, 48% were obese and 29% were overweight. MPM was found in 164 patients (13%): 46 patients had PST and 118 had ST. The median time for development of PST was 6.9 years prior to breast cancer diagnosis with the most common cancers being endometrial cancer (26%), lymphoma (17%) and melanoma (6%). The median time for the development of ST was 7.6 years after breast cancer diagnosis with the most common cancers being breast cancer (54%), endometrial cancer (13%) and colon cancer (5%) The risk for development of ST increased with length of follow up: 2.3% at 5 years and 10% at 10 years. Patients with ST were more likely to be obese (59%, p=0.03) and to have received radiotherapy (60%, p=0.01) than patients without ST. No differences were observed with race, age at diagnosis, tumor characteristics or breast cancer treatments in patients with MPM. The median overall survival was 5.7 years with no difference in overall survival in patients with MPM (p=0.57). Conclusions: Our study has some limitations typical of retrospective studies and the generalization of the results may be limited. MPM does not affect the overall survival of breast cancer patients and both primary cancers should receive appropriate management with curative intent. We found that obesity at diagnosis of breast cancer is associated with a higher risk of ST. Further studies are needed to define the association of obesity and ST in women with early stage breast cancer. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A73.

Laparoscopic radical cholecystectomy is worthwhile!

Multiple primary malignancies (MPM) have become increasingly prevalent worldwide. This investigation was aimed at establishing the clinicopathological characteristics of MPM patients and evaluating the impact of the living environment on MPM in the Taiwanese population. From January 2009 to December 2013, a total of 8,268 cancer patients were identified in our institutional center. Of these, 125 were diagnosed as MPM and thus enrolled. Data for clinicopathological features and treatment approaches for these MPM patients living in urban or suburb zone were obtained. Findings for the air pollution status in Taiwan were also collected. The most common cancer match of MPM was esophageal cancer with hypopharyngeal cancer (12.8%), followed by colorectal cancer with gastric cancer (6.4%) and colorectal cancer with breast cancer (5.6%). The air quality was significantly worse in the urban than in the suburban zone and there was a remarkably higher portion of MPM patients in the urban zone suffering from grade III and IV post-chemotherapeutic neutropenia (30.8% vs 15.1%, P=0.036). The tumor frequency and site distribution should be taken into the clinical evaluation because there is a relatively high risk of developing MPM. This study also highlighted the potential influence of environmental factors on post-chemotherapeutic neutropenia for patients with MPM.

Background: Improvement in the prognosis of colorectal cancer (CRC) patients has led to increasing occurrences of multiple primary malignancies (MPMs) alongside CRC but little is known about their characteristics. This study was undertaken to clarify the clinical and pathological features of MPMs, especially those at extra colonic sites, in patients with CRC. Methods: We reviewed 1,111 patients who underwent operations for primary sporadic CRC in Saitama Medical Center, Jichi Medical University between April 2007 and March 2012. Two patients with familial adenomatous polyposis, one with hereditary non-polyposis colorectal cancer, two with colitic cancer, and any patients with metastasis from CRC were excluded. We compared the clinicopathological features of CRC patients with and without MPMs. As a control, we used a database compiled of patients with gastric cancer (GC) detected by mass screening performed in the Saitama Prefecture in Japan 2010 and compared these with CRC patients with synchronous GC. Results: Multiple primary malignancies at extracolonic sites were identified in 117 of 1,111 CRC patients (10.5%). The median age was 68 (range, 29 to 96) versus 71 (50 to 92) (P<0.001). The incidence of GC (44.4% (52 of 117)) was the highest of all MPMs. All CRC patients with GC were older than 57 years. Synchronous GC was detected in 26 patients. By contrast, out of 200,007 screened people, 225 people were diagnosed as having GC in the Saitama Prefecture. The age-standardized incidence of synchronous GC in CRC patients was significantly higher (0.53%) than in the control group (0.03%) (odds ratio, 18.8; 95% confidence interval, 18.6 to 19.0; P<0.001). Conclusion: Patients with CRC who were older than 50 years preferentially developed GC synchronously and metachronously. Thus, this patient group should undergo careful perioperative screening for GC.

BACKGROUND Multiple primary malignancies in a single patient are considered to be quite rare. However, due to the wider availability of advanced imaging methods and, more regular check-ups, they are becoming more common in clinical practice. To determine the diagnosis of multiple primary malignancies, each tumor must be completely separate and cannot be from metastasis of one or the other. Coexisting hepatocellular carcinoma and gallbladder carcinoma are extremely rare, with only a few case reports published. We believe that to determine the most effective therapeutic management, the results of as many cases as possible should be documented. Regardless of limited data, curative resection may be the most beneficial treatment option in terms of overall survival. CASE REPORT We present the case of a 64-year-old man first diagnosed with hepatocellular carcinoma with possible infiltration of the gallbladder wall as appeared on a CT scan. However, the definitive histopathologic examination revealed the coexistence of hepatocellular carcinoma and gallbladder carcinoma. In this case report, we offer an insight into the entire diagnostic process, as well as the chosen surgical approach and adjuvant therapy. Moreover, we present our approach to preoperative biopsy, the decision-making process throughout the whole diagnostic and therapeutic course, and the achieved results. CONCLUSIONS In cases of double primary malignancies, the choice of therapeutic strategy depends on the type and stage of both malignancies, but procedures with curative intent are superior. We present the outcome and overall survival of the patient after the surgery and adjuvant chemotherapy for synchronous hepatocellular carcinoma and gallbladder carcinoma. Since the liver is the organ most commonly affected by metastatic dissemination of primary tumors, exclusion of metastatic disease is particularly important.

As a result of recent advances in diagnostic techniques and treatment modalities, the number of patients diagnosed with multiple primary malignancies has been increasing. We report the case of a 79-year-old male with multiple primary malignancies of three histological types in six different organs: Stomach, prostate, colon, urinary bladder, facial skin and pancreas, in chronological order. The first malignancy was upper gastric cancer diagnosed in 1998. The second and third malignancies were prostate cancer and ascending colon cancer, which were diagnosed in 2010. The fourth malignancy was bladder cancer diagnosed in 2011. The fifth and sixth malignancies were squamous cell skin cancer of the right cheek and intraductal papillary mucinous carcinoma (IPMC), respectively, diagnosed in 2014. The gastric cancer, colon cancer, bladder cancer, skin cancer and IPMC were surgically resected. The prostate cancer was treated by anti-androgen therapy. The patient died of local recurrence of IPMC in August 2016. Although multiple primary malignancies are not uncommon, diagnosis of six primary malignancies in a single patient, as reported in the present study, is extremely rare. It is important to understand the characteristics of multiple primary malignancies in order to administer suitable treatment and determine relevant follow-up plans for patients with cancer.