[Peritoneal carcinomatosis secondary to CUP syndrome : Diagnosis and indications for multimodal treatment]. / Peritonealkarzinose beim CUP­Syndrom : Diagnostik und Indikationsstellung für die multimodale Therapie.

CLINICAL PROBLEM: Peritoneal carcinomatosis secondary to cancer of unknown primary (CUP) syndrome is a rare entity for which there are no uniform treatment recommendations or guidelines. The median survival time is 3 months. DIAGNOSIS: Computed tomography (CT), magnetic resonance imaging (MRI), and 18F­FDG positron emission tomography (PET)/CT are valid imaging modalities for the detection of peritoneal carcinomatosis. The sensitivity of all techniques is highest for large, macronodular peritoneal carcinomatosis manifestations. A limitation of all imaging techniques is limited and small-nodular peritoneal carcinomatosis. Also, peritoneal metastasis in the small bowel mesentery or diaphragmatic domes can only be visualized with low sensitivity. Therefore, exploratory laparoscopy should be considered as the next diagnostic step. In half of these cases an unnecessary laparotomy can be avoided, because the laparoscopy revealed diffuse, small-nodule involvement of the small bowel wall and thus an irresectable situation. TREATMENT: In selected patients, performing complete cytoreduction followed by hyperthermic intra-abdominal chemotherapy (HIPEC) is a good therapeutic option. Therefore, the identification of the extent of peritoneal tumor manifestation as accurately as possible is important for the definition of the increasingly complex oncological therapy strategies.

Cancer of unknown primary (CUP) through the lens of precision oncology: a single institution perspective.

PURPOSE: For patients with cancer of unknown primary (CUP), treatment options are limited. Precision oncology, the interplay of comprehensive genomic profiling (CGP) and targeted therapies, aims to offer additional treatment options to patients with advanced and hard-to-treat cancers. We aimed to highlight the use of a molecular tumor board (MTB) in the therapeutic management of CUP patients. METHODS: In this single-center observational study, CUP patients, presented to the MTB of the Comprehensive Cancer Center Munich LMU, a tertiary care center, were analyzed retrospectively. Descriptive statistics were applied to describe relevant findings. RESULTS: Between June 2016 and February 2022, 61 patients with unfavorable CUP were presented to the MTB, detected clinically relevant variants in 74% (45/61) of patients, of which 64% (29/45) led to therapeutic recommendation. In four out of 29 patients (14%), the treatment recommendations were implemented, unfortunately without resulting in clinical benefit. Reasons for not following the therapeutic recommendation were mainly caused by the physicians' choice of another therapy (9/25, 36%), especially in the context of worsening of general condition, lost to follow-up (7/25, 28%) and death (6/25, 24%). CONCLUSION: CGP and subsequent presentation to a molecular tumor board led to a high rate of therapeutic recommendations in patients with CUP. Recommendations were only implemented at a low rate; however, late GCP diagnostic and, respectively, MTB referral were found more frequent for the patients with implemented treatment. This contrast underscores the need for early implementation of CGP into the management of CUP patients.

Skull Base Metastasis From Occult Renal Cell Carcinoma.

Skull base metastases are extremely rare. The authors report a case of a 65-year-old man who presented with a headache and diplopia secondary to a skull base metastasis from occult renal cell carcinoma. Since there were no other systemic metastases, radical nephrectomy and radiotherapy of the unresectable skull base location were performed. He subsequently received immunotherapy with sunitinib, everolimus, and sorafenib with local and systemic control of the disease after 53 months from surgery. When metastasis is unresectable radical nephrectomy and radiotherapy aimed at the metastasis may be of benefit improving quality of life. Immunotherapy may provide alternative treatment strategies improving the outcomes of patients affected by this rare pathology with historically poor prognosis.

AHNS Series: Do you know your guidelines? Guideline recommendations for head and neck cancer of unknown primary site.

This article reviews the clinical practice guidelines for head and neck oncology focusing on the management of head and neck cancers of unknown primary (CUP). The primary purpose of this series is to raise awareness of the current guidelines in head and neck oncology by reviewing the recommendations and the evidence supporting such recommendations, particularly those published by the National Comprehensive Cancer Network (NCCN). We review the importance of a thorough history and physical examination, the impact of the American Joint Committee on Cancer (AJCC) eighth edition changes and the importance of immunohistochemistry, the timing and type of imaging, the role of panendoscopy and tonsillectomy (palatine and lingual), and the role of surgery, radiation, and chemotherapy in the primary management of these tumors.

Population-based study of survival for women with serous cancer of the ovary, fallopian tube, peritoneum or undesignated origin - on behalf of the Swedish gynecological cancer group (SweGCG).

OBJECTIVE: The aim of the study was to determine survival outcome in patients with serous cancer in the ovary, fallopian tube, peritoneum and of undesignated origin. METHODS: Nation-wide population-based study of women≥18years with histologically verified non-uterine serous cancer, included in the Swedish Quality Registry for primary cancer of the ovary, fallopian tube and peritoneum diagnosed 2009-2013. Relative survival (RS) was estimated using the Ederer II method. Simple and multivariable analyses were estimated by Poisson regression models. RESULTS: Of 5627 women identified, 1246 (22%) had borderline tumors and 4381 had malignant tumors. In total, 2359 women had serous cancer; 71% originated in the ovary (OC), 9% in the fallopian tube (FTC), 9% in the peritoneum (PPC) and 11% at an undesignated primary site (UPS). Estimated RS at 5-years was 37%; for FTC 54%, 40% for OC, 34% for PPC and 13% for UPS. In multivariable regression analyses restricted to women who had undergone primary or interval debulking surgery for OC, FTC and PPC, site of origin was not independently associated with survival. Significant associations with worse survival were found for advanced stages (RR 2.63, P<0.001), moderate (RR 1.90, P<0.047) and poor differentiation (RR 2.20, P<0.009), neoadjuvant chemotherapy (RR1.33, P<0.022), residual tumor (RR 2.65, P<0.001) and platinum single (2.34, P<0.001) compared to platinum combination chemotherapy. CONCLUSION: Survival was poorer for serous cancer at UPS than for ovarian, fallopian tube and peritoneal cancer. Serous cancer at UPS needs to be addressed when reporting and comparing survival rates of ovarian cancer.

Cancer of unknown primary site.

BACKGROUND: Cancer of unknown primary (CUP) is the diagnosis given to patients with metastatic cancer with no known site of origin. OBJECTIVE: This review summarises the current knowledge regarding the epidemiology, diagnosis, treatment and care of CUP. DISCUSSION: The incidence and mortality rates of CUP are declining in Australia. CUP was the twelfth most common cancer and fifth most common cause of cancer death in 2011. Smoking is the only identified risk factor. Incidence patterns implicate reduced access to healthcare and many registered cases have only a clinical diagnosis. Favourable prognosis subtypes with specific clinical and histopathological criteria must be recognised and treated on the basis of the presumed primary site. Emerging data reveal high rates of emergency department admission, hospitalisations and psychological distress, and low rates of specialist consultations for patients with CUP. General practitioners (GPs) have a key role in earlier identification, integrated care and preventing patients with CUP from falling through the cracks.

[Structured diagnostics and therapy of the CUP syndrome]. / Strukturierte Diagnostik und internistische Therapie des CUP-Syndroms.

BACKGROUND: In the majority of cases, patients with cancer of unknown primary (CUP) have a poor prognosis with no prospect of being cured. Hence, a reasonable focus of diagnostics on its essential targets seems appropriate. PATIENTS: Particularly important is the identification of all patients who can be assigned to subgroups with a favorable prognosis and who might benefit from a specific therapy. For all other patients, platinum-based combination therapy is the standard cytostatic therapy. THERAPY: In addition to platinum derivatives, taxanes, gemcitabine and irinotecan can also be used. Promising innovative approaches include targeted therapies, in particular bevacizumab and erlotinib, and identification of the tissue origin with micro-RNA or gene expression analyses which can help identify the most suitable organ-specific therapy for individual patients. PERSPECTIVES: It would be desirable if the group of patients treated with unspecific therapy could be reduced by improved diagnostics so that these patients could be treated with organ-specific therapy or with molecularly targeted approaches. Micro-RNA and gene expression analyses appear to be interesting for this purpose. Another complementary approach is to improve the treatment results of patients receiving an unspecific standard combination therapy by additional administration of new targeted substances.

Selective neck dissection as a therapeutic option in management of squamous cell carcinoma of unknown primary.

Carcinoma of unknown primary of the neck (CUP) is a metastasis presenting in one or more cervical lymph nodes, with no primary mucosal site identified. Retrospective case notes review of 25 consecutive patients (median age 55, 72% males) diagnosed as CUP who underwent neck dissection in a UK tertiary referral comprehensive cancer centre between 2000 and 2011. Median follow-up was 33 months. Nineteen patients underwent comprehensive neck dissections (six extended), six patients had selective neck dissection. Five year disease specific survival and regional recurrence free survival were 76 and 80% respectively. The overall rate of occult disease (disease not identified on preoperative evaluation, but found on histopathologic examination) was 8%, with rates of 0% in level I and 6% in level V. Our study suggests that in patients without preoperative evidence of disease in levels I or V selective neck dissection might be considered as an option, to facilitate preservation of the submandibular gland and accessory nerve without compromising oncological outcome. Larger studies should be performed before a change in practice can be advised.

Occult primary breast cancer at a comprehensive cancer center.

BACKGROUND: Management of occult primary breast cancer (OPBC), that is, breast cancer that first presents through regional nodal or distant disease without clinical or mammographic evidence of disease in the breast, has been controversial and inconsistent. Here, we review OPBC patients treated at our institution. METHODS: We conducted a retrospective review of women diagnosed with a first primary breast cancer between March 1999 and September 2010 to identify patients who presented with isolated axillary lymphadenopathy proven to be histologically consistent with primary breast malignancy but had no evidence of a breast mass on physical examination, mammography, or ultrasound. Descriptions of treatments received, recurrence, morbidity, and mortality as of October 2012 are reported. RESULTS: Of 5533 patients reviewed, seven (0.1%) patients were identified. The median age was 65 y old (range, 40-72), and the median length of follow-up was 86 mo (range, 42-124). Four patients underwent modified radical mastectomy, one patient had a lumpectomy and axillary lymph node dissection, and two patients had axillary lymph node dissection without breast surgery. Four patients received adjuvant radiation therapy. All seven patients received chemotherapy. Three patients received endocrine therapy, and two patients received anti-HER2 therapy. At the last follow-up, all seven patients were alive with no evidence of disease. CONCLUSIONS: Although there was some variation in the management of OPBC at our institution, our patients had excellent outcomes after multimodal treatment. Our results support a curative intent approach to the treatment of OPBC and illustrate the need for individualized treatment algorithms based on tumor biology and extent of the disease at diagnosis.

Chemoembolization of intrahepatic cholangiocarcinoma with cisplatinum, doxorubicin, mitomycin C, ethiodol, and polyvinyl alcohol: a 2-center study.

BACKGROUND: Unresectable intrahepatic cholangiocarcinoma has a poor prognosis, with a median survival of 5 to 8 months without treatment. Response and survival after chemoembolization were evaluated. METHODS: Lobar or segmental chemoembolization with cisplatinum, doxorubicin, mitomycin-C, ethiodol, and polyvinyl alcohol particles was performed at monthly intervals for 1-4 sessions until the entire intrahepatic tumor burden was treated. Cross-sectional imaging and clinical and laboratory evaluation were performed before treatment, 1 month after treatment, and then every 3 months. A second cycle of treatment was performed for intrahepatic recurrence. Toxicity was assessed using NCI CTC v.3.0. Response was evaluated using RECIST criteria, and survival was estimated with Kaplan-Meier analysis. RESULTS: Sixty-two patients were treated. Thirty-seven had pathologically proven cholangiocarcinoma, and 25 had poorly differentiated adenocarcinoma of unknown primary, likely cholangiocarcinoma. One hundred and twenty-two total procedures were performed during the initial cycle of treatment (mean, 2.0 per patient). Twenty patients received a second cycle, for a total of 165 procedures. There were 5 major complications. Thirty-day disease-specific mortality was 0%. Forty-five of 62 patients were evaluable for morphologic response after completion of their initial cycle: 11% (n = 5) partial responses, 64% (n = 29) stable, and 24% (n = 11) progressed. Median time to progression from first chemoembolization was 8 months, with 28% free of progression at 12 months. Median survival from time of diagnosis was 20 months, with 1-, 2-, and 3-year survival of 75%, 39%, and 17%, respectively. Median survival from time of first chemoembolization was 15 months, with 1-, 2-, and 3-year survival of 61%, 27%, and 8%, respectively. There was no statistically significant difference in survival between patients with cholangiocarcinoma and those with poorly differentiated adenocarcinoma. Patients who also received systemic chemotherapy had improved overall survival (median 28 vs 16 months, P = .02; HR, 1.94; 95% CI, 1.13-3.33). CONCLUSIONS: Chemoembolization provided local disease control (PR + SD) of intrahepatic cholangiocarcinoma and adenocarcinoma of unknown primary in 76%. Overall survival after chemoembolization showed the best outcomes for those receiving multidisciplinary integrated liver-directed and systemic therapies.

Impact of clinical practice guidelines on the management for carcinomas of unknown primary site: a controlled "before-after" study.

BACKGROUND: In 2002, the French Federation of Comprehensive Cancer Centers published clinical practice guidelines (CPGs) for the management of carcinomas of unknown primary (CUP). METHODS: A controlled "before-after" study at two centers (experimental in Lyon, France and control in Edmonton, Canada) to assess the impact of CPGs on CUP management. Fifty-CUP patients treated in 2000-2001, i.e. before CPG publication, and 50 patients treated in 2003-2004, were analyzed for both centers. RESULTS: In both groups, compliance for diagnostic workup was the same before or after CPGs publication. Non-adenocarcinoma histology and performance status (PS) < 2 were independent factors for CPGs compliance. In the experimental group, 75% of patients underwent inappropriate investigations. The proportion of patients from this group with unfavourable clinicopathologic entity and PS < or = 1, who received cisplatin-based chemotherapy did not significantly change (2000-2001: 27% vs. 2003-2004: 37.5%; P = 0.45). However, most patients treated in the pre period received organ-specific regimens, while most patients treated in the post period received taxane or gemcitabine-based regimens. Patients from the control group generally received taxane/carboplatin. CONCLUSIONS: Our study show that simply distributing CUP CPGs did not change practice and underline the necessity to disseminate and implement CPGs, both to oncologists and organ-specialist physicians.

CUP (carcinoma of unknown primary) syndrome in head and neck: clinic, diagnostic, and therapy.

BACKGROUND: Up to 10% of all cervical lymph node metastases present without a known primary site. Between 70 and 80% of the found primary tumors are located in the head and neck region, because cervical lymph nodes represent the lymph drainage of the head and neck. PATIENTS AND METHODS: We demonstrate the clinic, diagnostic management and therapy of carcinoma of unknown primary (CUP) in this retrospective study of 75 patients who primarily presented cervical metastases with unknown primary tumor at the Otorhinolaryngological Department of the University of Leipzig, Germany. RESULTS: A primary tumor was found in 44% of the patients, and 76% of the primary tumors were localized in the head and neck region. The overall 5-year survival rate was 13.3%. The 34 patients with pretherapeutically detected primary tumors showed a tendency towards better survival, with a 5-year survival rate of 21% compared to 10% in patients with undetected primary. CONCLUSIONS: Following a thorough physical examination, radiologic imaging, i.e., computed tomography and/or magnetic resonance imaging, of the head and neck region as well a chest X ray, panendoscopy with biopsy of the most probable tumor sites, and diagnostic tonsillectomy should be performed. Further diagnostic procedures as gastroenterologic, urogenital and gynecological examinations should be performed, depending on histology and location of the node and under consideration of cost-benefit analysis. Curative treatment should at least include ipsilateral neck dissection and adjuvant irradiation of the complete cervical lymph drainage. In the literature, radiation of the laryngopharyngeal mucosa is still discussed controversially: some authors recommend the irradation of the pharyngeal mucosa extending from the nasopharynx to the upper esophagus, whereas others regard the resulting side effects as too high compared to the expected benefit.

[A CR case of amylase-producing tumor treated by hyperthermochemotherapy].

A 64-year-old female who was diagnosed with an amylase-producing tumor of unknown origin was treated by hyperthermochemotherapy. The patient was admitted with a complaint of abdominal fullness due to ascites. Laboratory examination showed high levels of serum amylase and tumor markers, including CA15-3, CA 125 and CA 72-4. Laparotomy showed peritoneal dissemination with histological findings of adenocarcinoma of unknown origin. After laparotomy, she was given hyperthermia combined with chemotherapy using carboplatin (CBDCA), mitomycin C (MMC) and doxifluridine (5'-DFUR). Hyperthermia (13.56 MHz radiofrequency for 40-50 min) was performed a total of six times within one and a half months. The total doses of CBDCA and MMC were 450 mg and 24 mg, respectively, and 600 mg of 5'-DFUR was orally administered every day. By these combined treatments, ascites disappeared and serum levels of amylase and all tumor markers were decreased and normalized. MRI and echo examination also showed complete disappearance of peritoneal metastasis. Two and a half years after the treatment, the patient is alive without any evidence of recurrence, which suggests that this combined therapy is one of the useful modalities for peritoneal dissemination as well as an inoperable tumor itself.

Recurrent Salmonella arizona infection after treatment for metastatic carcinoma.

Serious Salmonella arizona infection may be acquired through the ingestion of rattlesnake meat used as a folk medicine remedy. We report a patient with metastatic carcinoma and a remote history of rattlesnake meat ingestion who developed recurrent S. arizona bacteremia and reactivation of tuberculosis after receiving corticosteroid and radiation therapy. Physicians should be aware of the potential for rattlesnake-associated S. arizona infection to occur as either the presenting manifestation or as a complication in immunosuppressed patients who may take folk remedies, especially Hispanics who live along the United States-Mexico border.